a
stringlengths 138
8.15k
| b
stringlengths 138
8.15k
| label
int64 1
1
|
|---|---|---|
Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques.,Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique.,Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known.,To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques.,A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database.,Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”.,COPD-related events were recorded during an outcome year of follow-up.,The primary outcome measure was an incidence rate ratio (IRR) comparing the rate of exacerbations between study cohorts.,A secondary outcome compared average daily use of short-acting beta agonist (SABA).,The final study sample contained 8,225 patients in each cohort (mean age 67 [SD, 10], 57% males, 37% current smokers).,Patients in the similar-devices cohort had a lower rate of exacerbations compared with those in the mixed-devices cohort (adjusted IRR 0.82, 95% confidence interval [CI] 0.80-0.84) and were less likely to be in a higher-dose SABA group (adjusted proportional odds ratio 0.54, 95% CI 0.51-0.57).,COPD patients who were prescribed one or more additional inhaler devices requiring similar inhalation techniques to their previous device(s) showed better outcomes than those who were prescribed devices requiring different techniques.
|
Nighttime symptoms can negatively impact the quality of life of patients with chronic obstructive pulmonary disease (COPD).,The Nighttime Symptoms of COPD Instrument (NiSCI) was designed to measure the occurrence and severity of nighttime symptoms in patients with COPD, the impact of symptoms on nighttime awakenings, and rescue medication use.,The objective of this study was to explore item reduction, inform scoring recommendations, and evaluate the psychometric properties of the NiSCI.,COPD patients participating in a Phase III clinical trial completed the NiSCI daily.,Item analyses were conducted using weekly mean and single day scores.,Descriptive statistics (including percentage of respondents at floor/ceiling and inter-item correlations), factor analyses, and Rasch model analyses were conducted to examine item performance and scoring.,Test-retest reliability was assessed for the final instrument using the intraclass correlation coefficient (ICC).,Correlations with assessments conducted during study visits were used to evaluate convergent and known-groups validity.,Data from 1,663 COPD patients aged 40-93 years were analyzed.,Item analyses supported the generation of four scores.,A one-factor structure was confirmed with factor analysis and Rasch analysis for the symptom severity score.,Test-retest reliability was confirmed for the six-item symptom severity (ICC, 0.85), number of nighttime awakenings (ICC, 0.82), and rescue medication (ICC, 0.68) scores.,Convergent validity was supported by significant correlations between the NiSCI, St George’s Respiratory Questionnaire, and Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Respiratory Symptoms scores.,The results suggest that the NiSCI can be used to determine the severity of nighttime COPD symptoms, the number of nighttime awakenings due to COPD symptoms, and the nighttime use of rescue medication.,The NiSCI is a reliable and valid instrument to evaluate these concepts in COPD patients in clinical trials and clinical practice.,Scoring recommendations and steps for further research are discussed.
| 1
|
Physical activity (PA) is impaired from the early stages of COPD, is associated with a worsening of disease prognosis, and causes COPD patients to restrict their daily activities in order to avoid breathlessness.,The development of a simple tool to estimate physical activity level (PAL) could be useful for the management of COPD.,We investigated the differences in PA according to the modified Medical Research Council (mMRC) grade in patients with COPD.,A cross-sectional study was performed on stable outpatients with COPD.,PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea grade was evaluated in all patients using the mMRC scale.,Ninety-eight patients were recruited.,Significant differences in PA duration were observed at all intensities according to the mMRC grade.,Despite treatment with controller medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic equivalents multiplied by hour per day.,COPD patients with an mMRC grade ≥2, which was the most balanced cutoff point in the receiver operating characteristic curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at mMRC grade 3, and 100% at mMRC grade 4).,PA differed according to the mMRC grade, and mMRC grade ≥2 could predict a low PAL.,Therefore, assessment of breathlessness by the mMRC questionnaire would be useful to stratify the risks of reduced PA in COPD.
|
Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.
| 1
|
Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD).,Nevertheless, a minority of chronic heavy cigarette smokers develops COPD.,This suggests important contribution of other factors such as genetic predisposing.,Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment.,Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia.,Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR.,Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR = 4.07) and null-GSTM1/105Val/Val GSTP1 (OR = 3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153).,The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P = 0.01; P = 0.009; P = 0.008 and P = 0.001).,Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of ΔFEV1 in patients (P = 0.028).,In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.
|
The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.
| 1
|
CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor.,This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD).,This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study.,Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months.,Patients received CHF6001 800 or 1600 μg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler).,Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32.,Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32.,Of 61 randomised patients, 54 (88.5%) completed the study.,There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes.,CHF6001 800 μg significantly decreased the absolute number and percentage of macrophages vs placebo.,In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα).,In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo.,CHF6001 1600 μg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide).,The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy.,The study is registered on ClinicalTrials.gov (NCT03004417).,The online version of this article (10.1186/s12931-019-1142-7) contains supplementary material, which is available to authorized users.
|
Benralizumab, a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor α, depletes eosinophils and basophils by enhanced antibody-dependent cell-mediated cytotoxicity.,It demonstrated efficacy for patients with moderate to severe asthma and, in a Phase IIa trial, for chronic obstructive pulmonary disease (COPD) with eosinophilic inflammation.,We investigated effects of benralizumab 100 mg every 8 weeks (first three doses every 4 weeks) subcutaneous on blood inflammatory markers through proteomic and gene-expression analyses collected during two Phase II studies of patients with eosinophilic asthma and eosinophilic COPD.,Serum samples for proteomic analysis and whole blood for gene expression analysis were collected at baseline and 52 weeks (asthma study) or 32 weeks (COPD study) post-treatment.,Proteomic analyses were conducted on a custom set of 90 and 147 Rules-Based Medicine analytes for asthma and COPD, respectively.,Gene expression was profiled by Affymetrix Human Genome U133 plus 2 arrays (~ 54 K probes).,Gene set variation analysis (GSVA) was used to determine transcriptomic activity of immune signatures.,Treatment-related differences between analytes, genes, and gene signatures were analyzed for the overall population and for patient subgroups stratified by baseline blood eosinophil count (eosinophil-high [≥300 cells/μL] and eosinophil-low [< 300 cells/μL]) via t-test and repeated measures analysis of variance.,Eosinophil chemokines eotaxin-1 and eotaxin-2 were significantly upregulated (false discovery rate [FDR] < 0.05) by approximately 2.1- and 1.4-fold in the asthma study and by 2.3- and 1.7-fold in the COPD study following benralizumab treatment.,Magnitude of upregulation of these two chemokines was greater for eosinophil-high patients than eosinophil-low patients in both studies.,Benralizumab was associated with significant reductions (FDR < 0.05) in expression of genes associated with eosinophils and basophils, such as CLC, IL-5Rα, and PRSS33; immune-signaling complex genes (FCER1A); G-protein-coupled receptor genes (HRH4, ADORA3, P2RY14); and further immune-related genes (ALOX15 and OLIG2).,The magnitude of downregulation of gene expression was greater for eosinophil-high than eosinophil-low patients.,GSVA on immune signatures indicated significant treatment reductions (FDR < 0.05) in eosinophil-associated signatures.,Benralizumab is highly selective, modulating blood proteins or genes associated with eosinophils or basophils.,Modulated protein and gene expression patterns are most prominently altered in eosinophil-high vs. eosinophil-low patients.,NCT01227278 and NCT01238861.,The online version of this article (10.1186/s12931-018-0968-8) contains supplementary material, which is available to authorized users.
| 1
|
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability in all its stages, and death in patients with moderate or severe obstruction.,At present, COPD is suboptimally managed; current health is often not measured properly and hardly taken into account in management plans, and the future risk for patients with regard to health status and quality of life is not being evaluated.,This review addresses the effect of COPD on the lives of patients and examines ways in which existing assessment tools meet physicians’ needs for a standardized, simple method to measure consistently the full impact of COPD on patients in routine clinical practice.,Current assessment of COPD severity tends to focus on airflow limitation, but this does not capture the full impact of the disease and is not well correlated with patient perception of symptoms and health-related quality of life.,Qualitative studies have demonstrated that patients usually consider COPD impact in terms of frequency and severity of symptoms, and physical and emotional wellbeing.,However, patients often have difficulty expressing their disease burden and physicians generally have insufficient time to collect this information.,Therefore, it is important that methods are implemented to help generate a more complete understanding of the impact of COPD.,This can be achieved most efficiently using a quick, reliable, and standardized measure of disease impact, such as a short questionnaire that can be applied in daily clinical practice.,Questionnaires are precision instruments that contribute sensitive and specific information, and can potentially help physicians provide optimal care for patients with COPD.,Two short, easy-to-use, specific measures, ie, the COPD Assessment Test and the Clinical COPD Questionnaire, enable physicians to assess patients’ health status accurately and improve disease management.,Such questionnaires provide important measurements that can assist primary care physicians to capture the impact of COPD on patients’ daily lives and wellbeing, and improve long-term COPD management.
|
Early treatment of COPD exacerbations has shown to be important.,Despite a non-negligible negative impact on health related quality of life, a large proportion of these episodes is not reported (no change in treatment).,Little is known whether (low burden) strategies are able to capture these unreported exacerbations.,The Clinical COPD Questionnaire (CCQ) is a short questionnaire with great evaluative properties in measuring health status.,The current explorative study evaluates the discriminative properties of weekly CCQ assessment in detecting exacerbations.,In a multicentre prospective cohort study, 121 patients, age 67.4 ± 10.5 years, FEV1 47.7 ± 18.5% pred were followed for 6 weeks by daily diary card recording and weekly CCQ assessment.,Weeks were retrospectively labeled as stable or exacerbation (onset) weeks using the Anthonisen symptom diary-card algorithm.,Change in CCQ total scores are significantly higher in exacerbation-onset weeks, 0.35 ± 0.69 compared to -0.04 ± 0.37 in stable weeks (p < 0.001).,Performance of the Δ CCQ total score discriminating between stable and exacerbation onset weeks was sufficient (area under the ROC curve 0.75).,At a cut off point of 0.2, sensitivity was 62.5 (50.3-73.4), specificity 82.0 (79.3-84.4), and a positive and negative predictive value of 43.5 (35.0-51.0) and 90.8 (87.8-93.5), respectively.,Using this cut off point, 22 (out of 38) unreported exacerbations were detected while 39 stable patients would have been false positively 'contacted'.,Weekly CCQ assessment is a promising, low burden method to detect unreported exacerbations.,Further research is needed to validate discriminative performance and practical implications of the CCQ in detecting exacerbations in daily care.
| 1
|
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease.
|
The use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD) has been associated with an increased risk of pneumonia in controlled clinical trials and case-control analyses.,Using claims databases as a research model of real-world diagnosis and treatment, to determine if the use and dose of inhaled corticosteroids (ICS) among patients with newly diagnosed COPD are associated with increased risk of pneumonia.,This was a retrospective cohort analysis of patients diagnosed with COPD between January 01, 2006 and September 30, 2010, drawn from databases (years 2006-2010).,Patients (aged ≥45 years) were followed until first pneumonia diagnosis, end of benefit enrollment, or December 31, 2010, whichever was earliest.,A Cox proportional hazard model was used to assess the association of ICS use and risk of pneumonia, controlling for baseline characteristics.,Daily ICS use was classified into low, medium, and high doses (1 μg-499 μg, 500 μg-999 μg, and ≥1000 μg fluticasone equivalents daily) and was modeled as a time-dependent variable.,Among 135,445 qualifying patients with a total of 243,097 person-years, there were 1020 pneumonia incidences out of 5677 person-years on ICS (crude incidence rate, 0.180 per person-year), and 27,730 pneumonia incidences out of 237,420 person-years not on ICS (crude incidence rate, 0.117 per person-year).,ICS use was associated with a dose-related increase in risk of pneumonia, with adjusted hazard ratios (versus no use; (95% confidence interval) of 1.38 (1.27-1.49) for low-dose users, 1.69 (1.52-1.88) for medium-dose users, and 2.57 (1.98-3.33) for high-dose users (P < 0.01 versus no use and between doses).,The use of ICS in newly diagnosed patients with COPD is potentially associated with a dose-related increase in the risk of pneumonia.
| 1
|
Fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg is a once-daily inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment approved in the United States, Canada and Europe for the long-term maintenance therapy of COPD.,We report data from mixed treatment comparisons (MTC) of once-daily FF/VI against established twice-daily ICS/LABA combination therapies on clinical efficacy outcomes.,Data from 33 parallel-group randomised controlled trials (RCTs) of ICS/LABAs, of ≥8 weeks’ duration in patients ≥12 years of age with COPD, identified by systematic review, were analysed using covariate-adjusted Bayesian hierarchical models for three efficacy outcomes.,Lung function, assessed by change from baseline in forced expiratory volume in one second (FEV1), was the outcome of primary interest (n = 28 studies).,Secondary objectives were assessment of annual rate of moderate/severe exacerbations (n = 15) and patient-reported health status, measured by change from baseline in St George’s Respiratory Questionnaire (SGRQ) Total score (n = 20).,Overall, 25 different treatments were included in the MTC; we report findings, including probabilities of non-inferiority, for comparisons of once-daily FF/VI 100/25 mcg with twice-daily fluticasone propionate (FP)/salmeterol (SAL) 500/50 mcg and budesonide (BUD)/formoterol (FORM) 400/12 mcg.,For FEV1, FF/VI 100/25 mcg demonstrated >99% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg using a 50 mL margin.,For annual rate of moderate/severe exacerbations, FF/VI 100/25 mcg demonstrated 73% and 77% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg, respectively, using a 10% rate ratio margin.,For SGRQ Total score, the corresponding probabilities of non-inferiority were 99% and 98%, respectively, on a 2-unit margin.,Significant covariate effects were identified: increased age was associated with deterioration in FEV1 and reduced exacerbation frequency; shorter study duration was associated with reduced exacerbation frequency.,FF/VI 100/25 mcg was comparable with corresponding doses of FP/SAL and BUD/FORM on lung function and health status outcomes.,Non-inferiority on moderate/severe exacerbation rate was not demonstrated to the same degree of confidence, though observed rates were similar.,Model limitations include a weak treatment network for the exacerbation analysis and variability across the included studies.,Our data support previous RCT findings suggesting that the efficacy of FF/VI 100/25 mcg on lung function and health status in COPD is comparable with twice-daily ICS/LABAs.,The online version of this article (doi:10.1186/s12931-015-0184-8) contains supplementary material, which is available to authorized users.
|
Coadministration of mometasone furoate (MF) and formoterol fumarate (F) produces additive effects for improving symptoms and lung function and reduces exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD).,The present study assessed the relative systemic exposure to MF and characterized the pharmacokinetics of MF and formoterol in patients with COPD.,This was a single-center, randomized, open-label, multiple-dose, three-period, three-treatment crossover study.,The following three treatments were self-administered by patients (n = 14) with moderate-to-severe COPD: MF 400 μg/F 10 μg via a metered-dose inhaler (MF/F MDI; DULERA®/ZENHALE®) without a spacer device, MF/F MDI with a spacer, or MF 400 μg via a dry-powder inhaler (DPI; ASMANEX® TWISTHALER®) twice daily for 5 days.,Plasma samples for MF and formoterol assay were obtained predose and at prespecified time points after the last (morning) dose on day 5 of each period of the crossover.,The geometric mean ratio (GMR) as a percent and the corresponding 90% confidence intervals (CI) were calculated for treatment comparisons.,Systemic MF exposure was lower (GMR 77%; 90% CI 58, 102) following administration by MF/F MDI compared to MF DPI.,Additionally, least squares geometric mean systemic exposures of MF and formoterol were lower (GMR 72%; 90% CI 61, 84) and (GMR 62%; 90% CI 52, 74), respectively, following administration by MF/F MDI in conjunction with a spacer compared to MF/F MDI without a spacer.,MF/F MDI had a similar adverse experience profile as that seen with MF DPI.,All adverse experiences were either mild or moderate in severity; no serious adverse experience was reported.,Systemic MF exposures were lower following administration by MF/F MDI compared with MF DPI.,Additionally, systemic MF and formoterol exposures were lower following administration by MF/F MDI with a spacer versus without a spacer.,The magnitude of these differences with respect to systemic exposure was not clinically relevant.
| 1
|
Multimorbidity has already become common in primary care and will be a challenge in the future.,Primary care in Sweden participates to a great extent in the care of patients with two severe, chronic conditions: chronic obstructive pulmonary disease (COPD) and heart failure.,Both conditions are characterized by high mortality and often coexist.,Age, sex, heart failure and other comorbidities are considered to be the major predictors of mortality in patients with COPD.,We aimed to study the impact of heart failure, other comorbidities, age and sex on mortality in patients with COPD.,A register-based, prospective cohort study conducted in Blekinge County in Sweden with about 150,000 inhabitants.,The study population was comprised of people aged ≥35 years.,The data about diagnoses of COPD and heart failure came from the 2007 health care register, in which we found 984 individuals with a diagnosis of COPD.,Date of death was collected from January 1st, 2008 -August 31st, 2015.,The diagnosis-based Adjusted Clinical Groups (ACG) Case-Mix System 7.1 was used to describe comorbidity.,Each individual was assigned one of six comorbidity levels called resource utilization bands (RUB) graded from 0 to 5.,Estimated eight year mortality in patients with COPD and coexisting heart failure was seven times higher than in patients with COPD alone - odds ratio 7.06 (95% CI 3.88-12.84).,Adjusting for age and male sex resulted in odds ratio 3.75 (95% CI 1.97-7.15).,Further adjusting for other comorbidities resulted in odds ratio 3.26 (95% CI 1.70-6.25).,The mortality was strongly associated with the highest comorbidity level - RUB 5 where the odds ratio was 5.19 (95% CI 2.59-10.38).,Heart failure has an important impact on mortality in patients with COPD.,The mortality in patients with COPD and coexisting heart failure was strongly associated with age, male sex and other comorbidities.,Of those three predictors, only other comorbidities can be influenced.,Heart failure and other comorbidities should be recognized early and properly treated in order to improve survival in patients with coexisting COPD and heart failure.
|
Exacerbations are important outcomes in COPD both from a clinical and an economic perspective.,Most studies investigating predictors of exacerbations were performed in COPD patients participating in pharmacological clinical trials who usually have moderate to severe airflow obstruction.,This study was aimed to investigate whether predictors of COPD exacerbations depend on the COPD population studied.,A network of COPD health economic modelers used data from five COPD data sources - two population-based studies (COPDGene® and The Obstructive Lung Disease in Norrbotten), one primary care study (RECODE), and two studies in secondary care (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoint and UPLIFT) - to estimate and validate several prediction models for total and severe exacerbations (= hospitalization).,The models differed in terms of predictors (depending on availability) and type of model.,FEV1% predicted and previous exacerbations were significant predictors of total exacerbations in all five data sources.,Disease-specific quality of life and gender were predictors in four out of four and three out of five data sources, respectively.,Age was significant only in the two studies including secondary care patients.,Other significant predictors of total exacerbations available in one database were: presence of cough and wheeze, pack-years, 6-min walking distance, inhaled corticosteroid use, and oxygen saturation.,Predictors of severe exacerbations were in general the same as for total exacerbations, but in addition low body mass index, cardiovascular disease, and emphysema were significant predictors of hospitalization for an exacerbation in secondary care patients.,FEV1% predicted, previous exacerbations, and disease-specific quality of life were predictors of exacerbations in patients regardless of their COPD severity, while age, low body mass index, cardiovascular disease, and emphysema seem to be predictors in secondary care patients only.
| 1
|
Multiple factors can influence the severity of chronic obstructive pulmonary disease (COPD) and the functioning of patients with COPD, such as personal characteristics and systemic manifestations.,To evaluate the different factors that can influence the activity and psychosocial impact domains of the Saint George's Respiratory Questionnaire (SGRQ) in COPD patients.,Participants, recruited in a university-based hospital, responded to the SGRQ, and in addition, personal, anthropometric, and clinical data were collected.,The study was approved by the Institutional Ethics Committee.,Data were analyzed using multiple linear regression models, with the SGRQ activity and psychosocial impact scores as outcome variables, and 10 explanatory variables (age, gender, forced expiratory volume in the first second - FEV1, smoking load, body mass index, oxygen therapy, associated diseases, regular physical activity, participation in a formal rehabilitation program, and SGRQ symptoms score) were considered.,The best regression model for predicting the SGRQ activity score (r2=0.477) included gender, FEV1, and SGRQ symptoms.,In contrast, the predictive model with the highest proportion of explained variance in psychosocial impact score (r2=0.426) included the variables gender, oxygen therapy, and SGRQ symptoms.,The results indicate that the outcomes, while based on functioning parameters in COPD patients, could be partly explained by the personal and clinical factors analyzed, especially by the symptoms assessed by the SGRQ.,Thus, it appears that the health conditions of these patients cannot be described by isolated variables, including pulmonary function parameters.
|
Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable.
| 1
|
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.
|
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization and is associated with considerable mortality, for which clinicians are seeking useful and easily obtained biomarkers for prognostic evaluation.,This study aimed to determine the potential role of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as prognostic makers for hospital mortality in patients with AECOPD.,We included 303 patients with AECOPD in this retrospective study.,Clinical characteristics, NLR, PLR, and serum levels of C-reactive protein (CRP) and other data were collected.,Relationships between NLR/PLR and CRP were evaluated by Pearson’s correlation test.,Receiver operating characteristics curve and the area under the curve (AUC) were used to assess the ability of NLR and PLR to predict hospital mortality in patients with AECOPD.,Mean levels of NLR and PLR of all patients with AECOPD were 7.92±8.79 and 207.21±148.47, respectively.,NLR levels correlated with serum CRP levels (r=0.281, P<0.05).,The overall hospital mortality rate was 12.21% (37/303).,Levels of NLR and PLR were signifi-cantly higher among non-survivors compared to survivors of AECOPD (both P<0.05).,At a cut-off value of 6.24, the sensitivity and specificity of the NLR in predicting hospital mortality were 81.08% and 69.17%, respectively, with an AUC of 0.803.,At a cut-off of 182.68, the corresponding sensitivity, specificity and AUC of PLR were 64.86%, 58.27%, and 0.639.,The combination of NLR, PLR, and CRP increased the prognostic sensitivity.,NLR and PLR levels were increased in non-survivor patients with AECOPD, and the NLR may be simple and useful prognostic marker for hospital mortality in patients with AECOPD.,More studies should be carried out to confirm our findings.
| 1
|
Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality.,Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.,Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed.,To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD.,To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS).,To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.,The prevalence of PRISm in COPDGene is 12.3%.,Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models.,Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001).,Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.,PRISm subjects are clinically and genetically heterogeneous.,Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.,Clinicaltrials.gov Identifier: NCT000608764.,The online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users.
|
Exacerbations of COPD are defined clinically by worsening of chronic respiratory symptoms.,Chronic respiratory symptoms are common in the general population.,There are no data on the frequency of exacerbation-like events in individuals without spirometric evidence of COPD.,To determine the occurrence of ‘exacerbation-like’ events in individuals without airflow limitation, their associated risk factors, healthcare utilisation and social impacts.,We analysed the cross-sectional data from 5176 people aged 40 years and older who participated in a multisite, population-based study on lung health.,The study cohort was stratified into spirometrically defined COPD (post-bronchodilator FEV1/FVC < 0.7) and non-COPD (post bronchodilator FEV1/FVC ≥ 0.7 and without self-reported doctor diagnosis of airway diseases) subgroups and then into those with and without respiratory ‘exacerbation-like’ events in the past year.,Individuals without COPD had half the frequency of ‘exacerbation-like’ events compared with those with COPD.,In the non-COPD group, the independent associations with ‘exacerbations’ included female gender, presence of wheezing, the use of respiratory medications and self-perceived poor health.,In the non-COPD group, those with exacerbations were more likely than those without exacerbations to have poorer health-related quality of life (12-item Short-Form Health Survey), miss social activities (58.5% vs 18.8%), miss work for income (41.5% vs 17.3%) and miss housework (55.6% vs 16.5%), p<0.01 to <0.0001.,Events similar to exacerbations of COPD can occur in individuals without COPD or asthma and are associated with significant health and socioeconomic outcomes.,They increase the respiratory burden in the community and may contribute to the false-positive diagnosis of asthma or COPD.
| 1
|
Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD).,To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort.,Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed.,Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking.,The majority of these alterations occurred in a gender-independent manner.,The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers.,The correlations to clinical parameters in healthy never-smokers were minor.,The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers.,Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis.,Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals.,ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.,The online version of this article (10.1186/s12931-017-0695-6) contains supplementary material, which is available to authorized users.
|
Disease-specific alterations of the cell-free DNA methylation status are frequently found in serum samples and are currently considered to be suitable biomarkers.,Candidate markers were identified by bisulfite conversion-based genome-wide methylation screening of lung tissue from lung cancer, fibrotic ILD, and COPD. cfDNA from 400 μl serum (n = 204) served to test the diagnostic performance of these markers.,Following methylation-sensitive restriction enzyme digestion and enrichment of methylated DNA via targeted amplification (multiplexed MSRE enrichment), a total of 96 markers were addressed by highly parallel qPCR.,Lung cancer was efficiently separated from non-cancer and controls with a sensitivity of 87.8%, (95%CI: 0.67-0.97) and specificity 90.2%, (95%CI: 0.65-0.98).,Cancer was distinguished from ILD with a specificity of 88%, (95%CI: 0.57-1), and COPD from cancer with a specificity of 88% (95%CI: 0.64-0.97).,Separation of ILD from COPD and controls was possible with a sensitivity of 63.1% (95%CI: 0.4-0.78) and a specificity of 70% (95%CI: 0.54-0.81).,The results were confirmed using an independent sample set (n = 46) by use of the four top markers discovered in the study (HOXD10, PAX9, PTPRN2, and STAG3) yielding an AUC of 0.85 (95%CI: 0.72-0.95).,This technique was capable of distinguishing interrelated complex pulmonary diseases suggesting that multiplexed MSRE enrichment might be useful for simple and reliable diagnosis of diverse multifactorial disease states.,•The multiplexed MSRE enrichment strategy allowed a highly parallel assessment the cfDNA methylation status based on 400 μl of patient serum.,•The multivariate classification of the discovered biomarkers, thus, stabilized the prediction and allowed for differential diagnosis.,•This method including the biomarker set may be used to monitor the lung cancer risk in COPD and fibrotic ILD patients.,The multiplexed MSRE enrichment strategy allowed a highly parallel assessment the cfDNA methylation status based on 400 μl of patient serum.,The multivariate classification of the discovered biomarkers, thus, stabilized the prediction and allowed for differential diagnosis.,This method including the biomarker set may be used to monitor the lung cancer risk in COPD and fibrotic ILD patients.,We developed a multiplexed DNA methylation profiling strategy to track disease specific DNA methylation changes prevailing in 400 μl serum of lung cancer, fibrotic ILD and COPD patients.,Plasma or serum samples, often referred to as ‘liquid biopsies’ have several advantages over tissue sampling: (a) they are easily accessible, (b) are not subject to biopsy bias and (c) can be repeatedly drawn from the same patient.,The differential diagnosis attempt performed in the study on patients suffering from different lung diseases suggests that multiplexed cfDNA methylation profiling allows for the capture of these interconnected disease phenotypes, stabilizes the prediction and enhances diagnostic accuracy.
| 1
|
Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19).,This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients.,A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea.,The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model.,Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively.,The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs.,45.2%, P < 0.001) and male (52.5% vs.,36.6%, P < 0.001) patients than the non-COPD group.,Relatively greater proportions of patients with COPD received intensive critical care (7.1% vs.,3.7%, P = 0.041) and mechanical ventilation (5.7% vs.,2.4%, P = 0.015).,Multivariate analyses showed that COPD was not a risk factor for respiratory failure but was a significant independent risk factor for all-cause mortality (OR = 1.80, 95% CI 1.11-2.93) after adjustment for age, sex, and Charlson Comorbidity Index score.,Among COVID-19 patients, relatively greater proportions of patients with COPD received mechanical ventilation and intensive critical care.,COPD is an independent risk factor for all-cause mortality in COVID-19 patients in Korea.
|
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD.
| 1
|
Recurrent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, debilitating, costly and often difficult to prevent.,We reviewed records of patients who had COPD and immunoglobulin (Ig) treatment as adjunctive preventative treatment for AECOPD, and documented all AECOPD episodes for one year before and after initiation of Ig treatment.,We graded AECOPD episodes as moderate for prescription of antibiotics and/or corticosteroids or for visit to the Emergency Department, and as severe for hospital admission.,We conducted a retrospective within-subject self-controlled risk interval analysis to compare the outcome of annual AECOPD rate before and after treatment.,We identified 22 cases of certain COPD, of which three had early discontinuation of Ig treatment due to rash and local swelling to subcutaneous Ig, and five had incomplete records leaving 14 cases for analyses.,The median baseline IgG level was 5.9 g/L (interquartile range 4.1-7.4).,Eight had CT radiographic bronchiectasis.,Overall, the incidence of AECOPD was consistently and significantly reduced in frequency from mean 4.7 (± 3.1) per patient-year before, to 0.6 (± 1.0) after the Ig treatment (p = 0.0001).,There were twelve episodes of severe AECOPD (in seven cases) in the year prior, and one in the year after Ig treatment initiation (p = 0.016).,Ig treatment appears to decrease the frequency of moderate and severe recurrent AECOPD.,A prospective, controlled evaluation of adjunctive Ig treatment to standard therapy of recurrent AECOPD is warranted.
|
There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients.,We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.,We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.,Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.,Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively).,Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05).,Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads.,Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs.,No association was observed between inflammation and health status (p > 0.05).,Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique.,The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae.,However, discordance between inflammation and health status was observed.,The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users.
| 1
|
Objectives To determine the population level costs, effects, and cost effectiveness of selected, individual based interventions to combat chronic obstructive pulmonary disease (COPD) and asthma in the context of low and middle income countries.,Design Sectoral cost effectiveness analysis using a lifetime population model.,Setting Two World Health Organization sub-regions of the world: countries in sub-Saharan Africa with very high adult and high child mortality (AfrE); and countries in South East Asia with high adult and high child mortality (SearD).,Data sources Disease rates and profiles were taken from the WHO Global Burden of Disease study; estimates of intervention effects and resource needs were drawn from clinical trials, observational studies, and treatment guidelines.,Unit costs were taken from a WHO price database.,Main outcome measures Cost per disability adjusted life year (DALY) averted, expressed in international dollars ($Int) for the year 2005.,Results In both regions low dose inhaled corticosteroids for mild persistent asthma was considered the most cost effective intervention, with average cost per DALY averted about $Int2500.,The next best value strategies were influenza vaccine for COPD in Sear-D (incremental cost $Int4950 per DALY averted) and low dose inhaled corticosteroids plus long acting β agonists for moderate persistent asthma in Afr-E (incremental cost $Int9112 per DALY averted).,Conclusions COPD is irreversible and progressive, and current treatment options produce relatively little gains relative to the cost.,The treatment options available for asthma, however, generally decrease chronic respiratory disease burden at a relatively low cost.
|
Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers.
| 1
|
COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 and FEV1 <60% predicted or exacerbation risk requiring further evaluation for COPD.,This study tested CAPTURE’s ability to identify symptomatic patients with mild-to-moderate COPD (FEV1 60%-80% predicted) who may also benefit from diagnosis and treatment.,Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87).,SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were also estimated.,The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT™) were used to evaluate symptoms and health status.,Clinical Trial Registration: NCT01880177, https://ClinicalTrials.gov/ct2/show/NCT01880177?,term=NCT01880177&rank=1.,Mean age (+SD): 61 (+10.5) years; 41% male.,COPD: FEV1/FVC=0.60 (+0.1), FEV1% predicted=74% (+12.4).,SN and SP for differentiating mild-to-moderate and non-COPD patients (n=160): Questionnaire: 83.6%, 67.8%; PEF (≤450 L/min; ≤350 L/min): 83.6%, 66.7%; CAPTURE (Questionnaire+PEF): 71.2%, 83.9%.,COPD patients whose CAPTURE results suggested that diagnostic evaluation was warranted (n=52) were more likely to be symptomatic than patients whose results did not (n=21) (mMRC >2: 37% vs 5%, p<0.01; CAT>10: 86% vs 57%, p<0.01).,CAPTURE differentiated COPD from no COPD (n=346): SN: 88.0%, SP: 83.9%.,CAPTURE (450/350) may be useful for identifying symptomatic patients with mild-to-moderate airflow obstruction in need of diagnostic evaluation for COPD.
|
There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population.,The study examined COPD patients with moderate COPD exacerbations.,COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation.,This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation.,A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period.,A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs.,COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009).,COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution.,21,524 patients with a moderate COPD exacerbation were identified.,Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation.,Annual costs averaged $594 per patient.,A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis.,The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04).,After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91).,The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort.,However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05).,Total monthly COPD-related costs, as a result, did not differ between cohorts.,Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy.,Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC.
| 1
|
Dementia increases the risk of morbidity and mortality in hospitalized patients.,However, information on the potential effects of dementia on the risks of acute organ dysfunction, severe sepsis and in-hospital mortality, specifically among inpatients with chronic obstructive pulmonary disease (COPD), is limited.,The observational analytic study was inpatient claims during the period from 2000 to 2010 for 1 million people who were randomly selected from all of the beneficiaries of the Taiwan National Health Insurance in 2000.,In total, 1406 patients with COPD and dementia were admitted during the study period.,Hospitalized patients with COPD and free from a history of dementia were randomly selected and served as control subjects (n = 5334).,The patient groups were matched according to age (±3 years), gender, and the year of admission, with a control/dementia ratio of 4.,Only the first-time hospitalization data for each subject was analyzed.,Logistic regression models were used to calculate the odds ratio (OR) of outcome measures (acute organ dysfunction, severe sepsis, and mortality), controlling for confounding factors (age, sex, comorbidity, infection site, hospital level, and length of stay).,In COPD patients with dementia, the incidence rate of severe sepsis and hospital mortality was 17.1% and 4.8%, respectively, which were higher than the controls (10.6% and 2.3%).,After controlling for potential confounding factors, dementia was found to significantly increase the odds of severe sepsis and hospital mortality with an adjusted OR (OR) of 1.38 (95% confidence interval [CI] 1.10-1.72) and 1.69 (95% CI 1.18-2.43), respectively.,Dementia was also significantly associated with an increased OR of acute respiratory dysfunction (adjusted OR 1.39, 95% CI 1.09-1.77).,In hospitalized COPD patients, the presence of dementia may increase the risks of acute respiratory dysfunction, severe sepsis, and hospital mortality, which warrants the attention of health care professionals.
|
Cardiovascular diseases, osteoporosis, and depression are identified comorbidities of chronic obstructive pulmonary disease (COPD), but there have been few reports of chronic kidney disease (CKD) as a comorbidity of COPD.,The objective of this study was to investigate the prevalence of CKD in COPD patients using estimated glomerular filtration rate (eGFR) based on creatinine (Cr) and cystatin C (Cys) levels.,The prevalence of CKD and the values of various CKD-related parameters were compared between 108 stable COPD outpatients (COPD group) and a non-COPD control group consisting of 73 patients aged 60 years or more without a history of COPD or kidney disease.,CKD was defined as an eGFR less than 60 mL/min/1.73 m2.,The Cr level was significantly higher in the COPD group, but eGFR based on serum Cr (eGFRCr) was not significantly different between the two groups (73.3±25.3 vs 79.7±15.5 mL/min/1.73 m2).,The Cys level was significantly higher and eGFR based on serum Cys (eGFRCys) was significantly lower in the COPD group (60.0±19.4 vs 74.0±13.5 mL/min/1.73 m2, P<0.0001).,The prevalence of CKD evaluated based on eGFRCr was 31% in the COPD group and 8% in the non-COPD group with an odds ratio of 4.91 (95% confidence interval, 1.94-12.46, P=0.0008), whereas the evaluated prevalence based on eGFRCys was 53% in the COPD group and 15% in the non-COPD group with an odds ratio of 6.30 (95% confidence interval, 2.99-13.26, P<0.0001), demonstrating a higher prevalence of CKD when based on eGFRCys rather than on eGFRCr.,CKD is a comorbidity that occurs frequently in COPD patients, and we believe that renal function in Japanese COPD patients should preferably be evaluated based not only on Cr but on Cr in combination with Cys.
| 1
|
Cognitive behavioral therapy (CBT) is increasingly recommended in the management of people living with chronic obstructive pulmonary disease (COPD).,This rapid review presents the evidence base for CBT for people with COPD and describes 1) the nature of CBT interventions and comparators in controlled trials (high or low resource intensity); and 2) factors influencing intervention effects on health outcomes (anxiety, depression, breathlessness, quality of life and exercise capacity).,Primary studies reporting CBT interventions in adults with COPD were identified with data extracted by a single reviewer (20% of studies checked for data accuracy).,Studies were synthesized descriptively with meta-analyses (random effects models) of controlled trials undertaken to report mean standardized effect sizes (95% CI) for health outcomes.,Random effects meta-regression models explored whether CBT target, intervention dosage, intensity, facilitator profession, delivery mode, clinically significant anxiety/depression, trial design/quality and sample size predicted effect size.,The search identified 33 primary studies published between 1996 and 2019 (controlled trials n=24, single group cohort n=6, case exemplars n=2, phenomenological n=1).,Controlled trials frequently compared high-intensity CBT interventions against enhanced/usual care (n=12) or high-intensity CBT interventions against high-intensity comparators (n=11).,When all controlled studies were included, small, significant improvements favoring CBT were evident across all health outcomes (SMD ranged from −0.27 to 0.35, p<0.05).,When intensity dyads were considered, significant improvements were evident only when high-intensity CBT interventions were compared to enhanced usual care/usual care (SMDs ranged from −0.45 to 0.54, p <0.05).,No other variable consistently predicted intervention effect sizes across all health outcomes.,Overall, the evidence base supports the use of CBT for a range of health outcomes in people with COPD.,Consistent benefits were evident when high-resource-intensive CBT interventions were compared to usual care.,Low-resource-intensity CBT warrants further investigation in settings where cost of comprehensive care is prohibitive.
|
Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials.,Little is known on the correspondence between the two methods.,Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO.,Dyspnea was assessed by the mMRC scale and the BDI.,Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George’s Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained.,Correlations between mMRC and BDI scores were assessed using Spearman’s correlation coefficient.,An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores.,Data are given as median (interquartile ranges, [IQR]).,Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]).,The mMRC grade and BDI score were, respectively, 1 [1-3] and 6 [4-8].,Both BDI and mMRC scores were significantly correlated at the group level (rho =−0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade.,In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio.,The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index.,Dyspnea is a complex symptom with multiple determinants in COPD patients.,Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable.
| 1
|
The six-minute walk test (6MWT) is considered to be a simple and inexpensive tool for the assessment of functional tolerance of submaximal effort.,The aim of this work was 1) to background the nonlinear nature of the energy expenditure process due to physical activity, 2) to compare the results/scores of the submaximal treadmill exercise test and those of 6MWT in pulmonary patients and 3) to develop nonlinear mathematical models relating the two.,The study group included patients with the COPD.,All patients were subjected to a submaximal exercise test and a 6MWT.,To develop an optimal mathematical solution and compare the results of the exercise test and the 6MWT, the least squares and genetic algorithms were employed to estimate parameters of polynomial expansion and piecewise linear models.,Mathematical analysis enabled to construct nonlinear models for estimating the MET result of submaximal exercise test based on average walk velocity (or distance) in the 6MWT.,Submaximal effort tolerance in COPD patients can be effectively estimated from new, rehabilitation-oriented, nonlinear models based on the generalized MET concept and the 6MWT.
|
Fatigue is one of the most disabling symptoms in COPD, but little is known about the impact of fatigue on functional disability.,We explored the impact of fatigue and fatigue intensity on exercise tolerance after adjusting for other factors using multivariate analysis and compared it to that of dyspnoea.,A total of 119 patients with mainly moderate-severe stable COPD (38 % women, mean age 66 years) were enrolled.,We used the Medical Research Council dyspnoea scores (MRC), Manchester COPD fatigue scale (MCFS) and its three dimensions, Borg scales for fatigue and dyspnoea, six-minute walk distance (6MWD), St George’s Respiratory Questionnaire, the BODE index, and the Centre for Epidemiological Study on Depression scale (CES-D), and we measured spirometry, blood gases, systemic inflammatory markers and fat-free mass index (FFMI).,Fatigue measured using the MCFS was associated with 6MWD and explained 22 % of the variability in 6MWD (p < 0.001).,Fatigue remained associated with 6MWD after adjusting for MRC dyspnoea, FFMI and FEV1, FVC, PaO2, PaCO2, CES-D, TNF-alpha, smoking status, age and gender.,We found that 33, 50 and 23 % of patients reported an increase by 2 scores on Borg scales for fatigue, dyspnoea or both at the end of the 6MWT.,Fatigue scores (both before and after the 6MWT) were negatively correlated with 6MWD after adjusting for FEV1, FFMI, CES-D score and age (p = 0.007 and 0.001, respectively).,In moderate stable COPD, fatigue may be a central driver of functional disability, to the same extent as dyspnoea.,The online version of this article (doi:10.1007/s00408-016-9931-y) contains supplementary material, which is available to authorized users.
| 1
|
Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality.,Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.,Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed.,To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD.,To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS).,To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.,The prevalence of PRISm in COPDGene is 12.3%.,Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models.,Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001).,Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.,PRISm subjects are clinically and genetically heterogeneous.,Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.,Clinicaltrials.gov Identifier: NCT000608764.,The online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users.
|
Chronic obstructive pulmonary disease (COPD) is supposed to be classified on the basis of post-bronchodilator lung function.,Most longitudinal studies of COPD, though, do not have post-bronchodilator lung function available.,We used pre-and post bronchodilator lung function data from the Lung Health Study to determine whether these measures differ in their ability to predict mortality.,We limited our analysis to subjects who were of black or white race, on whom we had complete data, and who participated at either the 1 year or the 5 year follow-up visit.,We classified subjects based on their baseline lung function, according to COPD Classification criteria using both pre- and post-bronchodilator lung function.,We conducted a survival analysis and logistic regression predicting death and controlling for age, sex, race, treatment group, smoking status, and measures of lung function (either pre- or post-bronchodilator.,We calculated hazard ratios (HR) with 95% confidence intervals (CI) and also calculated area under the curve for the logistic regression models.,By year 15 of the study, 721 of the original 5,887 study subjects had died.,In the year 1 sample survival models, a higher FEV1 % predicted lower mortality in both the pre-bronchodilator (HR 0.87, 95% CI 0.81, 0.94 per 10% increase) and post-bronchodilator (HR 0.84, 95% CI 0.77, 0.90) models.,The area under the curve for the respective models was 69.2% and 69.4%.,Similarly, using categories, when compared to people with "normal" lung function, subjects with Stage 3 or 4 disease had similar mortality in both the pre- (HR 1.51, 95% CI 0.75, 3.03) and post-bronchodilator (HR 1.45, 95% CI 0.41, 5.15) models.,In the year 5 sample, when a larger proportion of subjects had Stage 3 or 4 disease (6.4% in the pre-bronchodilator group), mortality was significantly increased in both the pre- (HR 2.68, 95% CI 1.51, 4.75) and post-bronchodilator (HR 2.46, 95% CI 1.63, 3.73) models.,Both pre- and post-bronchodilator lung function predicted mortality in this analysis with a similar degree of accuracy.,Post-bronchodilator lung function may not be needed in population studies that predict long-term outcomes.
| 1
|
The aim of the present study was to evaluate the performance of the forced oscillation technique (FOT) for the early diagnosis of the effects of smoking and COPD.,The contributions of the integer-order (InOr) and fractional-order (FrOr) models were also evaluated.,In total, 120 subjects were analyzed: 40 controls, 40 smokers (20.3±9.3 pack-years) and 40 patients with mild COPD.,Initially, it was observed that traditional FOT parameters and the InOr and FrOr models provided a consistent description of the COPD pathophysiology.,Mild COPD introduced significant increases in the FrOr inertance, damping factor and hysteresivity (P<0.0001).,These parameters were significantly correlated with the spirometric parameters of central and small airway obstruction (P<0.0001).,The diagnostic accuracy analyses indicated that FOT parameters and InOr modeling may adequately identify these changes (area under the receiver operating characteristic curve - AUC >0.8).,The use of FrOr modeling significantly improved this process (P<0.05), allowing the early diagnosis of smokers and patients with mild COPD with high accuracy (AUC >0.9).,FrOr modeling improves our knowledge of modifications that occur in the early stages of COPD.,Additionally, the findings of the present study provide evidence that these models may play an important role in the early diagnosis of COPD, which is crucial for improving the clinical management of the disease.
|
Cardiovascular diseases and skeletal muscle dysfunction are common comorbidities in COPD.,Hand grip strength (HGS) is related to general muscle strength and is associated with cardiovascular disease and all-cause mortality, while the results from small selected COPD populations are contradictory.,The aim of this population-based study was to compare HGS among the subjects with and without COPD, to evaluate HGS in relation to COPD severity, and to evaluate the impact of heart disease.,Data were collected from the Obstructive Lung disease in Northern Sweden COPD study, where the subjects with and without COPD have been invited to annual examinations since 2005.,In 2009-2010, 441 subjects with COPD (postbronchodilator forced expiratory volume in 1 second [FEV1]/vital capacity <0.70) and 570 without COPD participated in structured interviews, spirometry, and measurements of HGS.,The mean HGS was similar when comparing subjects with and without COPD, but those with heart disease had lower HGS than those without.,When compared by Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, the subjects with GOLD 3-4 had lower HGS than those without COPD in both sexes (females 21.4 kg vs 26.9 kg, P=0.010; males 41.5 kg vs 46.3 kg, P=0.038), and the difference persisted also when adjusted for confounders.,Among the subjects with COPD, HGS was associated with FEV1% of predicted value but not heart disease when adjusted for height, age, sex, and smoking habits, and the pattern was similar among males and females.,In this population-based study, the subjects with GOLD 3-4 had lower HGS than the subjects without COPD.,Among those with COPD, HGS was associated with FEV1% of predicted value but not heart disease, and the pattern was similar in both sexes.
| 1
|
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD.
|
Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality.
| 1
|
The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.
|
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users.
| 1
|
Tiotropium (Spiriva) is an inhaled muscarinic antagonist for patients with chronic obstructive pulmonary disease (COPD), and is available in two forms: the HandiHaler and the Respimat inhaler.,The aim of this study was to investigate the handling of and preference for each device immediately after switching from the HandiHaler to the Respimat and 2-3 years after the switch.,The study comprised two surveys.,A questionnaire was first administered to 57 patients with COPD (male:female 52:5, mean age 73.6±7.1 years) 8 weeks after switching from the HandiHaler (18 μg) to the Respimat (5 μg).,A second similar but simplified questionnaire was administered to 39 of these patients who continued to use the Respimat and were available for follow-up after more than 2 years.,Pulmonary function was also measured during each period.,In the first survey, 17.5% of patients preferred the HandiHaler, and 45.6% preferred the Respimat.,There were no significant changes in pulmonary function or in the incidence of adverse events after the switch.,In the second survey, performed 2-3 years later, the self-assessed handling of the Respimat had significantly improved, and the number of patients who preferred the Respimat had increased to 79.5%.,The efficacy of the Respimat was similar to that of the HandiHaler.,This was clear immediately after the switch, even in elderly patients with COPD who were long-term users of the HandiHaler.,The preference for the Respimat increased with continued use.
|
Aerosols delivered by Respimat® Soft Mist™ Inhaler (SMI) are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs), improving the efficiency of pulmonary drug delivery to patients.,In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD) and with poor pMDI technique received radiolabelled Berodual® (fenoterol hydrobromide 50 μg/ipratropium bromide 20 μg) via Respimat® SMI or hydrofluoroalkane (HFA)-MDI (randomized order) on test days 1 and 2, with no inhaler technique training.,The procedure was repeated on test days 3 and 4 after training.,Deposition was measured by gamma scintigraphy.,All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted) inhaled too fast at screening (peak inspiratory flow rate [IF]: 69-161 L/min).,Whole lung deposition was higher with Respimat® SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose) and trained patients (53% of delivered vs 21% of metered dose) (pSign-Test].15; pANOVA < = 0.05).,Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time).,Drug delivery to the lungs with Respimat® SMI is more efficient than with pMDI, even with poor inhaler technique.,Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat® SMI.
| 1
|
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD.
|
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.
| 1
|
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally.
|
Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence.
| 1
|
Chronic respiratory diseases (CRDs) are leading causes of morbidity worldwide.,However, the spatial and temporal trends in prevalence and incidence of CRDs have not been estimated.,Based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, we analyzed the prevalence and incidence trends of CRDs from 1990 to 2017 according to age, sex, region and disease pattern.,Furthermore, the correlations between the incidence and the World Bank income levels, sociodemographic index (SDI), and human development index (HDI) levels were analyzed to assess the factors affecting incidence.,The total number of CRD cases increased by 39.5% from 1990 to 2017, nevertheless, the age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) showed decreasing trends.,The ASIRs of CRD, chronic obstructive pulmonary disease (COPD), pneumoconiosis, and asthma decreased, whereas the ASIR of interstitial lung disease and pulmonary sarcoidosis increased during the past 27 years.,Significant differences between males and females in the incidence rates of pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis were observed.,Elderly people especially suffered from CRDs, except for asthma.,For COPD, the ASIR decreased from low-SDI regions to high-SDI regions.,The ASIR of interstitial lung disease and pulmonary sarcoidosis in the high-SDI region was highest and have increased mostly.,The ASIRs for pneumoconiosis and asthma were inversely related to the HDI.,In 2017, CRDs were still the leading causes of morbidity worldwide.,A large proportion of the disease burden was attributed to asthma and COPD.,The incidence rates of all four types of CRDs varied greatly across the world.,Statistically significant correlation was found between the ASIR and SDI/HDI.
|
Spirometry is important in the diagnosis and management of chronic obstructive pulmonary disease (COPD), yet it is a common clinical observation that it is underused though the extent is unclear.,This survey aims to examine the use of spirometry in the diagnosis and management of COPD patients in a district in Hong Kong.,It is a cross-sectional survey involving four clinic settings: hospital-based respiratory specialist clinic, hospital-based mixed medical specialist clinic, general outpatient clinic (primary care), and tuberculosis and chest clinic.,Thirty physician-diagnosed COPD patients were randomly selected from each of the four clinic groups.,All of them had a forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio less than 0.70 and had been followed up at the participating clinic for at least 6 months for COPD treatment.,Of 126 patients who underwent spirometry, six (4.8%) did not have COPD.,Of the 120 COPD patients, there were 111 males and mean post-bronchodilator FEV1 was 46.2% predicted.,Only 22 patients (18.3%) had spirometry done during diagnostic workup, and 64 patients (53.3%) had spirometry done ever.,The only independent factor predicting spirometry done ever was absence of old pulmonary tuberculosis and follow-up at respiratory specialist clinic.,Age, sex, smoking status, comorbidities, duration of COPD, percentage predicted FEV1, body mass index, 6-minute walking distance, and Medical Research Council dyspnea score were not predictive.,We conclude that spirometry is underused in general but especially by nonrespiratory physicians and family physicians in the management of COPD patients.,More effort at educating the medical community is urgently needed.
| 1
|
The effects of chronic inhaled and systemic corticosteroids use on COVID-19 susceptibility and severity are unclear.,Since many patients with chronic pulmonary diseases rely on corticosteroids to control disease, it is important to understand the risks of their use during the pandemic.,We aim to study if the use of inhaled or systemic corticosteroids affects the likelihood of developing COVID-19 infection.,We used the National Jewish Health electronic medical record research database to identify a cohort of all subjects who were tested for suspected COVID-19 between March 11 - June 23, 2020.,Testing results, medication use, and comorbidities were obtained from the medical record.,Following a comparison of different propensity score weighting methods, overlap propensity score weighting was used to analyze the association between medication use and COVID-19 diagnosis.,The cohort consisted of 928 patients, of which 12% tested positive.,The majority (66%) of patients had a history of chronic pulmonary diseases.,There was no significant association between inhaled corticosteroid use and testing positive for COVID-19.,Interestingly, systemic corticosteroid use was associated with a lower odds ratio (0.95, 95% CI: 0.91-0.99) of testing positive for COVID-19.,Similar results were noted when the analysis was restricted to those with any chronic pulmonary diseases, with asthma or with chronic obstructive pulmonary disease (COPD).,Our study supports the recommendation that patients with chronic pulmonary diseases, including asthma and COPD who require treatment with either inhaled or systemic corticosteroids, should continue their use during the COVID-19 pandemic.
|
Morbidity and mortality from COVID‐19 caused by novel coronavirus SARS‐CoV‐2 is accelerating worldwide, and novel clinical presentations of COVID‐19 are often reported.,The range of human cells and tissues targeted by SARS‐CoV‐2, its potential receptors and associated regulating factors are still largely unknown.,The aim of our study was to analyze the expression of known and potential SARS‐CoV‐2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID‐19.,We performed RNA sequencing and explored available RNA‐Seq databases to study gene expression and co‐expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts.,We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID‐19 risk factor status.,ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells.,We also observed a distinct age‐related expression profile of these genes in the PBMCs and T cells from healthy children and adults.,Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL, or blood.,Additionally, CD147‐related genes correlated positively with age and BMI.,Interestingly, we also observed higher expression of CD147‐related genes in the lesional skin of patients with atopic dermatitis.,Our data suggest different receptor repertoire potentially involved in the SARS‐CoV‐2 infection at the epithelial barriers and in the immune cells.,Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID‐19 morbidity and severity patterns.,ACE2 and TMPRSS2 expression is unique for the epithelial barrier sites, whereas CD147, cyclophilins, and CD26 are expressed in both, epithelial and immune cells.,Age is a factor associated with the differential expression profiles of ACE2‐, CD147‐ and CD26‐related genes in the PBMCs and naive CD4+ T cells from healthy children and adults.,Asthma, COPD, hypertension, smoking, obesity, and male gender generally lead to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL or blood.,Abbreviations: ACE2, angiotensin‐converting enzyme 2; AD, atopic dermatitis; BAL, bronchoalveolar lavage; COPD, chronic obstructive pulmonary disease; CypA, cyclophilin A; CypB, cyclophilin B; GLUT1, glucose transporter 1; ILC, innate lymphoid cell; MCTs, monocarboxylate transporters; NF‐ATs, nuclear factor of activated T cells; PBMCs, peripheral blood mononuclear cells; SARS‐CoV‐2; severe acute respiratory syndrome coronavirus 2; SLC6A19, sodium‐dependent neutral amino acid transporter B(0)AT1; S100A9, protein S100‐A9; TMPRSS2, transmembrane protease serine.
| 1
|
There is large variation in the therapeutic response to inhaled corticosteroids (ICS) in COPD patients.,We present a pooled analysis of our previous studies investigating the effects of corticosteroids on lung macrophages, in order to robustly determine whether corticosteroid sensitivity in COPD cells is reduced compared to controls, and also to evaluate the degree of between individual variation in drug response.,Data from 20 never smokers (NS), 27 smokers (S) and 45 COPD patients was used.,Lung macropahges had been stimulated with lipopolysaccharide (LPS), with or without the corticosteroid dexamethasone, and tumour necrosis factor (TNF)-α, interleukin (IL)-6 and chemokine C-X-C motif ligand (CXCL) 8 production was measured.,There was no difference in the anti-inflammatory effects of corticosteroids when comparing group mean data of COPD patients versus controls.,The inhibition of TNF-α and IL-6 was greater than CXCL8.,The effects of corticosteroids varied considerably between subjects, particularly at lower corticosteroid concentrations.,We confirm that overall corticosteroid sensitivity in COPD lung macrophages is not reduced compared to controls.,The varied effect of corticosteroids between subjects suggests that some individuals have an inherently poor corticosteroid response.,The limited suppression of lung macrophage derived CXCL8 may promote neutrophilic inflammation in COPD.,The online version of this article (doi:10.1186/s12931-015-0260-0) contains supplementary material, which is available to authorized users.
|
Chronic obstructive pulmonary disease (COPD) is associated with local and systemic inflammation.,The knowledge of interaction and co-variation of the inflammatory responses in different compartments is meagre.,Healthy controls (n = 23), smokers with (n = 28) and without (n = 29) COPD performed spirometry and dental examinations.,Saliva, induced sputum, bronchoalveolar lavage (BAL) fluid and serum were collected.,Inflammatory markers were assessed in all compartments using ELISA, flow cytometry and RT-PCR.,Negative correlations between lung function and saliva IL-8 and matrix metalloproteinase-9 (MMP-9) were found in smokers with COPD.,IL-8 and MMP-9 in saliva correlated positively with periodontal disease as assessed by gingival bleeding in non-smokers.,Tumor necrosis factor-α (TNF-α) in saliva, serum and TNF-α mRNA expression on macrophages in BAL-fluid were lower in smokers than in non-smokers.,There were positive correlations between soluble TNF-α receptor 1 (sTNFR1) and soluble TNF-α receptor 2 (sTNFR2) in sputum, BAL-fluid and serum in all groups.,Sputum interleukin-8 (IL-8) or interleukin-6 (IL-6) was positively correlated with sTNFR1 or sTNFR2 in non-smokers and with sTNFR2 in COPD.,Saliva which is convenient to collect and analyse, may be suitable for biomarker assessment of disease activity in COPD.,An attenuated TNF-α expression was demonstrated by both protein and mRNA analyses in different compartments suggesting that TNF-α response is altered in moderate and severe COPD.,Shedding of TNFR1 or TNFR2 is similarly regulated irrespective of airflow limitation.
| 1
|
Bronchiectasis-chronic obstructive pulmonary disease (COPD) overlap presents a possible clinical phenotype of COPD, but it is unclear why it develops in a subset of patients.,We hypothesized that sensitization to Aspergillus fumigatus (A fum) is associated with bronchiectasis in COPD and occurs more frequently in vitamin D-deficient patients.,This observational study investigated sensitization to A fum in an outpatient clinical cohort of 300 COPD patients and 50 (ex-) smoking controls.,Total IgE, A fum-specific IgE against the crude extract and against the recombinant antigens and A fum IgG were measured using ImmunoCAP fluoroenzyme immunoassay.,Vitamin D was measured by radioimmunoassay, and computed tomography images of the lungs were scored using the modified Reiff score.,Sensitization to A fum occurred in 18% of COPD patients compared to 4% of controls (P=0.0110).,In all, 31 COPD patients (10%) were sensitized to the crude extract and 24 patients (8%) had only IgE against recombinant antigens.,A fum IgG levels were significantly higher in the COPD group (P=0.0473).,Within COPD, A fum-sensitized patients were more often male (P=0.0293) and more often had bronchiectasis (P=0.0297).,Pseudomonas aeruginosa and Serratia marcescens were more prevalent in historical sputum samples of A fum-sensitized COPD patients compared to A fum-non-sensitized COPD patients (P=0.0436).,Vitamin D levels were comparable (P=0.2057).,Multivariate analysis demonstrated that sensitization to recombinant f1 or f3 had a 2.8-fold increased risk for bronchiectasis (P=0.0030).,These results highlight a potential role for sensitization to A fum in COPD-related bronchiectasis.
|
Allergy and Aspergillus hypersensitivity (AH) were shown to be associated with severe symptoms or worse lung function in COPD patients.,The prevalence of elevated total IgE (T-IgE) and its association with clinical symptoms and lung function in COPD have not been studied.,The prevalence of AH and its correlation with clinical characteristics in a COPD cohort of larger sample size is also lacking.,273 patients with COPD were evaluated by respiratory symptoms, blood test, chest HRCT, lung function, serum detection of T-IgE and Aspergillus specific IgE.,Patients with T-IgE ≥ 1000 KU/L were further investigated for allergic bronchopulmonary aspergillosis (ABPA).,The prevalence of elevated T-IgE and AH in patients with COPD was 47.3% and 15.0%, respectively.,Eight patients (2.9%) met the diagnostic criteria for ABPA.,Compared with the normal T-IgE group, patients with elevated T-IgE had a longer history of dyspnea (p < 0.01), an earlier onset of dyspnea after chronic cough/expectoration (p < 0.01), and were more likely to wheeze (p < 0.01).,They also showed worse lung functions and more severe GOLD staging (p < 0.01).,Analysis of the clinical data in male patients with smoking as the risk factor showed the same results.,To evaluate the clinical characteristics of COPD with AH, patients with elevated T-IgE were further divided into subgroups with and without AH.,When compared with the normal T-IgE group, both the two subgroups showed longer history of dyspnea (p < 0.01), an earlier onset of dyspnea (p < 0.01) and a worse status of lung function (p < 0.05).,Correlation analysis demonstrated that T-IgE was correlated positively with the time length of dyspnea (r = 0.401, p < 0.001), and the ratio of duration of dyspnea to that of chronic cough/expectoration (r = 0.59, p < 0.001), but negatively with FEV1/FVC% (r = −0.194, p = 0.001), and FEV1%predicted (r = −0.219, p < 0.001).,There was a high prevalence of elevated serum T-IgE and AH in patients with COPD.,Serum T-IgE level was correlated with symptoms such as dyspnea and impairment of lung function.,Allergens other than Aspergillus may have similar effects on disease expression or progression of COPD.
| 1
|
Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD).,Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta2-agonist (LABA) treatment than therapy with a LABA alone.,This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients.,A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II-IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts).,Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment.,Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm3 (100-280 cells/mm3).,Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%.,Among non-Japanese patients, these values were 160 (100-250) cells/mm3, 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively.,The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients.,Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm3).,The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with non-Japanese patients.,These findings suggest that blood eosinophil data from global studies are of relevance in Japan.
|
Chronic obstructive pulmonary disease (COPD) places a major burden on health care systems and has substantial economic effects; however, the cost of stable disease in Greece has never been thoroughly explored.,The objective of the study was to estimate the annual COPD patient cost during the maintenance phase and explore the relationships between the cost and disease severity.,Data were collected from 245 COPD patients (male: 231, mean age: 69.5±8.8 years) who visited the outpatient unit of University Hospital of Larissa in 2014 and 2015.,Patients were classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, and the patients’ direct cost during the maintenance phase was calculated.,Eleven percent of COPD patients were stage I, 48.2% were stage II, 29% were stage III, and 11.8% were stage IV.,According to the GOLD groups, 23.3% of patients were grade A, 15.5% were grade B, 22.9% were grade C, and 38.4% were grade D.,The mean annual direct cost for stable disease was estimated at €1,034.55 per patient, of which €222.94 corresponded to out-of-pocket payments.,The annual cost ranged from €408.23 to €2,041.89 depending on GOLD stages (I-IV) and from €550.01 to €1,480.00 depending on GOLD groups (A-D).,The key cost driver was pharmaceutical treatment, which reflected almost 71% of the total expenses for the management of stable disease.,The mean annual per-patient cost was two to three times higher for those with advanced disease (stages III-IV) compared to those with stages I-II disease, and it doubled for “high-risk” patients (groups C-D) compared to “low-risk” patients (groups A-B).,The cost of COPD during the maintenance phase is remarkable, with the key cost driver found to be pharmaceutical treatment and social insurance funds the key payer for treating COPD patients in Greece.,The cost of stable disease is proportional to the severity of COPD, and it is doubled in patients who belong to high-risk groups.
| 1
|
Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients.
|
Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD).,This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.,Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days.,Treatment was repeated every 8 weeks for a total of six courses.,Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.,At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).,There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores.,There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006).,Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility.,There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).,Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline.,There were no unexpected adverse events and there was no evidence of resistance development.,ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov).
| 1
|
Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD) is complicated by the presence of comorbidities.,The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data.,This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES), 1999-2008.,COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded.,Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment.,Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs.,36.9%), depression (20.6% vs.,12.5%), osteoporosis (16.9% vs.,8.5%), cancer (16.5% vs.,9.9%), coronary heart disease (12.7% vs.,6.1%), congestive heart failure (12.1% vs.,3.9%), and stroke (8.9% vs.,4.6%).,Subjects with COPD were also more likely to report mobility difficulty (55.6% vs.,32.5%), use of >4 prescription medications (51.8% vs.,32.1), dizziness/balance problems (41.1% vs.,23.8%), urinary incontinence (34.9% vs.,27.3%), memory problems (18.5% vs.,8.8%), low glomerular filtration rate (16.2% vs.,10.5%), and visual impairment (14.0% vs.,9.6%).,All reported comparisons have p < 0.05.,Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities.,This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed), a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity.
|
The COPD Assessment Test (CAT™) is a new short health status measure for routine use.,New questionnaires require reference points so that users can understand the scores; descriptive scenarios are one way of doing this.,A novel method of creating scenarios is described.,A Bland and Altman plot showed a consistent relationship between CAT scores and scores obtained with the St George's Respiratory Questionnaire for COPD (SGRQ-C) permitting a direct mapping process between CAT and SGRQ items.,The severity associated with each CAT item was calculated using a probabilistic model and expressed in logits (log odds of a patient of given severity affirming that item 50% of the time).,Severity estimates for SGRQ-C items in logits were also available, allowing direct comparisons with CAT items.,CAT scores were categorised into Low, Medium, High and Very High Impact.,SGRQ items of corresponding severity were used to create scenarios associated with each category.,Each CAT category was associated with a scenario comprising 12 to 16 SGRQ-C items.,A severity 'ladder' associating CAT scores with exemplar health status effects was also created.,Items associated with 'Low' and 'Medium' Impact appeared to be subjectively quite severe in terms of their effect on daily life.,These scenarios provide users of the CAT with a good sense of the health impact associated with different scores.,More generally they provide a surprising insight into the severity of the effects of COPD, even in patients with apparently mild-moderate health status impact.
| 1
|
Pulmonary rehabilitation is widely advocated for people with chronic obstructive pulmonary disease (COPD) to improve exercise capacity, symptoms and quality of life, however only a minority of individuals with COPD are able to participate.,Travel and transport are frequently cited as barriers to uptake of centre-based programs.,Other models of pulmonary rehabilitation, including home-based programs, have been proposed in order to improve access to this important treatment.,Previous studies of home-based pulmonary rehabilitation in COPD have demonstrated improvement in exercise capacity and quality of life, but not all elements of the program were conducted in the home environment.,It is uncertain whether a pulmonary rehabilitation program delivered in its entirety at home is cost effective and equally capable of producing benefits in exercise capacity, symptoms and quality of life as a hospital-based program.,The aim of this study is to compare the costs and benefits of home-based and hospital-based pulmonary rehabilitation for people with COPD.,This randomised, controlled, equivalence trial conducted at two centres will recruit 166 individuals with spirometrically confirmed COPD.,Participants will be randomly allocated to hospital-based or home-based pulmonary rehabilitation.,Hospital programs will follow the traditional outpatient model consisting of twice weekly supervised exercise training and education for eight weeks.,Home-based programs will involve one home visit followed by seven weekly telephone calls, using a motivational interviewing approach to enhance exercise participation and facilitate self management.,The primary outcome is change in 6-minute walk distance immediately following intervention.,Measurements of exercise capacity, physical activity, symptoms and quality of life will be taken at baseline, immediately following the intervention and at 12 months, by a blinded assessor.,Completion rates will be compared between programs.,Direct healthcare costs and indirect (patient-related) costs will be measured to compare the cost-effectiveness of each program.,This trial will identify whether home-based pulmonary rehabilitation can deliver equivalent benefits to centre-based pulmonary rehabilitation in a cost effective manner.,The results of this study will contribute new knowledge regarding alternative models of pulmonary rehabilitation and will inform pulmonary rehabilitation guidelines for COPD.,ClinicalTrials.gov: NCT01423227.
|
Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds.
| 1
|
Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs.,No systematic review has examined the effectiveness of interventions designed to improve medication adherence.,Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords.,Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English.,Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria.,Of the 1,186 papers identified, seven studies met inclusion criteria.,Methodological quality of the studies was variable.,Five studies identified effective interventions.,Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams.,Further research is needed to establish the most effective and cost effective interventions.,Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations.,Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored.
|
Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death.
| 1
|
Chronic obstructive pulmonary disease (COPD) is associated with persistent systemic inflammation.,Anti-inflammatory therapies have been shown to decrease acute exacerbations of COPD.,The antidiabetic medication metformin decreases oxidative stress and inflammation and may benefit patients with COPD.,We aimed at investigating the effect of metformin on health care utilizations in patients with coexisting COPD and diabetes mellitus (DM).,We studied 5% Medicare beneficiaries with coexisting COPD and DM prescribed metformin or other antidiabetics during the period 2007-2010.,The primary outcome was COPD-specific emergency room (ER) visits and hospitalizations; the secondary outcome was all-cause ER visits and hospitalizations over the 2-year follow-up after the index antidiabetic prescription.,The effects of metformin were examined by COPD complexity and compared with the effects of other antidiabetic medications.,Among 11,260 patients, 3,193 were metformin users and 8,067 were nonusers.,Metformin users were younger, were less sick, were less likely to be on oxygen, and had fewer hospitalizations in the prior year compared with the nonusers.,Over a 2-year period, metformin users had lower COPD-specific and all-cause ER visits and hospitalizations (7.11% vs 9.61%, p<0.0001; and 61.63% vs 71.27%, p<0.0001, respectively).,In a stratified multivariable analysis, the odds of COPD-specific ER visits and hospitalizations were lower in patients with low-complexity COPD (adjusted odds ratio =0.66, 95% confidence interval =0.52-0.85).,However, patients with all COPD complexities get benefits of metformin on all-cause ER visits and hospitalizations.,The use of metformin in patients with coexisting COPD and DM was associated with fewer COPD-specific ER visits and hospitalizations, especially in low-complexity COPD.
|
To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors.,We conducted a random cross-sectional national survey of adults older than 40 years in Taiwan.,Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health.,Subjects with diagnosed COPD were subdivided by smoking status.,Subjects who fulfilled the case definition of COPD and smoked were designated as “possible COPD”.,Participants who did not fit the case definition of COPD were asked only about their personal circumstances and smoking habits.,Data from these groups were analyzed and compared.,Of the 6,600 participants who completed the survey, 404 (6.1%) fulfilled the epidemiological case definition of COPD: 137 with diagnosed COPD and 267 possible COPD.,The most common comorbidities of COPD were hypertension or cardiovascular diseases (36.1%).,Subjects with definite COPD had significantly higher COPD Assessment Test scores than the possible COPD group (14.6±8.32 vs 12.6±6.49, P=0.01) and significantly more comorbid illnesses (P=0.01).,The main risk factors contributing to health care utilization in each COPD cohort were higher COPD Assessment Test scores (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.26), higher modified Medical Research Council Breathlessness Scale scores (OR 1.97, 95% CI 1.11-3.51), and having more than one comorbidity (OR 5.19, 95% CI 1.05-25.61).,With estimated prevalence of 6.1% in the general population, COPD in Taiwan has been underdiagnosed.,Symptoms and comorbidities were independent risk factors for health care utilization in subjects with definite or possible COPD.,There is an urgent need to raise awareness of the importance of early evaluation and prompt treatment for subjects with chronic airway symptoms.
| 1
|
To date there are no head-to-head studies comparing different mucolytic/antioxidant agents.,Considering the inconsistent evidence resulting from the pivotal studies on mucolytic/antioxidant agents tested in chronic obstructive pulmonary disease (COPD), and the recent publication of Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD (RESTORE) study, we have performed a meta-analysis to compare the efficacy and safety of erdosteine 600 mg/day, carbocysteine 1500 mg/day, and N-acetylcysteine (NAC) 1200 mg/day in COPD.,A pairwise and network meta-analyses were performed to assess the efficacy of erdosteine, carbocysteine, and NAC on acute exacerbation of COPD (AECOPD), duration of AECOPD, and hospitalization.,The frequency of adverse events (AEs) was also investigated.,Data obtained from 2753 COPD patients were extracted from 7 RCTs published between 2004 and 2017.,In the pairwise meta-analysis mucolytic/antioxidant agents significantly reduced the risk of AECOPD (RR 0.74 95%CI 0.68-0.80).,The network meta-analysis provided the following rank of effectiveness: erdosteine>carbocysteine>NAC.,Only erdosteine reduced the risk of experiencing at least one AECOPD (P < 0.01) and the risk of hospitalization due to AECOPD (P < 0.05).,Erdosteine and NAC both significantly reduced the duration of AECOPD (P < 0.01).,The AEs induced by erdosteine, carbocysteine, and NAC were mild in severity and generally well tolerated.,The quality of evidence of this quantitative synthesis is moderate.,The overall efficacy/safety profile of erdosteine is superior to that of both carbocysteine and NAC.,Future head-to-head studies performed on the same COPD populations are needed to definitely confirm the results of this meta-analysis.,CRD42016053762.
|
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality.,Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties.,Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.,We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs.,The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.,Nine RCTs comprising 1666 patients met the inclusion criteria.,Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01).,Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective.,Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates.,The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups.,A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).,Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD.,However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance.,A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.
| 1
|
Chronic obstructive pulmonary disease (COPD) is associated with substantial health impact that may already become apparent in early disease.,This study aims to examine the features of subjects with COPD in a Dutch population-based sample and compare their physical status, mental status, and social status to non-COPD subjects.,This study made use of Longitudinal Aging Study Amsterdam (LASA) data.,Demographics, clinical characteristics, self-reported diseases, post-bronchodilator spirometry, physical, mental, and social status were assessed.,A number of 810 subjects (50.5% male, mean age 60.5 ± 2.9 years) were included.,Subjects with COPD (n = 68, mean FEV1 67.6 [IQR 60.4-80.4] %.) had a slower walking speed than non-COPD subjects, p = 0.033.,When compared to non-COPD subjects, COPD subjects gave a lower rating on their health (physical subscale of SF-12: 15 [IQR 16.0-19.0] vs.,18 [IQR 11.0-17.0] points) and life (EQ5D VAS: 75 [IQR 70.0-90.0] vs. 80 points [IQR 65.0-85.5]) surveys.,COPD subjects also had a more impaired disease-specific health status (CAT: 9.5 ± 5.9 vs.,6.7 ± 5.2, respectively), were less likely to have a partner (69% vs. 84%, respectively) and received emotional support less often (24% vs. 36%, respectively) compared to non-COPD subjects (All comparisons p < 0.001).,In a population-based sample, subjects with COPD had a reduced physical performance, a more impaired disease-specific health status and were more socially deprived compared to non-COPD subjects.,These impairments need to be taken into consideration when setting up a management program for patients with mild COPD.,Patients with early-stage chronic lung disease need holistic support to limit the physical, mental and social impacts of the condition.,There is more to chronic obstructive pulmonary disease (COPD) than persistent airflow limitation; systemic effects, including loss of muscle strength and higher risk of heart conditions, mental health and social problems can manifest from the early stages.,Frits Franssen at CIRO, the Netherlands, and co-workers interviewed 810 participants aged 55-65 from the Longitudinal Aging Study Amsterdam to investigate the physical, mental and social status of COPD sufferers and compare them with healthy controls.,Those with COPD were more likely to walk slower, tire easily and perceive themselves as having poor overall health.,Socially, COPD patients were less likely to have long-term partners and felt the need for more emotional support than their healthy peers.
|
Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL).,Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD.,Systematic review.,A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015).,A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000.,Primary outcome was QoL, assessed by validated measures.,Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions.,However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL.,Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies.,Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials.
| 1
|
Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations.,Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations.,Subsequently, ICS use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status.,ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone.,The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma-COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.,Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed.,Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness.,The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids.,The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity.,ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used.,In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms.,Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment.
|
To investigate the association between inhaled corticosteroid (ICS) exposure patterns and the risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients, we performed a nested case-control study.,Between 1998 and 2010, 51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849 control subjects selected from a cohort of COPD patients using ICSs via risk-set sampling of the database constructed by the National Health Research Institutes of Taiwan.,After adjusting for covariates, the current use of ICSs was associated with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.25, 95% confidence interval [CI] =1.20-1.30), and there was an increase in the OR with increase in the average daily dosage.,Additionally, users of fluticasone/salmeterol, fluticasone, and either fluticasone/salmeterol or fluticasone were more likely to be at a higher risk of pneumonia (OR =1.35, 95% CI =1.28-1.41; OR =1.22, 95% CI =1.10-1.35; and OR =1.33, 95% CI =1.27-1.39, respectively).,In contrast, there were no statistically significant associations between the risk of pneumonia and the use of budesonide/formoterol, budesonide, or either budesonide/formoterol or budesonide.,In conclusion, ICSs are significantly associated with an increased risk of pneumonia in COPD patients.,The effect is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs.
| 1
|
Biomass smoke is the leading cause of COPD in developing countries such as Turkey.,In rural areas of Turkey, females are more exposed to biomass smoke because of traditional lifestyles.,The aim of this study was to determine the adverse effects of biomass smoke on pulmonary functions and define the relationship between duration in years and an index (cumulative exposure index) with altered pulmonary function test results.,A total of 115 females who lived in the village of Kağizman (a borough of Kars located in the eastern part of Turkey) and were exposed to biomass smoke were included in the study.,The control group was generated with 73 individuals living in the same area who were never exposed to biomass smoke.,Twenty-seven (23.8%) females in the study group and four (5.5%) in the control group had small airway disease (P=0.038).,Twenty-two (19.1%) females in the study group and ten (13.7%) in the control group had obstruction (P=0.223).,Twenty (17.3%) females in the study group who were exposed to biomass smoke had restriction compared with ten (13%) in the control group (P=0.189).,The duration needed for the existence of small airway disease was 16 years, for obstructive airway disease was 17 years, and for restrictive airway disease was 17 years.,The intensity of biomass smoke was defined in terms of cumulative exposure index; it was calculated by multiplying hours per day, weeks per month, and total years of smoke exposure and dividing the result by three.,Exposure to biomass smoke is a serious public health problem, especially in rural areas of developing countries, because of its negative effects on pulmonary functions.,As the duration and the intensity of exposure increase, the probability of having altered pulmonary function test results is higher.
|
Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind.
| 1
|
Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated.
|
This study aimed to characterize patients with chronic obstructive pulmonary disease (COPD) newly prescribed a long-acting bronchodilator (LABD), and to assess changes in medication over 24 months.,A cohort of patients with COPD aged ≥40 years newly prescribed an LABD between January 1, 2007 and December 31, 2009 were identified from the Truven Marketscan® Commercial Database (Truven Health Analytics, Ann Arbor, MI, USA) and followed for 24 months.,Inclusion criteria included no prior prescription for an LABD or inhaled corticosteroids for 12 months prior to the LABD index date (baseline).,Patient characteristics were examined.,As LABDs were mainly long-acting muscarinic antagonists (LAMAs), additions, switches, discontinuation, adherence to (medication possession ratio), and persistence (proportion of days covered) with LAMA monotherapy were assessed for 24 months following the index date.,Adherence and persistence with long-acting β2-agonists (LABAs) were also assessed.,A cohort of 3,268 patients aged 40-65 years was identified (mean age 55.8 years, 48% male).,LAMA monotherapy was prescribed to 93% of patients who received an LABD.,During the 24-month follow-up, 16% of these patients added COPD medication, 10% switched to an inhaled corticosteroid-containing medication, and 25% discontinued after one LAMA prescription at baseline.,Over 12 and 24 months, adherence to LAMA was 40% and 33%, respectively, and adherence to LABA was 29% and 24%, respectively.,Over the same time periods, persistence with LAMA monotherapy was 19% and 15%, respectively, and persistence with LABA was 9% and 7%, respectively.,Adherence to newly initiated LAMA monotherapy was low, with one in four patients adding to or switching from LAMA and many patients discontinuing therapy.,Adherence to LABA was also low.,These results suggest that additional medication to a single LABD may be required in some patients with COPD to achieve optimal disease control.
| 1
|
Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality.,Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions.,However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known.,We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD.,We then determined what types of psychological and lifestyle interventions are most effective.,Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety.,CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012.,Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety.,Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis.,Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09).,Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18).,Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD.,Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population.
|
In the current study, the prevalence of the most common psychological disorders in COPD patients and their spouses was assessed cross-sectionally.,The influence of COPD patients’ and their spouses’ psychopathology on patient health-related quality of life was also examined.,The following measurements were employed: Forced expiratory volume in 1 second expressed in percentage predicted (FEV1%), Shuttle-Walking-Test (SWT), International Diagnostic Checklists for ICD-10 (IDCL), questionnaires on generic and disease-specific health-related quality of life (St.,George’s Respiratory Questionnaire (SGRQ), European Quality of Life Questionnaire (EuroQol), a modified version of a Disability-Index (CDI)), and a screening questionnaire for a broad range of psychological problems and symptoms of psychopathology (Symptom-Checklist-90-R (SCL-90-R)).,One hundred and forty-three stable COPD outpatients with a severity grade between 2 and 4 (according to the GOLD criteria) as well as 105 spouses took part in the study.,The prevalence of anxiety and depression diagnoses was increased both in COPD patients and their spouses.,In contrast, substance-related disorders were explicitly more frequent in COPD patients.,Multiple linear regression analyses indicated that depression (SCL-90-R), walking distance (SWT), somatization (SCL-90-R), male gender, FEV1%, and heart disease were independent predictors of COPD patients’ health-related quality of life.,After including anxiousness of the spouses in the regression, medical variables (FEV1% and heart disease) no longer explained disability, thus highlighting the relevance of spouses’ well-being.,The results underline the importance of depression and anxiousness for health-related quality of life in COPD patients and their spouses.,Of special interest is the fact that the relation between emotional distress and quality of life is interactive within a couple.
| 1
|
Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8.
|
The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.
| 1
|
Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide.,The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results.,Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease.,The bacterial metagenomes within sputum samples from eight COPD patients and ten ‘healthy’ smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus.,The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations.,Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism.,This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity.
|
The course of chronic obstructive pulmonary disease (COPD) is frequently aggravated by exacerbations, and changes in the composition and activity of the microbiome may be implicated in their appearance.,The aim of this study was to analyse the composition and the gene content of the microbial community in bronchial secretions of COPD patients in both stability and exacerbation.,Taxonomic data were obtained by 16S rRNA gene amplification and pyrosequencing, and metabolic information through shotgun metagenomics, using the Metagenomics RAST server (MG-RAST), and the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) programme, which predict metagenomes from 16S data.,Eight severe COPD patients provided good quality sputum samples, and no significant differences in the relative abundance of any phyla and genera were found between stability and exacerbation.,Bacterial biodiversity (Chao1 and Shannon indexes) did not show statistical differences and beta-diversity analysis (Bray-Curtis dissimilarity index) showed a similar microbial composition in the two clinical situations.,Four functional categories showed statistically significant differences with MG-RAST at KEGG level 2: in exacerbation, Cell growth and Death and Transport and Catabolism decreased in abundance [1.6 (0.2-2.3) vs 3.6 (3.3-6.9), p = 0.012; and 1.8 (0-3.3) vs 3.6 (1.8-5.1), p = 0.025 respectively], while Cancer and Carbohydrate Metabolism increased [0.8 (0-1.5) vs 0 (0-0.5), p = 0.043; and 7 (6.4-9) vs 5.9 (6.3-6.1), p = 0.012 respectively].,In conclusion, the bronchial microbiome as a whole is not significantly modified when exacerbation symptoms appear in severe COPD patients, but its functional metabolic capabilities show significant changes in several pathways.
| 1
|
The application of telemedicine in home pulmonary rehabilitation interventions for the management of patients with chronic obstructive pulmonary disease (COPD) has achieved promising results.,This study aimed to develop a WeChat official account (Pulmonary Internet Explorer Rehabilitation [PeR]) based on social media.,It further evaluated the effect of PeR on the quality of life, symptoms, and exercise self-efficacy of patients with COPD.,The functional modules of PeR were developed by a multidisciplinary team according to the electronic health-enhanced chronic care model (eCCM) components.,A total of 106 patients were randomly selected (53 in the PeR group and 53 in the outpatient face-to-face group [FtF]).,Pulmonary rehabilitation intervention was conducted for 3 months, and the outcome was observed for 3 months.,The primary outcome was patient quality of life measured with the COPD assessment test (CAT).,The secondary outcomes were evaluated using the modified Medical Research Council scale (mMRC), exercise self-regulatory efficacy scale (Ex-SRES), and St George’s Respiratory Questionnaire (SGRQ).,The intention-to-treat analysis was used in the study.,A total of 94 participants completed the 6-month pulmonary rehabilitation program.,No statistically significant differences were observed in CAT (F1,3=7.78, P=.001), Ex-SRES (F1,3=21.91, P<.001), and mMRC scores (F1,3=29.64, P<.001) between the two groups with the variation in time tendency.,The Ex-SRES score had a significant effect on the CAT score (P=.03).,The partial regression coefficient of Ex-SRES to CAT was 0.81, and Exp (B) was 2.24.,The telemedicine technology was effective using the eCCM combined with a behavioral intervention strategy centering on self-efficacy.,Pulmonary rehabilitation at home through PeR and FtF could improve the sense of self-efficacy and quality of life and alleviate symptoms in patients with COPD.,Chinese Clinical Trial Registry ChiCTR1900022770; https://tinyurl.com/tmmvpq3
|
Using a mobile health (mHealth) intervention, consisting of a smartphone and compatible medical device, has the potential to enhance chronic obstructive pulmonary disease (COPD) treatment outcomes while mitigating health care costs.,The aim of this study was to explore the potential facilitators and barriers among health care providers (HCPs) regarding the use of mHealth interventions for COPD management.,This was a qualitative study.,Semistructured individual interviews were conducted with HCPs, including nurses, pharmacists, and physicians who work directly with patients with COPD.,A flexible prompts guide was used to facilitate discussions.,Interview topics included the following: demographics, mHealth usage, perceptions toward challenges of mHealth adoption, factors facilitating mHealth adoption, and preferences regarding features of the mHealth intervention for COPD management.,Interviews were conversational in nature, and items were not asked verbatim or in the order presented.,The interviews were transcribed verbatim and compared against the digital recordings to ensure the accuracy of the content.,After creating a codebook for analysis, 2 researchers independently coded the remaining interview data using pattern coding.,They discussed commonalities and differences in coding until a consensus was reached.,A total of 30 nurses, physicians, and pharmacists participated.,The main facilitators to mHealth adoption are possible health benefits for patients, ease of use, educating patients and their HCPs, credibility, and reducing cost to the health care system.,Alternatively, the barriers to adoption are technical issues, privacy and confidentiality issues, lack of awareness, potential limited uptake from the elderly, potential limited connection between patients and HCPs, and finances.,It is important to understand the perceptions of HCPs regarding the adoption of innovative mHealth interventions for COPD management.,This study identifies some potential facilitators and barriers that may inform the successful development and implementation of mHealth interventions for COPD management.
| 1
|
Worldwide, chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease with considerable clinical and socioeconomic impact.,Pharmacologic maintenance drugs (such as bronchodilators and inhaled corticosteroids) play an important role in the treatment of COPD.,The cost effectiveness of these treatments has been frequently assessed, but studies to date have largely neglected the impact of treatment sequence and the exact stage of disease in which the drugs are used in real life.,We aimed to systematically review recently published articles that reported the cost effectiveness of COPD maintenance treatments, with a focus on key findings, quality and methodological issues.,We performed a systematic literature search in Embase, PubMed, the UK NHS Economic Evaluation Database (NHS-EED) and EURONHEED (European Network of Health Economics Evaluation Databases) and included all relevant articles published between 2011 and 2015 in either Dutch, English or German.,Main study characteristics, methods and outcomes were extracted and critically assessed.,The Quality of Health Economic Studies (QHES) instrument was used as basis for quality assessment, but additional items were also addressed.,The search identified 18 recent pharmacoeconomic analyses of COPD maintenance treatments.,Papers reported the cost effectiveness of long-acting muscarinic antagonist (LAMA) monotherapy (n = 6), phosphodiesterase (PDE)-4 inhibitors (n = 4), long-acting beta agonist/inhaled corticosteroid (LABA/ICS) combinations (n = 4), LABA monotherapy (n = 2) and LABA/LAMA combinations (n = 2).,All but two studies were funded by the manufacturer, and all studies indicated favourable cost effectiveness; however, the number of quality-adjusted life-years (QALYs) gained was small.,Less than half of the studies reported a COPD-specific outcome in addition to a generic outcome (mostly QALYs).,Exacerbation and mortality rates were found to be the main drivers of cost effectiveness.,According to the QHES, the quality of the studies was generally sufficient, but additional assessment revealed that most studies poorly represented the cost effectiveness of real-life medication use.,The majority of studies showed that pharmacologic COPD maintenance treatment is cost effective, but most studies poorly reflected real-life drug use.,Consistent and COPD-specific methodology is recommended.,The online version of this article (doi:10.1007/s40273-016-0448-2) contains supplementary material, which is available to authorized users.
|
The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care.,This study aimed to evaluate its cost-effectiveness.,An economic analysis was performed from the Belgian healthcare payer’s perspective.,A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care.,Three types of costs were calculated: intervention costs, medication costs and exacerbation costs.,Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year.,Follow-up was 1 year in the basecase analysis.,Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty.,In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon.,This reflects cost savings of €227 for the PHARMACOP-intervention.,The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care).,Results showed robust cost-savings in various sensitivity analyses.,Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies.
| 1
|
Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD).,However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD.,General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD.,Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed.,Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients.,Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers’ education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC.,The results provide insights for clinical practice and the development of key components for successful practice in a phase 0-2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients’ disease insight and training PHC nurses in care for end-stage COPD.,Research in Belgium provides insights into the possible implementation of early palliative care (PC) for patients with chronic obstructive pulmonary disease (COPD).,While many sufferers of end-stage COPD would benefit emotionally and physically from palliative home care in their final months, many only receive PC in their last few days.,Charlotte Scheerens at End-of-life Care Research Group, Ghent University and Vrije Universiteit Brussel (VUB) and co-workers at Ghent University and Vrije Universiteit Brussel (VUB) conducted focus group discussions with 28 general practitioners and 28 community nurses to establish the main barriers to and facilitators for palliative home care implementation for end-stage COPD.,Barriers included the unpredictability of the disease, lack of patient understanding of COPD, and complex communication issues between staff across primary care, hospitals and community settings.,Identifying ‘triggers’ to implement PC-oxygen dependence, for example-and improving communication and understanding of COPD at all levels could facilitate early integration of palliative home care (PHC).
|
Recent research shows that advance care planning (ACP) for patients with chronic obstructive pulmonary disease (COPD) is uncommon and poorly carried out.,The aim of the present study was to explore whether and to what extent structured ACP by a trained nurse, in collaboration with the chest physician, can improve outcomes in Dutch patients with COPD and their family.,A multicentre cluster randomised controlled trial in patients with COPD who are recently discharged after an exacerbation has been designed.,Patients will be recruited from three Dutch hospitals and will be assigned to an intervention or control group, depending on the randomisation of their chest physician.,Patients will be assessed at baseline and after 6 and 12 months.,The intervention group will receive a structured ACP session by a trained nurse.,The primary outcomes are quality of communication about end-of-life care, symptoms of anxiety and depression, quality of end-of-life care and quality of dying.,Secondary outcomes include concordance between patient's preferences for end-of-life care and received end-of-life care, and psychological distress in bereaved family members of deceased patients.,Intervention and control groups will be compared using univariate analyses and clustered regression analysis.,Ethical approval was received from the Medical Ethical Committee of the Catharina Hospital Eindhoven, the Netherlands (NL42437.060.12).,The current project provides recommendations for guidelines on palliative care in COPD and supports implementation of ACP in the regular clinical care.,NTR3940.
| 1
|
Hospitalization brings considerable economic pressure on COPD patients in China.,A clear understanding of hospitalization costs for patients with COPD is warranted to improve treatment strategies and to control costs.,Currently, investigation on factors contributing to hospitalization costs for patients with COPD in China is limited.,This study aimed to measure the hospitalization costs of COPD and to determine the contributing factors.,Medical record data from the First Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2016 were used for a retrospective analysis.,Patients who were hospitalized with a diagnosis of COPD were included.,Patient characteristics, medical treatment, and hospitalization costs were analyzed by descriptive statistics and multivariable regression.,Among the 1,943 patients included in this study, 87.85% patients were male; the mean (SD) age was 71.15 (9.79) years; 94.49% patients had comorbidities; and 82.30% patients had health insurance.,Regarding medical treatment, the mean (SD) length of stay was 9.38 (7.65) days; 11.12% patients underwent surgery; 87.91% used antibiotics; and 4.53% underwent emergency treatment.,For hospitalization costs, the mean (SD) of the total costs per COPD patient per admission was 24,372.75 (44,173.87) CNY (3,669.33 [6,650.38] USD), in which Western medicine fee was the biggest contributor (45.53%) followed by diagnosis fee (27.00%) and comprehensive medical fee (12.04%).,Regression found that reimbursement (−0.032; 95% CI −0.046 to 0.007), length of stay (0.738; 95% CI 0.832-0.892), comorbidity (0.044; 95% CI 0.029-0.093), surgery (0.145; 95% CI 0.120-0.170), antibiotic use (0.086; 95% CI 0.060-0.107), and emergency treatment (0.121; 95% CI 0.147-0.219) were significantly (P<0.01) associated with total hospitalization costs.,To control hospitalization costs for COPD patients in China, the significance of comorbidity, length of stay, antibiotic use, surgery, and emergency treatment suggests the importance of controlling the COPD progression and following clinical guidelines for inpatients.,Interventions such as examination of pulmonary function for early detection, quality control of medical treatment, and patient education warrant further investigation.
|
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD.
| 1
|
Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination.,This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).,In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks.,Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT).,Safety evaluations included adverse events (AEs).,Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001).,Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2-0.0]; P≤0.05).,More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01).,Improvements in SGRQ and CAT scores were similar between treatments.,The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).,UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone.
|
The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms.,The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.,In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.,The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.,Overall, 676 patients completed the study.,The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met.,QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001).,QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001).,QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use.,However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC.,Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%).,The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).,These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.
| 1
|
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy.
|
Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users.
| 1
|
Health-related quality of life measures are widely used in patients with chronic obstructive pulmonary disease (COPD).,However, they are extremely limited when used to evaluate patients outside the clinical trials.,The aim of this study was to analyse the burden of the disease using a simple, validated, self-administered questionnaire specifically developed for patients in daily clinical practice.,A total of 3935 patients (74.5% men; mean age, 67 years) participated in a cross-sectional study.,The burden of COPD on patients was measured using the Clinical COPD Questionnaire (CCQ).,COPD was rated at four levels by the forced expiratory volume in one second (FEV1) according to The Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale.,The disease mainly affects old men (more than 50% were over 65 years of age) and non-employed men (23% were employed).,Of the patients studied, 22.7% continued smoking, especially men (24.4% of men vs.,18.1% of women).,Most patients (54%) were diagnosed with moderate stage II COPD.,Severity of COPD was lower in women: 29.6% of men had severe COPD compared with 13.7% of women.,During the last year, 65.1% had at least one acute exacerbation and 36.6% were admitted to hospital because of COPD exacerbation.,No association was found between the body mass index and COPD stage.,The variable that most influenced the disease burden was dyspnoea, as progression from grade 0 to grade 4 increased the disease burden by 1.78 points for symptoms, 2.43 for functional state and 1.53 for mental state.,The functional classification of COPD also had a significant influence on the disease burden.,The present findings show that dyspnoea and the degree of airflow limitation are the clinical variables that most affect the burden of COPD from the patient’s point of view.
|
COPD is prevalent in Western society and its incidence is rising in the developing world.,Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden.,Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease.,COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality.,Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use.,Erythromycin has been shown to decrease the rate of COPD exacerbations.,Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life.,Noninvasive ventilation is associated with improved quality of life.,Long-term oxygen therapy improves mortality but only in hypoxic COPD patients.,The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of.,Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates.,Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles.
| 1
|
Using a mobile health (mHealth) intervention consisting of a smartphone and compatible medical device has the potential to enhance chronic obstructive pulmonary disease (COPD) treatment outcomes while mitigating health care costs.,This study aims to describe the demographics, use, and access to smartphones of patients with COPD.,It also aims to explore and develop an understanding of potential facilitators and barriers that might influence patients using mHealth interventions for COPD management.,This was an explanatory, sequential mixed methods study.,Patients who attended respirology clinics completed a questionnaire on technology access and use.,We conducted semistructured individual interviews with the patients.,Interview topics included the following: demographics, mHealth use, perceptions toward challenges of mHealth adoption, factors facilitating mHealth adoption, and preferences regarding features of mHealth interventions for COPD management.,A total of 100 adults completed the survey but 22 participants were excluded because they were not diagnosed with COPD.,Of these, 10 patients with COPD participated in the interview.,The quantitative component revealed that many patients with COPD owned a mobile phone, but only about one-fourth of the participants (18/77, 23%) owned a smartphone.,The likelihood of owning a smartphone was not associated with age, sex, marital status, or geographical location, but patients with high educational status were more likely to own a smartphone.,The qualitative component found that patients with COPD, in general, had a positive attitude toward mHealth adoption for COPD management, but several facilitators and barriers were identified.,The main facilitators of mHealth adoption are possible health benefits for patients, ease of use, educating patients, and credibility.,Alternatively, the barriers to adoption are technical issues, lack of awareness, potential limited uptake from older adults, privacy and confidentiality issues, finances, and lack of interest in mHealth,It is important to understand the perceptions of patients with COPD regarding the adoption of innovative mHealth interventions for COPD management.,This study identifies some potential facilitators and barriers that may inform the successful development and implementation of mHealth interventions for COPD management.
|
To determine the feasibility and efficacy of a six-month, cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease (COPD) following pulmonary rehabilitation.,Participants who completed a two-week run-in were randomly assigned to either MOBILE-Coached (n = 9) or MOBILE-Self-Monitored (n = 8).,All participants met with a nurse to develop an individualized exercise plan, were issued a pedometer and exercise booklet, and instructed to continue to log their daily exercise and symptoms.,MOBILE-Coached also received weekly reinforcement text messages on their cell phones; reports of worsening symptoms were automatically flagged for follow-up.,Usability and satisfaction were assessed.,Participants completed incremental cycle and six minute walk (6MW) tests, wore an activity monitor for 14 days, and reported their health-related quality of life (HRQL) at baseline, three, and six months.,The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18% predicted.,Participants reported that logging their exercise and symptoms (FEV1) of 40 ± was easy and that keeping track of their exercise helped them remain active.,There were no differences between groups over time in maximal workload, 6MW distance, or HRQL (p > 0.05); however, MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months (p =0.04).,We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring.,The latter finding needs to be interpreted with caution since this was a purely exploratory study.,ClinicalTrials.gov (NCT00373932).
| 1
|
Chronic obstructive pulmonary disease and lung cancer are leading causes of death with comparable symptoms at the end of life.,Cross-national comparisons of place of death, as an important outcome of terminal care, between people dying from chronic obstructive pulmonary disease and lung cancer have not been studied before.,We collected population death certificate data from 14 countries (year: 2008), covering place of death, underlying cause of death, and demographic information.,We included patients dying from lung cancer or chronic obstructive pulmonary disease and used descriptive statistics and multivariable logistic regressions to describe patterns in place of death.,Of 5,568,827 deaths, 5.8% were from lung cancer and 4.4% from chronic obstructive pulmonary disease.,Among lung cancer decedents, home deaths ranged from 12.5% in South Korea to 57.1% in Mexico, while hospital deaths ranged from 27.5% in New Zealand to 77.4% in France.,In chronic obstructive pulmonary disease patients, the proportion dying at home ranged from 10.4% in Canada to 55.4% in Mexico, while hospital deaths ranged from 41.8% in Mexico to 78.9% in South Korea.,Controlling for age, sex, and marital status, patients with chronic obstructive pulmonary disease were significantly less likely die at home rather than in hospital in nine countries.,Our study found in almost all countries that those dying from chronic obstructive pulmonary disease as compared with those from lung cancer are less likely to die at home and at a palliative care institution and more likely to die in a hospital or a nursing home.,This might be due to less predictable disease trajectories and prognosis of death in chronic obstructive pulmonary disease.,Structured palliative care similar to that offered to cancer sufferers should be in place for patients with chronic lung disease.,Joachim Cohen at Vrije University in Brussels and co-workers examined international death certificate data collected from 14 countries to determine place of death for patients with lung cancer and chronic obstructive pulmonary disease (COPD).,While patients with COPD suffer similar symptoms to lung cancer in their final days, few COPD patients receive palliative care or achieve the common wish of dying at home.,This may be partly due to the inherent unpredictability of final-stage COPD compared with lung cancer.,Cohen’s team found that, with the exception of Italy, Spain, and Mexico, patients with COPD were significantly more likely to die in hospital than at home.,They highlight the need for improved COPD palliative care provision.
|
To evaluate the nonclinical outcomes of a proactive palliative care program funded and operated by a health system for Medicare Advantage plan beneficiaries.,Observational, retrospective study using propensity‐based matching.,A health system in southern California.,Individuals who received the intervention between 2007 and 2014 (n = 368) were matched with 1,075 comparison individuals within each of four disease groups: cancer, chronic obstructive pulmonary disease, heart failure, and dementia.,All were known to be dead at the time of the retrospective study, were Medicare Advantage beneficiaries, and had 2 years of usage data before death.,Median age at death for each disease group was older than 80.,Home‐ and clinic‐based palliative care (PC) services provided by a multidisciplinary team.,Outcomes included hospital costs, other healthcare costs, readmission rates, hospital admissions and bed days, intensive care unit use in final 30 days of life, and death within 30 days of an admission.,Intervention participants in all four disease groups had less hospital use and lower hospital costs nonintervention participants, which drove lower overall healthcare costs.,In the final 6 months of life, healthcare costs for the intervention groups stayed largely the same from month to month, whereas costs for comparison participants increased dramatically.,In the context of an alternative payment model in which the provider was “at risk” of bearing the costs of care, a proactive PC program helped to avoid the escalation in hospital use and costs commonly seen in the final months of life.
| 1
|
Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).,Methods: The multidisciplinary panel created six research questions using a modified Delphi approach.,A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.,Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement).,Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.
|
Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management.
| 1
|
Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.,To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.,3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array.,An analysis of risk of COPD was carried out using ever smoking controls (n=4784).,Associations with %predicted FEV1 were tested in cases.,We followed-up signals of interest (p<10−5) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.,Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10−6, preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10−6).,In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10−6).,We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5.,No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10−7).,This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study.
|
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations.,The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract.,The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations.,In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD.,In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes.,This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans.
| 1
|
COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow.,It is mainly associated with exposure to cigarette smoke.,In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide.,Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells.,Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways.,The aims of these molecules are differentiation, proliferation and recruitment of neutrophils.,Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight.,In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract.,Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.
|
COPD is a chronic airway inflammatory disease characterized mainly by neutrophil airway infiltrations.,Interleukin (IL)-1β and IL-17 are the key mediators of neutrophilic airway inflammation in COPD.,This study was undertaken to evaluate the serum IL-1β and IL-17 levels and associations between these two key mediators with clinical parameters in COPD patients.,Serum samples were collected from 60 COPD subjects during the acute exacerbation of COPD, 60 subjects with stable COPD and 40 healthy control subjects.,Commercial enzyme-linked immunosorbent assay kits were used to measure the serum IL-1β and IL-17 concentrations.,The association between serum IL-1β and IL-17 with FEV1% predicted, C-reactive protein, neutrophil percentage and smoking status (pack-years) was assessed in the COPD patients.,We found that serum IL-1β and IL-17 levels in acute exacerbation of COPD subjects were significantly higher than that in stable COPD or control subjects and were positively correlated to serum C-reactive protein levels, neutrophil % and smoking status (pack-years) but negatively correlated with FEV1% predicted in COPD patients.,More importantly, serum IL-1β levels were markedly positively associated with serum IL-17 levels in patients with COPD (P=0.741, P<0.001).,In conclusion, elevated serum IL-1β and IL-17 levels may be used as a biomarker for indicating persistent neutrophilic airway inflammation and potential ongoing exacerbation of COPD.
| 1
|
The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a short questionnaire that has facilitated health status measurements in subjects with COPD.,However, it remains controversial as to whether the CAT can be used as a suitable substitute for the St George’s Respiratory Questionnaire (SGRQ).,This study investigated the reliability and score distributions of the CAT and SGRQ and evaluated which factors contributed to health status for each questionnaire.,A total of 109 consecutive subjects with stable COPD from a single center were enrolled in this study.,Each subject completed pulmonary function tests, exercise tests, and the following self-administered questionnaires: the Baseline Dyspnea Index, the Hospital Anxiety and Depression Scale, the CAT, and SGRQ.,Internal consistencies of CAT and SGRQ total scores were both excellent (Cronbach’s α coefficients =0.890 and 0.933).,Statistically significant correlations were observed between CAT and SGRQ total scores (R=0.668, P<0.001).,Correlations of CAT scores with parameters related to pulmonary function, dyspnea, exercise performance, and psychological factors were inferior to correlations with those parameters with SGRQ total scores.,Both multiple regression analyses and principal component analyses revealed that there were slight differences between SGRQ total scores and CAT scores.,The CAT is similar to SGRQ in terms of discriminating health status.,However, we demonstrated that what is assessed by the CAT may differ slightly from what is measured by SGRQ.
|
COPD is currently the fourth cause of morbidity and mortality in the developed world.,Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL).,The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease.,It is a multicenter, epidemiological, observational, descriptive study.,Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included.,Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected.,All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores.,10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66).,The mean value of FEV1 was 35.9 ± 10.0%.,Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively.,Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease.,The correlation with FEV1 was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12).,Predictors for both HRQoL components were sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.,Other independent predictors of PCS-12 were age, body mass index and educational level.,Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease.,The factors determining the HRQoL include sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.
| 1
|
The hedgehog (HH) pathway has been associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies and recent studies suggest that HH signalling could be altered in COPD.,We therefore used minimally invasive endobronchial procedures to assess activation of the HH pathway including the main transcription factor, Gli2, and the ligand, Sonic HH (Shh).,Thirty non-COPD patients and 28 COPD patients were included.,Bronchial brushings, bronchoalveolar lavage fluid (BALF) and bronchial biopsies were obtained from fiberoptic bronchoscopy.,Characterization of cell populations and subcellular localization were evaluated by immunostaining.,ELISA and RNAseq analysis were performed to identify Shh proteins in BAL and transcripts on lung tissues from non-COPD and COPD patients with validation in an external and independent cohort.,Compared to non-COPD patients, COPD patients exhibited a larger proportion of basal cells in bronchial brushings (26 ± 11% vs 13 ± 6%; p < 0.0001).,Airway basal cells of COPD subjects presented less intense nuclear staining for Gli2 in bronchial brushings and biopsies (p < 0.05).,Bronchial BALF from COPD patients contained lower Shh concentrations than non-COPD BALF (12.5 vs 40.9 pg/mL; p = 0.002); SHH transcripts were also reduced in COPD lungs in the validation cohort (p = 0.0001).,This study demonstrates the feasibility of assessing HH pathway activation in respiratory samples collected by bronchoscopy and identifies impaired bronchial epithelial HH signalling in COPD.
|
A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro.,Whether ADAM15 expression is increased in the lungs of COPD patients is not known.,ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavage (BAL) macrophage samples obtained from COPD patients, smokers, and non-smokers.,Soluble ADAM15 protein levels were measured in BAL fluid (BALF) and plasma samples from COPD patients and controls.,Cells expressing ADAM15 in the lungs were identified using immunostaining.,Staining for ADAM15 in different cells in the lungs was related to forced expiratory volume in 1 s (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history.,ADAM15 gene expression and/or protein levels were increased in alveolar macrophages and whole lung samples from COPD patients versus smokers and non-smokers.,Soluble ADAM15 protein levels were similar in BALF and plasma samples from COPD patients and controls.,ADAM15 immunostaining was increased in macrophages, CD8+ T cells, epithelial cells, and airway α-smooth muscle (α-SMA)-positive cells in the lungs of COPD patients.,ADAM15 immunostaining in macrophages, CD8+ T cells and bronchial (but not alveolar) epithelial cells was related inversely to FEV1 and FEV1/FVC, but not to pack-years of smoking history.,ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV1/FVC.,Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2.,These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD.
| 1
|
This systematic review aims to establish the role of CD8 + T lymphocytes in COPD.,Forty-eight papers published in the last 15 years were identified for inclusion.,CD8 + T-cells are increased in the lungs of patients with COPD (17 studies, 16 positive) whereas in the circulation, findings were inconclusive.,Activation of CD8 + T-cells was enhanced in lungs (four studies, three positive) but cell phenotype was unclear.,There was substantial evidence of a higher proportion of type 1 CD8 + (Tc1) cells in COPD (11 studies, 9 positive), though the population of type 2 (Tc2) cells was also increased (5 studies, 4 positive).,CD8 + T-cells in COPD exhibited greater expression of cytotoxic proteins (five studies, five positive).,Studies assessed a variety of questions so evidence was insufficient to draw firm conclusions.,The role of CD8 + T-cells at acute exacerbation of COPD and also their contribution to alveolar destruction can only be hypothesised at this stage.,Not only is the number of CD8 + T-cells increased in COPD, these cells have increased capacity to exert effector functions and are likely to contribute to disease pathogenesis.,Several mechanisms highlighted show promise for future investigation to consolidate current knowledge.,The online version of this article (10.1007/s00011-020-01408-z) contains supplementary material, which is available to authorized users.
|
Although elevated blood or sputum eosinophils are present in many patients with COPD, uncertainties remain regarding the anatomical distribution pattern of lung-infiltrating eosinophils.,Basophils have remained virtually unexplored in COPD.,This study mapped tissue-infiltrating eosinophils, basophils and eosinophil-promoting immune mechanisms in COPD-affected lungs.,Surgical lung tissue and biopsies from major anatomical compartments were obtained from COPD patients with severity grades Global Initiative for Chronic Obstructive Lung Disease stages I-IV; never-smokers/smokers served as controls.,Automated immunohistochemistry and in situ hybridisation identified immune cells, the type 2 immunity marker GATA3 and eotaxins (CCL11, CCL24).,Eosinophils and basophils were present in all anatomical compartments of COPD-affected lungs and increased significantly in very severe COPD.,The eosinophilia was strikingly patchy, and focal eosinophil-rich microenvironments were spatially linked with GATA3+ cells, including type 2 helper T-cell lymphocytes and type 2 innate lymphoid cells.,A similarly localised and interleukin-33/ST2-dependent eosinophilia was demonstrated in influenza-infected mice.,Both mice and patients displayed spatially confined eotaxin signatures with CCL11+ fibroblasts and CCL24+ macrophages.,In addition to identifying tissue basophilia as a novel feature of advanced COPD, the identification of spatially confined eosinophil-rich type 2 microenvironments represents a novel type of heterogeneity in the immunopathology of COPD that is likely to have implications for personalised treatment.,Highly localised Th2- and eosinophil-rich pockets were identified in COPD-affected lungs, which increased in number with increasing disease severity and included basophils.,This exemplifies a novel type of heterogeneity in the immunopathology of COPD.http://bit.ly/2HexTco
| 1
|
The development of chronic obstructive pulmonary disease (COPD) pathogenesis remains unclear, but emerging evidence supports a crucial role for inducible bronchus‐associated lymphoid tissue (iBALT) in disease progression.,Mechanisms underlying iBALT generation, particularly during chronic CS exposure, remain to be defined.,Oxysterol metabolism of cholesterol is crucial to immune cell localization in secondary lymphoid tissue.,Here, we demonstrate that oxysterols also critically regulate iBALT generation and the immune pathogenesis of COPD.,In both COPD patients and cigarette smoke (CS)‐exposed mice, we identified significantly upregulated CH25H and CYP7B1 expression in airway epithelial cells, regulating CS‐induced B‐cell migration and iBALT formation.,Mice deficient in CH25H or the oxysterol receptor EBI2 exhibited decreased iBALT and subsequent CS‐induced emphysema.,Further, inhibition of the oxysterol pathway using clotrimazole resolved iBALT formation and attenuated CS‐induced emphysema in vivo therapeutically.,Collectively, our studies are the first to mechanistically interrogate oxysterol‐dependent iBALT formation in the pathogenesis of COPD, and identify a novel therapeutic target for the treatment of COPD and potentially other diseases driven by the generation of tertiary lymphoid organs.
|
Pulmonary surfactant D (SP-D) has important regulatory functions for innate immunity and has been implicated as a biomarker for chronic obstructive pulmonary disease (COPD).,We hypothesized that COPD patients would have reduced bronchoalveolar lavage (BAL) fluid SP-D levels compared to healthy smoking and non-smoking controls.,BAL SP-D and phospholipids were quantified and corrected for dilution in 110 subjects (65 healthy never smokers, 23 smokers with normal spirometry, and 22 smokers with COPD).,BAL SP-D was highest in never smokers (mean 51.9 μg/mL ± 7.1 μg/mL standard error) compared to both smokers with normal spirometry (16.0 μg/mL ± 11.8 μg/mL) and subjects with COPD (19.1 μg/mL ± 12.9 μg/mL; P < 0.0001).,Among smokers with COPD, BAL SP-D correlated significantly with FEV1% predicted (R = 0.43; P < 0.05); however, the strongest predictor of BAL SP-D was smoking status.,BAL SP-D levels were lowest in current smokers (12.8 μg/mL ± 11.0 μg/mL), intermediate in former smokers (25.2 μg/mL ± 14.2 μg/mL; P < 0.008), and highest in never smokers.,BAL phospholipids were also lowest in current smokers (6.5 nmol ± 1.5 nmol), intermediate in former smokers (13.1 nmol ± 2.1 nmol), and highest in never smokers (14.8 nmol ± 1.1 nmol; P < 0.0001).,These data suggest that smokers, and especially current smokers, exhibit significantly reduced BAL SP-D and phospholipids compared to nonsmokers.,Our findings may help better explain the mechanism that leads to the rapid progression of disease and increased incidence of infection in smokers.
| 1
|
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide.,Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations.,Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation.,Long-acting β2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD.,The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects.,Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe.,Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA.,Several other agents are in the late stages of development, most of which offer once-daily dosing.,The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations.,These evolving treatments will provide new opportunities and challenges in the management of COPD.
|
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY
| 1
|
Public health is a priority for the Chinese Government.,Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance.,This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level.,We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017.,We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk.,We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI).,Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017.,Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017.,Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017.,Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs.,All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88.,The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain.,The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4).,China has made substantial progress in reducing the burden of many diseases and disabilities.,Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system.,China National Key Research and Development Program and Bill & Melinda Gates Foundation.
|
Exposure to environmental particulate matter (PM) ≤2.5 μm in diameter (PM2.5) and smoking are common contributors to COPD, and pertinent research implicates both factors in pulmonary inflammation.,Using in vivo mouse and in vitro human cellular models, we investigated the joint impact of PM2.5 pollution, and cigarette smoke (CS) in mice or cigarette-smoke extract (CSE) in cells on COPD inflammation, and explored potential mechanisms.,Tissue changes in lungs of C57BL/6 mice exposed to PM2.5 and CS were studied by light microscopy, H&E, immunochemistry, and immunofluorescence-stained sections.,Levels of inflammatory factors induced by PM2.5/CS in mice and PM2.5/CSE in 16HBE cells were also monitored by quantitative reverse-transcription (qRT)-PCR and ELISA.,Expression of genes related to the Wnt5a-signaling pathway was assessed at transcriptional and protein levels using immunofluorescence, qRT-PCR, and Western blotting.,Inflammatory response to combined exposure of PM2.5 and CS or CSE in mouse and 16HBE cells surpassed responses incited separately.,Although separate PM2.5 and CS/CSE exposure upregulated the expression of Wnt5a (a member of the Wnt-secreted glycoprotein family), combined PM2.5 and CS/CSE exposure produced a steeper rise in Wnt5a levels.,Use of a Wnt5a antagonist (BOX5) successfully blocked related inflammatory effects.,ERK phosphorylation appeared to mediate the effects of Wnt5a in the COPD model, promoting PM2.5 aggravation of CS/CSE-induced airway inflammation.,Our findings suggest that combined PM2.5 and CS/CSE exposure induce airway inflammation and Wnt5a expression in vivo in mice and in vitro in 16HBE cells.,Furthermore, PM2.5 seems to aggravate CS/CSE-induced inflammation via the Wnt5a-ERK pathway in the context of COPD.
| 1
|
Pulmonary hypertension (PH) is a frequent and important complication of chronic obstructive pulmonary disease (COPD).,It is associated with worse clinical courses with more frequent exacerbation episodes, shorter survival, and greater need of health resources.,PH is usually of moderate severity and progresses slowly, without altering right ventricular function in the majority of cases.,Nevertheless, a reduced subgroup of patients may present disproportionate PH, with pulmonary artery pressure (PAP) largely exceeding the severity of respiratory impairment.,These patients may represent a group with an exaggerated vascular impairment (pulmonary vascular phenotype) to factors that induce PH in COPD or be patients in whom idiopathic pulmonary arterial hypertension (PAH) coexist.,The present review addresses the current definition and classification of PH in COPD, the distinction among the different phenotypes of pulmonary vascular disease that might present in COPD patients, and the therapeutic approach to PH in COPD based on the available scientific evidence.
|
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation.
| 1
|
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation, mucus hypersecretion, and emphysema, which lead to reduced lung function and breathlessness.,The pathologies of COPD are due to an abnormal immune response.,Invariant natural killer T (iNKT) cells are an important population of innate lymphocytes and have been implicated in the regulation of immune responses associated with a broad range of diseases including COPD.,We have here analyzed the role of iNKT cells in a model of COPD induced by repeated intranasal administration of iNKT cell agonist α-galactosylceramide (α-GalCer).,Our results demonstrated that mice that received repeated intranasal administration of α-GalCer had molecular and inflammatory features of COPD including airway inflammation with significant increases in infiltration of macrophages and lymphocytes, CD8+ T cells, as well as proinflammatory cytokines IL-6 and TNF-α.,In particular, these mice also showed the presence of pulmonary emphysema, mucus production, and pulmonary fibrosis.,Furthermore, neutralization of IL-4 reduced α-GalCer induced emphysema.,This study indicates the importance of iNKT cells in the pathogenesis of COPD by an IL-4 dependent mechanism.
|
CD56+ natural killer (NK) and CD56+ T cells, from sputum or bronchoalveolar lavage of subjects with chronic obstructive pulmonary disease (COPD) are more cytotoxic to highly susceptible NK targets than those from control subjects.,Whether the same is true in lung parenchyma, and if NK activity actually contributes to emphysema progression are unknown.,To address these questions, we performed two types of experiments on lung tissue from clinically-indicated resections (n = 60).,First, we used flow cytometry on fresh single-cell suspension to measure expression of cell-surface molecules (CD56, CD16, CD8, NKG2D and NKp44) on lung lymphocytes and of the 6D4 epitope common to MICA and MICB on lung epithelial (CD326+) cells.,Second, we sequentially isolated CD56+, CD8+ and CD4+ lung lymphocytes, co-cultured each with autologous lung target cells, then determined apoptosis of individual target cells using Annexin-V and 7-AAD staining.,Lung NK cells (CD56+ CD3−) and CD56+ T cells (CD56+ CD3+) were present in a range of frequencies that did not differ significantly between smokers without COPD and subjects with COPD.,Lung NK cells had a predominantly “cytotoxic” CD56+ CD16+ phenotype; their co-expression of CD8 was common, but the percentage expressing CD8 fell as FEV1 % predicted decreased.,Greater expression by autologous lung epithelial cells of the NKG2D ligands, MICA/MICB, but not expression by lung CD56+ cells of the activating receptor NKG2D, correlated inversely with FEV1 % predicted.,Lung CD56+ lymphocytes, but not CD4+ or CD8+ conventional lung T cells, rapidly killed autologous lung cells without additional stimulation.,Such natural cytotoxicity was increased in subjects with severe COPD and was unexplained in multiple regression analysis by age or cancer as indication for surgery.,These data show that as spirometry worsens in COPD, CD56+ lung lymphocytes exhibit spontaneous cytotoxicity of autologous structural lung cells, supporting their potential role in emphysema progression.,ClinicalTrials.gov NCT00281229
| 1
|
Cigarette smoke (CS) induces lung cellular senescence that plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,How aging influences cellular senescence and other molecular hallmarks, and increases the risk of CS-induced damage remains unknown.,We hypothesized that aging-associated changes in lungs worsen the COPD/emphysema by CS exposure.,Younger and older groups of C57BL/6J mice were exposed to chronic CS for 6 months with respective age-matched air-exposed controls.,CS caused a decline in lung function and affected the lung structure of both groups of mice.,No alterations were observed in the induction of inflammatory mediators between the air-exposed younger and older controls, but aging increased the severity of CS-induced lung inflammation.,Aging per se increased lung cellular senescence and significant changes in damage-associated molecular patterns marker S100A8.,Gene transcript analysis using the nanoString nCounter showed a significant upregulation of key pro-senescence targets by CS (Mmp12, Ccl2, Cdkn2a, Tert, Wrn, and Bub1b).,Aging independently influenced lung function and structure, as well as increased susceptibility to CS-induced inflammation in emphysema, but had a negligible effect on cellular senescence.,Thus, aging solely does not contribute to the induction of cellular senescence by CS in a mouse model of COPD/emphysema.
|
Pulmonary emphysema is characterized by irreversible airflow obstruction, inflammation, oxidative stress imbalance and lung remodeling, resulting in reduced lung function and a lower quality of life.,Flavonoids are plant compounds with potential anti-inflammatory and antioxidant effects that have been used in folk medicine.,Our aim was to determine whether treatment with sakuranetin, a flavonoid extracted from the aerial parts of Baccharis retusa, interferes with the development of lung emphysema.,Intranasal saline or elastase was administered to mice; the animals were then treated with sakuranetin or vehicle 2 h later and again on days 7, 14 and 28.,We evaluated lung function and the inflammatory profile in bronchoalveolar lavage fluid (BALF).,The lungs were removed to evaluate alveolar enlargement, extracellular matrix fibers and the expression of MMP-9, MMP-12, TIMP-1, 8-iso-PGF-2α and p65-NF-κB in the fixed tissues as well as to evaluate cytokine levels and p65-NF-κB protein expression.,In the elastase-treated animals, sakuranetin treatment reduced the alveolar enlargement, collagen and elastic fiber deposition and the number of MMP-9- and MMP-12-positive cells but increased TIMP-1 expression.,In addition, sakuranetin treatment decreased the inflammation and the levels of TNF-α, IL-1β and M-CSF in the BALF as well as the levels of NF-κB and 8-iso-PGF-2α in the lungs of the elastase-treated animals.,However, this treatment did not affect the changes in lung function.,These data emphasize the importance of oxidative stress and metalloproteinase imbalance in the development of emphysema and suggest that sakuranetin is a potent candidate that should be further investigated as an emphysema treatment.,This compound may be useful for counteracting lung remodeling and oxidative stress and thus attenuating the development of emphysema.,The online version of this article (doi:10.1186/s12931-015-0233-3) contains supplementary material, which is available to authorized users.
| 1
|
Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD.,Traditional CV risk scores have been tested in different populations but not uniquely in COPD.,The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown.,We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.,Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used.,Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.,Five UK centres interested in COPD.,Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.,Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.,New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.,Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD.,The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction.,CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all).,However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).,Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.,ID 11101.
|
We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination.
| 1
|
Asthma and chronic obstructive pulmonary disease (COPD) share many characteristics and symptoms, and the differential diagnosis between the two diseases can be difficult in primary care.,This study explored potential overlap between both diseases in a primary care environment.,To quantify how commonly patients with COPD have a concomitant diagnosis of asthma, and how commonly patients with asthma have a concomitant diagnosis of COPD in UK primary care.,Additionally, the study aimed to determine the extent of possible misdiagnosis and missed opportunities for diagnosis.,Patients with validated asthma and patients with validated COPD in primary care were identified from the UK Clinical Practice Research Datalink (CPRD) in separate validation studies, and the diseases were confirmed by review of GP questionnaires.,The prevalence of concurrent asthma and COPD in validated cases of either disease was examined based on CPRD coding, GP questionnaires, and requested additional information.,In total, 400 patients with COPD and 351 patients with asthma in primary care were identified.,Of the patients with validated asthma, 15% (n = 52) had previously received a diagnostic COPD Read code, although COPD was only likely in 14.8% (95% confidence interval [CI] = 11.3 to 19.0) of patients with validated asthma.,More than half (52.5%, n = 210) of patients with validated COPD had previously received a diagnostic asthma Read code.,However, when considering additional evidence to support a diagnosis of asthma, concurrent asthma was only likely in 14.5% (95% CI = 11.2 to 18.3) of patients with validated COPD.,A concurrent asthma and COPD diagnosis appears to affect a relative minority of patients with COPD (14.5%) or asthma (14.8%).,Asthma diagnosis may be over-recorded in people with COPD.
|
Initial use of inhaled corticosteroid therapy is common in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) A or B chronic obstructive pulmonary disease, contrary to GOLD guidelines.,We investigated UK prescribing of inhaled corticosteroid therapy in these patients, to identify predictors of inhaled corticosteroid use in newly diagnosed chronic obstructive pulmonary disease patients.,A cohort of newly diagnosed GOLD A/B chronic obstructive pulmonary disease patients was identified from the UK Clinical Practice Research Datalink (June 2005-June 2015).,Patients were classified by prescribed treatment, with those receiving inhaled corticosteroid-containing therapy compared with those receiving long-acting bronchodilators without inhaled corticosteroid.,In all, 29,815 patients with spirometry-confirmed chronic obstructive pulmonary disease were identified.,Of those prescribed maintenance therapy within 3 months of diagnosis, 63% were prescribed inhaled corticosteroid-containing therapy vs. 37% prescribed non-inhaled corticosteroid therapy.,FEV1% predicted, concurrent asthma diagnosis, region, and moderate exacerbation were the strongest predictors of inhaled corticosteroid use in the overall cohort.,When concurrent asthma patients were excluded, all other co-variates remained significant predictors.,Other significant predictors included general practitioner practice, younger age, and co-prescription with short-acting bronchodilators.,Trends over time showed that initial inhaled corticosteroid prescriptions reduced throughout the study, but still accounted for 47% of initial prescriptions in 2015.,These results suggest that inhaled corticosteroid prescribing in GOLD A/B patients is common, with significant regional variation that is independent of FEV1% predicted.,Inhaled steroids are often prescribed to early-stage chronic lung disease patients in the UK despite guidelines to the contrary.,Patients newly diagnosed with early-stage chronic obstructive pulmonary disease (COPD) should not be prescribed inhaled corticosteroids (ICS), because they carry an increased risk of side effects such as pneumonia and osteoporosis.,ICS should be reserved for patients with severe COPD and frequent exacerbations.,James Chalmers at the Scottish Centre for Respiratory Research, Dundee, and co-workers examined prescribed medication data from the UK spanning 10 years, to determine key predictors of ICS prescription during early-stage COPD.,Of 29,815 patients identified, an average of 63% were prescribed ICS upon diagnosis, regardless of disease severity.,Younger patients were more likely to receive ICS, possibly due to co-morbidity with chronic asthma, and particular UK regions and medical practices prescribed ICS more readily than others.
| 1
|
Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users.
|
Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function.,This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol.,This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study.,Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4-14-day washout period.,ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients.,The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects.,Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point).,In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 μM versus 0.09 μM).,The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006).,Both treatments were well tolerated.,The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar.,In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide.,Trial registration number NCT00379028
| 1
|
Chronic obstructive pulmonary disease (COPD) exacerbations account for a substantial proportion of COPD-related costs.,To describe COPD exacerbation patterns and assess the association between exacerbation frequency and health care resource utilization (HCRU) and costs in patients with COPD in a Medicare population.,A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40-89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan.,Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period).,Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three).,HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively.,A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models.,Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively.,HCRU was significantly different among cohorts (all P<0.001).,In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively.,Mean all-cause total costs (medical and pharmacy) were more than twofold greater in patients with ≥three exacerbations compared to patients with zero exacerbations ($27,133 vs $56,033; P<0.001), whereas a greater than sevenfold difference was observed in mean COPD-related total costs ($1,605 vs $12,257; P<0.001).,COPD patients frequently experience exacerbations.,Increasing exacerbation frequency is associated with a multiplicative increase in all-cause and COPD-related costs.,This underscores the importance of identifying COPD patients at risk of having frequent exacerbations for appropriate disease management.
|
Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems.,Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity.,To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses.,Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings.,We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation.,Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality.,We pooled the results using fixed effects models where statistically significant heterogeneity (p ≤ 0.1) was absent.,We identified six trials including 230 patients.,Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12-0.54]) and mortality (0.45 [0.22-0.91]).,Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13-1.61) for the fatigue domain, 1.36 (0.94-1.77) for emotional function and 1.88 (1.67-2.09) for mastery.,Weighted mean differences for the St.,Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7).,In all trials, rehabilitation improved exercise capacity (64-215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48-115).,Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation.,Larger trials, however, are needed to further investigate the role of respiratory rehabilitation after acute exacerbation and its potential to reduce costs caused by COPD.
| 1
|
Uptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use.,The objective was to report and summarise the current evidence supporting the use of nutritional supplementation to improve outcomes during PR in stable COPD patients.,A systematic search was conducted up to 7 August 2019 (registration number CRD42018089142).,The preferred reporting items for systematic reviews and meta-analyses guidelines were used.,Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online, Allied and Complementary Medicine Database, the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE, Cumulative Index of Nursing and Allied Health Literature and Web of Science.,This systematic search generated 580 initial matches, of which 22 studies (917 COPD participants) met the pre-specified criteria and were included.,Sixteen of 19 studies that used nutritional supplements in addition to PR did not show additional benefit compared to PR alone when measuring exercise capacity.,Nutritional supplements significantly increased body weight in 7 of 11 studies.,Body mass index increased significantly in two of six studies.,Handgrip strength did not improve, while quadriceps muscle strength significantly improved in 3 of 11 studies.,Four of eight studies showed a significant improvement in inspiratory muscle function.,Only 2 of 14 studies demonstrated a significant improvement in quality of life with supplementation in addition to PR.,There remains insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD due to heterogeneity in supplements, outcome measures and PR programmes.,Therefore, controversy remains and further research is needed.
|
Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development.,We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year.,64 patients with stable COPD (FEV1 mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart.,Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation.,QMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04).,The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment.,Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001).,Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs.,+1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs.,+0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026).,Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations.,Factors predicting progression of quadriceps weakness could not be identified from the present cohort.
| 1
|
Dry powder inhalers (DPIs) are often used in asthma and chronic obstructive pulmonary disease (COPD) therapies.,Using the discrete choice experiment (DCE) methodology, this study conducted in France was designed to assess patients’ preferences for different attributes of DPIs.,Attributes of DPIs were defined based on a literature review, patient focus group discussions and interviews with healthcare professionals (qualitative phase of the study).,An online survey was then conducted among French patients with asthma or COPD to elicit patient preferences and willingness to pay (WTP) for these attributes using the DCE methodology (quantitative phase).,A fractional factorial design including three blocks of 12 choice sets was created.,Each choice set comprised three alternatives: two fictitious inhalers and the patient’s current inhaler.,Marginal utilities were estimated using a ranked ordered logit model.,Interactions between attributes and disease (asthma or COPD) were tested.,Six DPI attributes were defined based on the qualitative phase: ease of use/fool-proof priming; accurate and easy-to-read dose counter; dose confirmation; hygiene of the mouthpiece; flexibility of the device handling; ability to use the inhaler with breathing difficulties.,Overall, 201 patients with asthma and 93 with COPD were included in the online survey.,Patients with asthma placed most value on an inhaler that requires one step for dose preparation (WTP €4.83 [95% CI: €3.77-€5.90], relative to an inhaler requiring four steps) and one that could be used during episodes of breathing difficulties (WTP €4.49 [95% CI: €2.95-€6.02]).,Patients with COPD placed most value on an inhaler that could be used during episodes of breathing difficulties (WTP €7.70 [95% CI: €5.65-€9.76]) and on the accuracy of the dose counter (WTP €5.87 [95% CI: €3.98-€ 7.77]).,This study suggests that asthma and COPD patients would be willing to change their inhaler if they were offered the option of a new inhaler with improved characteristics and they place a high value on an inhaler with ease of use during breathing difficulty episodes.,The online version of this article (doi:10.1186/s12890-017-0439-x) contains supplementary material, which is available to authorized users.
|
Medications for respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD) are typically delivered to the lung by means of a handheld inhaler.,Patient preference for and ability to use the inhaler may influence their adherence to maintenance therapy, and adherence may affect treatment outcomes.,In this study, patient experience of using a dry powder inhaler (DPI), the ELLIPTA™ DPI, in clinical trials of a new maintenance therapy for asthma and COPD was investigated.,The ELLIPTA DPI has been designed to contain two separate blister strips from which inhalation powder can be delivered, and to be simple to use with a large, easy-to-read dose counter.,Semi-structured, in-depth, qualitative interviews were carried out 2-4 weeks after patients had completed one of six phase IIIa clinical trials using the ELLIPTA DPI.,Interview participants were asked about their satisfaction with various attributes of the inhaler and their preference for the ELLIPTA DPI relative to currently-prescribed inhalers, and responses were explored using an inductive content analysis approach.,Participants also rated the performance of the inhaler on several criteria, using a subjective 1-10 scale.,Participants with asthma (n = 33) and COPD (n = 42) reported high levels of satisfaction with the ELLIPTA DPI.,It was frequently described as straightforward to operate and easy to use by interview participants.,Ergonomic design, mouthpiece fit, and dose counter visibility and ease of interpretation emerged as frequently cited drivers of preference for the ELLIPTA DPI compared with their current prescribed inhaler.,Of participants with asthma, 71% preferred the ELLIPTA DPI to DISKUS™ and 60% to metered dose inhalers.,Of participants with COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHaler™, and 85% to metered dose inhalers.,Overall average performance scores were >9 (out of 10) in participants with asthma and COPD.,The ELLIPTA DPI was associated with high patient satisfaction and was preferred to other inhalers by interview participants with asthma and COPD.,The development of an inhaler that is regarded as easy and intuitive to use may have positive implications for adherence to therapy in asthma and COPD.,Asthma: NCT01165138, NCT01431950.,COPD: NCT01053988, NCT01054885, NCT01009463, NCT01017952.
| 1
|
Although a number of studies have suggested that the use of Telemonitoring (TM) in patients with Chronic Obstructive Pulmonary Disease (COPD) can be useful and efficacious, its real utility in detecting Acute Exacerbation (AE) signaling the need for prompt treatment is not entirely clear.,The current study aimed to investigate the benefits of a TM system in managing AE in advanced-stage COPD patients to improve their Health-Related Quality of Life (HRQL) and to reduce utilization of healthcare services.,A 12-month Randomised Controlled Trial (RCT) was conducted in the Veneto region (Italy).,Adult patients diagnosed with Class III-IV COPD in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification were recruited and provided a TM system to alert the clinical staff via a trained operator whenever variations in respiratory parameters fell beyond the individual’s normal range.,The study’s primary endpoint was HRQL, measured by the Italian version of the two Short Form 36-item Health Survey (SF36v2).,Its secondary endpoints were: scores on the Hospital Anxiety and Depression Scale (HADS); the number and duration of hospitalizations; the number of readmissions; the number of appointments with a pulmonary specialist; the number of visits to the emergency department; and the number of deaths.,Three hundred thirty-four patients were enrolled and randomized into two groups for a 1 year period.,At its conclusion, changes in the SF36 Physical and Mental Component Summary scores did not significantly differ between the TM and control groups [(-2.07 (8.98) vs -1.91 (7.75); p = 0.889 and -1.08 (11.30) vs -1.92 (10.92); p = 0.5754, respectively].,Variations in HADS were not significantly different between the two groups [0.85 (3.68) vs 0.62 (3.6); p = 0.65 and 0.50 (4.3) vs 0.72 (4.5); p = 0.71].,The hospitalization rate for AECOPD and/or for any cause was not significantly different in the two groups [IRR = 0.89 (95% CI 0.79-1,04); p = 0.16 and IRR = 0.91 (95% CI 0,75 - 1.04); p = 0.16, respectively].,The readmission rate for AECOPD and/or any cause was, however, significantly lower in the TM group with respect to the control one [IRR = 0.43 (95% CI 0.19-0.98); p = 0.01 and 0.46 (95% CI 0.24-0.89); p = 0.01, respectively].,Study results showed that in areas where medical services are well established, TM does not significantly improve HRQL in patients with COPD who develop AE.,Although not effective in reducing hospitalizations, TM can nevertheless facilitate continuity of care during hospital-to-home transition by reducing the need for early readmission.,Retrospectively registered on January 2012, ClinicalTrials.gov Identifier: NCT01513980.
|
Chronic obstructive pulmonary disease (COPD) is the leading cause of death worldwide, and poses a substantial economic and social burden.,Telemonitoring has been proposed as a solution to this growing problem, but its impact on patient outcome is equivocal.,This randomized controlled trial aimed to investigate effectiveness of telemonitoring in improving COPD patient outcome.,In total, 106 subjects were randomly assigned to the telemonitoring (n = 53) or usual care (n = 53) group.,During the two months following discharge, telemonitoring group patients had to report their symptoms daily using an electronic diary.,The primary outcome measure was time to first re-admission for COPD exacerbation within six months of discharge.,During the follow-up period, time to first re-admission for COPD exacerbation was significantly increased in the telemonitoring group than in the usual care group (p = 0.026).,Telemonitoring was also associated with a reduced number of all-cause re-admissions (0.23 vs.,0.68/patient; p = 0.002) and emergency room visits (0.36 vs.,0.91/patient; p = 0.006).,In conclusion, telemonitoring intervention was associated with improved outcomes among COPD patients admitted for exacerbation in a country characterized by a small territory and high accessibility to medical services.,The findings are encouraging and add further support to implementation of telemonitoring as part of COPD care.
| 1
|
Asthma and chronic obstructive pulmonary disease (COPD) share many characteristics and symptoms, and the differential diagnosis between the two diseases can be difficult in primary care.,This study explored potential overlap between both diseases in a primary care environment.,To quantify how commonly patients with COPD have a concomitant diagnosis of asthma, and how commonly patients with asthma have a concomitant diagnosis of COPD in UK primary care.,Additionally, the study aimed to determine the extent of possible misdiagnosis and missed opportunities for diagnosis.,Patients with validated asthma and patients with validated COPD in primary care were identified from the UK Clinical Practice Research Datalink (CPRD) in separate validation studies, and the diseases were confirmed by review of GP questionnaires.,The prevalence of concurrent asthma and COPD in validated cases of either disease was examined based on CPRD coding, GP questionnaires, and requested additional information.,In total, 400 patients with COPD and 351 patients with asthma in primary care were identified.,Of the patients with validated asthma, 15% (n = 52) had previously received a diagnostic COPD Read code, although COPD was only likely in 14.8% (95% confidence interval [CI] = 11.3 to 19.0) of patients with validated asthma.,More than half (52.5%, n = 210) of patients with validated COPD had previously received a diagnostic asthma Read code.,However, when considering additional evidence to support a diagnosis of asthma, concurrent asthma was only likely in 14.5% (95% CI = 11.2 to 18.3) of patients with validated COPD.,A concurrent asthma and COPD diagnosis appears to affect a relative minority of patients with COPD (14.5%) or asthma (14.8%).,Asthma diagnosis may be over-recorded in people with COPD.
|
Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject.
| 1
|
Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).,We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.,Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.,Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD.,While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella.,Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.,Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations.,These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.,The online version of this article (10.1186/s12931-019-1085-z) contains supplementary material, which is available to authorized users.
|
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD.
| 1
|
Emphysema and small-airway disease are the two major components of chronic obstructive pulmonary disease (COPD).,We propose a novel method of quantitative computed tomography (CT) emphysema air-trapping composite (EAtC) mapping to assess each COPD component.,We analyzed the potential use of this method for assessing lung function in patients with COPD.,A total of 584 patients with COPD underwent inspiration and expiration CTs.,Using pairwise analysis of inspiration and expiration CTs with non-rigid registration, EAtC mapping classified lung parenchyma into three areas: Normal, functional air trapping (fAT), and emphysema (Emph).,We defined fAT as the area with a density change of less than 60 Hounsfield units (HU) between inspiration and expiration CTs among areas with a density less than −856 HU on inspiration CT.,The volume fraction of each area was compared with clinical parameters and pulmonary function tests (PFTs).,The results were compared with those of parametric response mapping (PRM) analysis.,The relative volumes of the EAtC classes differed according to the Global Initiative for Chronic Obstructive Lung Disease stages (p < 0.001).,Each class showed moderate correlations with forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) (r = −0.659-0.674, p < 0.001).,Both fAT and Emph were significant predictors of FEV1 and FEV1/FVC (R2 = 0.352 and 0.488, respectively; p < 0.001). fAT was a significant predictor of mean forced expiratory flow between 25% and 75% and residual volume/total vital capacity (R2 = 0.264 and 0.233, respectively; p < 0.001), while Emph and age were significant predictors of carbon monoxide diffusing capacity (R2 = 0.303; p < 0.001). fAT showed better correlations with PFTs than with small-airway disease on PRM.,The proposed quantitative CT EAtC mapping provides comprehensive lung functional information on each disease component of COPD, which may serve as an imaging biomarker of lung function.
|
Exacerbations of COPD are a major burden to patients, and yet little is understood about heterogeneity.,It contributes to the current persistent one-size-fits-all treatment.,To replace this treatment by more personalized, precision medicine, new insights are required.,We assessed the heterogeneity of exacerbations by functional respiratory imaging (FRI) in 3-dimensional models of airways and lungs.,The trial was designed as a multicenter trial of patients with an acute exacerbation of COPD who were assessed by FRI, pulmonary function tests, and patient-reported outcomes, both in the acute stage and during resolution.,Forty seven patients were assessed.,FRI analyses showed significant improvements in hyperinflation (a decrease in total volume at functional residual capacity of −0.25±0.61 L, p≤0.01), airway volume at total lung capacity (+1.70±4.65 L, p=0.02), and airway resistance.,As expected, these improvements correlated partially with changes in the quality of life and in conventional lung function test parameters.,Patients with the same changes in pulmonary function differ in regional disease activity measured by FRI.,FRI is a useful tool to get a better insight into exacerbations of COPD, and significant improvements in its indices can be demonstrated from the acute phase to resolution even in relatively small groups.,It clearly visualizes the marked variability within and between individuals in ventilation and resistance during exacerbations and is a tool for the assessment of the heterogeneity of COPD exacerbations.
| 1
|
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy.
|
Poor inhalation techniques are associated with decreased medication delivery and poor disease control in chronic obstructive pulmonary disease (COPD).,The purpose of this study was to evaluate techniques for using inhaler devices in COPD patients.,A prospective cross-sectional study was conducted to assess patient compliance with correct techniques for using inhaler devices across four regimens, ie, the pressurized metered-dose inhaler (pMDI), the pMDI with a spacer, the Accuhaler®, and the Handihaler®.,The percentage of compliance with essential steps of correct device usage for each regimen was recorded without prior notification when COPD patients presented for a routine visit, and 1 month after receiving face-to-face training.,We compared the percentage of compliance between the devices and risk factors related to incorrect techniques using logistic regression analysis.,Percentage of patient compliance with correct techniques was compared between the two visits using the chi-square test.,Statistical significance was set at P<0.05.,A total of 103 COPD patients (mean age 71.2±9.2 years, males 64.1%, low education level 82.5%, and percent predicted forced expiratory volume in 1 second 51.9±22.5) were evaluated.,Seventy-seven patients (74.8%) performed at least one step incorrectly.,Patients using the Handihaler had the lowest compliance failure (42.5%), and the odds ratio for failure with the other devices compared with the Handihaler were 4.6 (95% confidence interval [CI] 1.8-11.8) for the pMDI, 3.1 (95% CI 1.2-8.2) for the pMDI with a spacer, and 2.4 (95% CI 1.1-5.2) for the Accuhaler.,Low education level was the single most important factor related to incorrect technique (adjusted odds ratio 4.1, 95% CI 1.2-13.4, P=0.022).,Formal training resulted in a statistically significant decrease in percentage of incorrect techniques for all devices and for the pMDI (59.4% vs 48.6%, P<0.001; 72.4% vs 48.3%, P=0.039, respectively).,Inhalation technique in COPD patients without face-to-face training was mostly unsatisfactory, especially in patients with low education levels.,The Handihaler was the inhaler device associated with the lowest technique failure.,Face-to-face inhalation technique training significantly increased technique compliance for the pMDI.
| 1
|
Pentraxin 3 (PTX3) is an acute phase protein, involved in antibacterial resistance.,Recent studies have shown PTX3 levels to be elevated in the presence of a bacterial infection and in a murine sepsis model.,We aim to investigate if sputum PTX3 can be used as a biomarker for bacterial infection in subjects with COPD.,Sputum samples from 142 COPD patients (102 men) with a mean (range) age of 69 years (45-85) and mean (SD) post-bronchodilator percentage predicted forced expiratory volume in 1 second (FEV1) of 50% (19) were analyzed for PTX3, using a commercial assay at stable state and during an exacerbation.,Association with bacteria, from culture, quantitative real-time polymerase chain reaction (qPCR) and colony-forming units (CFU) was investigated.,The geometric mean (95% CI) PTX3 level at stable state was 50.5 ng/mL (41.4-61.7).,PTX3 levels correlated with absolute neutrophil count in sputum (r=0.37; P<0.01), but not FEV1 or health status.,There was a weak correlation between PTX3 and bacterial load (CFU: r=0.29, P<0.01; 16S qPCR: r=0.18, P=0.05).,PTX3 was a poor predictor of bacterial colonization (defined as >105 CFU/mL at stable state) with a receiver-operating characteristic (ROC) area under the curve (AUC) of 0.59 and 95% confidence interval (CI) 0.43-0.76 (P=0.21).,During an exacerbation, there was a modest increase in PTX3 (fold difference 0.15, 95% of difference 0.02-0.29; P=0.02), and PTX3 fared better at identifying a bacteria-associated exacerbation (ROC AUC 0.65, 95% CI 0.52-0.78, P=0.03).,PTX3 is associated with bacterial infection in patients with COPD, but its utility as a biomarker for identifying a bacteria-associated exacerbation warrants further studies.
|
Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD).,However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking.,Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes.,Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia.,Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, and atypical pathogens.,Serum procalcitonin levels were measured on day 1 (admission), day 2, and at one month.,Clinical and laboratory features of subjects with viral and bacterial diagnoses were compared.,In total, 224 subjects with COPD were admitted for 240 respiratory illnesses.,Of these, 56 had pneumonia and 184 had AECOPD alone.,A microbiologic diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26 viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection).,Mean procalcitonin levels were significantly higher in patients with pneumonia compared with AECOPD.,However, discrimination between viral and bacterial infection using a 0.25 ng/mL threshold for bacterial infection in patients with AECOPD was poor.,Procalcitonin is useful in COPD patients for alerting clinicians to invasive bacterial infections such as pneumonia but it does not distinguish bacterial from viral and noninfectious causes of AECOPD.
| 1
|
Patients with chronic obstructive pulmonary disease (COPD) have increased cardiovascular risk.,Natriuretic peptides (NP) in other populations are useful in identifying cardiovascular disease, stratifying risk, and guiding therapy.,We performed a systematic literature review to examine NP in COPD, utilising Medline, EMBASE, and the Cochrane Library.,Fifty one studies were identified.,NP levels were lower in stable compared to exacerbation of COPD, and significantly increased with concomitant left ventricular systolic dysfunction or cor pulmonale.,Elevation occurred in 16 to 60% of exacerbations and persisted in approximately one half of patients at discharge.,Cardiovascular comorbidities were associated with increased levels.,Levels consistently correlated with pulmonary artery pressure and left ventricular ejection fraction, but not pulmonary function or oxygen saturation.,NP demonstrated high negative predictive values (0.80 to 0.98) to exclude left ventricular dysfunction in both stable and exacerbation of COPD, but relatively low positive predictive values.,NP elevation predicted early adverse outcomes, but the association with long term mortality was inconsistent.,NP reflect diverse aspects of the cardiopulmonary continuum which limits utility when applied in isolation.,Strategies integrating NP with additional variables, biomarkers and imaging require further investigation.
|
Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required.,Despite the importance of hospitalized exacerbations, relatively little is known about their determinants.,This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients.,This was a retrospective population-based cohort study.,We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011.,We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission.,We observed exacerbation frequency over the previous year (2011) and following year (2012).,We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4).,We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year.,Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients.,A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53-12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05).,Older age and several comorbidities, such as heart failure and diabetes, were similarly associated.,Hospitalized exacerbations occurred with all grades of airflow limitation.,A history of severe exacerbations was associated with new hospitalized exacerbations and mortality.
| 1
|
Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD).,However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear.,Patients diagnosed with COPD were recruited from St.,Paul’s Hospital, The Catholic University of Korea, between July 2009 and May 2012.,Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30).,Seventeen patients were enrolled as a control group (n = 17).,The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured.,We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters.,Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs.,COPD-stable vs.,COPD-exacerbation) (p = 0.002, p < 0.001).,Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent.,Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = -0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = -0.342, p = 0.014).,However, CRP level was not correlated with any measured parameter.,Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.
|
Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary disease (COPD) which carries substantial morbidity and mortality.,We explored the association between emphysema and body height in 726 patients with COPD using computed tomography as the reference diagnostic standard for emphysema.,We applied univariate analysis to look for differences between patients with emphysema and those without, and multivariate logistic regression to identify significant predictors of the risk of emphysema.,As covariates we included age, sex, body height, body mass index, pack-years of smoking, and forced expiratory volume in one second (FEV1) as percent predicted.,The overall prevalence of emphysema was 52%.,Emphysemic patients were significantly taller and thinner than non-emphysemic ones, and featured significantly higher pack-years of smoking and lower FEV1 (P < 0.001).,The prevalence of emphysema rose linearly by 10-cm increase in body height (r2 = 0.96).,In multivariate analysis, the odds of emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one-centimeter increase in body height, and remained unchanged after adjusting for all the potential confounders considered (P < 0.001).,The odds of emphysema were not statistically different between males and females.,In conclusion, body height is a strong, independent risk factor for emphysema in COPD.
| 1
|
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.
|
Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance.,Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD).,However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown.,We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC).,βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks.,Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured.,Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles.,Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice.,CS exposure further altered lung function measurements.,We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.
| 1
|
Guidelines are critical for facilitating cost-effective COPD care.,Development and implementation in low-and middle-income countries (LMICs) is challenging.,To guide future strategy, an overview of current global COPD guidelines is required.,We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation.,Scoping review of national COPD management guidelines.,We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards.,LMICs guidelines were compared with those from high-income countries (HICs).,Of the 61 national COPD guidelines identified, 30 were from LMICs.,Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines.,Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities.,More than 90% of all guidelines included smoking cessation advice.,Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%).,LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05).,LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05).,Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation.,Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated.,Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources.
|
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.,Hookah smoking is growing worldwide and particularly in Iran.,The aim of this study was to determine the prevalence of obstructive pulmonary dysfunction in hookah smokers.,We conducted a population-based study in Bushehr Province, Iran.,A total of 245 subjects aged 35 years or older who were taking hookah for at least 15 years and 245 healthy controls were enrolled in the study and spirometry was done.,Statistical analyses were performed using SPSS for windows software version 19.,The prevalence of COPD among the exposed group of hookah smoke was 10.2%, with the rate being significantly higher in the patients with older age (p < 0.001), duration of hookah smoking (p < 0.001), men (p = 0.026), ≥3 hookahs/day (p = 0.006), history of cough for ≥2 years (p = 0.002), in patients with a history of sputum for ≥2 years (p = 0.031), and in patients with a history of dyspnea for ≥2 years (p = 0.001).,The results of the logistic regression analysis demonstrated that older age, male gender, smoking, and occupational exposure were independent predictive factors for COPD.,The results of our study suggest that hookah smoking significantly increases the risk of COPD.,Given the importance of COPD in the global burden of diseases, it is necessary to carry out further studies on the relationship between hookah use and COPD.
| 1
|
The pathogenesis of chronic obstructive pulmonary disease (COPD) remains elusive.,Here, we assessed the correlation between CD8+ T cell frequencies and autophagy in COPD patients.,Subjects were divided into three groups (n = 30 patients/group): (1) COPD patients in the stable phase; (2) smokers with normal lung function; and (3) non-smokers with normal lung function.,Flow cytometry was used to enumerate CD8+ T cell subsets (CD8+, CD8+ effector, and CD8+ memory T cells) and quantitate T-cell apoptosis.,RT-PCR and western blotting were used to measure levels of LC3 and p62.,Frequencies of CD8+ T cell subsets and expression of p62 and LC3 II/I were significantly higher in COPD patients compared with the other two groups, while the rate of apoptosis was lower.,In COPD patients, LC3 II/I and p62 expression were positively correlated with CD8+ T cell subset frequencies.,Moreover, a significant correlation was observed between LC3 II/I and p62 expression and T cell subset frequencies.,Autophagy level is positively correlated with the frequencies of CD8+ T cells, suggesting that autophagy might be involved in COPD pathogenesis.
|
Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic particles, such as coal fly ash (CFA), diesel-exhaust particle (DEP), and cigarette smoke (CS), leading to chronic bronchitis, mucus production, and a subsequent lung dysfunction.,This study, using a mouse model of COPD, aimed to evaluate the effect of herbal combinational medication of Glycyrrhiza glabra (GG), Agastache rugosa (AR) containing glycyrrhizic acid (GA), and tilianin (TN) as active ingredients.,GA, a major active component of GG, possesses a range of pharmacological and biological activities including anti-inflammatory, anti-allergic, anti-oxidative.,TN is a major flavonoid that is present in AR.,It has been reported to have anti-inflammatory effects of potential utility as an anti-COPD agent.,The COPD in the mice model was induced by a challenge with CFA and DEP.,BALB/c mice received CFA and DEP alternately three times for 2 weeks to induce COPD.,The herbal mixture of GG, AR, and TN significantly decreased the number of neutrophils in the lungs and bronchoalveolar lavage (BAL) fluid.,It also significantly reduced the production of C-X-C motif chemokine ligand 2 (CXCL-2), IL-17A, CXCL-1, TNF-α, symmetric dimethylarginine (SDMA) in BALF and CXCL-2, IL-17A, CXCL-1, MUC5AC, transient receptor potential vanilloid-1 (TRPV1), IL-6, COX-2, NOS-II, and TNF-α mRNA expression in the lung tissue.,Notably, a combination of GG and AR was more effective at regulating such therapeutic targets than GG or AR alone.,The histolopathological lung injury was alleviated by treatment with the herbal mixture and their active ingredients (especially TN).,In this study, the herbal combinational mixture more effectively inhibited neutrophilic airway inflammation by regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway.,Therefore, a herbal mixture of GG and AR may be a potential therapeutic agent to treat COPD.
| 1
|
In patients with COPD, self-management skills are important to reduce the impact of exacerbations.,However, both detection and adequate response to exacerbations appear to be difficult for some patients.,Little is known about the underlying process of exacerbation-related self-management.,Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior.,A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated.,Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015.,Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed.,Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management.,Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms.,Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions.,This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients.,The conceptual model can be used as a framework for health care professionals providing self-management support.,In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account.
|
Although timely treatment of COPD exacerbations seems clinically important, nearly half of these exacerbations remain unreported and subsequently untreated.,Recent studies have investigated incidence and impact of failure to seek medical treatment during exacerbations.,Yet, little is known about type and timing of other self-management actions in periods of symptom deterioration.,The current prospective study aims at determining the relative incidence, timing and determinants of three types of patient responses.,In a multicentre observational study, 121 patients (age 67 ± 11 years, FEV1pred. 48 ± 19) were followed for 6 weeks by daily diary symptom recording.,Three types of action were assessed daily: planning periods of rest, breathing techniques and/or sputum clearing (type-A), increased bronchodilator use (type-B) and contacting a healthcare provider (type-C).,Type-A action was taken in 70.7%, type-B in 62.7% and type C in 17.3% of exacerbations (n = 75).,Smokers were less likely to take type-A and B actions.,Type-C actions were associated with more severe airflow limitation and increased number of hospital admissions in the last year.,Our study shows that most patients are willing to take timely self-management actions during exacerbations.,Future research is needed to determine whether the low incidence of contacting a healthcare provider is due to a lack of self-management or healthcare accessibility.
| 1
|
Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis.,We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD.,The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.,This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations.,Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.,In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%).,The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001).,In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%).,UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).,This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods.,UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy.
|
Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users.
| 1
|
Chronic bronchitis (CB) is one of the classic phenotypes of COPD.,The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population.,We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE).,CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years.,CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry.,Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls.,Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis.,For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A.,In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7).,We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6).,This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD.,ClinicalTrials.gov NCT00608764, NCT00292552,The online version of this article (doi:10.1186/s12931-014-0113-2) contains supplementary material, which is available to authorized users.
|
Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD).,Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results.,Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium).,To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample.,We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/−10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations.,The analysis included 16,936 genotyped and imputed SNPs.,No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3×10−5.,The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81×10−5), CNTN5 (P = 4.37×10−4), and TRPV4 (P = 1.58×10−3).,Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41×10−5), followed by PDE4D (P = 1.22×10−4).,The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38×10−4), and ESR1 (P = 5.42×10−4) among ever-smokers.,Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population.,Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.
| 1
|
The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.,Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD.,Physician-diagnosed GERD was ascertained by questionnaire.,Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD.,We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models.,Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs).,To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.,GERD was reported by 29% of subjects with female predominance.,Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs.,13.4.0%, p < 0.0001).,Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs.,1.8, p < 0.0001), and poorer quality of life (QOL) scores (St.,George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs.,34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs.,41.4, p < 0.0001).,In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006).,During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included.,PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.,In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up.,These associations are maintained after controlling for PPI use.,The PPI-exacerbations association could result from confounding-by-indication.
|
Computed tomography (CT) lung densitometry has been demonstrated to be the most sensitive and specific outcome measure for the assessment of emphysema-modifying therapy, but the optimum densitometric index has yet to be determined and targeted sampling may be more sensitive than whole lung assessment.,The EXAcerbations and CT scan as Lung Endpoints (EXACTLE) trial aimed to clarify the optimum approach to the use of CT densitometry data for the assessment of alpha 1-antitrypsin (AAT) augmentation therapy on the progression of emphysema in AAT deficiency (AATD).,Patients with AATD (n = 77) were randomised to weekly infusions of 60 mg/kg human AAT (Prolastin®) or placebo over 2 to 2.5 years.,Lung volume was included as a covariate in an endpoint analysis and a comparison was made of different CT densitometric indices (15th percentile lung density [PD15], mean lung density [MLD] and voxel index at a threshold of -910 [VI-910] and -950 [VI-950] Hounsfield Units) obtained from whole lung scans at baseline and at 24 to 30 months.,Targeted regional sampling was compared with whole lung assessment.,Whole lung analysis of the total change (baseline to last CT scan) compared with placebo indicated a concordant trend that was suggestive of a treatment effect for all densitometric indices (MLD [1.402 g/L, p = 0.204]; VI-910 [-0.611, p = 0.389]; VI-950 [-0.432, p = 0.452]) and that was significant using PD15 (1.472 g/L, p = 0.049).,Assessment of the progression of emphysema in the apical, middle and basal regions of the lung by measurement with PD15 showed that this treatment effect was more evident when the basal third was sampled (1.722 g/L, p = 0.040).,A comparison between different densitometric indices indicated that the influence of inspiratory variability between scans was greatest for PD15, but when adjustment for lung volume was made this index was the most sensitive measure of emphysema progression.,PD15 is the most sensitive index of emphysema progression and of treatment modification.,Targeted sampling may be more sensitive than whole lung analysis.,Registered in ClinicalTrials.gov as 'Antitrypsin (AAT) to Treat Emphysema in AAT-Deficient Patients'; ClinicalTrials.gov Identifier: NCT00263887.
| 1
|
The relationship of functional parameters such as lung mechanics, chest kinematics, metabolism and peripheral and respiratory muscle function with the level of exercise tolerance remains a controversial subject.,While it has been previously shown that pulmonary rehabilitation is capable of improving exercise tolerance in patients afflicted by COPD, as expressed by values of 6-minute walking test (6MWT), the degree of contribution to this change by each of the aforementioned parameters remains unclear.,To investigate the correlation between changes in exercise capacity and other functional markers following pulmonary rehabilitation in COPD and to determine which parameters are more closely related to improvements of exercise tolerance.,Three hundred and twenty-seven patients with COPD (with average, 95% CI for forced expiratory volume in the first second [FEV1]: 45% [25%-83%] predicted, age: 64 [48-80] years, and BMI: 27 [13.5-40.4] kg/m2) participated in this study.,Thirty percent of the patients had pulmonary hypertension as comorbidity.,Patients underwent a pulmonary rehabilitation program with 20-30 minutes sessions two to three times per day for 4 weeks.,The program was composed of chest wall-stretching, controlled breathing exercises, and a personalized training schedule for cycling and treadmill use.,Measurements of 6MWT, lung function, chest wall expansion, grip strength, maximal inspiratory pressure, and breath holding time were taken.,The Body mass index, airflow Obstruction, Dyspnea and Exercise capacity (BODE-index), body mass index [BMI], FEV1, 6MWT, modified Medical Research Dyspnea Scale score, and an alternative scale score (for BMI, FEV1, 6MWT, and COPD Assessment Test) were calculated.,Rehabilitation resulted in a generalized improvement in 6MWT among patients (average: 360 [95% CI: 178-543 m] vs average: 420 [95% CI: 238-601 m], p<0.05).,Improvements in exercise tolerance were found to be most closely associated with changes in composite BODE-index (R2=−0.6), Alternative Scale (R2=−0.56), dyspnea score (modified Medical Research Dyspnea Scale R2=−0.54), and health status (COPD Assessment Test R2=−0.4, p<0.05).,In addition, improvements in exercise tolerance were found to moderately correlate with improvements in inspiratory vital capacity (IVC, R2=0.34, p<0.05).,Post-rehabilitation changes in IVC displayed a connection with grip strength (R2=0.6) and chest expansion (R2=0.48).,Enhancements in exercise tolerance had correlation with changes in IVC, BODE-index, and the new Alternative Scale.,However, comprehensive assessment needs to include considerations of chest kinematics and peripheral and respiratory muscle function as well.
|
This study aimed to investigate the effects of weekly singings classes on pulmonary function parameters and quality of life (QoL) of COPD patients.,Forty-three patients were randomized to weekly classes of singing practice, or handcraft work.,They performed spirometry and completed maximal respiratory pressure measurements, evaluations of dyspnea, and the Saint George’s Respiratory Questionnaire, before and after 24 training classes.,A functional evaluation, immediately after 10 minutes of singing practice, was also performed at the end of the study.,Fifteen subjects completed the study in each group.,In comparison to controls the singing group exhibited transitory elevations on the dyspnea Borg scale (p = 0.02), and inspiratory capacity (p = 0.01), and decreases of expiratory reserve volume (p = 0.03), just after a short session of singing.,There was a significant difference on changes of maximal expiratory pressures in the comparison between groups at the end of training.,While the control group showed deterioration of maximal expiratory pressure, the singing group exhibited a small improvement (p = 0.05).,Both groups showed significant improvements of QoL in within group comparisons.,We have concluded that singing classes are a well tolerated activity for selected subjects with COPD.,Regular practice of singing may improve QoL, and preserve the maximal expiratory pressure of these patients.
| 1
|
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment.,The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status.,Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD.,Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD.,Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems.,It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism.,In the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group).,After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species.,Later, the comparisons of individual lipids were performed between controls and patients with COPD.,Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers.,Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated.,Our results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD.,Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change.,In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers.,Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity.,Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years.,Using lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD.,Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD.
|
COPD is underdiagnosed and its early assessment is problematic.,It has been suggested that symptomatic smokers with normal FEV1/FVC (Stage 0 COPD, GOLD criteria) can develop COPD in the future.,Potential early biomarkers in COPD include the matrix metallo-proteinases (MMPs).,It is not yet known, whether alterations in MMP expression are associated with smoking alone or with the risk of developing COPD.,In this cross-sectional study MMP-8, MMP-9 and MMP-12 were determined from induced sputum and plasma by ELISA, immunocytochemistry, zymography, and/or Western blot in non-smokers (n = 32), smokers with symptoms (Stage 0, GOLD criteria) (n = 23) or without symptoms (n = 23).,Only MMP-8 differentiated Stage 0 COPD from non-symptomatic smokers (p = 0.02).,MMP-9 levels were significantly elevated in the induced sputum of non-symptomatic smokers and Stage 0 COPD (p = 0.01, p < 0.001) compared to non-smokers, but did not differ between the two subgroups of smokers.,MMP-12 was higher only at Stage 0 compared to non-smokers (p = 0.04).,MMP-8, MMP-9 and MMP-12 immunoreactivity was localized in macrophages and neutrophils, especially in smokers.,MMP-8 levels correlated significantly with the small airway flow parameters (MEF50, MEF25) (p = 0.005 and p = 0.0004) and markers of neutrophil activation (myeloperoxidase, lactoferrin).,In conclusion MMP-8 may differentiate Stage 0 from healthy smokers.
| 1
|
The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown.,We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.,A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database.,Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009).,Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale.,Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations.,Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011.,The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%).,The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively.,General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.,Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly.
|
Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year.,Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.,1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly.,Exacerbations were defined by health care utilisation.,Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.,Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE.,More severe disease was associated with changing from IE to FE and less severe disease from FE to IE.,Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.,No parameter clearly predicts an imminent change in exacerbation frequency category.,SCO104960, clinicaltrials.gov identifier NCT00292552
| 1
|
To summarise and synthesise published qualitative studies to characterise factors that shape patient and caregiver experiences of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD).,Meta-review of qualitative systematic reviews and metasyntheses.,Papers analysed using content analysis.,CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science were searched from January 2000 to April 2015.,Systematic reviews and qualitative metasyntheses where the participants were patients, caregivers and which described experiences of care for CHF, COPD and CKD in primary and secondary care who were aged ≥18 years.,Searches identified 5420 articles, 53 of which met inclusion criteria.,Reviews showed that patients' and caregivers' help seeking and decision-making were shaped by their degree of structural advantage (socioeconomic status, spatial location, health service quality); their degree of interactional advantage (cognitive advantage, affective state and interaction quality) and their degree of structural resilience (adaptation to adversity, competence in managing care and caregiver response to demands).,To the best of our knowledge, this is the first synthesis of qualitative systematic reviews in the field.,An important outcome of this overview is an emphasis on what patients and caregivers value and on attributes of healthcare systems, relationships and practices that affect the distressing effects and consequences of pathophysiological deterioration in CHF, COPD and CKD.,Interventions that seek to empower individual patients may have limited effectiveness for those who are most affected by the combined weight of structural, relational and practical disadvantage identified in this overview.,We identify potential targets for interventions that could address these disadvantages.,PROSPERO CRD42014014547.
|
In chronic obstructive pulmonary disease (COPD), the problem of poor patient participation in studies of self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as COPD support programmes) is established.,Understanding this problem beyond the previously reported socio-demographics and clinical factors is critical.,The aim of this study was to explore factors that explain patient participation in studies of COPD support programmes.,Thematic ‘framework’ synthesis was conducted on literature published from 1984 to 1 February 2015.,Emergent themes and subthemes were mapped onto the adapted ‘attitude-social influence-external barriers’ and the ‘self-regulation’ models to produce analytical themes.,Ten out of 12 studies were included: PR (n=9) and SM (n=1).,Three descriptive themes with 38 subthemes were mapped onto the models' constructs, and it generated four analytical themes: ‘attitude’, ‘social influences’ and ‘illness’ and ‘intervention representations’.,The following factors influenced (1) attendance-helping oneself through health improvements, perceived control of worsening condition, perceived benefits and positive past experience of the programme, as well as perceived positive influence of professionals; (2) non-attendance-perceived negative effects and negative past experience of the programme, perceived physical/practical concerns related to attendance, perceived severity of condition/symptoms and perceived negative influence of professionals/friends; (3) dropout-no health improvements perceived after attending a few sessions of the programme, perceived severity of the condition and perceived physical/practical concerns related to attendance.,Psychosocial factors including perceived practical/physical concerns related to attendance influenced patients’ participation in COPD support programmes.,Addressing the negative beliefs/perceptions via behaviour change interventions may help improve participation in COPD support programmes and, ultimately, patient outcomes.
| 1
|
Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung.,The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation.,A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007.,Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication.,Multivariable negative binomial regression was performed with adjustment for potential confounding factors.,The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations.,We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications.,COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group.,In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81-0.92).,Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD.
|
Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression.,However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established.,Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema.,We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms.,Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity.,Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice.,Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice.,Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression.,Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS.,Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated.,Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1.,Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression.,Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation.
| 1
|
The decline in lung function can be reduced by long-term inhaled corticosteroid (ICS) treatment in subsets of patients with chronic obstructive pulmonary disease (COPD).,We aimed to identify which clinical, physiological and non-invasive inflammatory characteristics predict the benefits of ICS on lung function decline in COPD.,Analysis was performed in 50 steroid-naive compliant patients with moderate to severe COPD (postbronchodilator forced expiratory volume in one second (FEV1), 30-80% of predicted, compatible with GOLD stages II-III), age 45-75 years, >10 packyears smoking and without asthma.,Patients were treated with fluticasone propionate (500 μg bid) or placebo for 2.5 years.,Postbronchodilator FEV1, dyspnea and health status were measured every 3 months; lung volumes, airway hyperresponsiveness (PC20), and induced sputum at 0, 6 and 30 months.,A linear mixed effect model was used for analysis of this hypothesis generating study.,Significant predictors of attenuated FEV1-decline by fluticasone treatment compared to placebo were: fewer packyears smoking, preserved diffusion capacity, limited hyperinflation and lower inflammatory cell counts in induced sputum (p<0.04).,Long-term benefits of ICS on lung function decline in patients with moderate-to-severe COPD are most pronounced in patients with fewer packyears, and less severe emphysema and inflammation.,These data generate novel hypotheses on phenotype-driven therapy in COPD.,ClinicalTrials.gov NCT00158847
|
Smoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix.,This is thought to contribute to airway remodeling and airflow obstruction.,We have previously observed that long-term treatment with inhaled corticosteroids can not only reduce bronchial inflammation, but can also attenuate lung function decline in moderate-severe COPD.,We hypothesized that inhaled corticosteroids and current smoking modulate bronchial extracellular matrix components in COPD.,To compare major extracellular matrix components (elastic fibers; proteoglycans [versican, decorin]; collagens type I and III) in bronchial biopsies 1) after 30-months inhaled steroids treatment or placebo; and 2) between current and ex-smokers with COPD.,We included 64 moderate-severe, steroid-naive COPD patients (24/40 (ex)-smokers, 62±7 years, 46 (31-54) packyears, post-bronchodilator forced expiratory volume in one second (FEV1) 62±9% predicted) at baseline in this randomized, controlled trial. 19 and 13 patients received 30-months treatment with fluticasone or placebo, respectively.,Bronchial biopsies collected at baseline and after 30 months were studied using (immuno)histochemistry to evaluate extracellular matrix content.,Percentage and density of stained area were calculated by digital image analysis.,30-Months inhaled steroids increased the percentage stained area of versican (9.6% [CI 0.9 to 18.3%]; p = 0.03) and collagen III (20.6% [CI 3.8 to 37.4%]; p = 0.02) compared to placebo.,Increased collagen I staining density correlated with increased post-bronchodilator FEV1 after inhaled steroids treatment (Rs = 0.45, p = 0.04).,There were no differences between smokers and ex-smokers with COPD in percentages and densities for all extracellular matrix proteins.,These data show that long-term inhaled corticosteroids treatment partially changes the composition of extracellular matrix in moderate-severe COPD.,This is associated with increased lung function, suggesting that long-term inhaled steroids modulate airway remodeling thereby potentially preventing airway collapse in COPD.,Smoking status is not associated with bronchial extracellular matrix proteins.,ClinicalTrials.gov NCT00158847
| 1
|
No observational studies have evaluated the “real-world” effectiveness of dual bronchodilation comprising a long-acting β2-agonist plus a long-acting muscarinic antagonist vs that of triple therapy (long-acting β2-agonist plus long-acting muscarinic antagonist plus inhaled corticosteroid) in COPD.,DACCORD is a non-interventional, observational clinical study that recruited patients following COPD maintenance therapy initiation or change in maintenance therapy between or within therapeutic class.,Given the non-interventional nature of the study, the decision to initiate or change medication had to be made by the patients’ physicians prior to inclusion in DACCORD.,We used a matched-pairs analysis to compare disease progression in two patient groups: those receiving dual bronchodilation vs those receiving triple therapy (each group n=1,046).,In two subgroups of patients matched according to a broad range of demographic and disease characteristics, over 1 year, fewer patients receiving dual bronchodilation exacerbated than those receiving triple therapy (15.5% vs 26.6%; P<0.001), with a greater improvement from baseline in COPD Assessment Test total score at 1 year (mean±SD −2.9±5.8 vs −1.4±5.5;P<0.001).,When analyzed according to prior therapy, the highest rate of exacerbations was in patients on triple therapy prior to the study who remained on triple therapy.,Those changing from mono-bronchodilator to dual bronchodilation had the greatest COPD Assessment Test total score improvement.,In this “real-life” cohort of patients with COPD, most of whom had not exacerbated in the 6 months prior to entry, triple therapy did not seem to improve outcomes compared with dual bronchodilation in terms of either exacerbations or health status.,Our analyses clearly demonstrate the potential impact of prior medication on study results, something that should be taken into account when interpreting the results even of controlled clinical trials.
|
Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD) exacerbation and influence their outcomes.,We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006-2012.,We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%).,Pneumonia was frequent in first-time exacerbations (36.1%), but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation.,Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012.,Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period.,A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission (7.7% vs 12.5%), and several acute procedures.,Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17-1.24).,Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11-1.18), and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07-1.13).,In contrast, the aHR of a subsequent exacerbation was 8%-13% lower for patients with pneumonic exacerbations.,Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care utilization and higher mortality.,Nonpneumonic COPD exacerbations predict increased risk of subsequent exacerbations.
| 1
|
Chronic obstructive pulmonary disease (COPD) exacerbations are associated with lung function decline, lower quality of life, and increased mortality, and can be prevented by pharmacological treatment and rehabilitation.,To examine management including examination, treatment, and planned follow-up of COPD exacerbation visits in primary care patients and to explore how measures and management at exacerbation visits are related to subsequent exacerbation risk.,A clinical population of 775 COPD patients was randomly selected from 56 Swedish primary healthcare centres.,Data on patient characteristics and management of COPD exacerbations were obtained from medical record review and a patient questionnaire.,In the study population of 458 patients with at least one exacerbation, Cox regression analyses estimated the risk of a subsequent exacerbation with adjustment for age and sex.,During a follow-up period of 22 months, 238 patients (52%) had a second exacerbation.,A considerable proportion of the patients were not examined and treated as recommended by guidelines.,Patients with a scheduled extra visit to an asthma/COPD nurse following an exacerbation had a decreased risk of further exacerbations compared with patients with no extra follow-up other than regularly scheduled visits (adjusted hazard ratio 0.60 (95% confidence interval 0.37 to 0.99), p=0.045).,Guidelines for examination and emergency treatment at COPD exacerbation visits are not well implemented.,Scheduling an extra visit to an asthma/COPD nurse following a COPD exacerbation may be associated with a decreased risk of further exacerbations in primary care patients.
|
Asthma and COPD require different management strategies, but differentiation in primary care is difficult.,This primary care support initiative observed the impact of spirometry and clinical assessment on the diagnosis of airway disease.,Of 61 191 patients aged ≥40 years being treated for respiratory conditions within 1003 UK primary care practices, 43 203 underwent a diagnostic review including standardized spirometric assessment.,The proportion of patients in whom the diagnosis was changed by the additional information was determined.,The relationship of various patient characteristics was compared with the baseline and review diagnoses and with any change in diagnosis.,Asthma was initially diagnosed in 43% of patients, COPD in 35%, mixed disease in 9%, and other respiratory condition in 13%.,Patients initially diagnosed with asthma, mixed disease, or another condition were more likely to have their diagnosis changed at review (54%, 46%, and 63%, respectively) than those initially diagnosed with COPD (14%).,A change from asthma to COPD was associated with male gender, smoking, older age, and reduced lung function, the opposite being associated with a change from COPD to asthma.,In this study, a clinical review supplemented by additional information including spirometry highlights apparent mislabeling of significant numbers of patients with chronic obstructive disease in general practice with significant implications for individual treatment and healthcare provision.,This study shows that the addition of more clinical information can have a major effect on diagnostic tendency in patients with airway disease.,An initial diagnosis of COPD seems less likely to change following review than an asthma diagnosis.,While it is likely that greater information leads to a more accurate diagnosis, the differential effect of new information on diagnostic labeling highlights the insecurity of the diagnostic process in primary care in the UK.
| 1
|
Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD.,This was a multicenter, double-blind, randomized, placebo-controlled study.,Patients (aged ≥ 40 years with baseline FEV1 ≤ 65% predicted, FEV1 > 0.50 L, FEV1/FVC ≤ 70%, and ≥ 15 pack-year smoking history) received arformoterol (n = 420) or placebo (n = 421) for 1 year.,The primary assessment was time from randomization to respiratory death or first COPD exacerbation-related hospitalization.,Among 841 patients randomized, 103 had ≥ 1 primary event (9.5% vs 15.0%, for arformoterol vs placebo, respectively).,Patients who discontinued treatment for any reason (39.3% vs 49.9%, for arformoterol vs placebo, respectively) were followed for up to 1 year postrandomization to assess for primary events.,Fewer patients receiving arformoterol than placebo experienced COPD exacerbation-related hospitalizations (9.0% vs 14.3%, respectively).,Twelve patients (2.9%) receiving arformoterol and 10 patients (2.4%) receiving placebo died during the study.,Risk for first respiratory serious adverse event was 50% lower with arformoterol than placebo (P = .003).,Numerically more patients on arformoterol (13; 3.1%) than placebo (10; 2.4%) experienced cardiac serious adverse events; however, time-to-first cardiac serious adverse event was not significantly different.,Improvements in trough FEV1 and FVC were greater with arformoterol (least-squares mean change from baseline vs placebo: 0.051 L, P = .030 and 0.075 L, P = .018, respectively).,Significant improvements in quality of life (overall St.,George’s Hospital Respiratory Questionnaire and Clinical COPD Questionnaire) were observed with arformoterol vs placebo (P < .05).,Arformoterol demonstrated an approximately 40% lower risk of respiratory death or COPD exacerbation-related hospitalization over 1 year vs placebo.,Arformoterol was well-tolerated and improved lung function vs placebo.,ClinicalTrials.gov; No.: NCT00909779; URL: www.clinicaltrials.gov
|
The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function.,The aims of this study were to investigate total mortality risks in GOLD stages 0-4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1-4.,Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits.,Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses.,Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0-4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group.,HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1-4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.,The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively.,The proportion of smokers among men was 50% and among women 40%.,Self reported comorbidity was present in 4.6% of the men and 6.6% of the women.,Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32-2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31-1.70).,The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98-1.29).,Among male smokers with stage 1; HR: 2.04 (1.34-3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38-7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.,Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2).
| 1
|
Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations.,Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial.,Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations.,The bacteria were identified by the semiquantitative culture of the expectorated sputum.,The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections.,Viruses were isolated from 16 (22.2%) of the 72 patients enrolled.,The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus.,A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae.,Five patients (6.9%) had both positive sputum cultures and virus identification.,The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different.,Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation.,WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits.,Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations.
|
Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection.,Biomarkers that can identify bacterial infections may reduce antibiotic prescription.,We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD.,Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008.,Demographics, clinical data, and blood samples were collected.,Procalcitonin and CRP concentrations were measured from available sera.,Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied.,Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001).,Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]).,The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00).,A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80%-97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia.,Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma.,CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness.
| 1
|
The Patient Reported Outcomes Measurement Information System 43-item short form (PROMIS-43) and the five-level EQ-5D (EQ-5D-5L) are recently developed measures of health-related quality of life (HRQL) that have potentially broad application in evaluating treatments and capturing burden of respiratory-related diseases.,The aims of this study were: (1) to examine their psychometric properties in patients with chronic obstructive pulmonary disease (COPD), and (2) to identify dimensions of HRQL that differ and do not differ by lung function.,We conducted a multi-center, cross-sectional study (“COPD Outcomes-based Network for Clinical Effectiveness & Research Translation” [CONCERT]).,We analyzed patients who met spirometric criteria for COPD, and completed EQ-5D-5L and PROMIS questionnaires.,Disease severity was graded based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification.,Pulmonary function test, PROMIS-43, EQ-5D (index score and EQ-Visual Analog Scale [EQ-VAS]), six minute walk test (6MWT), and three dyspnea scales (mMRC, Borg, FACIT-Dyspnea) were administered.,Validity and reliability of EQ-5D-5L and PROMIS-43 were examined, and differences in HRQL by GOLD grade were assessed.,Data from 670 patients with COPD were analyzed (mean age 68.5 years; 58% male).,More severe COPD was associated with more problems with mobility, self-care and usual activities (all p-values <0.01) according to EQ-5D-5L.,Related domains on EQ-5D-5L, PROMIS and clinical measures were moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) correlated.,A statistically significant trend of decreasing HRQL with more severe lung functions was observed for EQ-5D-5L index scores, EQ-VAS scores, and PROMIS physical function and social roles.,Results supported the validity of EQ-5D-5L and PROMIS-43 in COPD patients, and indicate that physical function and social activities decrease with level of lung function by GOLD grade, but not pain, mental health, sleep or fatigue as reported by patients.
|
Fatigue in COPD impairs functional status; however there are few studies examining mechanistic pathways of this symptom.,The aims of this study are to compare fatigue between COPD patients and healthy age-matched subjects, and to identify predictors of fatigue in COPD.,Seventy four COPD patients, mean age 69.9 (49-87) yrs, mean (SD) % predicted FEV1 46.5 (20.0) % and FEV1/FVC ratio 0.45 (0.13) and 35 healthy subjects, mean age 67.1 (50-84) yrs completed the Multidimensional Fatigue Inventory (MFI 20).,Patients' assessment included Depression (HADS), lung function, BMI, muscle strength, incremental shuttle walk test (ISWT), exercise oxygen saturation (SpO2), Borg breathlessness (CR-10) and exertion (RPE).,Serum level of Interleukin 6 (IL-6) was recorded.,Differences in MFI 20 between groups were examined and predictors of fatigue identified using logistic regression.,Significant differences (p < 0.01) were found between the COPD and healthy subjects for all MFI 20 dimensions.,There were significant differences when classified according to GOLD and dyspnoea stages for selected dimensions only.,Predictors of General Fatigue were depression, muscle strength and end SpO2 (R2 = .62); of Physical Fatigue: depression, % predicted FEV1, ISWT and age (R2 = .57); Reduced Activity: % predicted FEV1, BMI and depression (R2 = .36); Reduced Motivation: RPE, depression and end SpO2 (R2 = .37) and Mental Fatigue: depression and end SpO2 (R2 = .38).,All dimensions of fatigue were higher in COPD than healthy aged subjects.,Predictive factors differ according to the dimension of fatigue under investigation.,COPD-RF is a multi component symptom requiring further consideration.
| 1
|
Complications of pneumonia development in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroid (ICS) therapy have been documented.,The aim of this study was to focus on clinical efficacy and the incidence of pneumonia between COPD patients receiving medium and high doses of ICS.,This prospective, randomized study included COPD patients identified from three tertiary medical centers from 2010 to 2012.,The patients were randomized into two groups: high dose (HD; fluticasone 1,000 μg + salmeterol 100 μg/day) and medium dose (MD; fluticasone 500 μg + salmeterol 100 μg/day).,Lung function with forced expiratory volume in 1 second (FEV1), forced vital capacity, and COPD-assessment test (CAT) were checked every 2 months.,The frequency of acute exacerbations and number of pneumonia events were measured.,The duration of the study period was 1 year.,In total, 237 COPD patients were randomized into the two treatment arms (115 in the HD group, 122 in the MD group).,The FEV1 level was significantly improved in the patients in the HD group compared with those in the MD group (HD 103.9±26.6 mL versus MD 51.4±19.7 mL, P<0.01) at the end of the study.,CAT scores were markedly improved in patients using an HD compared to those using an MD (HD 13±5 versus MD 16±7, P=0.05).,There was a significant difference in the percentage of annual rates in acute exacerbations (HD 0.16 versus MD 0.34, P<0.01) between the two groups.,The incidence of pneumonia was similar in the two groups (HD 0.08 versus MD 0.10, P=0.38).,COPD patients treated with high doses of ICS had more treatment benefits and no significant increases in the incidence in pneumonia.,Higher-dose ICS treatment may be suitable for COPD therapy.
|
Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials.
| 1
|
Chronic obstructive pulmonary disease (COPD), one of the most common chronic diseases and a leading cause of death, has historically been considered a disease of men.,However, there has been a rapid increase in the prevalence, morbidity, and mortality of COPD in women over the last two decades.,This has largely been attributed to historical increases in tobacco consumption among women.,But the influence of sex on COPD is complex and involves several other factors, including differential susceptibility to the effects of tobacco, anatomic, hormonal, and behavioral differences, and differential response to therapy.,Interestingly, nonsmokers with COPD are more likely to be women.,In addition, women with COPD are more likely to have a chronic bronchitis phenotype, suffer from less cardiovascular comorbidity, have more concomitant depression and osteoporosis, and have a better outcome with acute exacerbations.,Women historically have had lower mortality with COPD, but this is changing as well.,There are also differences in how men and women respond to different therapies.,Despite the changing face of COPD, care providers continue to harbor a sex bias, leading to underdiagnosis and delayed diagnosis of COPD in women.,In this review, we present the current knowledge on the influence of sex on COPD risk factors, epidemiology, diagnosis, comorbidities, treatment, and outcomes, and how this knowledge may be applied to improve clinical practices and advance research.
|
Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation.
| 1
|
High-flow nasal cannula (HFNC) oxygen therapy in acute hypoxic respiratory failure is becoming increasingly popular.,However, evidence to support the use of HFNC in acute respiratory failure (ARF) with hypercapnia is limited.,Chronic obstructive pulmonary disease (COPD) patients with moderate hypercapnic ARF (arterial blood gas pH 7.25-7.35, PaCO2>50 mmHg) who received HFNC or non-invasive ventilation (NIV) in the intensive care uint from April 2016 to March 2018 were analyzed retrospectively.,The endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa), and 28-day mortality.,Eighty-two COPD patients (39 in the HFNC group and 43 in the NIV group) were enrolled in this study.,The mean age was 71.8±8.2 and 54 patients (65.9%) were male.,The treatment failed in 11 out of 39 patients with HFNC (28.2%) and in 17 of 43 patients with NIV (39.5%) (P=0.268).,No significant differences were found for 28-day mortality (15.4% in the HFNC group and 14% in the NIV group, P=0.824).,During the first 24 hrs of treatment, the number of nursing airway care interventions in the HFNC group was significantly less than in the NIV group, while the duration of device application was significantly longer in the HFNC group (all P<0.05).,Skin breakdown was significantly more common in the NIV group (20.9% vs 5.1%, P<0.05).,Among COPD patients with moderate hypercarbic ARF, the use of HFNC compared with NIV did not result in increased rates of treatment failure, while there were fewer nursing interventions and skin breakdown episodes reported in the HFNC group.
|
This study investigated the long-term effects of humidified high-flow nasal cannula (HFNC) in COPD patients with chronic hypoxemic respiratory failure treated with long-term oxygen therapy (LTOT).,A total of 200 patients were randomized into usual care ± HFNC.,At inclusion, acute exacerbation of COPD (AECOPD) and hospital admissions 1 year before inclusion, modified Medical Research Council (mMRC) score, St George’s Respiratory Questionnaire (SGRQ), forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT) and arterial carbon dioxide (PaCO2) were recorded.,Patients completed phone interviews at 1, 3 and 9 months assessing mMRC score and AECOPD since the last contact.,At on-site visits (6 and 12 months), mMRC, number of AECOPD since last contact and SGRQ were registered and FEV1, FEV1%, PaCO2 and, at 12 months, 6MWT were reassessed.,Hospital admissions during the study period were obtained from hospital records.,Hours of the use of HFNC were retrieved from the high-flow device.,The average daily use of HFNC was 6 hours/day.,The HFNC group had a lower AECOPD rate (3.12 versus 4.95/patient/year, p<0.001).,Modeled hospital admission rates were 0.79 versus 1.39/patient/year for 12- versus 1-month use of HFNC, respectively (p<0.001).,The HFNC group had improved mMRC scores from 3 months onward (p<0.001) and improved SGRQ at 6 and 12 months (p=0.002, p=0.033) and PaCO2 (p=0.005) and 6MWT (p=0.005) at 12 months.,There was no difference in all-cause mortality.,HFNC treatment reduced AECOPD, hospital admissions and symptoms in COPD patients with hypoxic failure.
| 1
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.