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There is a paucity of information on coronavirus disease 2019 (COVID-19) outcomes in asthmatics.,To identify risk factors associated with admission and subsequent mortality among COVID-19-infected asthmatics.,Adults at our institution with a positive polymerase chain reaction for COVID-19 between March 14 and April 27, 2020, were retrospectively identified.,Comorbidities, laboratory results, and mortality rates during hospitalization were recorded.,In total, 737 of 951 (77.5%) asthma patients with COVID-19 were seen in the emergency department (ED), and 78.8% of these ED patients (581 of 737) were admitted.,Individuals with previously measured mean absolute eosinophil counts (AEC) ≥150 cells/μL were less likely to be admitted (odds ratio [OR] = 0.46, 95% confidence interval [CI]: 0.21-0.98, P = .04), whereas concomitant heart failure (CHF), chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD) were risk factors for admission.,Hospitalized patients with asthma with peak hospital-measured AEC ≥150 cells/μL (n = 104) were less likely to die compared with those whose AEC remained <150 cells/μL (n = 213) (mortality rate 9.6% vs 25.8%; OR = 0.006, 95% CI: 0.0001-0.64, P = .03).,This group had also higher preadmission mean AEC (237 ± 181 vs 163 ± 147 cells/μL, P = .001, OR = 2012, 95% CI: 27.3-14,816).,The mortality rate in patients with asthma alone (no associated CHF, CKD, COPD, diabetes, or hypertension) was similar to that of patients without asthma or any of these comorbidities.,In asthmatics, pre-existing eosinophilia (AEC ≥150 cells/μL) was protective from COVID-19-associated admission, and development of eosinophilia (AEC ≥150 cells/μL) during hospitalization was associated with decreased mortality.,Preadmission AEC influenced the AEC trend during hospitalization.,Having a Th2-asthma phenotype might be an important predictor for reduced COVID-19 morbidity and mortality that should be further explored in prospective and mechanistic studies. | Evaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly.,A nested case-control design using confirmed case reports released from the news or the national/provincial/municipal health commissions of China between 18 December 2019 and 8 March 2020.,Patients with confirmed SARS-CoV-2 infection, excluding asymptomatic patients, in mainland China outside of Hubei Province.,Patient demographics, survival time and status, and history of comorbidities.,A total of 94 publicly reported deaths in locations outside of Hubei Province, mainland China, were included as cases.,Each case was matched with up to three controls, based on gender and age ±1 year old (94 cases and 181 controls).,The inverse probability-weighted Cox proportional hazard model was performed, controlling for age, gender and the early period of the outbreak.,Of the 94 cases, the median age was 72.5 years old (IQR=16), and 59.6% were men, while in the control group the median age was 67 years old (IQR=22), and 64.6% were men.,Adjusting for age, gender and the early period of the outbreak, poor health conditions were associated with a higher risk of COVID-19 mortality (HR of comorbidity score, 1.31 [95% CI 1.11 to 1.54]; p=0.001).,The estimated mortality risk in patients with pre-existing coronary heart disease (CHD) was three times that of those without CHD (p<0.001).,The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old woman with no other comorbidities) was 0.53 (95% CI 0.34 to 0.82), while it was 0.85 (95% CI 0.79 to 0.91) for those without CHD.,Older age was also associated with increased mortality risk: every 1-year increase in age was associated with a 4% increased risk of mortality (p<0.001).,Extra care and early medical interventions are needed for patients with pre-existing comorbidities, especially CHD. | 1 |
Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor.,This study evaluated the effectiveness of a multifactorial intervention on improving the therapeutic adherence in chronic obstructive pulmonary disease (COPD) patients with scheduled inhalation therapy.,The study design consisted of a randomised controlled trial in a primary care setting. 146 patients diagnosed with COPD were randomly allocated into two groups using the block randomisation technique.,One-year follow-ups with three visits were performed.,The intervention consisted of motivational aspects related to adherence (beliefs and behaviour) in the form of group and individual interviews, cognitive aspects in the form of information about the illness and skills in the form of training in inhalation techniques.,Cognitive-emotional aspects and training in inhalation techniques were reinforced during all visits of the intervention group.,The main outcome measure was adherence to the medication regimen.,Therapeutic adherence was determined by the percentage of patients classified as good adherent as evaluated by dose or pill count.,Of the 146 participants (mean age 69.8 years, 91.8% males), 41.1% reported adherence (41.9% of the control group and 40.3% of the intervention group).,When multifactorial intervention was applied, the reported adherence was 32.4% for the control group and 48.6% for the intervention group, which showed a statistically significant difference (p = 0.046).,Number needed to treat is 6.37.,In the intervention group, cognitive aspects increased by 23.7% and skilled performance of inhalation techniques increased by 66.4%.,The factors related to adherence when multifactorial intervention was applied were the number of exacerbations (OR = 0.66), visits to health centre (OR = 0.93) and devices (OR = 2.4); illness severity (OR = 0.67), beta-2-adrenergic (OR = 0.16) and xantine (OR = 0.19) treatment; activity (OR = 1.03) and impact (OR = 1.03) scales of the Saint George Respiratory Questionnaire.,Application of the multifactorial intervention designed for this study (COPD information, dose reminders, audio-visual material, motivational aspects and training in inhalation techniques) resulted in an improvement in therapeutic adherence in COPD patients with scheduled inhalation therapy.,Current Controlled Trials ISRCTN18841601. | Investigate long-term effects 4 years after the end of a 1-year self-management program (SMP) with 30 hours of education and 16 hours of physical activity in patients with chronic obstructive pulmonary disease (COPD).,Prospective observational outcome study.,SMP focused on improving disease related self-care skills.,Main outcome measures were health-related quality of life, HRQoL, (St Georges Respiratory Questionnaire, SGRQ total) and exercise capacity (6-minute walk test, 6MWT).,Thirty patients participated, 47% women.,Baseline mean age was 67 years and mean pre-bronchodilator FEV1 (forced expiratory volume in 1 second) percentage predicted was 41.3.,HRQoL showed a statistical significant improvement during the 1-year intervention.,Four years after the end of the program SGRQ total was similar to baseline value, 1.4 points (95% CI: −3.6 to 6.3, P = 0.580).,Also 6MWT was similar to baseline value at the same test point, −10 m (95% CI: −27 to 8, P = 0.262), and 63% reported having continued to exercise regularly a minimum of three times per week during the follow-up period.,The participants in a 1-year self-management program with additional training had maintained their pre-intervention level of HRQoL and exercise capacity 4 years after the end of the program.,Two out of three participants had continued to exercise regularly. | 1 |
The physiological effects of high-flow nasal cannula O2 therapy (HFNC) have been evaluated mainly in patients with hypoxemic respiratory failure.,In this study, we compared the effects of HFNC and conventional low-flow O2 therapy on the neuroventilatory drive and work of breathing postextubation in patients with a background of chronic obstructive pulmonary disease (COPD) who had received mechanical ventilation for hypercapnic respiratory failure.,This was a single center, unblinded, cross-over study on 14 postextubation COPD patients who were recovering from an episode of acute hypercapnic respiratory failure of various etiologies.,After extubation, each patient received two 1-h periods of HFNC (HFNC1 and HFNC2) alternated with 1 h of conventional low-flow O2 therapy via a face mask.,The inspiratory fraction of oxygen was titrated to achieve an arterial O2 saturation target of 88-92%.,Gas exchange, breathing pattern, neuroventilatory drive (electrical diaphragmatic activity (EAdi)) and work of breathing (inspiratory trans-diaphragmatic pressure-time product per minute (PTPDI/min)) were recorded.,EAdi peak increased from a mean (±SD) of 15.4 ± 6.4 to 23.6 ± 10.5 μV switching from HFNC1 to conventional O2, and then returned to 15.2 ± 6.4 μV during HFNC2 (conventional O2: p < 0.05 versus HFNC1 and HFNC2).,Similarly, the PTPDI/min increased from 135 ± 60 to 211 ± 70 cmH2O/s/min, and then decreased again during HFNC2 to 132 ± 56 (conventional O2: p < 0.05 versus HFNC1 and HFNC2).,In patients with COPD, the application of HFNC postextubation significantly decreased the neuroventilatory drive and work of breathing compared with conventional O2 therapy.,The online version of this article (10.1186/s13054-018-2107-9) contains supplementary material, which is available to authorized users. | Nasal highflow (NHF) provides a warmed and humidified air stream up to 60 L/min.,Recent data demonstrated a positive effect in patients with acute hypoxemic respiratory failure, especially when caused by pneumonia.,Preliminary data show a decrease in hypercapnia in patients with COPD.,Therefore, NHF should be evaluated as a new ventilatory support device.,This study was conducted to assess the impact of different flow rates on ventilatory parameters in patients with COPD.,This interventional clinical study was performed with patients suffering from severe COPD.,The aim was to characterize flow-dependent changes in mean airway pressure, breathing volumes, breathing frequency, and decrease in partial pressure of CO2 (pCO2).,Mean airway pressure was measured in the nasopharyngeal space (19 patients).,To evaluate breathing volumes, we used a polysomnographic device (18 patients).,All patients received 20 L/min, 30 L/min, 40 L/min, and 50 L/min and - to illustrate the effects - nasal continuous positive airway pressure and nasal bilevel positive airway pressure.,Capillary blood gas analyses were performed in 54 patients with hypercapnic COPD before and two hours after the use of NHF.,We compared the extent of decrease in pCO2 when using 20 L/min and 30 L/min.,Additionally, comfort and dyspnea during the use of NHF were surveyed.,NHF resulted in a minor flow dependent increase in mean airway pressure.,Tidal volume increased, and breathing rate decreased.,The calculated minute volume decreased under NHF breathing.,In spite of this fact, hypercapnia decreased with increasing flow (20 L/min vs 30 L/min).,Additionally, an improvement in dyspnea was observed.,The rapid shallow breathing index shows a decrease when using NHF.,NHF leads to a flow-dependent reduction in pCO2.,This is most likely achieved by a washout of the respiratory tract and a functional reduction in dead space.,In summary, NHF enhances effectiveness of breathing in patients with COPD, reduces pCO2, the work of breathing, and rapid shallow breathing index as an indicator of respiratory work load. | 1 |
Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell.,Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants.,If however, this balance is disturbed a situation called oxidative stress occurs.,Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer.,Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease.,Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress.,In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression.,In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings. | The incidence and severity of chronic lung diseases is growing and affects between 100 and 150 million people worldwide and is associated with a significant rate of mortality.,Unfortunately, the initial cause that triggers most chronic lung diseases remains unknown and current available therapies only ameliorate, but do not cure the disease.,Thus, there is a need for identification of new targets and development of novel therapies especially for those most severely affected.,IL-6, like other inflammatory cytokines, has been shown to be elevated in different lung diseases, but it was considered a byproduct of ongoing inflammation in the lung.,However, recent studies support a dissociation of IL-6 from inflammation in the lung and suggest that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD.,IL-6 may therefore be a germane target for treatment of these and other chronic lung disease.,Here, we provide an overview of the studies in mouse models and human patients that provide support for the involvement of IL-6 in lung diseases. | 1 |
Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients.,The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1).,Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors.,Systematic approaches were used to guide the analysis.,In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1.,Higher concentrations of potassium and sodium were associated with lower FEV1.,Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health.,In addition other novel associations found in this study merit further investigation. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a common airway disease characterized by an exaggerated pulmonary inflammatory response.,Long noncoding MIR155 host gene (lncRNA MIR155HG) has been identified to be related to the macrophage polarization in COPD.,However, the detailed function of MIR155HG in cigarette smoke (CS)-mediated COPD remains largely unknown.,The expression level of MIR155HG was elevated while miR-218-5p was decreased in lung tissues of smokers without or with COPD, especially in smokers with COPD, and cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cell (HPMECs) in a dose- and time-dependent manner.,Then, functional experiments showed that MIR155HG deletion could reverse CSE exposure-induced apoptosis and inflammation in HPMECs.,MiR-218-5p was confirmed to be a target of MIR155HG and rescue assay showed miR-218-5p inhibitor attenuated the inhibitory action of MIR155HG knockdown on CSE-induced HPMECs.,Subsequently, miR-218-5p was found to target bromodomain containing 4 (BRD4) directly, and miR-218-5p overexpression overturned CSE-induced injury of HPMECs via regulating BRD4.,Additionally, co-expression analysis indicated MIR155HG indirectly regulated BRD4 expression in HPMECs via miR-218-5p.,Thus, we concluded that MIR155HG contributed to the apoptosis and inflammation of HPMECs in smoke-related COPD by regulating miR-128-5p/BRD4 axis, providing a novel insight on the pathogenesis of COPD and a therapeutic strategy on COPD treatments. | 1 |
To develop a practicable nomogram aimed at predicting the risk of severe exacerbations in COPD patients at three and five years.,COPD patients with prospective follow-up data were extracted from Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) obtained from National Heart, Lung and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center.,We comprehensively considered the demographic characteristics, clinical data and inflammation marker of disease severity.,Cox proportional hazard regression was performed to identify the best combination of predictors on the basis of the smallest Akaike Information Criterion.,A nomogram was developed and evaluated on discrimination, calibration, and clinical efficacy by the concordance index (C-index), calibration plot and decision curve analysis, respectively.,Internal validation of the nomogram was assessed by the calibration plot with 1000 bootstrapped resamples.,Among 1711 COPD patients, 523 (30.6%) suffered from at least one severe exacerbation during follow-up.,After stepwise regression analysis, six variables were determined including BMI, severe exacerbations in the prior year, comorbidity index, post-bronchodilator FEV1% predicted, and white blood cells.,Nomogram to estimate patients’ likelihood of severe exacerbations at three and five years was established.,The C-index of the nomogram was 0.74 (95%CI: 0.71-0.76), outperforming ADO, BODE and DOSE risk score.,Besides, the calibration plot of three and five years showed great agreement between nomogram predicted possibility and actual risk.,Decision curve analysis indicated that implementation of the nomogram in clinical practice would be beneficial and better than aforementioned risk scores.,Our new nomogram was a useful tool to assess the probability of severe exacerbations at three and five years for COPD patients and could facilitate clinicians in stratifying patients and providing optimal therapies. | Intergenerational associations in chronic obstructive pulmonary disease (COPD) have been well recognized and may result from genetic, gene environment, or exposure to life course factors.,Consequently, adult offspring of parents with COPD may be at a greater risk of developing COPD.,The aim of this study was to review the prevalence of co-occurrence of COPD in adult offspring with one or both parents having COPD independent of specific genetic variations.,In total, five databases were searched for original studies in which prevalence of COPD was reported in both offspring (children) and one or both parents.,Studies were excluded if COPD was not clearly defined, COPD was linked to specific genetic variations, COPD was combined with other chronic respiratory conditions, or estimates included other first-degree relatives.,Data extraction (ie, sample characteristics, prevalence of COPD, and odds ratio [OR] if reported) was completed by two independent reviewers.,A meta-analysis of prevalence and OR was conducted, where possible.,Of the 3,382 citations, 129 full texts were reviewed to include eight studies (six case-control, one cross-sectional, and one cohort) reflecting either prevalence of COPD in offspring of parents with COPD (descendent approach, n=3), which ranged from 0% to 17.3%, or prevalence of people with COPD reporting positive parental history of COPD (antecedent approach, n=5), for which the pooled prevalence was 28.6%.,Offspring of people with COPD had 1.57 times greater odds (95% confidence interval =1.29-1.93; P<0.001) of having COPD compared with people not having a parental history of COPD.,The prevalence of COPD in adult offspring of people with COPD is greater than population-based estimates, and the ORs indicate a higher risk in this group.,This offers clinicians a potential strategy for opportunistic screening, early identification, and intervention in this at-risk group. | 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. | Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | 1 |
To describe the temporal and spatial trends of mortality and disability adjusted life years (DALYs) due to chronic respiratory diseases, by age and sex, across the world during 1990-2017 using data from the Global Burden of Disease Study 2017.,Systematic analysis.,The Global Burden of Diseases, Injuries, and Risk Factors Study 2017.,Mortality and DALYs from chronic respiratory diseases were estimated from the Global Burden of Disease Study 2017 using DisMod-MR 2.1, a Bayesian meta-regression tool.,The estimated annual percentage change of the age standardised mortality rate was calculated using a generalised linear model with a Gaussian distribution.,Mortality and DALYs were stratified according to the Socio-demographic index.,The strength and direction of the association between the Socio-demographic index and mortality rate were measured using the Spearman rank order correlation.,Risk factors for chronic respiratory diseases were analysed from exposure data.,Between 1990 and 2017, the total number of deaths due to chronic respiratorydiseases increased by 18.0%, from 3.32 (95% uncertainty interval 3.01 to 3.43) million in 1990 to 3.91 (3.79 to 4.04) million in 2017.,The age standardised mortality rate of chronic respiratory diseases decreased by an average of 2.41% (2.28% to 2.55%) annually.,During the 27 years, the annual decline in mortality rates of chronic obstructive pulmonary disease (COPD; 2.36%, uncertainty interval 2.21% to 2.50%) and pneumoconiosis (2.56%, 2.44% to 2.68%) has been slow, whereas the mortality rate for interstitial lung disease and pulmonary sarcoidosis (0.97%, 0.92% to 1.03%) has increased.,Reductions in DALYs for asthma and pneumoconiosis have been seen, but DALYs due to COPD, and interstitial lung disease and pulmonary sarcoidosis have increased.,Mortality and the annual change in mortality rate due to chronic respiratory diseases varied considerably across 195 countries.,Assessment of the factors responsible for regional variations in mortality and DALYs and the unequal distribution of improvements during the 27 years showed negative correlations between the Socio-demographic index and the mortality rates of COPD, pneumoconiosis, and asthma.,Regions with a low Socio-demographic index had the highest mortality and DALYs.,Smoking remained the major risk factor for mortality due to COPD and asthma.,Pollution from particulate matter was the major contributor to deaths from COPD in regions with a low Socio-demographic index.,Since 2013, a high body mass index has become the principal risk factor for asthma.,Regions with a low Socio-demographic index had the greatest burden of disease.,The estimated contribution of risk factors (such as smoking, environmental pollution, and a high body mass index) to mortality and DALYs supports the need for urgent efforts to reduce exposure to them. | Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide.,The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes.,These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease.,A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer.,In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent.,In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression.,The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death.,Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks.,Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer.,In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer. | 1 |
Pulmonary hypertension and exercise-induced oxygen desaturation (EID) influence acute exacerbation of COPD.,Computed tomography (CT)-detected pulmonary artery (PA) enlargement is independently associated with acute COPD exacerbations.,Associations between PA to aorta (PA:A) ratio and EID in patients with COPD have not been reported.,We hypothesized that the PA:A ratio correlated with EID and that results of the 6-minute walk test (6MWT) would be useful for predicting the risk associated with PA:A >1.,We retrospectively measured lung function, 6MWT, emphysema area, and PA enlargement on CT in 64 patients with COPD.,The patients were classified into groups with PA:A ≤1 and >1.,Receiver-operating characteristic curves were used to determine the threshold values with the best cutoff points to predict patients with PA:A >1.,The PA:A >1 group had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1:FVC ratio, diffusion capacity of lung carbon monoxide, 6MW distance, and baseline peripheral oxygen saturation (SpO2), lowest SpO2, highest modified Borg scale results, percentage low-attenuation area, and history of acute COPD exacerbations ≤1 year, and worse BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index results (P<0.05).,Predicted PA:A >1 was determined for SpO2 during 6MWT (best cutoff point 89%, area under the curve 0.94, 95% confidence interval 0.88-1).,SpO2 <90% during 6MWT showed a sensitivity of 93.1, specificity of 94.3, positive predictive value of 93.1, negative predictive value of 94.3, positive likelihood ratio of 16.2, and negative likelihood ratio of 0.07.,Lowest SpO2 during 6MWT may predict CT-measured PA:A, and lowest SpO2 <89% during 6MWT is excellent for detecting pulmonary hypertension in COPD. | The functional work capacity of chronic obstructive pulmonary disease (COPD) patients is usually assessed with walk tests such as the 6-minute walk test (6MWT) or the shuttle test.,Because these exercise modalities require a controlled environment which limits their use by pulmonologists and severely restricts their use among general practitioners, different modalities of a short (1 minute or less) sit-to-stand test were recently proposed.,In this study, we evaluated a new modality of a semipaced 3-minute chair rise test (3CRT) in 40 patients with COPD, and compared the reproducibility of physiological responses and symptoms during the 3CRT and their interchangeability with the 6MWT.,The results demonstrate that physiological variables, heart rate, pulse oxygen saturation, work done, and symptoms (Borg dyspnea and fatigue scores), during the 3CRT were highly reproducible, and that the physiological responses and symptoms obtained during the 3CRT and the 6MWT were interchangeable for most patients.,Moreover, these preliminary data suggest that patients able to perform more than 50 rises during 3 minutes had no significant disability.,The simplicity and ease of execution of the 3CRT will facilitate the assessment of exercise symptoms and disability in COPD patients during routine consultations with pulmonologists and general practitioners, and will thus contribute to the improved management of COPD patients. | 1 |
COPD patients suffer from respiratory symptoms and limitations in daily life.,We aimed to characterize the impact of disease on overall health, daily life, and perceived well-being in COPD outpatients.,We conducted a national, cross-sectional study among pulmonologists and general practitioners (GPs).,The St.,George’s Respiratory Questionnaire for COPD patients (SGRQ-C) was used.,Inclusion criteria were a physician’s diagnosis of COPD and age ≥40 years.,Subjects with a history of lung surgery, lung cancer or COPD exacerbation within the last four weeks were excluded.,Sixty-seven pulmonologists and 6 GPs enrolled 1175 COPD patients.,Two hundred forty-eight of those did not fulfill GOLD criteria for COPD (FEV1/FVC <0.7) and 77 were excluded due to missing data.,Finally, 850 patients (62.8% men; mean age 66.2 ± 0.3 (SE) years; mean FEV1%pred.,51.5 ± 0.6 (SE)) were analyzed.,Last year, 55.4% reported at least one exacerbation, and 12.7% were hospitalized for COPD exacerbation.,Mean SGRQ-C total score was 43.1 ± 0.83 (SE) and mean component scores for symptoms, activity and impacts were 55.6, 55.4 and 30.5, respectively.,Half of the patients (50.3%) reported not being able to do any sports and 78.7% stated that their respiratory symptoms did not allow them doing anything they would like to do.,In patients with less severe COPD (FEV1pred ≥50% and non-frequent exacerbations), global health status was overrated, ie, estimated as better by the physician than by the patient, while it was underrated in more severe COPD.,In Austria, the burden of disease in COPD outpatients tends to be underestimated in patients with milder airway obstruction and less exacerbations and overestimated in patients with more severe airway obstruction and frequent exacerbations.,Our finding suggests that validated assessment of global health status might decrease these differences of perception. | COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | 1 |
Previous studies have reported that anemia increased mortality in patients with COPD.,However, it is unclear whether anemia is associated with increased COPD mortality in the general population.,The purpose of our study is to identify whether anemia is related to long-term mortality in COPD using a large population-based database.,Using the National Health Insurance Service-Health Screening Cohort, we identified COPD patients with available hemoglobin level.,We analyzed mortality among patients with COPD from 2003 to 2013 according to hemoglobin level.,A total of 7,114 patients with COPD were identified.,Mean age was 65.0±9.3 years, and 62.9% were male.,Anemia was present in 469 patients (6.6%).,The overall mortality rate was 46.5% in anemia and 32.1% in non-anemia groups (p<0.001).,The hazard ratio of anemia for mortality was 1.31 (95% CI, 1.11-1.54).,Among patients with anemia, the hemoglobin level correlated well with mortality.,Anemia was associated with increased long-term mortality of COPD, and even mild anemia was related to a significantly increased risk. | Low concentrations of hemoglobin have previously been demonstrated in many patients with COPD.,There is evidence of anemia as a prognostic factor in acute exacerbations, but the detailed relationship between concentrations of hemoglobin and mortality is not known.,A register-based cohort of patients admitted for the first time to Danish hospitals for acute exacerbations of COPD from 2007 through 2012 was established.,Age, sex, comorbidities, medication, renal function, and concentrations of hemoglobin were retrieved.,Sex-specific survival analyses were fitted for different rounded concentrations of hemoglobin.,The cohort encompassed 6,969 patients.,Hemoglobin below 130 g/L was present in 39% of males and below 120 g/L in 24% of females.,The in-hospital mortality rates for patients with hemoglobin below or above these limits were 11.6% and 5.4%, respectively.,After discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22-1.73), adjusted HR 1.37 (95% CI 1.15-1.64).,Compared to hemoglobin 120 g/L, the HR for females with hemoglobin 110 g/L was 1.4 (95% CI 1.17-1.68), adjusted HR 1.28 (95% CI 1.06-1.53).,In conclusion, low concentrations of hemoglobin are frequent in COPD patients with acute exacerbations, and predict long-term mortality. | 1 |
Significant positive effects, particularly on psychological state in patients who completed the follow-up pulmonary rehabilitation programs, are indicated by a large number of studies.,Yet, a remarkable proportion of selected patients drop out from these programs.,In this study, we investigated existing differences on psychological variables among COPD patients who complete and those who drop out from pulmonary rehabilitation programs.,The study included 144 patients, 43 (29.9%) of whom did not complete the program.,SCL-90 was used for the assessment of psychological symptoms.,On the SCL-90-R scale 55.6% of patients had abnormal findings.,Patients who discontinued the program had higher rates of depression and somatization compared to those who completed it.,Regarding the psychopathology scales of SCL-90R, we found that patients who discontinued the program showed higher levels of psychopathology on the scales of somatization, depression, paranoid ideation, and psychotism compared to those who completed the program.,The final regression model showed that patients with low educational status and psychotism were more likely to leave the program.,In conclusion, psychopathology contributes to patients dropping out from a COPD rehabilitation program; thus, psychological assessment prior to inclusion in rehabilitation programs may reduce dropouts. | Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes.,However, very little attention has been paid to the timing of the failure.,This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor.,The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony.,The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation.,The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure.,However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate.,Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance.,Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV.,Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation. | 1 |
Current evidence suggests that a higher blood eosinophil cell count at admission for acute exacerbation of COPD (AECOPD) is associated with a favorable response to systemic steroids.,However, the impact of blood eosinophil counts at admission on post-hospitalization outcomes is still unclear.,The main objective of this study is to investigate readmission outcomes associated with blood eosinophilia following severe COPD exacerbation in patients with infrequent COPD hospitalizations.,This is an observational cohort study design.,We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013.,Patients were stratified into the eosinophilic group if the blood eosinophil count on admission was ≥200 cells/µL and/or ≥2% of the total white blood cell (WBC) count.,The primary outcome was 1-year COPD-related readmission.,Secondary outcomes included 1-year all-cause mortality, 1-year all-cause readmission, length of stay, time to COPD-related readmission, and number of 1-year COPD-associated emergency department (ED) and ambulatory visits.,A total of 479 patients were included.,Of whom, 173 were stratified into the eosinophilic group.,Higher blood eosinophil cell count was associated with an increased risk of 1-year COPD-related readmission (OR, 1.83 [95% CI, 1.16-2.89]; P<0.01), a shorter time to first COPD-related readmission (HR, 1.64 [95% CI, 1.14-2.36]; P<0.01), and an increased number of 1-year COPD-related ED visits (incidence rate ratio, 1.78 [95% CI, 1.21-2.61]; P<0.01).,All-cause mortality, all-cause readmission, length of stay, and number of ambulatory visits did not differ between groups.,Higher blood eosinophil cell count at admission for a COPD exacerbation is associated with increased COPD readmission rates in patients with infrequent COPD hospitalizations. | In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations.,To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels.,The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications.,Three-year survival between groups was compared using Kaplan-Meier analysis.,Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos.,Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%).,For all cutoffs, there was no difference between Eos+ and Eos− groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories).,In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival.,In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis.,These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping. | 1 |
Few studies have investigated the quantitative computed tomography (CT) features associated with the severity of bronchiectasis in COPD patients.,The purpose of this study was to identify the quantitative CT features and clinical values to determine the extent of bronchiectasis in moderate-to-severe COPD patients.,A total of 127 moderate-to-severe COPD patients were selected from the cohort of COPD in Dusty Areas (CODA).,The study subjects were classified into three groups according to the extent of bronchiectasis on CT: no bronchiectasis, mild bronchiectasis, and moderate-to-severe bronchiectasis.,The three groups were compared with respect to demographic data, symptoms, medical history, serum inflammatory markers, pulmonary function, and quantitative CT values.,Among 127 moderate-to-severe COPD subjects, 73 patients (57.5%) were detected to have bronchiectasis, 51 patients (40.2%) to have mild bronchiectasis, and 22 patients (17.3%) to have moderate-to-severe bronchiectasis.,Compared with COPD patients without bronchiectasis, those with bronchiectasis were older and had higher frequency of prior tuberculosis, lower prevalence of bronchodilator reversibility (BDR), and more severe air trapping (P < 0.05).,Moderate-to-severe bronchiectasis patients had lower body mass index (BMI), higher frequency of prior tuberculosis, lower prevalence of BDR, worse pulmonary function, and more severe air trapping (P < 0.05) than those in the mild bronchiectasis group.,Moderate-to-severe bronchiectasis was associated with a history of pulmonary tuberculosis, lower BMI, severe airflow obstruction, and lower BDR in moderate-to-severe COPD patients.,Quantitative analysis of CT showed that severe air trapping was associated with the extent of bronchiectasis in these patients. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses.,In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up.,We analyzed dusty areas cohort comprising 272 patients with COPD.,The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline.,The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data.,The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups.,PCA revealed that six independent components accounted for 77.3% of variance.,Three distinct subgroups were identified through the cluster analysis.,Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up.,Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up.,Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization.,Cluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes.,These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD.,The online version of this article (10.1186/s12890-017-0553-9) contains supplementary material, which is available to authorized users. | 1 |
It is extremely important to objectively take a view of population health to provide useful information to decision makers, health-sector leaders, researchers, and informed citizens.,This study aims to examine the burden of disease in Korea as of 2015, and to study how the burden of disease changes with the passage of time.,We used results from the Korean National Burden of Disease and Injuries Study 2015 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive disability-adjusted life years (DALYs) by gender and age groups from 2007 to 2015.,DALYs were calculated as the sum of the years of life lost (YLLs) and the years lived with disability (YLDs).,In 2015, the burden of disease for Korean people was calculated at 29,476 DALYs per 100,000 population.,DALYs caused by low back pain were the highest, followed by diabetes mellitus and chronic obstructive pulmonary disease.,The burden of disease showed a consistently increasing trend from 2007 to 2015.,Although YLLs have been on the decrease since 2011, the increase in YLDs has contributed to the overall rise in DALYs.,The DALYs per 100,000 population in 2015 increased by 28.1% compared to 2007.,As for the diseases for which the burden of disease is substantially increasing, it is needed to establish appropriate policies in a timely manner.,The results of this study are expected to be the basis for prioritizing public health and health care policies in Korea. | The underdiagnosis of chronic obstructive pulmonary disease (COPD) could be improved through screening using portable devices simpler than conventional spirometers in specific healthcare settings to reach a higher percentage of the at-risk population.,This study was designed to assess the validity and reliability of the COPD-6 portable device to screen for COPD in non-specialized healthcare settings.,Prospective cohort study to validate a diagnostic test.,Three cohorts were recruited: primary care (PC), emergency services (ES) and community pharmacies (CPh).,Study population: individuals with risk factors for COPD (>40 years, smoking >10 pack-years, with respiratory symptoms).,The values measured using the COPD-6 were FEV1, FEV6 and the FEV1/FEV6 ratio.,Subsequently, participants underwent conventional spirometry at hospital, using a post-bronchodilator FEV1/FVC value <0.7 as the gold standard criterion for the COPD diagnosis.,437 participants were included, 362 were valid for the analysis.,COPD was diagnosed in 114 patients (31.5%).,The area under the ROC curve for the COPD-6 for COPD screening was 0.8.,The best cut-off point for the FEV1/FEV6 ratio was 0.8 (sensitivity, 92.1%) using spirometry with the bronchodilator test as the gold standard.,There were practically no differences in the COPD-6 performancein the different settings and also regarding age, gender and smoking status.,The COPD-6 device is a valid tool for COPD screening in non-specialized healthcare settings.,In this context, the best cut-off point for the FEV1/FEV6 ratio is 0.8. | 1 |
Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms. | 1 |
Inhaled bronchodilators are the cornerstone of treatment for chronic obstructive pulmonary disease (COPD).,Soft mist inhalers (SMIs) are devices that deliver bronchodilators.,Although correct device use is paramount to successful medication delivery, patient errors are common.,This global systematic literature review and meta-analysis examined device use errors with SMIs among patients with obstructive lung diseases.,PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify studies published between 2010 and 2019 that met the following inclusion criteria: (a) English language; (b) a diagnosis of COPD, bronchitis, or emphysema; and (c) reported device use errors among adults receiving long-acting bronchodilator treatment with Respimat® SMI (i.e.,Spiriva®, Stiolto®, Spiolto®, and Striverdi®).,Descriptive statistics examined sociodemographics, clinical characteristics, and device use errors.,Meta-analysis techniques were employed with random-effects models to generate pooled mean effect sizes and 95% confidence intervals (CIs) for overall and step-by-step errors.,The I 2 statistic measured heterogeneity.,Twelve studies (n = 1288 patients) were included in this meta-analysis.,Eighty-eight percent of patients had COPD, and most had moderate/very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease spirometric stages II to IV).,Aggregate results revealed that 58.9% (95% CI: 42.4-75.5; I 2 = 92.8%) of patients made ≥1 device use errors.,Among 11 studies with step-by-step data, the most common errors were failure to (1) exhale completely and away from the device (47.8% (95% CI: 33.6-62.0)); (2) hold breath for up to 10 seconds (30.6% (95% CI: 17.5-43.7)); (3) take a slow, deep breath while pressing the dose release button (27.9% (95% CI: 14.5-41.2)); (4) hold the inhaler upright (22.6% (95% CI: 6.2-39.0)); and (5) turn the base toward the arrows until it clicked (17.6% (95% CI: 3.0-32.2)).,Device use errors occurred in about 6 of 10 patients who used SMIs.,An individualized approach to inhalation device selection and ongoing training and monitoring of device use are important in optimizing bronchodilator treatment. | Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD).,The major objective of the management of these patients is the prevention and effective treatment of exacerbations.,Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy.,It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens.,In some patients, systemic corticosteroids are also indicated to improve symptoms.,In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence.,It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy.,Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition.,Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations.,Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations.,There is a need to design long-term studies to evaluate these interventions in the natural history of the disease.,The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions. | 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. | Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years.,This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients.,A four-center, open-label randomized controlled method was conducted.,A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine).,The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up.,A total of 306 patients completed the study fully.,The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306.,After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire.,There were no differences between the trial and control group in FVC, FEV1% and adverse events.,Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events.,This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406. | 1 |
Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD.,An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed.,Doubt has been cast on the role by observational studies.,The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.,We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS.,Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used.,Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL.,Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out.,Initial analysis included all studies of ICS vs. any non-ICS regimen.,Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators.,Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients.,Eleven studies (25,881 patients) were post-hoc analyses of RCTs.,Five studies (109,704 patients) were retrospective observational studies.,The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78).,No association was found in four out of five observational studies.,This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds.,Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed.,The lack of association found in the observational studies questions the relevance of these observations to a “real world” COPD population.,To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
More advanced knowledge is needed on how COPD alters the clinical presentation of obstructive sleep apnea (OSA) and how the association of both diseases, known as ‘overlap syndrome’ (OVS), impacts on cardiovascular health.,To investigate differences between patients with OVS and those with moderate-to-severe OSA alone.,A cross-sectional study conducted in the French National Sleep Apnea Registry between January 1997 and January 2017.,Univariable and multivariable logistic regression models were used to compare OVS versus OSA alone on symptoms and cardiovascular health.,46,786 patients had moderate-to-severe OSA.,Valid spirometry was available for 16,466 patients: 14,368 (87%) had moderate-to-severe OSA alone and 2098 (13%) had OVS.,A lower proportion of OVS patients complained of snoring, morning headaches and excessive daytime sleepiness compared to OSA alone (median Epworth Sleepiness Scale score: 9 [interquartile range (IQR) 6-13] versus 10 (IQR 6-13), respectively; P <0.02).,Similarly, a lower proportion of OVS patients (35.6% versus 39.4%, respectively; P <0.01) experienced sleepiness while driving.,In contrast, 63.5% of the OVS population experienced nocturia compared to 58.0% of the OSA population (P<0.01).,Apnea hypopnea index (36 [25; 52] vs 33.1 [23.3; 50]), oxygen desaturation index (28 [15; 48] vs 25.2 [14; 45]) and mean nocturnal SaO2 (92 [90; 93.8] vs 93 [91.3; 94]) were significantly more altered in the OVS group.,Associated COPD had no effect on the prevalence of hypertension and stroke.,After controlling for main confounders, COPD severity was associated in a dose-response relationship with a higher prevalence of coronary heart disease, heart failure and peripheral arteriopathy.,In adults with moderate-to-severe OSA, OVS was minimally symptomatic, but exhibited higher odds for prevalent coronary heart disease, heart failure and peripheral arteriopathy. | Overlap syndrome (OVS) is the concurrence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), and is associated with poor outcomes.,We hypothesized that physiological changes in COPD may affect the pathogenesis of OSA in important ways.,We therefore sought to measure the anatomical and nonanatomical OSA traits in individuals with OVS and compare to those with OSA alone.,Patients with established OVS were recruited, along with age, gender, and BMI matched OSA only controls.,Smoking and relevant comorbidities or medications were excluded.,Subjects underwent baseline polysomnography followed by an overnight physiological research study to measure the OSA traits (Veupnea, Varousal, Vpassive, Vactive, and loop gain).,Fifteen subjects with OVS and 15 matched controls with OSA alone were studied (overall 66 ± 8 years, 20% women, BMI 31 ± 4 kg/m2, apnea‐hypopnea index 49 ± 36/hr).,Mixed‐modeling was used to incorporate each measurement (range 52-270 measures/trait), and account for age, gender, and BMI.,There were no significant differences in the traits between OVS and OSA subjects, although OVS subjects potentially tolerated a lower ventilation before arousal (i.e., harder to wake; p = .06).,Worsened lung function was significantly associated with worsened upper airway response and more unstable breathing (p < .05 for all).,Consistent differences in key OSA traits were not observed between OVS and OSA alone.,However, worse lung function does appear to exert an influence on several OSA traits.,These findings indicate that a diagnosis of OVS should not generally influence the approach to OSA, but that lung function might be considered if utilizing OSA trait‐specific treatment.,This is the first study to comprehensively measure both anatomical and non‐anatomical OSA traits during sleep in those with COPD + OSA (Overlap syndrome) and compare them to those with OSA alone.,No consistent differences were found between the two groups, while worsened lung function did impact upper airway function and control of breathing.,These findings have implications towards mechanisms underlying OSA, as well as management of sleep apnea. | 1 |
Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy.,We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population.,In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190- -30 HU; skeletal muscle -29-150 HU.,Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03).,Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength.,Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72-0.95).,Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes.,CT-based skeletal muscle adiposity markers reflect muscle quality in COPD and help identify patients with fibre shifthttp://ow.ly/xolWA | The influence of gender on the expression of COPD has received limited attention.,Quality of Life (QoL) has become an important outcome in COPD patients.,The aim of our study was to explore factors contributing to gender differences in Quality of Life of COPD patients.,In 146 men and women with COPD from a pulmonary clinic we measured: Saint George's Respiratory Questionnaire (SGRQ), age, smoking history, PaO2, PaCO2, FEV1, FVC, IC/TLC, FRC, body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC), degree of comorbidity (Charlson index) and exacerbations in the previous year.,We explored differences between genders using Mann-Whitney U-rank test.,To investigate the main determinants of QoL, a multiple lineal regression analysis was performed using backward Wald's criteria, with those variables that significantly correlated with SGRQ total scores.,Compared with men, women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01, symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p = 0.01).,SGRQ total scores correlated in men with: FEV1% (-0.378, p < 0.001), IC/TLC (-0.368, p = 0.002), PaO2 (-0.379, p = 0.001), PaCO2 (0.256, p = 0.05), 6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index (0.380, p = 0.001) and MMRC (0.654, p < 0.001).,In women, the scores correlated only with FEV1% (-0.293, p = 0.013) PaO2 (-0.315, p = 0.007), exacerbations (0.290, p = 0.013) and MMRC (0.628, p < 0.001).,Regression analysis (B, 95% CI) showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8), IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women manifested the highest independent associations with SGRQ scores.,In moderate to severe COPD patients attending a pulmonary clinic, there are gender differences in health status scores.,In turn, the clinical and physiological variables independently associated with those scores differed in men and women.,Attention should be paid to the determinants of QoL scores in women with COPD. | 1 |
Transforming growth factor (TGF)-β is an evolutionarily conserved pleiotropic factor that regulates a myriad of biological processes including development, tissue regeneration, immune responses, and tumorigenesis.,TGF-β is necessary for lung organogenesis and homeostasis as evidenced by genetically engineered mouse models.,TGF-β is crucial for epithelial-mesenchymal interactions during lung branching morphogenesis and alveolarization.,Expression and activation of the three TGF-β ligand isoforms in the lungs are temporally and spatially regulated by multiple mechanisms.,The lungs are structurally exposed to extrinsic stimuli and pathogens, and are susceptible to inflammation, allergic reactions, and carcinogenesis.,Upregulation of TGF-β ligands is observed in major pulmonary diseases, including pulmonary fibrosis, emphysema, bronchial asthma, and lung cancer.,TGF-β regulates multiple cellular processes such as growth suppression of epithelial cells, alveolar epithelial cell differentiation, fibroblast activation, and extracellular matrix organization.,These effects are closely associated with tissue remodeling in pulmonary fibrosis and emphysema.,TGF-β is also central to T cell homeostasis and is deeply involved in asthmatic airway inflammation.,TGF-β is the most potent inducer of epithelial-mesenchymal transition in non-small cell lung cancer cells and is pivotal to the development of tumor-promoting microenvironment in the lung cancer tissue.,This review summarizes and integrates the current knowledge of TGF-β signaling relevant to lung health and disease. | Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover.,Recently, activation of the WNT/β-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases.,We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of β-catenin in fibroblast phenotype and function.,We assessed the expression of WNT-pathway genes and the functional role of β-catenin, using MRC-5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD.,Pulmonary fibroblasts expressed mRNA of genes required for WNT signaling.,Stimulation of fibroblasts with TGF-β1, a growth factor important in COPD pathogenesis, induced WNT-5B, FZD8, DVL3 and β-catenin mRNA expression.,The induction of WNT-5B, FZD6, FZD8 and DVL3 mRNA by TGF-β1 was higher in fibroblasts of individuals with COPD than without COPD, whilst basal expression was similar.,Accordingly, TGF-β1 activated β-catenin signaling, as shown by an increase in transcriptionally active and total β-catenin protein expression.,Furthermore, TGF-β1 induced the expression of collagen1α1, α-sm-actin and fibronectin, which was attenuated by β-catenin specific siRNA and by pharmacological inhibition of β-catenin, whereas the TGF-β1-induced expression of PAI-1 was not affected.,The induction of transcriptionally active β-catenin and subsequent fibronectin deposition induced by TGF-β1 were enhanced in pulmonary fibroblasts from individuals with COPD.,β-catenin signaling contributes to ECM production by pulmonary fibroblasts and contributes to myofibroblasts differentiation.,WNT/β-catenin pathway expression and activation by TGF-β1 is enhanced in pulmonary fibroblasts from individuals with COPD.,This suggests an important role of the WNT/β-catenin pathway in regulating fibroblast phenotype and function in COPD. | 1 |
Symptomatic relief is an important treatment goal for patients with COPD.,To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines.,The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need.,The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation.,The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.,This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international).,Subjects completed the E-RS as part of a daily eDiary.,Tests of reliability, validity, and responsiveness were conducted in each dataset.,In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74).,RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV1% predicted (−0.19, −0.14, −0.15); St.,George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests.,Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity.,RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001).,RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001).,Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.,Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.,MPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516,The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users. | Dyspnoea is a debilitating and distressing symptom that is reflected in different verbal descriptors.,Evidence suggests that dyspnoea, like pain perception, consists of sensory quality and affective components.,The objective of this study was to develop an instrument that measures overall dyspnoea severity using descriptors that reflect its different aspects.,81 dyspnoea descriptors were administered to 123 patients with chronic obstructive pulmonary disease (COPD), 129 with interstitial lung disease and 106 with chronic heart failure.,These were reduced to 34 items using hierarchical methods.,Rasch analysis informed decisions regarding further item removal and fit to the unidimensional model.,Principal component analysis (PCA) explored the underlying structure of the final item set.,Validity and reliability of the new instrument were further assessed in a separate group of 53 patients with COPD.,After removal of items with hierarchical methods (n = 47) and items that failed to fit the Rasch model (n = 22), 12 were retained.,The “Dyspnoea-12” had good internal reliability (Cronbach’s alpha = 0.9) and fit to the Rasch model (χ2 p = 0.08).,Items patterned into two groups called “physical”(n = 7) and “affective”(n = 5).,In the separate validation study, Dyspnoea-12 correlated with the Hospital Anxiety and Depression Scale (anxiety r = 0.51; depression r = 0.44, p<0.001, respectively), 6-minute walk distance (r = −0.38, p<0.01) and MRC (Medical Research Council) grade (r = 0.48, p<0.01), and had good stability over time (intraclass correlation coefficient = 0.9, p<0.001).,Dyspnoea-12 fulfills modern psychometric requirements for measurement.,It provides a global score of breathlessness severity that incorporates both “physical” and “affective” aspects, and can measure dyspnoea in a variety of diseases. | 1 |
Dyspnea is a predictor of mortality.,The effects of dyspnea severity and changes in dyspnea status on all-cause and cause-specific mortality remain unclear.,The Vlagtwedde/Vlaardingen study started in 1965 and subjects were re-examined every 3 years until 1989/1990.,Vital status of all 8,465 subjects on December 31st, 2008 was assessed.,Associations between mortality and dyspnea severity and changes in dyspnea status were investigated using Cox regression adjusted for gender, age, FEV1 %predicted, place of residence, smoking and BMI.,After 43 years of follow-up, 2,883 (39 %) of 7,360 subjects examined for dyspnea severity had died, 1,386 (19 %) due to cardiovascular disease, 267 (4 %) due to chronic obstructive pulmonary disease (COPD).,Subjects with moderate and severe dyspnea had increased all-cause and cardiovascular mortality [moderate: HR = 1.3 (95 % CI 1.2-1.5) and 1.4 (1.1-1.6), severe: 1.5 (1.1-2.0) and 1.9 (1.3-2.6) respectively] compared to asymptomatics.,Severe dyspnea was significantly associated with COPD mortality [3.3 (2.0-5.2)].,Subjects who lost dyspnea had hazard ratios for all-cause and cause-specific mortality comparable to asymptomatics.,Persistent dyspnea and dyspnea development were risk factors for all-cause, cardiovascular and COPD mortality [persistent: 2.0 (1.4-2.8), 1.9 (1.2-3.3) and 3.3 (1.2-8.9), development: 1.5 (1.2-1.8), 2.0 (1.5-2.6) and 3.8 (2.3-6.3) respectively].,Additionally, dyspnea effects on mortality were more pronounced in overweight/obese and older subjects and in subjects with better lung function.,These results show that dyspnea is associated with mortality in a severity-dependent manner.,Furthermore this study is the first showing that dyspnea remission normalizes mortality risk.,Having or developing dyspnea is a risk factor for mortality.,The online version of this article (doi:10.1007/s10654-012-9736-0) contains supplementary material, which is available to authorized users. | The aims of this study were: (1) to compare the discriminative ability of a disease-specific instrument, the St.,George's Respiratory Questionnaire (SGRQ) to generic instruments (i.e., EQ-5D and SF-36); and (2), to evaluate the strength of associations among clinical and health-related quality of life (HRQL) measures in chronic obstructive pulmonary disease (COPD).,We analyzed data collected from 120 COPD patients in a Veterans Affairs hospital.,Patients self-completed two generic HRQL measures (EQ-5D and SF-36) and the disease-specific SGRQ.,The ability of the summary scores of these HRQL measures to discriminate COPD disease severity based on Global Obstructive Lung Disease (GOLD) stage was assessed using relative efficiency ratios (REs).,Strength of correlation was used to further evaluate associations between clinical and HRQL measures.,Mean total scores for PCS-36, EQ-VAS and SGRQ were significantly lower for the more severe stages of COPD (p < 0.05).,Using SGRQ total score as reference, the summary scores of the generic measures (PCS-36, MCS-36, EQ index, and EQ-VAS) all had REs of <1.,SGRQ exhibited a stronger correlation with clinical measures than the generic summary scores.,For instance, SGRQ was moderately correlated with FEV1 (r = 0.43), while generic summary scores had trivial levels of correlation with FEV1 (r < 0.2).,The SGRQ demonstrated greater ability to discriminate among different levels of severity stages of COPD than generic measures of health, suggestive that SGRQ may provide COPD studies with greater statistical power than EQ-5D and SF-36 summary scores to capture meaningful differences in clinical severity. | 1 |
Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome.,In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation.,RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1β (IL-1β), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry.,NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1β in RAW 264.7 cells.,The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC.,CSE and DEPs increased the secretion of IL-1β in lung tissues from both the normal and elastase-induced emphysema groups.,The secretion of IL-1β by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05).,NAC inhibited CSE- and DEP-induced IL-1β secretion in both the normal and elastase-induced emphysema groups.,NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC.,The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC. | Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented.,However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited.,Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons.,We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002).,Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects.,No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA.,Co-occurrence analysis suggests the presence of networks of co-occurring bacteria.,Four communities of positively correlated bacteria were revealed.,The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype.,Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells.,This might result in a changed interplay with the host immune system. | 1 |
Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD).,However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear.,PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers.,The HDAC2 and NF-κB p65 expression were quantified by Western Blot.,HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit.,Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA.,HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers.,Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers.,The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients.,Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers.,HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity.,The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation.,Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function. | Dysfunctional innate responses of alveolar macrophages to nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae contribute to morbidity in chronic obstructive pulmonary disease (COPD).,Our earlier studies discovered impaired COPD alveolar macrophage responses to Toll-like receptor (TLR) ligands of nontypeable H. influenzae and provide rationale for further evaluation of TLR signaling.,While the role of TLR single nucleotide polymorphisms is increasingly recognized in inflammatory diseases, TLR single nucleotide polymorphisms in COPD have only recently been explored.,We hypothesized that specific TLR polymorphisms are associated with dysfunctional innate immune COPD alveolar macrophage responses and investigated polymorphisms of TLR2(Arg753Gln), TLR4(Thr399Ile; Asp299Gly), and TLR9(T1486C; T1237C).,DNA was purified from cells of 1) healthy nonsmokers (n = 20); 2) COPD ex-smokers (n = 83); 3) COPD active smokers (n = 93).,DNA amplifications (polymerase chain reaction) were performed for each SNP.,Alveolar macrophages from each group were incubated with nontypeable H. influenzae, M. catarrhalis and S. pneumoniae.,Cytokine induction of macrophage supernatants was measured and the association with TLR single nucleotide polymorphism expression was determined.,No significant inter-group differences in frequency of any TLR SNP existed.,However both TLR9 single nucleotide polymorphisms were expressed in high frequency.,Among COPD ex-smokers, diminished IL-8 responsiveness to nontypeable H. influenzae, M. catarrhalis and S. pneumoniae was strongly associated with carriage of TLR9(T1237C) (p = 0.02; p = 0.008; p = 0.02), but not TLR9(T1486C).,Carriage of TLR9(T1237C), but not TLR9(T1486C), correlated with diminished FEV1%predicted (p = 0.037).,Our results demonstrate a notable association of TLR9(T1237C) expression with dysfunctional innate alveolar macrophage responses to respiratory pathogens and with severity of COPD. | 1 |
The objective of this study was to determine if gene-environment interactions between cigarette smoking and interleukin-6 (IL6), interferon-γ (IFNG), interleukin-1β (IL1B), or interleukin-1 receptor antagonist (IL1RN) single nucleotide polymorphisms are associated with lung function decline and cardiovascular disease in chronic obstructive pulmonary disease (COPD).,Single nucleotide polymorphisms (SNPs) in IL6, IFNG, IL1B, and IL1RN were genotyped in the Lung Health Study and correlated with rate of decline of forced expiratory volume in 1 second (FEV1) over 5 years, baseline FEV1, serum protein levels, cardiovascular disease, and interactions with smoking.,The IL6 rs2069825 single nucleotide polymorphism was associated with the rate of decline of prebronchodilator FEV1 (P = 0.049), and was found to have a significant interaction (P = 0.004) with mean number of cigarettes smoked per day.,There was also a significant interaction of IFNG rs2069727 with smoking on prebronchodilator (P = 0.008) and postbronchodilator (P =0.01) FEV1.,The IL6 polymorphism was also associated with cardiovascular disease in heterozygous individuals (P = 0.044), and was found to have a significant interaction with smoking (P = 0.024).,None of the genetic variants were associated with their respective serum protein levels.,The results suggest interactions of IL6 rs2069825 and IFNG rs2069727 single nucleotide polymorphisms with cigarette smoking on measures of lung function.,The IL6 rs2069825 single nucleotide polymorphism also interacted with smoking to affect the risk of cardiovascular disease in COPD patients. | Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD).,To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD.,The aim of this study was to examine the association between haplotypes of CRP, IL6 and FGB genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition).,Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers.,Plasma levels of CRP, IL-6 and FG were measured in the total study group.,Differences in haplotype distributions were tested using the global and haplotype-specific statistics.,Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients.,However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile).,Global test for haplotype effect indicated association of CRP gene and CRP plasma levels (P = 0.0004) and IL6 gene and COPD (P = 0.003).,Subsequent analysis has shown that IL6 haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005).,None of the genes were associated with COPD-related phenotypes.,Our findings suggest that common genetic variation in CRP and IL6 genes may contribute to heterogeneity of COPD population associated with systemic inflammation. | 1 |
To investigate the cost-effectiveness of a chronic obstructive pulmonary disease (COPD) disease management (COPD-DM) programme in primary care, called RECODE, compared to usual care.,A 2-year cluster-randomised controlled trial.,40 general practices in the western part of the Netherlands.,1086 patients with COPD according to GOLD (Global Initiative for COPD) criteria.,Exclusion criteria were terminal illness, cognitive impairment, alcohol or drug misuse and inability to fill in Dutch questionnaires.,Practices were included if they were willing to create a multidisciplinary COPD team.,A multidisciplinary team of caregivers was trained in motivational interviewing, setting up individual care plans, exacerbation management, implementing clinical guidelines and redesigning the care process.,In addition, clinical decision-making was supported by feedback reports provided by an ICT programme.,We investigated the impact on health outcomes (quality-adjusted life years (QALYs), Clinical COPD Questionnaire, St.,George's Respiratory Questionnaire and exacerbations) and costs (healthcare and societal perspective).,The intervention costs were €324 per patient.,Excluding these costs, the intervention group had €584 (95% CI €86 to €1046) higher healthcare costs than did the usual care group and €645 (95% CI €28 to €1190) higher costs from the societal perspective.,Health outcomes were similar in both groups, except for 0.04 (95% CI −0.07 to −0.01) less QALYs in the intervention group.,This integrated care programme for patients with COPD that mainly included professionally directed interventions was not cost-effective in primary care.,Netherlands Trial Register NTR2268. | Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems.,Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.,Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency.,Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database.,Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.,Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001).,The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs.,Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6).,Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.,Comorbidity burden determines elevated utilization for COPD patients.,Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients. | 1 |
It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies.,Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy.,Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up.,It would be advantageous to identify these patients over a shorter time period, especially in mild disease.,Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex- or never-smokers) either without spirometric COPD or with mild COPD.,Where possible, retrospective spirometry data were included.,Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.,Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline.,Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months.,Furthermore, there was no agreement between rate of decline from either 6 or 18 months’ data when compared to data collected over 3 years.,The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.,This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function.,There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity. | The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation.,We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.,Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits.,Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays.,Low-dose CT scans evaluated emphysema.,Sputum neutrophil % increased with GOLD stage.,There was a weak association between % sputum neutrophils and FEV1 % predicted (univariate r2 = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression).,Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre.,There were no associations between neutrophils and exacerbation rates or emphysema.,Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak.,The mean change over 1 year in neutrophil % was an increase of 3.5%.,Sputum neutrophil measurements in COPD are associated weakly with FEV1 % predicted and health status.,Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation. | 1 |
Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm.,C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD.,It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status.,This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care.,Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing.,Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes.,Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority.,Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation.,Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up.,A health economic evaluation and qualitative process evaluation will be carried out.,If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance.,PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD.,ISRCTN registry, ID: ISRCTN24346473.,Registered on 20 August 2014.,The online version of this article (doi:10.1186/s13063-017-2144-8) contains supplementary material, which is available to authorized users. | Increased prescribing of inhaled long-acting anti-muscarinic (LAMA) and combined inhaled long-acting β2-agonist and corticosteroid (LABA+ICS) drugs for the treatment of chronic obstructive pulmonary disease (COPD) has led to hopes of reduced hospital admissions from this disease.,To investigate the impact of rising primary care prescribing of LAMA and LABA+ICS drugs on COPD admissions.,This retrospective cohort study of general practice COPD admission and prescribing data between 2007 and 2010 comprised a representative group of 806 English general practices (population 5,264,506).,Outcome measures were practice rates of COPD patient admissions and prescription costs of LAMA and LABA+ICS.,General practice characteristics were based on the UK quality and outcomes framework.,Rates of COPD admissions remained stable from 2001 to 2010.,Practice-prescribing volumes of LAMA per practice patient and LABA+ICS per practice patient increased by 61 and 26%, respectively, between 2007 and 2010.,Correlation between costs of LAMA and those of LABA+ICS increased year on year, and was the highest in 2010 (Pearson’s r=0.68; 95% confidence interval (CI), 0.64-0.72).,Practice COPD admission rates were positively predicted by practice-prescribing volumes of LAMA (2010: B=1.23, 95% CI, 0.61-1.85) and of LABA+ICS (2010: B=0.32, 95% CI, 0.12-0.52) when controlling for practice list size, COPD prevalence and deprivation.,The increase in the prescribing of LAMA and LABA+ICS inhalers was not associated with the predicted fall in hospital admission rates for COPD patients.,The positive correlation between high practice COPD prescribing and high practice COPD admissions was not explained. | 1 |
Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli.,More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs).,LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management.,Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres.,Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD.,The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings.,The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs.,This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings.,We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2).,To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2.,We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry.,We will report ROC areas, sensitivity and specificity.,Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs.,The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers.,The control group will receive COPD education and standard of care treatment provided by local health providers.,Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St.,George’s Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year.,The primary endpoint is SGRQ at 12 months.,Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated.,We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD.,This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings.,NCT03359915 (GECo1).,Registered on 2 December 2017 and NCT03365713 (GECo2).,Registered on 7 December 2017.,Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2).,The online version of this article (10.1186/s13063-018-2909-8) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | 1 |
The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries.,Using data from this survey we evaluated the economic impact of COPD.,This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology.,Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications.,Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale.,Combined direct and indirect costs estimated the total societal costs per patient.,The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs.,The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%.,Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities.,The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities.,Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | More than two-fifths of the world’s population uses solid fuels, mostly biomass, for cooking.,The resulting biomass smoke exposure is a major cause of chronic obstructive pulmonary disease (COPD) among women in developing countries.,To assess whether lower woodsmoke exposure from use of a stove with a chimney, compared to open fires, is associated with lower markers of airway inflammation in young women.,We carried out a cross-sectional analysis on a sub-cohort of participants enrolled in a randomized controlled trial in rural Guatemala, RESPIRE.,We recruited 45 indigenous women at the end of the 18-month trial; 19 women who had been using the chimney stove for 18-24 months and 26 women still using open fires.,We obtained spirometry and induced sputum for cell counts, gene expression of IL-8, TNF-α, MMP-9 and 12, and protein concentrations of IL-8, myeloperoxidase and fibronectin.,Exhaled carbon monoxide (CO) and 48-hr personal CO tubes were measured to assess smoke exposure.,MMP-9 gene expression was significantly lower in women using chimney stoves.,Higher exhaled CO concentrations were significantly associated with higher gene expression of IL-8, TNF-α, and MMP-9.,Higher 48-hr personal CO concentrations were associated with higher gene expression of IL-8, TNF- α, MMP-9 and MMP-12; reaching statistical significance for MMP-9 and MMP-12.,Compared to using an open wood fire for cooking, use of a chimney stove was associated with lower gene expression of MMP-9, a potential mediator of airway remodeling.,Among all participants, indoor biomass smoke exposure was associated with higher gene expression of multiple mediators of airway inflammation and remodeling; these mechanisms may explain some of the observed association between prolonged biomass smoke exposure and COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic airway inflammation and emphysema, and is caused by exposure to noxious particles or gases, e.g. cigarette smoke.,Smoking and oxidative stress lead to accelerated formation and accumulation of advanced glycation end products (AGEs), causing local tissue damage either directly or by binding the receptor for AGEs (RAGE).,This study assessed the association of AGEs or RAGE in plasma, sputum, bronchial biopsies and skin with COPD and lung function, and their variance between these body compartments.,Healthy smoking and never-smoking controls (n = 191) and COPD patients (n = 97, GOLD stage I-IV) were included.,Autofluorescence (SAF) was measured in the skin, AGEs (pentosidine, CML and CEL) and sRAGE in blood and sputum by ELISA, and in bronchial biopsies by immunohistochemistry. eQTL analysis was performed in bronchial biopsies.,COPD patients showed higher SAF values and lower plasma sRAGE levels compared to controls and these values associated with decreased lung function (p <0.001; adjusting for relevant covariates).,Lower plasma sRAGE levels significantly and independently predicted higher SAF values (p < 0.001).,One SNP (rs2071278) was identified within a region of 50 kB flanking the AGER gene, which was associated with the gene and protein expression levels of AGER and another SNP (rs2071278) which was associated with the accumulation of AGEs in the skin.,In COPD, AGEs accumulate differentially in body compartments, i.e. they accumulate in the skin, but not in plasma, sputum and bronchial biopsies.,The association between lower sRAGE and higher SAF levels supports the hypothesis that the protective mechanism of sRAGE as a decoy-receptor is impaired in COPD.,The online version of this article (doi:10.1186/s12931-016-0363-2) contains supplementary material, which is available to authorized users. | 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 |
In the combined use of bronchodilators of different classes, ie, long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), bronchodilation is obtained both directly, through LABA-mediated stimulation of β2-adrenergic receptors, and indirectly, through LAMA-mediated inhibition of acetylcholine action at muscarinic receptors.,The clinical trial data for LABAs/LAMAs in the treatment of chronic obstructive pulmonary disease (COPD) continue to be promising, and these combinations will provide the convenience of delivering the two major bronchodilator classes, recommended as first-line maintenance options in COPD treatment guidelines.,COPD is a complex condition that has pulmonary and extrapulmonary manifestations.,These clinical manifestations are highly variable, and several are associated with different responses to currently available therapies.,The concept of a COPD phenotype is rapidly evolving from one focusing on the clinical characteristics to one linking the underlying biology to the phenotype of the disease.,Identification of the peculiarities of the different COPD phenotypes will permit us to implement a more personalized treatment in which the patient’s characteristics, together with his or her genotype, will be key to choosing the best treatment option.,At present in Japan, fixed combinations of inhaled corticosteroids (ICSs) and LABAs are frequently prescribed in the earlier stages of COPD.,However, ICSs increase the risk of pneumonia.,Notably, 10%-30% of patients with COPD with or without a history of asthma have persistent circulating and airway eosinophilia associated with an increased risk of exacerbations and sensitivity to steroids.,Thus, sputum or blood eosinophil counts might identify a subpopulation in which ICSs could have potentially deleterious effects as well as a subpopulation that benefits from ICSs.,In this review, I propose one plausible approach to position ICSs and LABAs/LAMAs in clinical practice, based on both the extent of airflow obstruction and the presence of an asthma component or airway eosinophilic inflammation.,This approach is a tentative move toward personalized treatment for COPD patients, and with progress in knowledge and developments in physiology, lung imaging, medical biology, and genetics, identification of COPD phenotypes that provide prognostic and therapeutic information that can affect clinically meaningful outcomes is an urgent medical need. | 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 |
To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease.,The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality.,The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number.,The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure.,The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions.,Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels.,The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization.,The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013.,Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years.,Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups.,Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions).,From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%.,Mean age at diagnosis was 66 years and 52.0% were male.,Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81-0.85) for GOLD A to 2.51 (95% CI: 2.47-2.55) for GOLD D.,General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74-4.93) for GOLD A to 7.44 (95% CI: 7.31-7.61) for GOLD D.,COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84).,Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits.,Better patient management to stabilize the disease progression could allow for an improvement in exacerbation frequency and a reduction in health care resource utilization. | 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 |
Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear.,Induced sputum was obtained from adults with COPD (n = 22), and healthy controls (n = 29) and was processed for differential cell counts.,The sputum supernatant was assayed for innate immune mediators using ELISA, whilst sputum gene expression was measured using real-time PCR.,Peripheral blood neutrophils were isolated and their response to lipopolysaccaride (LPS) stimulation was assessed in a subgroup of participants with COPD (n = 13) and healthy controls (n = 21).,Participants with COPD had significantly higher protein levels of interleukin (IL)-8, and neutrophil elastase (NE) and detection of oncostatin M (OSM) compared to healthy controls.,Gene expression for toll-like receptor (TLR) 2, IL-8 and OSM were also significantly higher in COPD participants.,The level of IL-1β, surfactant protein (SP)-A, matrix metalloproteinase (MMP)-9 and TLR4 mRNA was not significantly different between groups.,The level of innate immune response markers were highly associated with the presence of sputum neutrophils, each other and the degree of airflow limitation (FEV1/FVC).,Peripheral blood neutrophils from participants with COPD had an increased response to stimulation by LPS; with a greater fold increase in the production of IL-8 and MMP-9 protein, and gene expression of IL-8, TLR2 and TLR4.,The innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis. | The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation.,We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.,Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits.,Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays.,Low-dose CT scans evaluated emphysema.,Sputum neutrophil % increased with GOLD stage.,There was a weak association between % sputum neutrophils and FEV1 % predicted (univariate r2 = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression).,Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre.,There were no associations between neutrophils and exacerbation rates or emphysema.,Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak.,The mean change over 1 year in neutrophil % was an increase of 3.5%.,Sputum neutrophil measurements in COPD are associated weakly with FEV1 % predicted and health status.,Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation. | 1 |
Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required. | Smoking activates and recruits inflammatory cells and proteases to the airways.,Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema.,However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown.,We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago.,39 COPD outpatients - smokers (n = 22) and ex-smokers (n = 17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups.,IS and BAL samples were obtained for differential and MMP-12+-macrophages count analysis.,The number of IS neutrophils was higher in both COPD groups compared to both controls.,The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers.,The number of BAL MMP-12+-macrophages was higher in COPD smokers (1.6 ± 0.3 × 106/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9 ± 0.4, 0.4 ± 0.2, 0.2 ± 0.1 × 106/ml respectively, p < 0.05).,The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation.,Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients. | 1 |
Pulmonary hypertension (PH) in patients with COPD is associated with reduced exercise capacity.,A subgroup of COPD patients has normal mean pulmonary artery pressure (mPAP) at rest, but develops high mPAP relative to cardiac output (CO) during exercise, a condition we refer to as exercise-induced pulmonary hypertension (EIPH).,We hypothesized that COPD patients with EIPH could be identified by cardiopulmonary exercise test (CPET) and that these patients have lower exercise capacity and more abnormal CPET parameters compared to COPD patients with normal hemodynamic exercise response.,Ninety-three stable outpatients with COPD underwent right heart catheterization with the measurement of mPAP, CO, and capillary wedge pressure at rest and during supine exercise.,Resting mPAP <25 mmHg with ΔmPAP/ΔCO slope above or below 3 mmHg/L/min were defined as COPD-EIPH and COPD-normal, respectively.,Pulmonary function tests and CPET with arterial blood gases were performed.,Linear mixed models were fitted to estimate differences between the groups with adjustment for gender, age, and airflow obstruction.,EIPH was observed in 45% of the study population.,Maximal workload was lower in COPD-EIPH compared to COPD-normal, whereas other CPET measurements at peak exercise in % predicted values were similar between the two groups.,After adjustment for gender, age, and airflow obstruction, patients with COPD-EIPH showed significantly greater increase in oxygen uptake, ventilation, respiratory frequency, heart rate, and lactate with increasing work load, as well as more reduction in pH compared to those with normal hemodynamic responses.,COPD-EIPH could not be discriminated from COPD-normal by CPET.,However, COPD-EIPH experienced a higher cost of exercise in terms of higher oxygen uptake, ventilation, respiratory frequency, heart rate, and lactate for a given increase in workload compared to COPD-normal. | COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation.,Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease.,We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response.,Patients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA<− 950), small airways disease (E/I MLD) and bronchial wall thickening (Pi10).,At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR.,122 subjects were included in this analysis.,Emphysema and small airways disease had independent associations with airflow obstruction (β = − 0.34, p < 0.001 and β = − 0.56, p < 0.001).,%LAA<− 950 had independent associations with gas transfer (β = − 0.37, p < 0.001) and E/I MLD with RV/TLC (β = 0.30, p =0.003).,The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (β = 0.73, p < 0.001).,Pi10 did not show any independent associations with lung function or functional parameters.,No CT parameters had any associations with sputum inflammatory cells.,Greater emphysema was associated with lower levels of systemic inflammation (CRP β = − 0.34, p < 0.001 and fibrinogen β = − 0.28, p =0.003).,There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not.,This study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status.,In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.,The online version of this article (10.1186/s12931-018-0734-y) contains supplementary material, which is available to authorized users. | 1 |
Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD.,This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of “fixed triple” (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form “open triple” combinations.,Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium.,Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio.,Furthermore, triple therapy showed a promising signal in terms of improved survival.,The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia.,Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap. | Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden.,Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study.,Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg.,FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study.,Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs.,Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%).,Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs.,32.7%).,Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs.,£763.32 and £749.22 vs.,£988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs.,£1,267.45).,This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol.,ClinicalTrials.gov number: NCT02345161.,GSK,The online version of this article (doi:10.1007/s12325-017-0604-x) contains supplementary material, which is available to authorized users. | 1 |
Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users. | Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | 1 |
Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited.,The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass.,Eighty‐one COPD patients with low muscle mass, admitted to out‐patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega‐3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training.,The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid.,Intention‐to‐treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048).,After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001).,Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (−18%,P = 0.005).,High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction.,Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo. | Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people.,The relevance of frailty to chronic respiratory disease and its management is unknown.,To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation.,816 outpatients with COPD (mean (SD) age 70 (10) years, FEV1% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015.,Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation.,Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex.,209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail.,Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01).,Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission.,However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001).,After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty.,Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion.,However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term. | 1 |
Although chronic obstructive pulmonary disease (COPD) is regarded as a chronic inflammatory lung disease, the disease mechanism is still not known.,Intriguingly, aging lungs are quite similar to COPD-affected lungs in many ways, and COPD has been viewed as a disease of accelerated premature aging of the lungs.,In this paper, based on a literature review, we would like to propose immunosenescence, age-associated decline in immunity, as a critical mechanism for the development of COPD.,Immunosenescence can cause a low-grade, systemic inflammation described as inflammaging.,This inflammaging may be directly involved in the COPD pathogenesis.,The potential contributors to the development of inflammaging in the lungs possibly leading to COPD are discussed in the review paper.,A notable fact about COPD is that only 15% to 20% of smokers develop clinically significant COPD.,Given that there is a substantial inter-individual variation in inflammaging susceptibility, which is genetically determined and significantly affected by the history of the individual's exposure to pathogens, immunosenescence and inflammaging may also provide the answer for this unexpectedly low susceptibility of smokers to clinically significant COPD. | Chronic obstructive pulmonary disease (COPD) is characterized by continuous flow limitation and the immune system including macrophages and regulatory T lymphocytes (Tregs) is involved in COPD pathogenesis.,In our previous study, we investigated that TGF-β/BAMBI pathway was associated with COPD by regulating the balance of Th17/Treg.,However, the role of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a pseudoreceptor of TGF-β signalling pathway, in regulating the immune system of COPD patients has not been fully studied.,Hence, we speculate that the pseudoreceptor BAMBI may play roles in the regulation of M2 macrophages to induce the differentiation of CD4+ naïve T cells into Tregs and influence the immune response in COPD.,Peripheral blood mononuclear cells (PBMCs) were isolated from healthy nonsmokers (n = 12), healthy smokers (n = 10) and COPD patients (n = 20).,Naïve CD4+ T cells and monocytes-induced macrophages were used for coculture assays.,The phenotypic characteristics of macrophages and Tregs were determined by flow cytometry.,The expression levels of BAMBI and the TGF-β/Smad pathway members in M2 macrophages were measured by a Western blot analysis.,The monocyte-derived macrophages were stimulated with cigarette smoke extract (CSE, concentration of 0.02%) to simulate the smoking process in humans. pCMV-BAMBI was transfected into monocyte-derived M2 macrophages for subsequent co-culture assays and signalling pathway analysis.,Our results showed that M2 macrophages could induce the differentiation of Tregs through the TGF-β/Smad signalling pathway.,In addition, monocyte-derived macrophages from COPD patients highly expressed BAMBI, and had a low capacity to induce Tregs differentiation.,The expression of BAMBI and the forced expiratory volume in 1 second (FEV1%) were negatively correlated in COPD.,Furthermore, overexpression of BAMBI promoted the conversion of M2 macrophages to M1 macrophages via the TGF-β/Smad pathway.,We demonstrated that BAMBI could promote the polarization process of M2 macrophages to M1 macrophages via the TGF-β/Smad signalling pathway and that overexpression of BAMBI could decrease the ability of M2 macrophages to induce Treg differentiation.,These findings may provide a potential mechanism by which blocking BAMBI could improve immune function to regulate COPD inflammatory conditions. | 1 |
A growing number of studies clearly demonstrate a substantial association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD), although little is known about the shared genetics that contribute to this association.,We conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (Ncase = 12,550, Ncontrol = 46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) (N = 458,969), high blood pressure (HBP) (Ncase = 144,793, Ncontrol = 313,761), coronary artery disease (CAD)(Ncase = 60,801, Ncontrol = 123,504), and stroke (Ncase = 40,585, Ncontrol = 406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data.,RHR and HBP had modest genetic correlation, and CAD had borderline evidence with COPD at a genome-wide level.,We found evidence of local genetic correlation with particular regions of the genome.,Cross-trait meta-analysis of COPD identified 21 loci jointly associated with RHR, 22 loci with HBP, and 3 loci with CAD.,Functional analysis revealed that shared genes were enriched in smoking-related pathways and in cardiovascular, nervous, and immune system tissues.,An examination of smoking-related genetic variants identified SNPs located in 15q25.1 region associated with cigarettes per day, with effects on RHR and CAD.,A Mendelian randomization analysis showed a significant positive causal effect of COPD on RHR (causal estimate = 0.1374, P = 0.008).,In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.,The online version of this article (10.1186/s12931-019-1036-8) contains supplementary material, which is available to authorized users. | Although studies have shown that chronic obstructive pulmonary disease (COPD) and hypertension are linked as comorbidities, it remains unclear whether COPD is independently associated with the risk of hypertension or is caused by common risk factors such as age and smoking.,The objective of this study was to investigate the relationship between COPD and hypertension by using nationally representative data.,This cross-sectional study analyzed data from the Korea National Health and Nutrition Examination Survey V conducted during 2010 to 2012.,Hypertension was defined as a mean systolic blood pressure ≥ 140 mm Hg and/or a diastolic blood pressure ≥ 90 mm Hg, or current consumption of antihypertensive medications.,A diagnosis of COPD was defined as a smoking history of at least 10 pack-years with airflow limitation on spirometry.,Multivariate logistic regression was performed to investigate the independent association between COPD and hypertension after adjusting for covariates.,Survey design analyses were conducted for all analyses.,Among 4043 men (aged ≥ 40 years) who underwent spirometry, 2190 (54.2%) had hypertension.,Even after adjusting for age, body mass index, smoking status, diabetes, metabolic syndrome, and stroke, COPD was independently associated with hypertension (adjusted odds ratio, 1.71; 95% confidence interval, 1.37-2.13; P < .001).,Adjusted pulse pressure significantly increased as the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity and FEV1 decreased.,COPD is independently associated with hypertension, and this could explain the link between the risk of cardiovascular diseases and COPD. | 1 |
Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD).,However, choice of parameters and score complexity restrict clinical applicability.,Our aim was to provide and validate a simplified COPD risk index independent of lung function.,The PROMISE study (n=530) was used to develop a novel prognostic index.,Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality.,External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).,Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C.,It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05).,Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively).,External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).,The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk.,The B-AE-D indices allow a simple and accurate assessment of COPD-related risk in the absence of lung functionhttp://ow.ly/XFBox | Identifying those patients who underperform in the 6-minute walk test (6MWT <350 m), and the reasons for their poor performance, is a major concern in the management of chronic obstructive pulmonary disease.,To explore the accuracy and relevance of the 4-m gait-speed (4MGS) test, and the 5-repetition sit-to-stand (5STS) test, as diagnostic markers, and clinical determinants, of poor performance in the 6MWT.,We recruited 137 patients with stable chronic obstructive pulmonary disease to participate in our cross-sectional study.,Patients completed the 4MGS and 5STS tests, with quantitative (in seconds) and qualitative ordinal data collected; the latter were categorized using a scale of 0 to 4.,The following potential covariates and clinical determinants of poor 6MWT were collated: age, quadriceps muscle-strength (QMS), health status, dyspnea, depression, and airflow limitation.,Area under the receiver-operating characteristic curve data (AUC) was used to assess accuracy, with logistic regression used to explore relevance as clinical determinants.,The AUCs generated using the 4MGS and 5STS tests were comparable, at 0.719 (95% confidence interval [CI] 0.629-0.809) and 0.711 (95% CI 0.613-0.809), respectively.,With ordinal data, the 5STS test was most accurate (AUC of 0.732; 95% CI 0.645-0.819); the 4MGS test showed poor discriminatory power (AUC <0.7), although accuracy improved (0.726, 95% CI 0.637-0.816) when covariates were included.,Unlike the 4MGS test, the 5STS test provided a significant clinical determinant of a poor 6MWT (odds ratio 1.23, 95% CI 1.05-1.44).,The 5STS test reliably predicts a poor 6MWT, especially when using ordinal data.,Used alone, the 4MGS test is reliable when measured with continuous data. | 1 |
Smoke exposure is known to decrease total pulmonary surfactant and alter its composition, but the role of surfactant in chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to analyze the compositional changes in the surfactant lipidome in COPD and identify specific lipids associated with pulmonary function decline.,Bronchoalveolar lavage (BAL) fluid was obtained from 12 former smokers with COPD and 5 non-smoking, non-asthmatic healthy control volunteers.,Lipids were extracted and analyzed by liquid chromatography and mass spectrometry.,Pulmonary function data were obtained by spirometry, and correlations of lung function with lipid species were determined.,Wild-type C57BL/6 mice were exposed to 6 months of second-hand smoke in a full-body chamber.,Surfactant lipids were decreased by 60% in subjects with COPD.,All phospholipid classes were dramatically decreased, including ether phospholipids, which have not been studied in pulmonary surfactant.,Availability of phospholipid, cholesterol, and sphingomyelin in BAL strongly correlated with pulmonary function and this was attributable to specific lipid species of phosphatidylcholine with surface tension reducing properties, and of phosphatidylglycerol with antimicrobial roles, as well as to other less studied lipid species.,Mice exposed to smoke for six months recapitulated surfactant lipidomic changes observed in human subjects with COPD.,In summary, we show that the surfactant lipidome is substantially altered in subjects with COPD, and decreased availability of phospholipids correlated with decreased pulmonary function.,Further investigation of surfactant alterations in COPD would improve our understanding of its physiopathology and reveal new potential therapeutic targets. | Atherosclerosis and COPD are both systemic inflammatory diseases that may influence each other.,The aim of the present study was to determine the prevalence of COPD in patients with cerebral and/or peripheral artery disease and to assess factors associated with the presence of COPD.,Following the diagnosis of cerebral and/or peripheral artery disease by means of duplex sonography, 166 consecutive patients underwent body plethysmography with capillary blood gas analysis.,Thereafter, blood tests with determination of different parameters such as lipid profile, inflammatory and coagulation markers were conducted in remaining 136 patients who fulfilled inclusion criteria of the study.,Thirty-six out of 136 patients suffered from COPD, mostly in early stages of the disease.,Residual volume indicating emphysema was increased (162.9%±55.9% vs 124.5%±37.0%, p<0.05) and diffusion capacity was decreased (55.1%±19.5% vs 75.3%±18.6%, p<0.05) in COPD patients vs non-COPD group.,In capillary blood gas analysis, COPD patients had lower partial pressure of oxygen (70.9±11.5 vs 75.2±11.0 mmHg, p<0.05) and higher partial pressure of carbon dioxide (36.8±7.5 vs 34.4±4.4 mmHg, p<0.05) compared with non-COPD individuals.,Presence of COPD was associated with predominance of diabetes mellitus, interleukin-8-related systemic neutrophilic inflammation and anemia.,In conclusion, COPD is highly prevalent in patients with atherosclerotic artery disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | 1 |
Biomarkers for the management of chronic obstructive pulmonary disease (COPD) are limited.,The aim of this study was to explore new plasma biomarkers in patients with COPD.,Thyroxine-binding globulin (THBG) was initially identified by proteomics in a discovery panel and subsequently verified by enzyme-linked immunosorbent assay in another verification panel with a 1-year follow-up.,THBG levels were elevated in patients with COPD (9.2±2.3 μg/mL) compared to those of the controls (6.6±2.0 μg/mL).,Receiver operating characteristic curves suggested that THBG was able to slightly differentiate between patients with COPD and controls (area under the curve [AUC]: 0.814) and performed better if combined with fibrinogen (AUC: 0.858).,THBG was more capable of distinguishing Global Initiative for Obstructive Lung Disease stages I-III and IV (AUC: 0.851) compared with fibrinogen (AUC 0.582).,THBG levels were negatively associated with predicted percentage forced expiratory volume in 1 s and positively related to predicted percentage residual volume, RV/percentage total lung capacity, and percentage low-attenuation area.,COPD patients with higher baseline THBG levels had a greater risk of acute exacerbation (AE) than those with lower THBG levels (P=0.014, by Kaplan-Meier curve; hazard ratio: 4.229, by Cox proportional hazards model).,In summary, THBG is a potential plasma biomarker of COPD and can assist in the management of stable stage and AEs in COPD patients. | Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD).,We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations.,Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period.,The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL.,Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79-2.95).,In the longitudinal adjusted models, fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39-1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27-1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07-1.74).,Similar findings were seen with continuous fibrinogen levels.,In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD. | 1 |
Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | 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 |
COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes.,Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies.,As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes.,The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites.,Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions.,However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies.,Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis.,This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms.,It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors.,Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid illness and new therapeutic strategies for both the diseases.,However, further research is needed to clarify factors that may be directly causal as opposed to confounding relationships. | The Global Initiative defines COPD for chronic obstructive lung disease as an entirely preventable and treatable disease characterized by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status.,The World Health Organization (WHO) estimates that COPD will become the fourth-most common cause of death worldwide, just behind ischemic heart disease, cerebrovascular disease and HIV/AIDS, by 2030.,The aim of this study was to determine the main structure feature of sputum potentially pathogenic microorganisms in subjects with COPD during the clinical stable state.,We employed a molecular genetics-based investigation of the bacteria community, including DNA isolation, PCR amplification and DGGE profiling.,PCR-denaturing gradient gel electrophoresis (DGGE) with universal primers targeting the V3 region of the 16S rRNA gene was employed to characterize the overall COPD patient sputum microbiota composition, and some excised gel bands were cloned for sequencing.,Real-time PCR was further utilized to quantitatively analyze the subpopulation of microbiota using group-specific primers targeting Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa.,The DGGE profiles of two groups displayed significant differences between COPD and healthy groups (P < 0.05).,Real-time PCR revealed significant increases of Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa (P < 0.05) in the COPD group compared with the healthy group.,This study revealed strong relationship between alterations of sputum microbiota and COPD.,By determining the content of several types of bacteria, we can provide evidence to aid in the diagnosis and treatment of COPD. | 1 |
Pixin Ran, Nanshan Zhong, and colleagues report that cleaner cooking fuels and improved ventilation were associated with better lung function and reduced COPD among a cohort of villagers in Southern China.,Please see later in the article for the Editors' Summary,Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning.,The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD.,A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China.,Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011.,That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes.,Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions.,Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders.,The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y).,The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05).,The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements.,Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD.,Chinese Clinical Trial Register ChiCTR-OCH-12002398,Please see later in the article for the Editors' Summary,Nearly 3 billion people in developing countries heat their homes and cook by burning biomass-wood, crop waste, and animal dung-in open fires and leaky stoves.,Burning biomass this way releases pollutants into the home that impair lung function and that are responsible for more than a million deaths from chronic obstructive pulmonary disease (COPD) every year.,COPD is a group of diseases that interfere with breathing.,Normally, air is breathed in through the nose or mouth and travels down the windpipe into two bronchial tubes (airways) in the lungs.,These tubes branch into smaller tubes (bronchioles) that end in bunches of tiny air sacs (alveoli).,Oxygen in the air passes through the thin walls of these sacs into small blood vessels and is taken to the heart for circulation round the body.,The two main types of COPD-chronic bronchitis (long-term irritation and swelling of the bronchial tubes) and emphysema (damage to the walls of the alveoli)-make it hard for people to breathe.,Most people with COPD have both chronic bronchitis and emphysema, both of which are caused by long-term exposure to cigarette smoke, indoor air pollution, and other lung irritants.,Symptoms of COPD include breathlessness during exercise and a persistent cough that produces large amounts of phlegm (mucus).,There is no cure for COPD, but drugs and oxygen therapy can relieve its symptoms, and avoiding lung irritants can slow disease progression.,Exposure to indoor air pollution has been associated with impaired lung function and COPD in several studies.,However, few studies have assessed the long-term effects on lung function and on the incidence of COPD (the proportion of a population that develops COPD each year) of replacing biomass with biogas (a clean fuel produced by bacterial digestion of biodegradable materials) for cooking and heating, or of improving kitchen ventilation during cooking.,Here, the researchers undertook a nine-year prospective cohort study in rural southern China to investigate whether these interventions are associated with any effects on lung function and on the incidence of COPD.,A prospective cohort study enrolls a group of people, determines their characteristics at baseline, and follows them over time to see whether specific characteristic are associated with specific outcomes.,The researchers offered nearly 1,000 people living in 12 villages in southern China access to biogas and to improved kitchen ventilation.,All the participants, who adopted these interventions according to personal preferences, completed a questionnaire about their smoking habits and occupational exposure to pollutants and had their lung function measured using a spirometry test at the start and end of the study.,Some participants also completed a questionnaire and had their lung function measured three and six years into the study.,Finally, the researchers measured levels of indoor air pollution in a randomly selected subset of homes at the end of the study to confirm that the interventions had reduced indoor air pollution.,Compared with non-use, the use of clean fuels and of improved ventilation were both associated with a reduction in the decline in lung function over time after adjusting for known characteristics that affect lung function, such as smoking.,The use of both interventions reduced the decline in lung function more markedly than either intervention alone, and the benefits of using the interventions increased with length of use.,Notably, the combined use of both interventions reduced the risk of COPD occurrence among the study participants.,These findings suggest that, among people living in rural southern China, the combined interventions of use of biogas instead of biomass and improved kitchen ventilation were associated with a reduced decline in lung function over time and with a reduced risk of COPD.,Because participants were not randomly allocated to intervention groups, the people who adopted the interventions may have shared other unknown characteristics (confounders) that affected their lung function (for example, having a healthier lifestyle).,Thus, it is not possible to conclude that either intervention actually caused a reduction in the decline in lung function.,Nevertheless, these findings suggest that the use of biogas as a substitute for biomass for cooking and heating and improvements in kitchen ventilation might lead to a reduction in the global burden of COPD associated with biomass smoke.,Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001621.,The US National Heart, Lung, and Blood Institute provides detailed information for the public about COPD,The US Centers for Disease Control and Prevention provides information about COPD and links to other resources (in English and Spanish),The UK National Health Service Choices website provides information for patients and carers about COPD, personal stories, and links to other resources,The British Lung Foundation, a not-for-profit organization, provides information about COPD in several languages,The Global Initiative for Chronic Obstructive Lung Disease works to improve prevention and treatment of COPD around the world,The World Health Organization provides information about all aspects of indoor air pollution and health (in English, French, and Spanish),MedlinePlus provides links to other information about COPD (in English and Spanish) | Recent guidelines for chronic obstructive pulmonary disease (COPD) state that COPD is both preventable and treatable.,To gain a more positive outlook on the disease it is interesting to investigate factors associated with good, self-rated health and quality of life in subjects with self-reported COPD in the population.,In a cross-sectional study design, postal survey questionnaires were sent to a stratified, random population in Sweden in 2004 and 2008.,The prevalence of subjects (40-84 years) who reported having COPD was 2.1% in 2004 and 2.7% in 2008.,Data were analyzed for 1475 subjects.,Regression models were used to analyze the associations between health measures (general health status, the General Health Questionnaire, the EuroQol five-dimension questionnaire) and influencing factors.,The most important factor associated with good, self-rated health and quality of life was level of physical activity.,Odds ratios for general health varied from 2.4 to 7.7 depending on degree of physical activity, where subjects with the highest physical activity level reported the best health and also highest quality of life.,Social support and absence of economic problems almost doubled the odds ratios for better health and quality of life.,In this population-based public health survey, better self-rated health status and quality of life in subjects with self-reported COPD was associated with higher levels of physical activity, social support, and absence of economic problems.,The findings indicated that of possible factors that could be influenced, promoting physical activity and strengthening social support are important in maintaining or improving the health and quality of life in subjects with COPD.,Severity of the disease as a possible confounding effect should be investigated in future population studies. | 1 |
Impaired cognitive function is increasingly recognized in COPD.,Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied.,The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls.,A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education.,Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment.,By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility.,General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models.,General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls.,Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001).,General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls. | Several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment.,These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group.,This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD.,In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy.,We used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD.,Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points.,Disease severity was using Forced Expiratory Volume in one second (FEV1); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index.,Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking.,COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043-6.64).,Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases).,Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014-29.2; P = 0.048).,Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07-0.27; P < 0.0001).,COPD is a major risk factor for cognitive impairment.,Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective.,Health care providers should consider screening their COPD patients for cognitive impairment. | 1 |
Patients with COPD need to cope with a disabling disease, which leads to health status impairment.,To investigate the long term change of health status in subjects with mild to moderate airflow obstruction and to compare this to subjects without airflow obstruction, with and without a smoking history.,Second, to investigate the factors potentially associated to rapid health status decline in our total cohort.,Two hundred and one subjects were included.,Generic [Short form 36 health survey (SF36) and EuroQol - 5 dimensions (EQ-5D)] and disease specific [Clinical COPD questionnaire (CCQ) and COPD Assessment Test (CAT)] health status questionnaires were regularly repeated over a six years period.,Other functional outcomes comprised measures of lung function, physical fitness, physical activity and emotional state.,On average, health status decline did not differ between groups with the exception of the EQ-5D index, which deteriorated faster in subjects with airflow obstruction compared to the never smoking control group [− 0.018(0.008) versus 0.00006(0.003), p = 0.03].,Subjects presenting at least one exacerbation had faster rate of deterioration measured with CAT [0.91(0.21) versus − 0.26(0.25), p < 0.01].,Characteristics of the fast declining group were older age, worse lung function, physical fitness, physical activity and disease specific baseline health status.,Subjects with airflow obstruction had a 2.5 (95% CI 1.36-4.71) higher risk of presenting fast overall health status decline.,Fast overall decline was associated with the presence of acute exacerbation(s) (44% of the subjects with exacerbation(s) versus 17% of subjects without exacerbation, p = 0.03).,Changes in fat free mass, functional exercise capacity and in symptoms of anxiety and depression correlated weakly to changes in health status measured with all questionnaires.,Subjects with mild airflow obstruction present a significant deterioration of health status, which is generally not much faster compared to smoking and never smoking controls.,Subjects with fast decline in overall health status are older and more likely to have airflow obstruction, acute respiratory exacerbation(s), reduced physical fitness, physical activity and impaired COPD specific health status at baseline.,NCT01314807 - retrospectively registered on March 2011.,The online version of this article (10.1186/s12931-019-1061-7) contains supplementary material, which is available to authorized users. | Pulmonary rehabilitation programs only modestly enhance daily physical activity levels in patients with chronic obstructive pulmonary disease (COPD).,This randomised controlled trial investigates the additional effect of an individual activity counselling program during pulmonary rehabilitation on physical activity levels in patients with moderate to very severe COPD.,Eighty patients (66±7 years, 81% male, forced expiratory volume in 1 second 45±16% of predicted) referred for a six‐month multidisciplinary pulmonary rehabilitation program were randomised.,The intervention group was offered an additional eight-session activity counselling program.,The primary outcomes were daily walking time and time spent in at least moderate intense activities.,Baseline daily walking time was similar in the intervention and control group (median 33 [interquartile range 16-47] vs 29 [17-44]) whereas daily time spent in at least moderate intensity was somewhat higher in the intervention group (17[4-50] vs 12[2-26] min).,No significant intervention*time interaction effects were observed in daily physical activity levels.,In the whole group, daily walking time and time spent in at least moderate intense activities did not significantly change over time.,The present study identified no additional effect of eight individual activity counselling sessions during pulmonary rehabilitation to enhance physical activity levels in patients with COPD.,clinicaltrials.gov NCT00948623 | 1 |
The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease.,High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region.,A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD.,The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design.,This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A-D for simplicity and clarity.,At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed.,Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues.,Bronchodilators should not be discontinued except in the case of significant side effects.,At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation.,Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
COPD, characterized by long-term poorly irreversible airway limitation and persistent respiratory symptoms, has resulted in enormous challenges to human health worldwide, with increasing rates of prevalence, death, and disability.,Although its origin was thought to be in the interactions of genetic with environmental factors, the effects of environmental factors on the disease during different life stages remain little known.,Without clear mechanisms and radical cure for it, early screening and prevention of COPD seem to be important.,In this review, we will discuss the etiologic origins for poor lung function and COPD caused by specific adverse effects during corresponding life stages, as well as try to find new insights and potential prevention strategies for this disease. | Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status. | 1 |
Muscle dysfunction represents a pathophysiological feature of chronic obstructive pulmonary disease (COPD).,Muscle impairment contributes to decreased effort capacity in these patients at least in the same proportion as pulmonary function limitation.,Maximal inspiratory pressure (MIP) is a reliable, noninvasive parameter for assessing the respiratory muscle capacity.,The aim of the present study was to determine the role of MIP in effort capacity decrease in COPD patients.,MIP was measured in 121 COPD patients without hyperinflation (RV < 150%) together with the following investigations: body plethysmography, body impedance analysis, dynamometry, 6-minute walking test (6MWT), determination of SaO2 and serum levels of highly sensitive C-reactive protein (hsCRP).,MIP (kPa) was significantly decreased in moderate-severe stages (6.19 ± 2.42, COPD II; 5.35 ± 2.49, COPD III; 4.56 ± 1.98, COPD IV vs 7.90 ± 2.61 in controls, P < 0.001), whereas the muscle force assessed by dynamometry was decreased only in advanced stages of disease (0.47 ± 0.12, COPD III; 0.41 ± 0.07, COPD IV vs 0.71 ± 0.16 in controls, P < 0.001).,The values of MIP correlated (r = 0.53, P = 0.0003) with the distance walked in 6MWT.,MIP may provide additive information concerning the general profile of muscle dysfunction in COPD patients. | In this study, we analyzed maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values in a stable COPD population compared with normal subjects.,We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD.,Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values.,110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study.,Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe.,Both MIP and MEP were lower in patients with severe airway impairment than in normal subjects.,Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), PEF (peak expiratory flow), TLC (total lung capacity) and height.,MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV1.,The measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD. | 1 |
Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations.,It is not known what impact ICS cause in terms of COVID-19 positivity or disease severity in COPD.,This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March 8th and September 16th, 2020.,Electronic health records were used to determine diagnosis of COPD, ICS use, and clinical outcomes.,Multivariate logistic regression was used to adjust for demographics, month of COVID-19 testing, and comorbidities known to be associated with increased risk for severe COVID-19 disease.,Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive for COVID-19 versus 47.2% who tested negative for COVID-19 (p = 0.033).,Of those who tested positive for COVID-19 (n = 1288), 371 (28.8%) required hospitalization.,In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of ICU admission (36.8% [74/201] vs 31.2% [53/170], p = 0.30), endotracheal intubation (21.9% [44/201] vs 16.5% [28/170], p = 0.24), or mortality (18.4% [37/201] vs 20.0% [34/170], p = 0.80).,Multivariate logistic regression demonstrated no significant differences in hospitalization (adj OR 1.12, CI: 0.90-1.38), ICU admission (adj OR: 1.31, CI: 0.82-2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69-4.02), or mortality (OR: 0.80, CI: 0.43-1.49).,In conclusion, ICS therapy did not increase COVID-19 related healthcare utilization or mortality outcome in patients with COPD followed at the Cleveland Clinic health system.,These findings should encourage clinicians to continue ICS therapy for COPD patients during the COVID-19 pandemic. | Data on patients with coronavirus disease 2019 (COVID-19) who return to hospital after discharge are scarce.,Characterization of these patients may inform post-hospitalization care.,To describe clinical characteristics of patients with COVID-19 who returned to the emergency department (ED) or required readmission within 14 days of discharge.,Retrospective cohort study of SARS-COV-2-positive patients with index hospitalization between February 27 and April 12, 2020, with ≥ 14-day follow-up.,Significance was defined as P < 0.05 after multiplying P by 125 study-wide comparisons.,Hospitalized patients with confirmed SARS-CoV-2 discharged alive from five New York City hospitals.,Readmission or return to ED following discharge.,Of 2864 discharged patients, 103 (3.6%) returned for emergency care after a median of 4.5 days, with 56 requiring inpatient readmission.,The most common reason for return was respiratory distress (50%).,Compared with patients who did not return, there were higher proportions of COPD (6.8% vs 2.9%) and hypertension (36% vs 22.1%) among those who returned.,Patients who returned also had a shorter median length of stay (LOS) during index hospitalization (4.5 [2.9,9.1] vs 6.7 [3.5, 11.5] days; Padjusted = 0.006), and were less likely to have required intensive care on index hospitalization (5.8% vs 19%; Padjusted = 0.001).,A trend towards association between absence of in-hospital treatment-dose anticoagulation on index admission and return to hospital was also observed (20.9% vs 30.9%, Padjusted = 0.06).,On readmission, rates of intensive care and death were 5.8% and 3.6%, respectively.,Return to hospital after admission for COVID-19 was infrequent within 14 days of discharge.,The most common cause for return was respiratory distress.,Patients who returned more likely had COPD and hypertension, shorter LOS on index-hospitalization, and lower rates of in-hospital treatment-dose anticoagulation.,Future studies should focus on whether these comorbid conditions, longer LOS, and anticoagulation are associated with reduced readmissions.,The online version of this article (10.1007/s11606-020-06120-6) contains supplementary material, which is available to authorized users. | 1 |
To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD.,COPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks.,The primary outcome was the annualized rate of moderate/severe COPD exacerbations.,In total, 1,765 patients were randomized.,There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%).,None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402).,There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084).,Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039).,There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077).,There were more St George’s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054).,EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066).,Acute β2-agonist-induced effects and 24-hour Holter findings were similar for all treatments.,Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses.,Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively.,Adverse events were otherwise similar across treatment groups.,FP/FORM did not reduce exacerbation rates versus FORM.,Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores.,Few efficacy differences were evident between FP/FORM 250/10 µg and FORM.,Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low.,Adverse events were otherwise similar between treatments. | Symptomatic relief is an important treatment goal for patients with COPD.,To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines.,The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need.,The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation.,The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.,This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international).,Subjects completed the E-RS as part of a daily eDiary.,Tests of reliability, validity, and responsiveness were conducted in each dataset.,In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74).,RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV1% predicted (−0.19, −0.14, −0.15); St.,George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests.,Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity.,RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001).,RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001).,Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.,Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.,MPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516,The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users. | 1 |
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. | The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD).,We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy.,Twenty patients who completed the 12-month treatment period were analyzed.,No clinically significant adverse events were observed during azithromycin treatment.,Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01).,The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations.,Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations.,Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD. | 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. | Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated.,Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture.,We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013.,The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention.,Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD.,Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy).,Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture.,The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up.,This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture. | 1 |
Recent literature has suggested that emphysema and chronic bronchitis, traditionally considered to be entities overlapping within chronic obstructive pulmonary disease (COPD), may be distinct disorders.,Few studies have examined the differences in patient characteristics and health outcomes between these conditions.,This study examined whether COPD phenotypes represent distinct patient populations, in a large nationally representative US sample.,Data were obtained from the 2010 US National Health and Wellness Survey (NHWS).,NHWS respondents (n = 75,000) were categorized as a COPD phenotype based on their self-reported diagnosis of COPD only (n = 970), emphysema only (n = 399), or chronic bronchitis only (n = 2071).,Phenotypes were compared on demographics, health characteristics, treatment patterns, health outcomes, work productivity, and resource use.,Variables were compared using Chi-square and analysis of variance tests for categorical and continuous outcomes, respectively.,Health outcomes were also examined using regression modeling, controlling for demographic and health characteristic covariates.,Patients with chronic bronchitis were significantly younger (51.38 years versus 63.24 years for COPD versus 63.30 years for emphysema, P < 0.05) and more likely to be employed (46.98% versus 23.81% for COPD versus 28.33% for emphysema, P < 0.05).,Relative to the other phenotypes, patients with chronic bronchitis were also significantly more likely to be female, nonwhite, and to exercise currently (all P < 0.05), and were significantly less likely to be a current or former smoker (P < 0.05).,Controlling for demographic and health characteristics, patients self-identified as having COPD only reported significantly worse physical quality of life (adjusted mean 36.69) and health utilities (adjusted mean 0.65) and significantly more absenteeism (adjusted mean 7.08%), presenteeism (adjusted mean 30.73%), overall work impairment (adjusted mean 34.06%), and activity impairment (adjusted mean 46.59%) than the other phenotypes (all P < 0.05).,These results suggest considerable heterogeneity among different COPD phenotypes with respect to demographics, health characteristics, disease characteristics, treatment patterns, and health outcomes.,Research aimed at understanding the differences in patient characteristics and disease presentation of these phenotypes could be used to guide treatment recommendations. | Emphysema is mainly caused by cigarette smoking and is characterized by the loss of alveolar integrity and an enlargement of the alveolar space.,However, mechanisms involved in its development are not fully understood.,Alveolar cell apoptosis has been previously investigated in the lung of emphysematous subjects as a potential contributor to the loss of alveolar cell and has been found abnormally elevated.,Though, mechanisms involved in the increased alveolar apoptosis that occurs in emphysema have now become a prolific field of research.,Those mechanisms are reviewed here with special focus on how they affect cell viability and how they may be implicated in emphysema.,Moreover, we suggest a model that integrates all those mechanisms to explain the increased alveolar apoptosis observed in emphysema.,This review also includes some reflections and suggestions on the research to come. | 1 |
Randomized controlled trials, evidence-based medicine, clinical guidelines, and total quality management are some of the approaches used to render science-based health care services.,The clinical pathway for hospitalized patients suffering from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is poorly established, although a clinical pathway is an integral part of total quality management.,To evaluate the outcomes of patients hospitalized with AECOPD in Japan, treated with a clinical pathway following published guidelines.,Prospective data were collected for patients with AECOPD admitted to a general hospital over a 5-year period since 2003.,The clinical pathway was designed to establish general rules for the entire treatment protocol.,The clinical pathway indicates which treatments and interventions should be performed, and when.,In this study, health care providers were required to check the clinical pathway sheets to determine the next step of treatment.,This study analyzed 276 hospitalizations in 165 patients.,The clinical pathway was interrupted and defined as a dropout in 45 cases (16.3%).,Nine patients died during hospitalization (3.3%).,Oxygen was administered in 232 hospitalizations (84.1%).,Noninvasive positive pressure ventilation (NPPV) treatment was administered in 110 hospitalizations (39.9%).,The rate of intubation in those cases where NPPV treatment had been administered was 8.2% (9 cases out of 110).,The average length of stay (LOS) was 20.3 days, and the median value was 15 days.,The LOS was longer than 30 days in 34 admissions (12.3%), mainly due to complications.,AECOPD can be managed using a clinical pathway.,This clinical pathway could fill the gap between guidelines and clinical practice. | Hospital treatment of chronic obstructive pulmonary disease (COPD) frequently does not follow published evidences.,This lack of adherence can contribute to the high morbidity, mortality and readmissions rates.,The European Quality of Care Pathway (EQCP) study on acute exacerbations of COPD (NTC00962468) is undertaken to determine how care pathways (CP) as complex intervention for hospital treatment of COPD affects care variability, adherence to evidence based key interventions and clinical outcomes.,An international cluster Randomized Controlled Trial (cRCT) will be performed in Belgium, Italy, Ireland and Portugal.,Based on the power analysis, a sample of 40 hospital teams and 398 patients will be included in the study.,In the control arm of the study, usual care will be provided.,The experimental teams will implement a CP as complex intervention which will include three active components: a formative evaluation of the quality and organization of care, a set of evidence based key interventions, and support on the development and implementation of the CP.,The main outcome will be six-month readmission rate.,As a secondary endpoint a set of clinical outcome and performance indicators (including care process evaluation and team functioning indicators) will be measured in both groups.,The EQCP study is the first international cRCT on care pathways.,The design of the EQCP project is both a research study and a quality improvement project and will include a realistic evaluation framework including process analysis to further understand why and when CP can really work.,NCT00962468 | 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. | Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303. | 1 |
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. | 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. | 1 |
Frailty can inform management approaches for individuals with COPD.,However, inpatient measures of frailty are seldom employed because they are time-consuming or inapplicable for bed-bound patients.,We investigated the feasibility and potential of an innovative sensor-based upper-extremity function (UEF) test for frailty assessment in predicting adverse outcomes.,Hospitalized patients with COPD-related exacerbations (aged ≥55 years) were recruited and performed the UEF test within 24 hours of admission.,UEF parameters were obtained and fed into our previously developed frailty model to calculate frailty status (non-frail, pre-frail, and frail) and frailty score (0: extreme resilience to 1: extreme frailty).,In-hospital (length of stay) and post-discharge (discharge disposition, 30-day exacerbation with treatment, and all-cause 30-day readmission) outcomes were collected.,Associations between UEF frailty and outcomes were investigated using ANOVA and logistic models adjusted for demographic data.,In total, 42 patients were recruited.,All participants were able to perform the UEF test.,Based on UEF, participants were stratified into three groups of non-frail (n=6, frailty score =0.18±0.09), pre-frail (n=14, frailty score =0.45±0.09), and frail (n=22, frailty score =0.78±0.11).,Both frailty status and frailty score were significantly associated with unfavorable discharge disposition (P<0.005) and all-cause 30-day readmission (P<0.05).,On the other hand, UEF frailty measures were associated with neither hospital length of stay (P>0.5) nor 30-day exacerbation with treatment (P>0.70).,Age was only significantly associated with unfavorable discharge disposition (P=0.048).,In agreement with previous work, the current findings underline the importance of measuring frailty for risk-stratification of COPD patients.,The UEF was feasible and easily performed among all hospitalized COPD patients.,In this study, we have shown that, using our quick and objective frailty measures, COPD patients can be prospectively risk-stratified in terms of unfavorable discharge disposition and all-cause 30-day readmissions. | Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress, also having many nonrespiratory manifestations that affect both function and mobility.,Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with COPD.,Our objective was to investigate balance performance in two groups of COPD patients with different body compositions and to observe which of these groups are more likely to experience falls in the future.,We included 27 stable COPD patients and 17 healthy individuals who performed a series of balance tests.,The COPD patients were divided in two groups: emphysematous and bronchitic.,Patients completed the activities balance confidence scale and the COPD assessment test questionnaire and afterward performed the Berg Balance Scale, timed up and go, single leg stance and 6-minute walking distance test.,We analyzed the differences in the balance tests between the studied groups.,Bronchitic COPD was associated with a decreased value when compared to emphysematous COPD for the following variables: single leg stance (8.7 vs 15.6; P<0.001) and activities balance confidence (53.2 vs 74.2; P=0.001).,Bronchitic COPD patients had a significantly higher value of timed up and go test compared to patients with emphysematous COPD (14.7 vs 12.8; P=0.001).,Patients with COPD have a higher balance impairment than their healthy peers.,Moreover, we observed that the bronchitic COPD phenotype is more likely to experience falls compared to the emphysematous phenotype. | 1 |
Exacerbation history is used to grade the risk of COPD exacerbation, but its reliability and relationship to other risk factors and prior therapy is unclear.,To examine these interrelationships, we conducted a post hoc analysis of patients in the TIOSPIR trial with ≥2 years’ follow-up or who died on treatment.,Patients were grouped by their annual exacerbation rate on treatment into nonexacerbators, infrequent, and frequent exacerbators (annual exacerbation rates 0, ≤1, and >1, respectively), and baseline characteristics discriminating among the groups were determined.,We used univariate and multivariate analyses to explore the effect of baseline characteristics on risk of exacerbation, hospitalization (severe exacerbation), and death (all causes).,Of 13,591 patients, 6,559 (48.3%) were nonexacerbators, 4,568 (33.6%) were infrequent exacerbators, and 2,464 (18.1%) were frequent exacerbators; 45% of patients without exacerbations in the previous year exacerbated on treatment.,Multivariate analysis identified baseline pulmonary maintenance medication as a predictive factor of increased exacerbation risk, with inhaled corticosteroid treatment associated with increased exacerbation risk irrespective of exacerbation history.,Our data confirm established risk factors for exacerbation, but highlight the limitations of exacerbation history when categorizing patients and the importance of prior treatment when identifying exacerbation risk. | ‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations.,ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg.,This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.,A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George’s Respiratory Questionnaire (SGRQ) total score (≥4 units).,A ‘sustained’ CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time.,CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18.,AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05).,Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01).,AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).,AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.,Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011.,Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.,The online version of this article (doi:10.1186/s12931-017-0583-0) contains supplementary material, which is available to authorized users. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic inflammatory respiratory diseases, which impose a substantial burden on healthcare systems and society.,Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA), often administered using dry powder inhalers (DPIs), are frequently prescribed to control persistent asthma and COPD.,Use of DPIs has been associated with poor inhalation technique, which can lead to increased healthcare resource use and costs.,A model was developed to estimate the healthcare resource use and costs associated with asthma and COPD management in people using commonly prescribed DPIs (budesonide + formoterol Turbuhaler® or fluticasone + salmeterol Accuhaler®) over 1 year in Spain, Sweden and the United Kingdom (UK).,The model considered direct costs (inhaler acquisition costs and scheduled and unscheduled healthcare costs), indirect costs (productive days lost), and estimated the contribution of poor inhalation technique to the burden of illness.,The direct cost burden of managing asthma and COPD for people using budesonide + formoterol Turbuhaler® or fluticasone + salmeterol Accuhaler® in 2015 was estimated at €813 million, €560 million, and €774 million for Spain, Sweden and the UK, respectively.,Poor inhalation technique comprised 2.2-7.7 % of direct costs, totalling €105 million across the three countries.,When lost productivity costs were included, total expenditure increased to €1.4 billion, €1.7 billion and €3.3 billion in Spain, Sweden and the UK, respectively, with €782 million attributable to poor inhalation technique across the three countries.,Sensitivity analyses showed that the model results were most sensitive to changes in the proportion of patients prescribed ICS and LABA FDCs, and least sensitive to differences in the number of antimicrobials and oral corticosteroids prescribed.,The cost of managing asthma and COPD using commonly prescribed DPIs is considerable.,A substantial, and avoidable, contributor to this burden is poor inhalation technique.,Measures that can improve inhalation technique with current DPIs, such as easier-to-use inhalers or better patient training, could offer benefits to patients and healthcare providers through improving disease outcomes and lowering costs.,The online version of this article (doi:10.1186/s12913-016-1482-7) 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 |
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD).,In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new.,In combination, these variants strongly predict COPD in independent patient populations.,Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups.,We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants.,This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD. | People with COPD have cognitive dysfunction, which is greater in those hospitalized for exacerbations than in stable outpatients.,We tested the hypothesis that cognitive dysfunction at exacerbation is a disease-specific feature of COPD, rather than a nonspecific feature of hospitalization for acute illness, by comparing cognition between patients hospitalized for acute COPD exacerbations and those with worsening heart failure (HF).,A total of 40 hospital inpatients were recruited, 20 patients with COPD exacerbations and 20 patients with congestive or left-sided HF.,Exclusion criteria included previous stroke, known neurological disease, and marked alcohol excess.,Participants completed the Montreal cognitive assessment (MoCA) and Hospital Anxiety and Depression Scale (HADS) and underwent spirometry and review of clinical records.,Age (mean±SD, COPD 73±10; HF 76±11 years), acute illness severity (Acute Physiology and Chronic Health Evaluation [APACHE]-II, COPD 15.4±3.5; HF 15.9±3.0), comorbidities (Charlson index, COPD 1.3±1.9; HF 1.6±1.5), and educational background were similar between COPD and HF groups.,MoCA total was significantly lower in COPD than in HF (COPD 20.6±5.6; HF 24.8±3.5, P=0.007); however, significance was lost after correction for age, sex, and pack year smoking history.,When compared with HF patients, the COPD cohort performed worse on the following domains of the MoCA: visuospatial function (median [IQR], COPD 0 [1]; HF 2 [1], P=0.003), executive function (COPD 2 [1]; HF 3 [1], P=0.035), and attention (COPD 4 [3]; HF 6 [2], P=0.020).,Age (P=0.012) and random glucose concentration (P=0.041) were associated with cognitive function in whole group analysis, with pack year smoking history reaching borderline significance (P=0.050).,Total MoCA score for COPD and HF indicated that both groups had mild cognitive impairment, although this was greater in people with COPD.,Mechanisms underlying the observed cognitive dysfunction in COPD remain unclear but appear related to blood glucose concentrations and greater lifetime smoking load. | 1 |
To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD.,A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution.,The patients underwent dual-energy X-ray absorptiometry.,The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects.,Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index.,We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2.,Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status.,Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction).,The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001).,Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009).,The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage.,In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.,Avaliar a prevalência de sarcopenia em pacientes com DPOC e determinar se sarcopenia está correlacionada com a gravidade e o prognóstico de DPOC.,Estudo retrospectivo em pacientes com DPOC atendidos no ambulatório de pneumologia de nossa instituição.,Os pacientes realizaram absorciometria de dupla energia por raios X.,O diagnóstico de sarcopenia foi baseado no índice de massa muscular esquelética, definido como massa magra apendicular/altura2 somente para indivíduos com baixo peso, sendo ajustado pela massa gorda para aqueles com peso normal/sobrepeso.,A gravidade da doença (estádio da DPOC) foi avaliada com os critérios da Global Initiative for Chronic Obstructive Lung Disease (GOLD).,O grau de obstrução e o prognóstico foram determinados pelo índice Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE).,Foram incluídos 91 pacientes (50 mulheres), com média de idade de 67,4 ± 8,7 anos e média de IMC de 25,8 ± 6,1 kg/m2.,Sarcopenia foi diagnosticada em 36 (39,6%) dos pacientes, sem diferenças relacionadas a sexo, idade ou status tabágico.,Não houve associação de sarcopenia com estádios GOLD ou VEF1 (utilizado como indicador do grau de obstrução).,O IMC, a porcentagem de gordura corporal e a massa magra total foram menores nos pacientes com sarcopenia do que naqueles sem a doença (p < 0,001).,A prevalência de sarcopenia foi maior nos pacientes com BODE nos quartis 3 ou 4 que naqueles com BODE nos quartis 1 ou 2 (p = 0,009).,A análise multivariada mostrou que os quartis do BODE estavam significativamente associados à sarcopenia, independentemente de idade, gênero, status tabágico e estádio GOLD.,Em pacientes com DPOC, sarcopenia parece estar associada a alterações desfavoráveis na composição corporal e pior prognóstico. | Diet and nutrition may be important modifiable risk factors for the development, progression and management of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).,This review examines the relationship between dietary patterns, nutrient intake and weight status in obstructive lung diseases, at different life stages, from in-utero influences through childhood and into adulthood.,In vitro and animal studies suggest important roles for various nutrients, some of which are supported by epidemiological studies.,However, few well-designed human intervention trials are available to definitively assess the efficacy of different approaches to nutritional management of respiratory diseases.,Evidence for the impact of higher intakes of fruit and vegetables is amongst the strongest, yet other dietary nutrients and dietary patterns require evidence from human clinical studies before conclusions can be made about their effectiveness. | 1 |
Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signalling by 9-cis retinoic acid, a vitamin A derivative.,RXRs play key roles not only as homodimers but also as heterodimeric partners, e.g., for retinoic acid receptors, vitamin D receptors, and peroxisome proliferator-activated receptors.,The NR family may also play important roles in the development of emphysema.,However, the role of RXRs in the pathogenesis of emphysema is not well defined.,We developed a novel RXR partial agonist (NEt-4IB) and investigated its effect and mechanism compared to a full agonist (bexarotene) in a murine model of emphysema.,For emphysema induction, BALB/c mice received intraperitoneal cigarette smoke extract (CSE) or intratracheal porcine pancreas elastase (PPE).,Treatment with RXR agonists was initiated before or after emphysema induction.,Treatment with NEt-4IB significantly suppressed the increase in static lung compliance and emphysematous changes in CSE-induced emphysema and PPE-induced established and progressive emphysema.,NEt-4IB significantly suppressed PPE-induced neutrophilic airway inflammation and the levels of keratinocyte chemoattractant (KC), C-X-C motif ligand5 (CXCL5), interferon (IFN)-γ and IL-17.,NEt-4IB also improved the matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and the reduced anti-oxidant activity in bronchoalveolar lavage (BAL) fluid.,NEt-4IB suppressed PPE-induced vascular endothelial growth factor (VEGF) expression in the airway.,Treatment with NEt-4IB and bexarotene significantly suppressed the increase in static lung compliance and emphysematous changes.,However, adverse effects of RXR agonists, including hypertriglyceridemia and hepatomegaly, were observed in bexarotene-treated mice but not in NEt-4IB-treated mice.,These data suggest that RXRs play crucial roles in emphysema and airway inflammation, and novel partial RXR agonists could be potential therapeutic strategies for the treatment of PPE- and CSE-induced emphysema.,The online version of this article (10.1186/s12931-018-0963-0) contains supplementary material, which is available to authorized users. | The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process.,We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state.,Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD.,Thirty-three of 56 known Wnt-related genes were expressed in the SAE.,Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes.,Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry.,Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro.,Smoking down-regulates the Wnt pathway in the human airway epithelium.,In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders. | 1 |
Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma.,Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM).,To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals.,By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM.,The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients. | Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD).,Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism.,We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages.,In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks.,Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages.,In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK.,Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways.,This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism. | 1 |
GOLD guidelines classify COPD patients into A-D groups based on health status as assessed by COPD Assessment Test (CAT) or mMRC tools and exacerbations and recommend single or dual long-acting bronchodilators as maintenance therapy, with additional inhaled corticosteroids (ICS) if the disease remains uncontrolled.,We aimed to classify primary care COPD patients into A-D groups, assess usual treatment and adherence to guidelines, potential mismatches between CAT-and mMRC-based classification and described symptoms within groups.,A total of 257 primary care COPD patients were enrolled between 2015 and 2016 in Greece.,Physicians used structured interviews to collect cross-sectional data including demographics, symptoms, CAT, mMRC scores, and medications.,Patients were classified into A-D groups based on CAT and mMRC, and prevalence of symptoms and medication was estimated within A-D groups.,Interviews with physicians were also performed to explore additional issues about treatment and adherence to guidelines.,Mean (SD) age was 65 (12.3) years with 79% males.,The majority of patients reported uncontrolled symptoms (91% and 61% with ≥10 CAT or ≥2 mMRC scores, respectively).,Thirty-seven percentage had $2 exacerbations in the past year.,Group B was the largest followed by Groups D, A, and C.,Patients were classified as more severe by CAT than by mMRC.,In all groups, the majority were treated with combined long-acting beta agonist/ICS (> 50%).,When patients were asked to report their main symptoms, dyspnea and cough were the most important symptoms mentioned, and there was a great variation between the A-D groups.,However, Groups A-C reported mainly morning symptoms, whereas Group D suffered symptoms all day.,Physicians reported a significant number of barriers to implementing guidelines, eg, frequent lack of guideline updates, access to diagnostic procedures, and prescription-reimbursement issues.,Our study confirms poor adherence to guidelines regarding treatment with an overuse of ICS and important barriers to implementation.,A mismatch in classification occurs depending on the tool used, which can mislead clinicians in their choice of treatment. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | The respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear.,Cross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing.,The microbiome composition was analysed with QIIME.,We observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with ≥2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p = 0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels ≥2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p = 0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p = 0.020], and a significant increase in the RAs of 20 genera.,The respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels.,The online version of this article (10.1186/s12890-019-0867-x) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk.,We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.,After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37).,Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly.,By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively).,Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).,The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012.,Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not.,Patients were followed up to assess lung cancer risk or protective factors.,In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use.,The index date of statin use was the COPD confirmation date.,To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs).,Patients receiving < 28 cDDDs were defined as nonstatin users.,Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients.,Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential. | Small airway fibrosis is the main contributor in airflow obstruction in chronic obstructive pulmonary disease.,Epithelial mesenchymal transition (EMT) has been implicated in this process, and in large airways, is associated with angiogenesis, ie, Type-3, which is classically promalignant.,In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways in subjects with chronic airflow limitation (CAL) and what type of EMT is present on the basis of vascularity.,We evaluated epithelial activation, reticular basement membrane fragmentation (core structural EMT marker) and EMT-related mesenchymal biomarkers in small and large airways from resected lung tissue from 18 lung cancer patients with CAL and 9 normal controls.,Tissues were immunostained for epidermal growth factor receptor (EGFR; epithelial activation marker), vimentin (mesenchymal marker), and S100A4 (fibroblast epitope).,Type-IV collagen was stained to demonstrate vessels.,There was increased expression of EMT-related markers in CAL small airways compared to controls: EGFR (P<0.001), vimentin (P<0.001), S100A4 (P<0.001), and fragmentation (P<0.001), but this was less than that in large airways.,Notably, there was no hypervascularity in small airway reticular basement membrane as in large airways.,Epithelial activation and S100A4 expression were related to airflow obstruction.,EMT is active in small airways, but less so than in large airways in CAL, and may be relevant to the key pathologies of chronic obstructive pulmonary disease, small airway fibrosis, and airway cancers. | 1 |
Cachectic patients with chronic obstructive pulmonary disease (COPD) may benefit from nutritional support.,This double‐blind, randomized, controlled trial evaluated the safety and efficacy of targeted medical nutrition (TMN) vs. an isocaloric comparator in pre‐cachectic and cachectic patients with COPD.,Patients aged ≥50 years with moderate‐to‐severe COPD and involuntary weight loss or low body mass index (16-18 kg/m2) were randomized 1:1 to receive TMN (~230 kcal; 2 g omega‐3 fatty acids; 10 μg 25‐hydroxy‐vitamin D3) or isocaloric comparator twice daily for 12 weeks (ClinicalTrials.gov Identifier: NCT02442908).,Primary safety endpoints comprised adverse events and changes in vital signs, laboratory parameters, and concomitant medications.,Secondary efficacy endpoints included changes in weight, body composition, exercise tolerance, metabolic biomarkers, and systemic inflammation.,Forty‐five patients were randomized to receive TMN (n = 22; mean 69.2 years) or isocaloric comparator (n = 23; mean 69.7 years).,TMN was well tolerated.,Adverse events were similar in number and type in both groups.,Compliance to both products was good (TMN, 79%; comparator, 77%).,Both groups gained weight, but the TMN group gained comparatively more fat mass (P = 0.0013).,Reductions in systolic blood pressure (P = 0.0418) and secondary endpoints of triglycerides (P = 0.0217) and exercise‐induced fatigue (P = 0.0223) and dyspnoea (P = 0.0382), and increases in high‐density lipoprotein cholesterol (P = 0.0254), were observed in the TMN vs. the comparator group by week 12.,Targeted medical nutrition containing high‐dose omega‐3 fatty acids, vitamin D, and high‐quality protein is well tolerated with a good safety profile and has positive effects on blood pressure and blood lipids and on exercise‐induced fatigue and dyspnoea.,Therefore, this TMN could be clinically beneficial in the nutritional and metabolic support of pre‐cachectic and cachectic patients with COPD. | Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis.,Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects.,The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.,In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital.,The primary outcomes were changes in 6-min walk distance (6-MWD) and the St.,George Respiratory Questionnaire (SGRQ) score.,Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength.,At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment.,In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant.,At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group.,Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021).,Ghrelin treatment was well tolerated.,In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.,UMIN Clinical Trial Registry C000000061 | 1 |
The Korean Health Insurance Review and Assessment Service (HIRA) has launched the Chronic Obstructive Pulmonary Disease (COPD) Quality Assessment Program (CQAP) since 2014.,We aimed to reveal the influence of this national program on clinical outcomes and the burden of COPD in Korea.,The CQAP is conducted annually.,We used healthcare claims data linked with the results of the program provided by HIRA between May 2014 and April 2017.,Patients were considered to have COPD if they visited a hospital for COPD management during the assessment term.,Those who visited a medical institution for COPD and were prescribed COPD medications at least twice were assessed by the CQAP (assessed subjects, AS; not-assessed subjects, NAS).,CQAP evaluated the pulmonary function test conduction rate, regular visitation rate, and prescription rates of COPD medications.,Among the 560,000 patients with COPD, about 140,000 were assessed by the CQAP annually.,In both groups, the pulmonary function test conduction rate and inhaled bronchodilator prescription rate improved since 2014.,Compared to the NAS group, the risk of admission and all-cause mortality rate in the AS group were significantly reduced by 21.2% and 40.7%, respectively.,In patients who were assessed for 3 consecutive years, all of the above variables were high at baseline and were not improved much from implementation of CQAP.,In matching analysis, we observed this improvement to be limited in the COPD quality assessment year.,The CQAP by the health insurance bureau has improved the management protocol and prognosis of COPD. | To describe the temporal and spatial trends of mortality and disability adjusted life years (DALYs) due to chronic respiratory diseases, by age and sex, across the world during 1990-2017 using data from the Global Burden of Disease Study 2017.,Systematic analysis.,The Global Burden of Diseases, Injuries, and Risk Factors Study 2017.,Mortality and DALYs from chronic respiratory diseases were estimated from the Global Burden of Disease Study 2017 using DisMod-MR 2.1, a Bayesian meta-regression tool.,The estimated annual percentage change of the age standardised mortality rate was calculated using a generalised linear model with a Gaussian distribution.,Mortality and DALYs were stratified according to the Socio-demographic index.,The strength and direction of the association between the Socio-demographic index and mortality rate were measured using the Spearman rank order correlation.,Risk factors for chronic respiratory diseases were analysed from exposure data.,Between 1990 and 2017, the total number of deaths due to chronic respiratorydiseases increased by 18.0%, from 3.32 (95% uncertainty interval 3.01 to 3.43) million in 1990 to 3.91 (3.79 to 4.04) million in 2017.,The age standardised mortality rate of chronic respiratory diseases decreased by an average of 2.41% (2.28% to 2.55%) annually.,During the 27 years, the annual decline in mortality rates of chronic obstructive pulmonary disease (COPD; 2.36%, uncertainty interval 2.21% to 2.50%) and pneumoconiosis (2.56%, 2.44% to 2.68%) has been slow, whereas the mortality rate for interstitial lung disease and pulmonary sarcoidosis (0.97%, 0.92% to 1.03%) has increased.,Reductions in DALYs for asthma and pneumoconiosis have been seen, but DALYs due to COPD, and interstitial lung disease and pulmonary sarcoidosis have increased.,Mortality and the annual change in mortality rate due to chronic respiratory diseases varied considerably across 195 countries.,Assessment of the factors responsible for regional variations in mortality and DALYs and the unequal distribution of improvements during the 27 years showed negative correlations between the Socio-demographic index and the mortality rates of COPD, pneumoconiosis, and asthma.,Regions with a low Socio-demographic index had the highest mortality and DALYs.,Smoking remained the major risk factor for mortality due to COPD and asthma.,Pollution from particulate matter was the major contributor to deaths from COPD in regions with a low Socio-demographic index.,Since 2013, a high body mass index has become the principal risk factor for asthma.,Regions with a low Socio-demographic index had the greatest burden of disease.,The estimated contribution of risk factors (such as smoking, environmental pollution, and a high body mass index) to mortality and DALYs supports the need for urgent efforts to reduce exposure to them. | 1 |
Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs.,Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated.,Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD.,Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year.,Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%).,No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline.,No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001).,In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02].,The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001).,In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D.,This association was independent of patients’ characteristics and comorbidities.,The online version of this article (doi:10.1186/s12931-014-0131-0) contains supplementary material, which is available to authorized users. | Vitamin D deficiency is common among persons with chronic obstructive pulmonary disease (COPD).,Whether vitamin D affects the development and deterioration of COPD or is a consequence of the disease lacks clarity.,We investigated the association between vitamin D status and prevalent and incident COPD in the general population.,We included a total of 12,041 individuals from three general population studies conducted in 1993-94, 1999-2001, and 2006-2008, respectively, with vitamin D measurements.,Information on COPD was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death.,There were 85 prevalent and 463 incident cases of COPD (median follow-up 9.7 years).,We found a statistically significant inverse association between vitamin D status and prevalent COPD with odds ratio = 0.89 (95% confidence interval, CI: 0.79, 1.0), but no statistically significant association with incident COPD with a hazard ratio = 0.98 (95% CI: 0.94, 1.0), respectively, per 10 nmol/l higher vitamin D status, when adjusted for possible confounders.,We found a statistically significant inverse cross-sectional association between vitamin D status and COPD, but no association between vitamin D status and incident COPD. | 1 |
Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy.,We compared long-acting muscarinic antagonist/long-acting β2-agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID.,CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naïve patients with COPD.,We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID.,Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat®) in two replicate, 52-week, parallel-group, double-blind studies (TONADO® 1/2).,CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St.,George’s Respiratory Questionnaire score, or moderate/severe exacerbation.,Time to first occurrence of one of these events was recorded as time to first CID.,Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P < 0.0001).,Significant reductions were also observed in patients with low exacerbation history (241 versus 170; HR 0.73 [0.64, 0.83]; P < 0.0001), GOLD 2 patients (241 versus 169; 0.72 [0.61, 0.84]; P < 0.0001) and maintenance-naïve patients (233 versus 171; 0.75 [0.62, 0.91]; P = 0.0030).,In patients with COPD, including patients with low exacerbation history, GOLD 2 patients and maintenance-naïve patients, tiotropium/olodaterol reduced the risk of CID versus tiotropium.,These results demonstrate the advantages of treatment optimisation with tiotropium/olodaterol over tiotropium monotherapy.,ClinicalTrials.gov identifier: TONADO® 1 and 2 (NCT01431274 and NCT01431287, registered 8 September 2011).,The online version of this article (10.1007/s12325-020-01528-2) contains supplementary material, which is available to authorized users. | Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile.,Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.,Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks.,Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks.,Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.,Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively.,In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo.,Secondary end points supported the efficacy of olodaterol.,These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. | 1 |
Despite chronic obstructive pulmonary disease (COPD) being the commonest non-communicable disease in Nepal, there is limited research evidence estimating the spirometry-based burden of COPD.,This study aims to estimate the prevalence of COPD and its correlates through a community-based survey in Pokhara Metropolitan City, a semi-urban area of Western Nepal.,A cross-sectional household survey was conducted among 1459 adults ≥40 years.,COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as a post-bronchodilator ratio of forced expiratory volume in 1st second (FEV1) to forced vital capacity (FVC) <0.70 with the presence of symptoms.,COPD was also defined by the lower limit of normal (LLN) threshold - FEV1/FVC < LLN cut-off values with the presence of symptoms.,Study participants were interviewed about sociodemographic and behavioural characteristics and respiratory symptoms.,Descriptive statistics and logistic regression analysis were applied.,Spirometry reports were acceptable in 1438 participants.,The mean age of the participants was 55 (±10) years, and, 54% were female.,The prevalence of GOLD-defined COPD was 8.5% (95% CI: 7.1-10.0) and based on the LLN threshold of 5.4% (95% CI: 4.2-6.6).,The multivariate logistic regression showed that increasing age, low body mass index, illiterate, current or former smoker, and biomass fuel smoke increased the odds of COPD in both the definitions.,COPD is highly prevalent at community level and often underdiagnosed.,Strategies aiming at early diagnosis and treatment of COPD, especially for the elderly, illiterate, and reducing exposure to smoking and biomass fuel smoke and childhood lung infection could be effective. | 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. | 1 |
The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment.,The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial.,Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients.,A total of 404 patients received treatment, with 165 participating in the ESWT substudy.,A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% (p = 0.02)] but not with tiotropium/olodaterol 2.5/5 µg [9% (p = 0.14)] versus placebo.,In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 µg [21% (p = 0.055)] and tiotropium/olodaterol 2.5/5 µg [21% (p = 0.056)] versus placebo.,Tiotropium/olodaterol 5/5 µg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time.,[ClinicalTrials.gov identifier: NCT01525615.] | Tiotropium-olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA), commercialized under the name of Spiolto or Stiolto.,The efficacy of tiotropium-olodaterol 5-5 μg once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration.,Tiotropium-olodaterol 5-5 μg not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance.,Improvements exceeded the minimal clinically important difference (MCID) for forced expiratory volume in 1 second (FEV1), dyspnea, and quality of life.,Differences between tiotropium-olodaterol 5-5 μg and the respective monocomponents were statistically significant for FEV1, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID.,However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life.,Moreover, tiotropium-olodaterol 5-5 μg was significantly more effective than salmeterol-fluticasone (FDC) twice daily at improving pulmonary function.,Differences between tiotropium-olodaterol and other LAMA/LABA FDCs were not observed for FEV1 or other efficacy markers.,Therefore, tiotropium-olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy. | 1 |
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most common reason for the hospitalization and death of pulmonary patients.,The use of antibiotics as adjuvant therapy for AECOPD, however, is still a matter of debate.,In this study, we searched the PubMed, EmBase, and Cochrane databases for randomized controlled trials published until September 2016 that evaluated the use of antibiotics for AECOPD treatment.,The major outcome variables were clinical cure rate and adverse effects.,The microbiological response rate, relapse of exacerbation, and mortality were also analysed.,A random-effect network was used to assess the effectiveness and tolerance of each antibiotic used for AECOPD treatment.,In this meta-analysis, we included 19 articles that assessed 17 types of antibiotics used in 5906 AECOPD patients.,The cluster ranking showed that dirithromycin had a high clinical cure rate with a low rate of adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole had high clinical cure rates with median rates of adverse effects.,In terms of the microbiological response rate, only doxycycline was significantly better than placebo (odds ratio (OR), 3.84; 95% confidence interval (CI), 1.96-7.54; p < 0.001).,There were no other significant results with respect to the frequency of recurrence or mortality.,Our study indicated that dirithromycin is adequate for improving the clinical cure rate of patients with AECOPD with few adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole are also recommended for disease treatment.,However, caution should still be exercised when using antibiotics to treat AECOPD.,Trial Registration Not applicable.,The online version of this article (doi: 10.1186/s12890-017-0541-0) contains supplementary material, which is available to authorized users. | Exacerbations of COPD are clinically relevant events with therapeutic and prognostic implications.,Yet, significant heterogeneity of clinical presentation and disease progression exists within acute exacerbations of COPD (AECOPD).,Currently, different phenotypes have been widely used to describe the characteristics among patients with AECOPD.,This has proved to be significant in the treatment and prediction of the outcomes of the disease.,In this review of published literature, the phenotypes of AECOPD were classified according to etiology, inflammatory biomarkers, clinical manifestation, comorbidity, the frequency of exacerbations, and so on.,This review concentrates on advancements in the use of phenotypes of AECOPD. | 1 |
The morphologic alterations of pulmonary small vessels measured by computed tomography (CT) have been used to evaluate chronic obstructive pulmonary disease (COPD).,However, the relationship between small pulmonary vascular alteration and acute exacerbations of COPD (AECOPD) is not well understood.,The aim of this study was to evaluate the cross-sectional area (CSA) of small pulmonary vessel alterations measured on CT images and investigate its relationship with the COPD severity staged by the degree of airflow limitation and the occurrence of AECOPD.,We retrospectively reviewed CT scans, clinical characteristics, and pulmonary function test results of 153 patients with COPD.,All the patients were divided into AECOPD and non-AECOPD group according to the COPD staging and pulmonary function test results.,The percentages of the total CSA less than 5 mm2 and equal to 5-10 mm2 over the lung area (%CSA<5 and %CSA5-10, respectively) were measured.,The %CSA<5 steadily decreased in relation to the increase of COPD severity.,In addition, %CSA<5 of the AECOPD group was significantly lower than that of the non-AECOPD group (0.41±0.13 versus 0.68±0.18, P<0.001), and the optimal cutoff value was 0.56 (sensitivity, 0.863; specificity, 0.731).,Therefore, small pulmonary vascular alteration, as measured by %CSA<5, could indicate not only the degree of COPD severity, but also the occurrence of AECOPD. | The popular methods for evaluating the initial therapeutic effect (ITE) of noninvasive positive pressure ventilation (NPPV) can only roughly reflect the therapeutic outcome of a patient’s ventilation because they are subjective, invasive and time-delayed.,In contrast, vibration response imaging (VRI) can monitor the function of a patient’s ventilation over the NPPV therapy in a non-invasive manner.,This study aimed to investigate the value of VRI in evaluating the ITE of NPPV for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Thirty-six AECOPD patients received VRI at three time points: before NPPV treatment (T1), at 15 min of NPPV treatment (T2), and at 15 min after the end of NPPV treatment (T4).,Blood gas analysis was also performed at T1 and at 2 hours of NPPV treatment (T3).,Thirty-nine healthy volunteers also received VRI at T1 and T2.,VRI examination at the time point T2 in either the patients or volunteers did not require any interruption of the on-going NPPV.,The clinical indices at each time point were compared between the two groups.,Moreover, correlations between the PaCO2 changes (T3 vs T1) and abnormal VRI scores (AVRIS) changes (T2 vs T1) were analyzed.,No significant AVRIS differences were found between T1 and T2 in the healthy controls (8.51 ± 3.36 vs.,8.53 ± 3.57, P > 0.05).,The AVRIS, dynamic score, MEF score and EVP score showed a significant decrease in AECOPD patients at T2 compared with T1 (P < 0.05), but a significant increase at T4 compared with T2 (P < 0.05).,We also found a positive correlation (R2 = 0.6399) between the PaCO2 changes (T3 vs T1) and AVRIS changes (T2 vs T1).,VRI is a promising noninvasive tool for evaluating the initial therapeutic effects of NPPV in AECOPD patients and predicting the success of NPPV in the early stage. | 1 |
Previously we generated a chronic obstructive pulmonary disease (COPD) specific knowledge base (http://www.copdknowledgebase.eu) from clinical and experimental data, text-mining results and public databases.,This knowledge base allowed the retrieval of specific molecular networks together with integrated clinical and experimental data.,The COPDKB has now been extended to integrate over 40 public data sources on functional interaction (e.g. signal transduction, transcriptional regulation, protein-protein interaction, gene-disease association).,In addition we integrated COPD-specific expression and co-morbidity networks connecting over 6 000 genes/proteins with physiological parameters and disease states.,Three mathematical models describing different aspects of systemic effects of COPD were connected to clinical and experimental data.,We have completely redesigned the technical architecture of the user interface and now provide html and web browser-based access and form-based searches.,A network search enables the use of interconnecting information and the generation of disease-specific sub-networks from general knowledge.,Integration with the Synergy-COPD Simulation Environment enables multi-scale integrated simulation of individual computational models while integration with a Clinical Decision Support System allows delivery into clinical practice.,The COPD Knowledge Base is the only publicly available knowledge resource dedicated to COPD and combining genetic information with molecular, physiological and clinical data as well as mathematical modelling.,Its integrated analysis functions provide overviews about clinical trends and connections while its semantically mapped content enables complex analysis approaches.,We plan to further extend the COPDKB by offering it as a repository to publish and semantically integrate data from relevant clinical trials.,The COPDKB is freely available after registration at http://www.copdknowledgebase.eu. | Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation.,Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy.,Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate.,In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators.,Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles.,Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization.,These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | 1 |
Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).,To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.,In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg).,Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.,In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD.,Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients.,In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals −46, 315mL) with a probability that the true treatment ratio was >0% (Pr(θ>0)) of 93% was observed in AECOPD.,However, FRI endpoints remained unchanged.,We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group.,We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD. | ► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences. | 1 |
This study aimed to investigate the serum inflammatory cytokines levels in patients with COPD, pneumonia and lung cancer, and assess the correlation between the levels of inflammatory cytokines levels and development of these diseases.,Two hundred thirty-two patients including 114 patients with pneumonia, 76 patients with chronic obstructive pulmonary disease (COPD) and 42 patients with lung cancer, and 62 age-matched healthy volunteers as controls were enrolled.,The pro-inflammatory cytokine IL-6, IL-2, IFN-γ, TNF-α, anti-inflammatory cytokines IL-4 and IL-10 in serum were analyzed by flow cytometry microsphere array (CBA).,We found that the levels of TNF-α and IL-10 in patients with lung cancer, COPD and pneumonia were significantly higher than control group.,The IL-6 in the lung cancer group were significantly increased compared with the controls and COPD group, pneumonia group.,IFN-γ and IL-2 levels were lower in lung cancer compared with controls and COPD group, pneumonia group.,TNF-α, IL-4 and IL-10 levels were increased in patients with COPD and pneumonia compared with controls.,In addition, the concentrations of IFN-γ and IL-6 were increased in acute exacerbation COPD (AECOPD) group compared with stable COPD group.,In conclusion, elevated TNF-α and IL-10 levels in serum may be related with lung diseases including lung cancer, COPD and pneumonia.,Additionally, IFN-γ and IL-6 might be potential biomarkers for the further deterioration of lung disease patients.,The increased concentrations of IFN-γ and IL-6 might be used to predict the exacerbation of COPD. | Microparticles (MPs) are small membrane vesicles of 0.1-1 µm which are released by cells following chemical, physical, and apoptotic stimuli.,MPs represent more than a miniature version of the cell.,Their composition and function depend not only on cellular origin, but also on stimuli.,Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by nearly irreversible lung destruction which results in airway limitation.,We investigated the presence and source of MPs in sputum of COPD patients to evaluate if changes in MP number and origin may reflect the pathophysiological conditions of disease and may serve as potential biomarkers for diagnostic and prognostic use.,Induced sputum samples were collected from 18 male subjects and liquefied with Sputasol.,MPs obtained were immunolabeled for leukocyte (CD11a), granulocyte (CD66b), monocyte-macrophage (CD11b), platelets and megakaryocytic cells (CD41), endothelial cells (CD31), and red blood cells (CD235ab) and analyzed by cytofluorimetry.,There was a negative correlation between CD31-MPs and forced expiratory volume in 1 second (R=−53, P<0.05) and CD66b-MP level was correlated with worse performance index of COPD such as the Body mass index airflow Obstruction, Dyspnea, and Exercise capacity (BODE); they were negatively correlated with 6-minute walking test: 0.65 and −0.64, respectively (P<0.05).,CD235ab-MPs showed a negative correlation with body mass index (R=−0.86, P<0.05), while there was a positive correlation with dyspnea index (R=0.91, P<0.05).,The main finding of this study was that MPs were detected in the sputum of patients affected by COPD.,The phenotype of some of them was related to the main COPD parameters.,These results suggest that MPs could be implicated in the pathogenesis of COPD. | 1 |
Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes.,In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies.,Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765.,One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD).,We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers).,We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10−35 and <10−8 respectively).,Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone.,Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10−6).,In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10−20) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968.,This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior.,This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia.,The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD.,We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017.,ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry.,Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa.,Propensity score matched models were used as sensitivity analyses.,A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up.,ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use).,A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001).,Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa.,Caution should be taken when administering high doses of ICS in severely ill patients with COPD.,These results should be confirmed in comparable cohorts and other settings. | COPD is a progressive inflammatory airway disease characterized by increased numbers of alveolar macrophages in the lungs.,Bacterial colonization of the lungs is a common feature in COPD and can promote inflammation through continual and repeated Toll-like receptor (TLR) stimulation.,We have studied the response of COPD alveolar macrophages to repetitive stimulation with TLR2 and TLR4 ligands.,We investigated the effect of sequential stimulation with different ligands to determine whether this results in tolerance or amplification of the immune response.,We stimulated alveolar macrophages from COPD patients (n=9) and smokers (n=8) with the TLR4 agonist lipopolysaccharide (LPS) or the TLR2 agonist Pam3CSK4 for 24 hours before restimulating again for 24 hours.,Cytokine protein release and gene expression were investigated.,Repetitive stimulation of COPD and smokers macrophages with LPS for both 24-hour periods caused a reduction in tumor necrosis factor α, CCL5, and IL-10 production compared to cells that were not exposed initially to LPS.,IL-6 and CXCL8 production were not significantly altered following repetitive LPS stimulation.,The same pattern was observed for repeated stimulation with Pam3CSK4.,Using COPD macrophages, LPS followed by Pam3CSK4 stimulation increased the levels of all cytokines compared to media followed by Pam3CSK4.,TLR tolerance in COPD alveolar macrophages occurs after repetitive stimulation with the same TLR ligand, but this only occurs for selected cytokines.,CXCL8 production is not reduced after repetitive TLR stimulation with the same ligand; this may be an important mechanism for the increased CXCL8 levels that have been observed in COPD.,We showed that TLR4 stimulation followed by TLR2 stimulation does not cause tolerance, but enhances cytokine production.,This may be a relevant mechanism by which bacteria cause excessive inflammation in COPD patients. | 1 |
A head-to-head study demonstrated the superiority of once-daily umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 mcg on trough forced expiratory volume in 1 s (FEV1) versus once-daily tiotropium/olodaterol (TIO/OLO) 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease (COPD).,This analysis evaluated the cost effectiveness of UMEC/VI versus TIO/OLO from a Spanish National Healthcare System perspective, using data from this study and Spanish literature.,This analysis was conducted from the perspective of the Spanish National Healthcare System with a 3-year horizon as base case.,A disease progression model using a linked risk equation approach was used to estimate disease progression and associated healthcare costs, and quality-adjusted life years (QALYs).,The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was used to develop the statistical risk equations for clinical endpoints, and costs were calculated using a health state approach (by dyspnea severity).,Utilities for QALY calculation were estimated using patient baseline characteristics within a regression fit to Spanish observational data.,Treatment effect, expressed as change from baseline in FEV1 was obtained from the head-to-head study and used in the model (UMEC/VI minus TIO/OLO difference: + 52 mL [95% confidence interval: 28, 77]).,Baseline patient characteristics were sourced from Spanish literature or the head-to-head study if unavailable.,A scenario analysis using only the intent-to-treat (ITT) population from the head-to-head study, and sensitivity analyses (including probabilistic sensitivity analyses), were conducted.,Direct healthcare costs (2017 Euro) were obtained from Spanish sources and costs and benefits were discounted at 3% per annum.,UMEC/VI was associated with small improvements in QALYs (+ 0.029) over a 3-year time horizon, compared with TIO/OLO, alongside cost savings of €393/patient.,The ITT scenario analysis and sensitivity analyses had similar results.,All probabilistic simulations resulted in UMEC/VI being less costly and more effective than TIO/OLO.,UMEC/VI dominated TIO/OLO (more effective and less expensive).,These results may aid payers and decision-makers in Spain when making judgements on which long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) treatments can be considered cost effective in Spain.,The online version of this article (10.1186/s12931-018-0916-7) contains supplementary material, which is available to authorized users. | The aim of this study was to evaluate the cost-effectiveness of the long-acting beta-2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator indacaterol/glycopyrronium (IND/GLY) as a maintenance treatment for COPD patients from the perspective of health care payer in Taiwan.,We adopted a patient-level simulation model, which included a cohort of COPD patients aged ≥40 years.,The intervention used in the study was the treatment using IND/GLY, and comparators were tiotropium or salmeterol/fluticasone combination (SFC).,Data related to the efficacy of drugs, incidence of exacerbation, and utility were obtained from clinical studies.,Direct costs were estimated from claims data based on the severity of COPD.,The cycle length was 6 months (to match forced expiratory volume in 1 second [FEV1] data), and the time horizons included 1, 3, 5, 10 years, and lifetime.,Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the model results.,Costs were expressed in US dollars with a discount rate of 3.0%.,Compared to tiotropium and SFC, the incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY) gained of patients treated with IND/GLY were US$5,987 and US$14,990, respectively.,One-way sensitivity analysis revealed that the improvement in FEV1 provided by IND/GLY, the distribution of patients with regard to the severity of COPD, and acute exacerbation rate ratio were the key drivers behind cost-effectiveness.,Adopting a willingness to pay of US$60,000 per QALY gained as the threshold, there was a 98.7% probability that IND/GLY was cost-effective compared to tiotropium.,Similarly, there was a 99.9% probability that IND/GLY was cost-effective compared to SFC.,As a maintenance treatment for COPD, we consider the dual bronchodilator IND/GLY as a cost-effective strategy when compared to either tiotropium or SFC. | 1 |
Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia.,We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn.,Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies.,Data extraction was completed independently by two reviewers.,The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration.,We included four trials; the quality of three was adequate.,In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant.,Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice.,There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes.,Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication.,In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly.,Intention to treat analyses should be used and interpreted appropriately. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer.,Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls.,Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers.,We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type.,From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history.,Genome-wide miRNA profiles were generated and evaluated using machine learning techniques.,For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family.,The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5).,We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis.,For selected miRNAs, qRT-PCR analysis was applied to validate the results.,In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer. | Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally.,Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD.,In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD.,Integrative analysis of whole-genome and exome sequencing data revealed that COPD and non-COPD groups showed high concordance in mutational burden and spectra.,Notably, we also found that EGFR mutations were more prevalent in LUAD patients without COPD, whereas mutated LRP1B was more frequently observed in LUAD patients with COPD.,In addition, multi-variable analysis with logistic regression demonstrated that mutation of LRP1B was a predictive marker for the presence of COPD in the patients with LUAD.,Our analysis demonstrated for the first time the high concordance in genomic alterations between the tumors from LUAD patients with and without COPD.,We also identified higher prevalence of LRP1B among the LUAD patients with COPD, which might help understand the underlying mechanisms which link COPD and lung cancer. | 1 |
To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden.,Primary health care centres (PHCCs) in Stockholm, Sweden.,A total of 59 PCPs.,Semi-structured individual and focus-group interviews between 2012 and 2014.,Data were analysed inspired by grounded theory methods (GTM).,Time-pressured patient-doctor consultations lead to deprioritization of COPD.,During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients.,The reasons PCPs gave for deprioritizing COPD are: “Not becoming aware of COPD”, “Not becoming concerned due to clinical features”, “Insufficient local routines for COPD care”, “Negative personal attitudes and views about COPD”, “Managing diagnoses one at a time”, and “Perceiving a patient’s motivation as low’’.,De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi-morbidity.,A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines.,Key pointsUnder-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.,Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.,Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD. | Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world, and its associated health burdens and costs are mounting.,Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively fruitless effort, since treatments other than already ubiquitous smoking-cessation efforts were unlikely to alter its course.,However, there is strong evidence to suggest that the majority of patients with objective COPD are not aware of their condition, and this leads to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment.,Novel methods of diagnostic testing, community health programs, and primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages - where recent evidence suggests a rapid decline in lung function occurs and may be prevented if acted upon.,This review explores the evidence to support the efforts to justify programs aimed at early diagnosis, alternative diagnostic strategies that may augment traditional spirometry, therapeutic modalities that could potentially be used in the future to alter early lung-function decline, and emphasizes the necessary cooperative role that physicians, patients, communities, and governments need to play to realize the significant health impact that stands to be gained. | 1 |
Cigarette smoking causes Chronic Obstructive Pulmonary Disease (COPD), the 3rd leading cause of death in the U.S.,CFTR ion transport dysfunction has been implicated in COPD pathogenesis, and is associated with chronic bronchitis.,However, susceptibility to smoke induced lung injury is variable and the underlying genetic contributors remain unclear.,We hypothesized that presence of CFTR mutation heterozygosity may alter susceptibility to cigarette smoke induced CFTR dysfunction.,Consequently, COPD patients with chronic bronchitis may have a higher rate of CFTR mutations compared to the general population.,Primary human bronchial epithelial cells derived from F508del CFTR heterozygotes and mice with (CFTR+/-) and without (CFTR+/+) CFTR heterozygosity were exposed to whole cigarette smoke (WCS); CFTR-dependent ion transport was assessed by Ussing chamber electrophysiology and nasal potential difference measurements, respectively.,Caucasians with COPD and chronic bronchitis, age 40 to 80 with FEV1/FVC < 0.70 and FEV1 < 60% predicted, were selected for genetic analysis from participants in the NIH COPD Clinical Research Network’s Azithromycin for Prevention of Exacerbations of COPD in comparison to 32,900 Caucasian women who underwent prenatal genetic testing.,Genetic analysis involved an allele-specific genotyping of 89 CFTR mutations.,Exposure to WCS caused a pronounced reduction in CFTR activity in both CFTR (+/+) cells and F508del CFTR (+/-) cells; however, neither the degree of decrement (44.7% wild-type vs.,53.5% F508del heterozygous, P = NS) nor the residual CFTR activity were altered by CFTR heterozygosity.,Similarly, WCS caused a marked reduction in CFTR activity measured by NPD in both wild type and CFTR heterozygous mice, but the severity of decrement (91.1% wild type vs.,47.7% CF heterozygous, P = NS) and the residual activity were not significantly affected by CFTR genetic status.,Five of 127 (3.9%) COPD patients with chronic bronchitis were heterozygous for CFTR mutations which was not significantly different from controls (4.5%) (P = NS).,The magnitude of WCS induced reductions in CFTR activity was not affected by the presence of CFTR mutation heterozygosity.,CFTR mutations do not increase the risk of COPD with chronic bronchitis.,CFTR dysfunction due to smoking is primarily an acquired phenomenon and is not affected by the presence of congenital CFTR mutations. | Factors determining the onset and severity of chronic obstructive pulmonary disease remain poorly understood.,Previous studies demonstrated that airway surface dehydration in βENaC-overexpressing (βENaC-Tg) mice on a mixed genetic background caused either neonatal mortality or chronic obstructive lung disease suggesting that the onset of lung disease was modulated by the genetic background.,To test this hypothesis, we backcrossed βENaC-Tg mice onto two inbred strains (C57BL/6 and BALB/c) and studied effects of the genetic background on neonatal mortality, airway ion transport and airway morphology.,Further, we crossed βENaC-Tg mice with CFTR-deficient mice to validate the role of CFTR in early lung disease.,We demonstrate that the C57BL/6 background conferred increased CFTR-mediated Cl− secretion, which was associated with decreased mucus plugging and mortality in neonatal βENaC-Tg C57BL/6 compared to βENaC-Tg BALB/c mice.,Conversely, genetic deletion of CFTR increased early mucus obstruction and mortality in βENaC-Tg mice.,We conclude that a decrease or absence of CFTR function in airway epithelia aggravates the severity of early airway mucus obstruction and related mortality in βENaC-Tg mice.,These results suggest that genetic or environmental factors that reduce CFTR activity may contribute to the onset and severity of chronic obstructive pulmonary disease and that CFTR may serve as a novel therapeutic target. | 1 |
The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED).,Such information could help stratify these patients and guide medical decision-making.,The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit.,This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals.,Recruitment started in June 2008 and ended in September 2010.,Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up.,Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit.,Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample.,The score was compared with other published prediction rules for patients with stable COPD.,In total, 2,487 patients were included in the study.,Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85).,Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model.,The same variables were predictors of death at 1 month (AUC = 0.85).,Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better.,Five clinical predictors easily available in the ED, and also in the primary care setting, can be used to create a simple and easily obtained score that allows clinicians to stratify patients with eCOPD upon ED arrival and guide the medical decision-making process. | Chronic obstructive lung disease (COPD) exacerbations are a significant cause of morbidity and mortality.,Data regarding factors which causes or prevents exacerbations is very limited.,The aim of this systematic review is to summarize the results from available studies to identify potential risk factors for hospital admission and/or re-admission among patients experiencing COPD exacerbations.,We undertook a systematic review of the literature.,Potential studies were identified by searching the electronic databases: PubMed, EMBASE, BIOSIS, CINAHL, PsycINFO, Cochrane library, reference lists in trial reports, and other relevant articles.,Seventeen articles that met the predefined inclusion criteria were identified.,Heterogeneity of study designs, risk factors and outcomes restrict the result to only a systematic review and precluded a formal meta-analysis.,In this review, three predictive factors: previous hospital admission, dyspnea and oral corticosteroids were all found to be significant risk factors of readmissions and variables including using long term oxygen therapy, having low health status or poor health related quality of life and not having routine physical activity were all associated with an increased risk of both admission and readmission to hospital.,There are a number of potential modifiable factors that are independently associated with a higher risk of COPD exacerbation requiring admission/readmission to the hospital.,Identifying these factors and the development of targeted interventions could potentially reduce the number and severity of such exacerbations. | 1 |
A variety of large randomized controlled trials (RCT’s) evaluating pharmacotherapy in chronic obstructive pulmonary disease (COPD) patients does exist.,One of the drugs that has been tested is the new long-acting anticholinergic glycopyrronium bromide.,As the generalizability of results from RCT’s is questionable we designed a longitudinal, prospective non-interventional study (DACCORD) of two years duration plus two years extension with at least 6000 participants in approximately 500 primary and secondary care practices in Germany (within the new established COPD National Prospective Registry), to assess patient reported outcomes (PRO’s), lung function, adherence and drug safety.,To circumvent the hurdle of inappropriate COPD diagnosis in a non-interventional trial, patients have to fulfill the inclusion criteria of the COPD disease management program (DMP) of the German statutory health insurances.,Patient management should follow the German national COPD guidelines, which are based on Global Initiative for Chronic Obstructive Lung Disease 2007 (GOLD) report.,Labels of prescribed drugs should also be taken into account.,Patients received treatment as part of their standard care: at the discretion of the investigator patients were included in one of two arms.,A: standard care with glycopyrronium containing regimen, and arm B: standard care without glycopyrronium.,For 2016 we expect important results regarding longitudinal development of PRO’s including exacerbations, lung function, adherence and side effects.,We also investigate applicability of the new GOLD staging system in usual care.,Data on diagnostic and treatment modalities in current German primary and secondary care, as well as pharmaco-economic data will be generated.,1.,German Register for non-interventional studies: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb.,2.,EMA EnCePP http://www.encepp.eu/. | In this narrative review, we put self-management in the context of a 50-year history of research about how patients with COPD respond to their illness.,We review a definition of self-management, and emphasize that self-management should be combined with disease management and the chronic care model in order to be effective.,Reviewing the empirical status of self-management in COPD, we conclude that self-management is part and parcel of modern, patient-oriented biopsychosocial care.,In pulmonary rehabilitation programs, self-management is instrumental in improving patients’ functional status and quality of life.,We conclude by emphasizing how studying the way persons with COPD make sense of their illness helps in refining self-management, and thereby patient-reported outcomes in COPD. | 1 |
High-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation.,However, evidence to support the use of HFNC in chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited.,This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure.,COPD patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to HFNC or NIV at extubation at two large tertiary academic teaching hospitals.,The primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (NIV for patients in the NFNC group or vice versa).,Ninety-six patients were randomly assigned to the HFNC group or NIV group.,After secondary exclusion, 44 patients in the HFNC group and 42 patients in the NIV group were included in the analysis.,The treatment failure rate in the HFNC group was 22.7% and 28.6% in the NIV group-risk difference of − 5.8% (95% CI, − 23.8-12.4%, p = 0.535), which was significantly lower than the non-inferior margin of 9%.,Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of − 50.0% (95% CI, − 74.6 to − 12.9%, p = 0.015).,One hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation (p < 0.050).,Twenty-four hours after extubation, the respiratory rate of the HFNC group had returned to baseline, but the NIV group was still higher than the baseline.,Forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline.,The average number of daily airway care interventions in the NIV group was 7 (5-9.3), which was significantly higher than 6 (4-7) times in the HFNC group (p = 0.006).,The comfort score and incidence of nasal and facial skin breakdown of the HFNC group was also significantly better than that of the NIV group [7 (6-8) vs 5 (4-7), P < 0.001] and [0 vs 9.6%, p = 0.027], respectively.,Among COPD patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of HFNC after extubation did not result in increased rates of treatment failure compared with NIV.,HFNC also had better tolerance and comfort than NIV.,chictr.org (ChiCTR1800018530).,Registered on 22 September 2018, http://www.chictr.org.cn/usercenter.aspx | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide.,Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown.,Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell-cell communication tools.,They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases.,Recently, EVs have attracted considerable attention in pulmonary research.,In this review, we summarize the recent findings of EV-mediated COPD pathogenesis.,We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD. | COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. | 1 |
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