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Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,COPD is characterized by poor treatment adherence, and patient medication preferences may contribute to adherence.,A discrete choice experiment with an internet panel drawn from the USA was used to evaluate preference and willingness to pay (WTP) of COPD patients for long-acting maintenance medications.,Key attributes derived from earlier qualitative research (brief literature review and focus groups) with COPD patients on maintenance therapy included symptom relief, speed of feeling medication start to work, inhaler ease of use, rescue medication use, side effects, and monthly out-of-pocket co-pay.,Patients were presented with hypothetical medications with different profiles and asked which they preferred.,Utilities and marginal WTP in monthly co-pay dollars were estimated for all patients and by severity.,Utilities for 515 participants were in the expected direction and highest for the most favorable attribute levels.,Each attribute evaluated was important, and participants were willing to pay a premium to obtain each benefit.,On average, WTP was as high as $US64 for complete symptom relief, $US59 for no side effects, $US32 to rarely use rescue medication, $US16 for a quick and easy to use inhaler, and $US13 for feeling medication work quickly (within 5 min; average WTP $US18/month for patients with severe/very severe COPD).,As expected, efficacy and safety were most valued by patients; however, this study showed that other COPD medication attributes, such as rescue medication, ease of use, and feeling medication work quickly, are also important in patient preferences. | For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction.,The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies.,The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD.,Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use.,Patients’ preference was assessed after completion of both study periods.,Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler.,For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively.,In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).,Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities.,Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler.,These are important factors for optimum dose delivery and successful COPD management. | 1 |
Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period.,However, longer period follow-up studies are still lacking.,Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.,A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study.,We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years.,Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.,IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance.,In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02].,CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.,The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.,No.:NCT00605540 | Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide.,Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.,The objective of this study was to assess IL-1 α and β expression in COPD patients and to investigate their respective roles in perpetuating cigarette smoke-induced inflammation.,Functional studies were pursued in smoke-exposed mice using gene-deficient animals, as well as blocking antibodies for IL-1α and β.,Here, we demonstrate an underappreciated role for IL-1α expression in COPD.,While a strong correlation existed between IL-1α and β levels in patients during stable disease and periods of exacerbation, neutrophilic inflammation was shown to be IL-1α-dependent, and IL-1β- and caspase-1-independent in a murine model of cigarette smoke exposure.,As IL-1α was predominantly expressed by hematopoietic cells in COPD patients and in mice exposed to cigarette smoke, studies pursued in bone marrow chimeric mice demonstrated that the crosstalk between IL-1α+ hematopoietic cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation.,IL-1α/IL-1R1-dependent activation of the airway epithelium also led to exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed mice, a previously reported model of COPD exacerbation.,This study provides compelling evidence that IL-1α is central to the initiation of smoke-induced neutrophilic inflammation and suggests that IL-1α/IL-1R1 targeted therapies may be relevant for limiting inflammation and exacerbations in COPD. | 1 |
The COVID-19 pandemic has impacted specialty chronic obstructive pulmonary disease (COPD) care.,We examined the degree to which care has moved to remote approaches, eliciting clinician and patient perspectives on what is appropriate for ongoing remote delivery.,Using an online research platform, we conducted a survey and consensus-building process involving clinicians and patients with COPD.,Fifty-five clinicians and 19 patients responded.,The majority of clinicians felt able to assess symptom severity (n=52, 95%), reinforce smoking cessation (n=46, 84%) and signpost to other healthcare resources (n=44, 80%).,Patients reported that assessing COPD severity and starting new medications were being addressed through remote care.,Forty-three and 31 respondents participated in the first and second consensus-building rounds, respectively.,When asked to rate the appropriateness of using remote delivery for specific care activities, respondents reached consensus on 5 of 14 items: collecting information about COPD and overall health status (77%), providing COPD education and developing a self-management plan (74%), reinforcing smoking cessation (81%), deciding whether patients should seek in-person care (72%) and initiating a rescue pack (76%).,Adoption of remote care delivery appears high, with many care activities partially or completely delivered remotely.,Our work identifies strengths and limitations of remote care delivery. | COPD remains a major health problem in Japan.,Patients with COPD experience a reduced quality of life (QoL) and have a higher chance of work impairment and productivity loss.,However, there is a lack of data on the impact of COPD in terms of QoL and work activity impairment in Japan.,This study assessed the socioeconomic burden of COPD in Japan and the impact it may have on the working age population.,This was a 2-year retrospective chart review in COPD patients aged ≥40 years, with at least one health care visit to clinic or hospital in the previous 12 months.,Patients were required to have available medical charts for at least the previous 24 months.,Symptoms were assessed using COPD assessment test score; EuroQoL Group 5 Dimension (EQ-5D-5L) and work productivity and activity impairment general health questionnaires were used to evaluate health-related QoL and work productivity, and health care resource utilization data were obtained from clinical charts.,In total, 71 patients aged <65 years, and 151 patients aged ≥65 years were included; the majority of patients had moderate or severe airflow limitation.,Exacerbations (moderate or severe) were reported by ~35% of patients in both age groups; 52.1% and 62.9% of patients in the <65-year and ≥65-year age groups had COPD assessment test scores ≥10.,EQ-5D-5L index scores in the <65-year and ≥65-year age groups were 0.79 and 0.77, respectively.,Work productivity and activity impairment scores were higher in <65-year age group.,Annual costs of health care resource use per patient in the <65-year and ≥65-year age groups were ¥438,975 (US$4,389) and ¥467,871 (US$4,678), respectively.,Costs due to productivity loss were estimated to be ¥5,287,024 (US$52,870) in the <65-year age group and ¥3,018,974 (US$30,187) in the ≥65-year age group.,COPD represents a significant socioeconomic burden in Japan.,Patients with COPD report significant use of health care resources.,Higher impact on work impairment and productivity loss was observed frequently in the working age population. | 1 |
Chronic obstructive pulmonary disease (COPD) is a severe public health threat world-wide.,Cigarette smoke (CS)-induced airway epithelial cell death is a major pathway of pathogenesis in emphysema, a subtype of COPD.,Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that catalyzes mono- and di-methylation on arginine residues within histone and non-histone proteins to modulate a variety of life processes, such as apoptosis.,However, its role in CS-induced lung epithelial death has not been fully elucidated.,Here we report that PRMT6 was decreased in mouse lung tissues from a cigarette smoke extract (CSE)-mediated experimental emphysematous model and in CSE treated or cigarette smoke exposed lung epithelial cells.,Depletion of PRMT6 increased the protein levels of phosphatase PTEN and PI3K regulatory subunit p85 but decreased a downstream kinase PDK1, resulting in AKT dephosphorylation and thereafter, lung epithelial cell death.,Knockout of PRMT6 inhibited epithelial survival and promoted CSE-mediated epithelial cell death, while ectopic expression of PRMT6 protein partially reversed epithelial cell death via PI3K/AKT-mediated cell survival signaling in CSE cellular models.,These findings demonstrate that PRMT6 plays a crucial role in CS-induced bronchial epithelial cell death that may be a potential therapeutic target against the airway cell death in CS-induced COPD. | Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs.,Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet.,We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade.,Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke.,The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied.,However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between.,Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively.,Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 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 |
To evaluate the relationship between alcohol consumption and the risk of acute exacerbation of COPD (AECOPD).,We conducted a secondary analysis of data previously collected in a large, multicenter trial of daily azithromycin in COPD.,To analyze the relationship between amount of baseline self-reported alcohol consumption in the past 12 months and subsequent AECOPD, we categorized the subjects as minimal (<1 drink/month), light-to-moderate (1-60 drinks/month), or heavy alcohol users (>60 drinks/month).,The primary outcome was time to first AECOPD and the secondary outcome was AECOPD rate during the 1-year study period.,Of the 1,142 enrolled participants, 1,082 completed baseline alcohol questionnaires and were included in this analysis.,Six hundred and forty-five participants reported minimal alcohol intake, 363 reported light-to-moderate intake, and 74 reported heavy intake.,There were no statistically significant differences in median time to first AECOPD among minimal (195 days), light-to-moderate (241 days), and heavy drinkers (288 days) (P=0.11).,The mean crude rate of AECOPD did not significantly differ between minimal (1.62 events per year) and light-to-moderate (1.44 events per year) (P=0.095), or heavy drinkers (1.68 events per year) (P=0.796).,There were no significant differences in hazard ratios for AECOPD after adjustment for multiple covariates.,Among persons with COPD at high risk of exacerbation, we found no significant relationship between self-reported baseline alcohol intake and subsequent exacerbations.,The number of patients reporting heavy alcohol intake was small and further study is needed to determine the effect of heavy alcohol intake on AECOPD risk. | Influenza vaccination rates are low in adults with chronic obstructive pulmonary disease (COPD).,A diagnostic breathing test in adults with COPD may increase vaccination rates; however, research has not demonstrated this relationship.,The purpose of this research was to determine if adults with COPD diagnosed by a breathing test were more likely to have had an influenza vaccination during the past 12 months when compared to those with COPD diagnosed without a breathing test.,This was a cross-sectional study using data from the 2011 Behavioral Risk Factor Surveillance System.,Logistic regression examined the relationship between influenza vaccination among adults with COPD diagnosed with a breathing test (n = 13,201) compared to those diagnosed without a breathing test (n = 3,108), after controlling for all potential confounders.,Overall, 49% of respondents with COPD received an influenza vaccination within the past 12 months and 78% reported their COPD was diagnosed by a breathing test.,The prevalence of influenza vaccination in the past 12 months was greater in those with COPD diagnosed by a breathing test (53%) compared to those diagnosed without a breathing test (36%).,In adjusted analysis, adults with COPD who had a breathing test were 31% (confidence interval 1.1, 1.6) more likely to have received an influenza vaccination in the past 12 months compared to those without a breathing test.,A diagnostic breathing test for COPD was associated with increased likelihood of having had an influenza vaccination in the past 12 months.,This may be an indicator of the relationship between knowledge of lung function and the need for preventative care, a sign of quality healthcare, or good health-seeking behaviors in patients with COPD.,This research is the first to use a nationally representative sample to suggest that spirometry diagnosis of COPD may increase rates of influenza vaccination. | 1 |
The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear.,Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults.,A cross-sectional study was conducted in southern China.,Seven clusters were randomly selected from four cities across Guangdong province.,Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry.,COPD was defined as a post-bronchodilator FEV1/FVC less than 70%.,Atmosphere PM sampling was conducted across the clusters along with our survey.,Of the subjects initially recruited, 84.4% (n=5993) were included for analysis.,COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters.,COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1.,A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI −43 to −9) decrease in FEV1, a 28 mL (−49 to −8) decrease in FVC and a 0.09% decrease (−0.170 to −0.010) in FEV1/FVC ratio.,The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker.,Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function.,ChiCTR-OO-14004264; Post-results. | Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution.,However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far.,Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women.,We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.,In consecutive cross sectional studies conducted between 1985-1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany.,NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data.,Lung function was determined and COPD was defined by using the GOLD criteria.,Chronic respiratory symptoms and possible confounders were defined by questionnaire data.,Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.,The prevalence of COPD (GOLD stages 1-4) was 4.5%.,COPD and pulmonary function were strongest affected by PM10 and traffic related exposure.,A 7 μg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%-7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%-5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03-1.72) for COPD.,Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06-3.02) than for those living farther away.,Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.,Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function. | 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. | We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades.,However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up.,We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies.,Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD.,In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association.,22 studies comprising 21,150 participants were included in this analysis.,Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR = 1.34, 95% CI = 1.01-1.78), whereas overweight (RR = 0.47, 95% CI = 0.33-0.68) and obese (RR = 0.59, 95% CI = 0.38-0.91) patients were associated with lower mortality.,We further performed a baseline risk-adjusted analysis and obtained statistically similar results.,Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality.,However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies. | 1 |
Previous studies have suggested that chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer.,There are some evidence that people with diabetes are at a risk of developing many forms of cancer, but inconclusive with regard to lung cancer.,The aim of this study was to evaluate whether COPD with or without type 2 diabetes mellitus (T2DM) influences the risk of developing lung cancer.,This is a retrospective cohort study consisting of 20,730 subjects newly diagnosed with COPD (“cases”).,Their data was collected from the National Health Insurance system of Taiwan from 1998 to 2010.,Among these patients, 5,820 patients had T2DM and 14,910 patients did not have T2DM.,The retrospective matched control group consisted of 20,729 subjects without either COPD or T2DM.,The control group was matched with the cases for sex, age, and index year (the year that the patient was diagnosed with COPD).,The subjects were followed until the end of 2011.,The findings of our study showed that the risk of lung cancer was higher in the COPD group than in the non-COPD group, with adjusted hazard ratio (HR) of 5.02 [95% confidence interval (CI) = 4.23-5.94] among total case group, adjusted HR was 5.38 (95% CI = 4.52-6.40) in the cohort without T2DM and adjusted HR was 4.05 (95% CI = 3.26-5.03) in the cohort with T2DM.,We observed a significantly protective effect from lung cancer (adjusted HR = 0.75, 95% CI = 0.63-0.90) of diabetic cohort than non-diabetic cohort among patients with COPD.,Patients with COPD had a significantly higher risk of developing lung cancer than healthy people.,However, there was a protective effect of T2DM for lung cancer among patients with COPD.,Further investigation may be needed to corroborate the mechanism or bring up reliable reasons. | Many people with COPD report difficulties falling asleep or staying asleep, insufficient sleep duration, or nonrestorative sleep.,Cognitive behavioral therapy for insomnia (CBT-I) has proved effective not only in people with primary insomnia but also in people with insomnia comorbid with psychiatric and medical illness (eg, depression, cancer, and chronic pain).,However, CBT-I has rarely been tested in those with COPD who have disease-related features that interfere with sleep and may lessen the effectiveness of such therapies.,The purpose of this study was to determine the feasibility of applying a CBT-I intervention for people with COPD and to assess the impact of CBT-I on insomnia severity and sleep-related outcomes, fatigue, mood, and daytime functioning.,The study had two phases.,In Phase 1, a 6-weekly session CBT-I intervention protocol in participants with COPD was assessed to examine feasibility and acceptability.,Phase 2 was a small trial utilizing a prospective two-group pre- and post-test design with random assignment to the six-session CBT-I or a six-session wellness education (WE) program to determine the effects of each intervention, with both interventions being provided by a nurse behavioral sleep medicine specialist.,Fourteen participants (five in Phase 1 and nine in Phase 2) completed six sessions of CBT-I and nine participants completed six sessions of WE.,Participants indicated that both interventions were acceptable.,Significant positive treatment-related effects of the CBT-I intervention were noted for insomnia severity (P = 0.000), global sleep quality (P = 0.002), wake after sleep onset (P = 0.03), sleep efficiency (P = 0.02), fatigue (P = 0.005), and beliefs and attitudes about sleep (P = 0.000).,Significant positive effects were noted for depressed mood after WE (P = 0.005).,Results suggest that using CBT-I in COPD is feasible and the outcomes compare favorably with those obtained in older adults with insomnia in the context of other chronic illnesses. | 1 |
The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD).,To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use.,Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication.,The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire).,Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device.,Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years).,Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs.,27.3%; P<0.001).,Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs.,5.3, respectively; P<0.001).,After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs.,3.3%, respectively).,Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler.,The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler. | For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction.,The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies.,The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD.,Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use.,Patients’ preference was assessed after completion of both study periods.,Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler.,For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively.,In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).,Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities.,Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler.,These are important factors for optimum dose delivery and successful COPD management. | 1 |
People with chronic obstructive pulmonary disease (COPD) sometimes experience anxiety, depression and comorbid cognitive deficits.,Rather than being merely a consequence of symptom-related physical impairments these additional problems may be part of the clinical course of the condition.,The relationship between the physical and psychological aspects of the condition is illustrated by the patterns of use of non-invasive ventilation (NIV); NIV is often rejected or used inappropriately, resulting in clinical deterioration and an increase in health care costs.,The study aims to analyse the effects of psychological support on the acceptance of, and adherence to, NIV.,The primary outcome will be a latent variable related to indices of use of NIV equipment and adherence to treatment regime; while survival rates and psychological variables will constitute the secondary outcomes.,A two-arm randomised controlled trial will be conducted.,We aim to recruit 150 COPD patients for whom NIV is indicated.,The experimental group will receive a brief course of psychological support that will include counselling, relaxation and mindfulness-based exercises.,In some cases, it will also include neuropsychological rehabilitation exercises.,Support will be delivered via four to eight meetings at the HD Respiratory Rehabilitation Unit, at home or via telemedicine.,Controls will receive standard care and watch educational videos related to the management of their disease.,This investigation will gain insight about the role of a psychological intervention as part of a treatment plan during the process of adaptation to NIV in COPD patients.,ClinicalTrials.gov, ID: NCT02499653.,Registered on 14 July 2015.,The online version of this article (doi:10.1186/s13063-017-1802-1) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease characterized by nonreversible airway obstruction.,Well-characterized symptoms such as exertional dyspnea and fatigue have a negative impact on patients’ quality of life (QoL) and restrict physical activity in daily life.,The impact of COPD symptoms on QoL is often underestimated; for example, 36% of patients who describe their symptoms as being mild-to-moderate also admit to being too breathless to leave the house.,Additionally, early morning and nighttime symptoms are a particular problem.,Methods are available to allow clinicians to accurately assess COPD symptoms, including patient questionnaires.,Integrated approaches to COPD management, particularly pulmonary rehabilitation, are effective strategies for addressing symptoms, improving exercise capacity and, potentially, also increasing physical activity.,Inhaled bronchodilators continue to be the mainstay of drug therapy in COPD, where options can be tailored to meet patients’ needs with careful selection of the inhaled medication and the device used for its delivery.,Overall, an integrated approach to disease management should be considered for improving QoL and subsequent patient outcomes in COPD. | 1 |
Although patients with COPD often have various comorbidities and symptoms, limited data are available on the contribution of these aspects to health care costs.,This study analyzes the association of frequent comorbidities and common symptoms with the annual direct and indirect costs of patients with COPD.,Self-reported information on 33 potential comorbidities and symptoms (dyspnea, cough, and sputum) of 2,139 participants from the baseline examination of the German COPD cohort COSYCONET was used.,Direct and indirect costs were calculated based on self-reported health care utilization, work absence, and retirement.,The association of comorbidities, symptoms, and COPD stage with annual direct/indirect costs was assessed by generalized linear regression models.,Additional models analyzed possible interactions between COPD stage, the number of comorbidities, and dyspnea.,Unadjusted mean annual direct costs were €7,263 per patient.,Other than COPD stage, a high level of dyspnea showed the strongest driving effect on direct costs (+33%).,Among the comorbidities, osteoporosis (+38%), psychiatric disorders (+36%), heart disease (+25%), cancer (+24%), and sleep apnea (+21%) were associated with the largest increase in direct costs (p<0.01).,A sub-additive interaction between advanced COPD stage and a high number of comorbidities reduced the independent cost-driving effects of these factors.,For indirect costs, besides dyspnea (+34%), only psychiatric disorders (+32%) and age (+62% per 10 years) were identified as significant drivers of costs (p<0.04).,In the subsequent interaction analysis, a high number of comorbidities was found to be a more crucial factor for increased indirect costs than single comorbidities.,Detailed knowledge about comorbidities in COPD is useful not only for clinical purposes but also to identify relevant cost factors and their interactions and to establish a ranking of major cost drivers.,This could help in focusing therapeutic efforts on both clinically and economically important comorbidities in COPD. | Anxiety and depression are common and treatable risk factors for re-hospitalisation and death in patients with COPD.,The degree of lung function impairment does not sufficiently explain anxiety and depression.,The BODE index allows a functional classification of COPD beyond FEV1.,The aim of this cross-sectional study was (1) to test whether the BODE index is superior to the GOLD classification for explaining anxious and depressive symptoms; and (2) to assess which components of the BODE index are associated with these psychological aspects of COPD.,COPD was classified according to the GOLD stages based on FEV1%predicted in 122 stable patients with COPD.,An additional four stage classification was constructed based on the quartiles of the BODE index.,The hospital anxiety and depression scale was used to assess anxious and depressive symptoms.,The overall prevalence of anxious and depressive symptoms was 49% and 52%, respectively.,The prevalence of anxious symptoms increased with increasing BODE stages but not with increasing GOLD stages.,The prevalence of depressive symptoms increased with both increasing GOLD and BODE stages.,The BODE index was superior to FEV1%predicted for explaining anxious and depressive symptoms.,Anxious symptoms were explained by dyspnoea.,Depressive symptoms were explained by both dyspnoea and reduced exercise capacity.,The BODE index is superior to the GOLD classification for explaining anxious and depressive symptoms in COPD patients.,These psychological consequences of the disease may play a role in future classification systems of 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. | Nontypeable Haemophilus influenzae is an important pathogen in patients with chronic obstructive pulmonary disease (COPD).,To elucidate the bacterial pathways undergoing in vivo evolutionary adaptation, we compared bacterial genomes collected over time from 13 COPD patients and identified recurrent genetic changes arising in independent bacterial lineages colonizing different patients.,Besides finding changes in phase-variable genes, we found recurrent loss-of-function mutations in the ompP1 (fadL) gene.,We show that loss of OmpP1/FadL function reduces this bacterium’s ability to infect cells via the hCEACAM1 epithelial receptor but also increases its resistance to bactericidal fatty acids enriched within the COPD lung, suggesting a case of antagonistic pleiotropy that restricts ΔfadL strains’ niche.,These results show how H. influenzae adapts to host-generated inflammatory mediators in the COPD airways.,Tracking bacterial evolution during chronic infection provides insights into how host selection pressures shape bacterial genomes.,The human-restricted opportunistic pathogen nontypeable Haemophilus influenzae (NTHi) infects the lower airways of patients suffering chronic obstructive pulmonary disease (COPD) and contributes to disease progression.,To identify bacterial genetic variation associated with bacterial adaptation to the COPD lung, we sequenced the genomes of 92 isolates collected from the sputum of 13 COPD patients over 1 to 9 years.,Individuals were colonized by distinct clonal types (CTs) over time, but the same CT was often reisolated at a later time or found in different patients.,Although genomes from the same CT were nearly identical, intra-CT variation due to mutation and recombination occurred.,Recurrent mutations in several genes were likely involved in COPD lung adaptation.,Notably, nearly a third of CTs were polymorphic for null alleles of ompP1 (also called fadL), which encodes a bifunctional membrane protein that both binds the human carcinoembryonic antigen-related cell adhesion molecule 1 (hCEACAM1) receptor and imports long-chain fatty acids (LCFAs).,Our computational studies provide plausible three-dimensional models for FadL’s interaction with hCEACAM1 and LCFA binding.,We show that recurrent fadL mutations are likely a case of antagonistic pleiotropy, since loss of FadL reduces NTHi’s ability to infect epithelia but also increases its resistance to bactericidal LCFAs enriched within the COPD lung.,Supporting this interpretation, truncated fadL alleles are common in publicly available NTHi genomes isolated from the lower airway tract but rare in others.,These results shed light on molecular mechanisms of bacterial pathoadaptation and guide future research toward developing novel COPD therapeutics. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | Many people with COPD report difficulties falling asleep or staying asleep, insufficient sleep duration, or nonrestorative sleep.,Cognitive behavioral therapy for insomnia (CBT-I) has proved effective not only in people with primary insomnia but also in people with insomnia comorbid with psychiatric and medical illness (eg, depression, cancer, and chronic pain).,However, CBT-I has rarely been tested in those with COPD who have disease-related features that interfere with sleep and may lessen the effectiveness of such therapies.,The purpose of this study was to determine the feasibility of applying a CBT-I intervention for people with COPD and to assess the impact of CBT-I on insomnia severity and sleep-related outcomes, fatigue, mood, and daytime functioning.,The study had two phases.,In Phase 1, a 6-weekly session CBT-I intervention protocol in participants with COPD was assessed to examine feasibility and acceptability.,Phase 2 was a small trial utilizing a prospective two-group pre- and post-test design with random assignment to the six-session CBT-I or a six-session wellness education (WE) program to determine the effects of each intervention, with both interventions being provided by a nurse behavioral sleep medicine specialist.,Fourteen participants (five in Phase 1 and nine in Phase 2) completed six sessions of CBT-I and nine participants completed six sessions of WE.,Participants indicated that both interventions were acceptable.,Significant positive treatment-related effects of the CBT-I intervention were noted for insomnia severity (P = 0.000), global sleep quality (P = 0.002), wake after sleep onset (P = 0.03), sleep efficiency (P = 0.02), fatigue (P = 0.005), and beliefs and attitudes about sleep (P = 0.000).,Significant positive effects were noted for depressed mood after WE (P = 0.005).,Results suggest that using CBT-I in COPD is feasible and the outcomes compare favorably with those obtained in older adults with insomnia in the context of other chronic illnesses. | 1 |
There is a large gap in the treatments for patients with COPD according to the Global Initiative for COPD (GOLD) recommendations.,Determining the situation of therapies in the real world is necessary.,This study aimed to characterize the real-world practical therapies of COPD and prognosis of patients after treatment for 1 year.,This study was a multicenter prospective observational study performed using a database set up by the Second Xiangya Hospital of Center South University.,Detailed usage information for pharmacotherapies and nonpharmacotherapies for patients was collected, as well as the consistency of recommendations and patient adherence.,Moreover, the effect of therapies after 1 year was calculated by comparing lung function and symptoms.,Ultimately, 4,796 patients with COPD from 12 hospitals in China were eligible.,LAMA (39.1%), LAMA + LABA/ICS (39.0%) and LABA/ICS (14.4%) were the top three inhalants.,We found that 42.7% of Group A patients, 61.6% of Group B patients and 30% of Group C patients were following inappropriate therapy, especially overuse of ICS.,Only 3.9% (95% CI 2.4, 5.4) of patients used oxygen therapy, and 1.8% (95% CI 1.5, 2.3) used noninvasive positive pressure ventilation at home.,Among these patients, 33.2% had poor adherence.,A total of 452 patients completed 1 year of follow-up.,After 1 year of treatment, the lung function of FEV1/FVC decreased (P=0.001) and the mMRC score increased (P<0.001).,There was no change in CAT scores (P>0.05).,This study highlights a significant discrepancy between recommendations for managing patients with COPD in GOLD report, and in real-world clinical practice in China.,Over-prescription of ICS and under-prescription of nonpharmacologic therapy were common.,The adherence to treatment of patients was poor, and the real-life treatment effectiveness was unsatisfactory.,More attention should be paid to the implementation of recommendations and standardized administration of therapies. | Patients with COPD often have multiple comorbidities requiring use of multiple medications, and adherence rates for maintenance COPD (mCOPD) medications are already known to be suboptimal.,Presence of comorbidities in COPD patients, and use of medications used to treat those comorbidities (non-COPD medications), may have an adverse impact on adherence to mCOPD medications.,The objective of the study was to evaluate the association between non-adherence to mCOPD medications and non-COPD medications in COPD patients.,COPD patients were identified using a large administrative claims database.,Selected patients were 40-89 years old and continuously enrolled for 12 months prior to and 24 months after the first identified COPD diagnosis (index date) during January 1, 2009 to December 31, 2010.,Patients were required to have ≥1 prescription for a mCOPD medication within 365 days of the index date and ≥1 prescription for one of 12 non-COPD medication classes within ±30 days of the first COPD prescription.,Adherence (proportion of days covered [PDC]) was measured during 365 days following the first COPD prescription.,The association between non-adherence (PDC <0.8) to mCOPD and non-adherence to non-COPD medications was determined using logistic regression, controlling for baseline patient characteristics.,A total of 14,117 patients, with a mean age of 69.9 years, met study criteria.,Of these, 40.9% were males and 79.2% were non-adherent to mCOPD medications with a mean PDC of 0.47.,Non-adherence to mCOPD medications was associated with non-adherence to 10 of 12 non-COPD medication classes (odds ratio 1.38-1.78, all P<0.01).,Adherence to mCOPD medications is low.,Non-adherence (or adherence) to mCOPD medications is positively related to non-adherence (or adherence) to non-COPD medications, implying that the need to take medications prescribed for comorbid conditions does not adversely impact adherence to mCOPD medications. | 1 |
The aim of this study was to analyze the association between therapy adherence to inhaled corticosteroids (ICSs) and tiotropium on the one hand and morbidity and mortality in COPD on the other hand.,Therapy adherence to ICSs and tiotropium over a 3-year period of, respectively, 635 and 505 patients was collected from pharmacy records.,It was expressed as percentage and deemed optimal at ≥75-≤125%, suboptimal at ≥50%-<75%, and poor at <50% (underuse) or >125% (overuse).,The association between adherence and time to first hospital admission for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), community acquired pneumonia (CAP), and mortality was analyzed, with optimal use as the reference category.,Suboptimal use and underuse of ICSs and tiotropium were associated with a substantial increase in mortality risk: hazard ratio (HR) of ICSs was 2.9 (95% CI 1.7-5.1) and 5.3 (95% CI 3.3-8.5) and HR of tiotropium was 3.9 (95% CI 2.1-7.5) and 6.4 (95% CI 3.8-10.8) for suboptimal use and underuse, respectively.,Suboptimal use and overuse of tiotropium were also associated with an increased risk of CAP, HR 2.2 (95% CI 1.2-4.0) and HR 2.3 (95% CI 1.2-4.7), respectively.,Nonadherence to tiotropium was also associated with an increased risk of severe AECOPD: suboptimal use HR 3.0 (95% CI 2.01-4.5), underuse HR 1.9 (95% CI 1.2-3.1), and overuse HR 1.84 (95% CI 1.1-3.1).,Nonadherence to ICSs was not related to time to first AECOPD or first CAP.,Poor adherence to ICSs and tiotropium was associated with a higher mortality risk.,Furthermore, nonadherence to tiotropium was associated with a higher morbidity.,The question remains whether improving adherence can reduce morbidity and mortality. | Pulmonary surfactant protein D (SP-D) is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum.,The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear.,In a cross-sectional study comprising non-smokers (n = 10), young - (n = 10), elderly smokers (n = 20), and smokers with COPD (n = 20) we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis.,Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis.,In COPD, median (IQR) pulmonary SP-D levels were lower (129(68) ng/ml) compared to smokers (young: 299(190), elderly: 296(158) ng/ml; p < 0.01) and non-smokers (967(708) ng/ml; p < 0.001).,The opposite was observed in serum, with higher concentrations in COPD (140(89) ng/ml) as compared to non-smokers (76(47) ng/ml; p < 0.01).,SP-D levels were reproducible and correlated with the degree of airway obstruction in all smokers.,In addition, smoking lead to disruption of the quaternary structure.,Pulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state.,Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker.,no interventional trial | 1 |
COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction.,COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US.,Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease.,Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD.,A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers.,These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity.,In an independent validation set, this model correctly predicted COPD in 8/10 individuals.,These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels.,Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways.,Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD. | Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD).,Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors.,In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner.,Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation.,Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations.,In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation. | 1 |
COPDPredict™ is a novel digital application dedicated to providing early warning of imminent COPD (chronic obstructive pulmonary disease) exacerbations for prompt intervention.,Exacerbation prediction algorithms are based on a decision tree model constructed from percentage thresholds for disease state changes in patient-reported wellbeing, forced expiratory volume in one second (FEV1) and C-reactive protein (CRP) levels.,Our study determined the validity of COPDPredict™ to identify exacerbations and provide timely notifications to patients and clinicians compared to clinician-defined episodes.,In a 6-month prospective observational study, 90 patients with COPD and frequent exacerbations registered wellbeing self-assessments daily using COPDPredict™ App and measured FEV1 using connected spirometers.,CRP was measured using finger-prick testing.,Wellbeing self-assessment submissions showed 98% compliance.,Ten patients did not experience exacerbations and treatment was unchanged.,A total of 112 clinician-defined exacerbations were identified in the remaining 80 patients: 52 experienced 1 exacerbation; 28 had 2.2±0.4 episodes.,Sixty-two patients self-managed using prescribed rescue medication.,In 14 patients, exacerbations were more severe but responded to timely escalated treatment at home.,Four patients attended the emergency room; with 2 hospitalised for <72 hours.,Compared to the 6 months pre-COPDPredict™, hospitalisations were reduced by 98% (90 vs 2, p<0.001).,COPDPredict™ identified COPD-related exacerbations at 7, 3 days (median, IQR) prior to clinician-defined episodes, sending appropriate alerts to patients and clinicians.,Cross-tabulation demonstrated sensitivity of 97.9% (95% CI 95.7-99.2), specificity of 84.0% (95% CI 82.6-85.3), positive and negative predictive value of 38.4% (95% CI 36.4-40.4) and 99.8% (95% CI 99.5-99.9), respectively.,High sensitivity indicates that if there is an exacerbation, COPDPredict™ informs patients and clinicians accurately.,The high negative predictive value implies that when an exacerbation is not indicated by COPDPredict™, risk of an exacerbation is low.,Thus, COPDPredict™ provides safe, personalised, preventative care for patients with COPD. | For the high prevalence of frail in patients with chronic obstructive pulmonary disease (COPD), further study should explore an in-depth understanding of the relationship between frailty and prognosis of COPD.,To determine the correlation between frailty and risk of acute exacerbation, hospitalizations, and mortality in older patients with stable COPD.,Consecutive older adults (≥65) diagnosed with stable COPD from January 2018 to July 2019, with an average follow-up of 546 days (N = 309).,Frailty was defined by the Fried frailty phenotype.,Poisson regression was performed to assess the influence of frailty on the incidence of acute exacerbations of COPD (AECOPD) and all-cause hospitalizations in a year.,Cox regression was performed to evaluate the effect of frailty on all-cause mortality in patients with stable COPD.,The prevalence of frailty was 49.8%.,The most common phenotypic characteristics were weakness (99.4%) followed by slowness (92.9%).,After adjustment, frailty increased the incidence of AECOPD (IRR = 1.75, 95% CI: 1.09-2.82) and all-cause hospitalizations (IRR = 1.39, 95% CI 1.04-1.87) within a year.,Slowness was associated with AECOPD (IRR = 1.77, 95% CI: 1.03-3.03), and weakness was associated with increased all-cause hospitalizations (IRR = 1.53, 95% CI: 1.04-2.25).,The all-cause mortality risk was more than twofold higher in frail patients (HR = 2.54, 95% CI: 1.01-6.36) than non-frail patients.,Low physical activity (HR = 2.66, 95% CI: 1.17-6.05) and weight loss (HR = 2.15, 95% CI: 1.02-4.51) were significantly associated with increased all-cause mortality in patients with COPD.,Frailty increased the incidence of acute exacerbation and hospitalization, as well as increased mortality in older patients with stable COPD.,This knowledge will help physicians identify high-risk groups with COPD and frailty who may benefit from targeted interventions to prevent disease progression. | 1 |
Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD).,Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks.,At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured.,Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo.,Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo).,However, inclusion of contaminated samples did not affect the overall trend of the outcome.,Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils.,Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo.,Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant.,This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population.,In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo.,Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo. | Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users. | 1 |
Arformoterol is the (R,R)-enantiomer of formoterol.,Preclinical studies suggest that it is a stronger bronchodilator than the racemic (R,R/S,S)-formoterol; however, its potential clinical advantages have not been demonstrated.,This study compared the length of stay (LOS), 30-day readmission rates, and doses of rescue medication administered in hospitalized patients with COPD who were treated with nebulized arformoterol or nebulized formoterol.,This retrospective analysis utilized data from Premier, Inc.,(Charlotte, NC, USA), the largest nationwide hospital-based administrative database.,COPD patients ≥40 years of age were included if they were hospitalized between January 2011 and July 2014, had no asthma diagnoses, and were treated with nebulized arformoterol or nebulized formoterol.,LOS was measured from the day the patients initiated the study medication (index day).,Rescue medications were defined as short-acting bronchodilators used from the index day onward.,Multivariate statistical models included a random effect for hospital and controlled for patient demographics, hospital characteristics, admission characteristics, prior hospitalizations, comorbidities, pre-index service use, and pre-index medication use.,A total of 7,876 patients received arformoterol, and 3,612 patients received nebulized formoterol.,There was no significant difference in 30-day all-cause (arformoterol =11.9%, formoterol =12.1%, odds ratio [OR] =0.981, P=0.82) or COPD-related hospital readmission rates (arformoterol =8.0%, formoterol =8.0%, OR =1.002, P=0.98) after adjusting for covariates.,The adjusted mean LOS was significantly shorter for arformoterol-treated vs formoterol-treated patients (4.6 vs 4.9 days, P=0.039), and arformoterol-treated patients used significantly fewer doses of rescue medications vs formoterol-treated patients (5.9 vs 6.6 doses, P=0.006).,During inpatient stays, treating with arformoterol instead of nebulized formoterol may lead to shorter LOS and lower rescue medication use. | 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 | 1 |
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. | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | Psychiatric symptoms of anxiety, depression and cognitive dysfunction often occur in patients suffering from somatic conditions such as asthma and chronic obstructive pulmonary disease (COPD) which constitute a major and growing public health problem.,In the present study we therefore aimed at analyzing depressive symptoms as well as symptoms of anxiety and cognitive problems in patients with mild to moderate asthma and COPD. 59 participants-17 with asthma, 24 with COPD and 18 healthy controls were enrolled.,Depressiveness was assessed with the beck depression inventory (BDI); anxiety symptoms were measured with the State-Trait Anxiety Inventory Part 1 and 2, and cognitive function levels were estimated with the Trail Making Test Part A and B.,A score above the threshold indicative for depression was found by 33 % (n = 8) of COPD patients, 29 % (n = 5) of asthma patients compared to 0.05 % (n = 1) of the control group.,Clinically relevant anxiety levels were found in 42 % (n = 10) of the COPD group, 41 % (n = 7) of the asthma patients and 17 % (n = 3) of the controls.,Patients with COPD performed significantly worse on the TMT than other groups.,Psychoemotional state and cognitive functions were found to be correlated with exposure to tobacco smoke (measured in pack-years) and airway obstruction (measured with FEV1).,In conclusion, patients with mild to moderate asthma and COPD exhibit significantly higher levels of depressive and anxiety symptoms as well as cognitive dysfunctions than controls.,The prevalence of these symptoms is related to the amount of exposure to tobacco smoke and the severity of airflow obstruction. | 1 |
This study investigated the validity and reliability of fixed strain gauge measurements of isometric quadriceps force in patients with chronic obstructive pulmonary disease (COPD).,A total cohort of 138 patients with COPD were assessed.,To determine validity, maximal volitional quadriceps force was evaluated during isometric maximal voluntary contraction (MVC) manoeuvre via a fixed strain gauge dynamometer and compared to (a) potentiated non-volitional quadriceps force obtained via magnetic stimulation of the femoral nerve (twitch (Tw); n = 92) and (b) volitional computerized dynamometry (Biodex; n = 46) and analysed via correlation coefficients.,Test-retest and absolute reliability were determined via calculations of intra-class correlation coefficients (ICCs), smallest real differences (SRDs) and standard errors of measurement (SEMs).,For this, MVC recordings in each device were performed across two test sessions separated by a period of 7 days (n = 46).,Strain gauge measures of MVC demonstrated very large correlation with Tw and Biodex results (r = 0.86 and 0.88, respectively, both p < 0.0001).,ICC, SEM and SRD were numerically comparable between strain gauge and Biodex devices (ICC = 0.96 vs.,0.93; SEM = 8.50 vs.,10.54 N·m and SRD = 23.59 vs.,29.22 N·m, respectively).,The results support that strain gauge measures of quadriceps force are valid and reliable in patients with COPD. | Chronic obstructive pulmonary disease (COPD) is a common disease worldwide.,This study aimed to investigate the health status of patients with newly diagnosed COPD.,A total of 45 healthy controls and 218 patients with newly diagnosed COPD were recruited.,Pulmonary function test (PFT) values, COPD assessment test (CAT) scores, exacerbation history, and demographics were recorded.,Forced expiratory volume in 1 s percent (FEV1%) predicted was significantly decreased and the CAT score was significantly increased in patients with COPD compared with healthy controls (P <0.001).,Among the COPD patients, the most commonly reported respiratory symptoms were cough (86.7%), sputum (80.3%), and dyspnea (45%).,A total of 86.2% patients were in the moderate or severe stage (spirometric classification) of COPD, and 71.5% were in Group C or Group D (combined assessment).,A total of 33.9% of the patients had 2 or more exacerbations in the previous year.,Nearly half of the patients (45.4%) had a high CAT score of ≥10.,Patients with a history of more exacerbations had a higher CAT score.,Most COPD patients were symptomatic and appeared to have moderate to severe airflow limitation or a high risk of exacerbation before definitely being diagnosed with COPD using the PFT. | 1 |
COPD is a leading cause of morbidity and mortality worldwide.,Patients with COPD often require admission to intensive care units (ICU) during an acute exacerbation.,This study aimed to identify the factors independently associated with hospital mortality in patients requiring ICU admission for acute exacerbation of COPD.,Patients admitted to the ICU of Frankston Hospital between January 2005 and June 2016 with an admission diagnosis of COPD were retrospectively identified from ICU databases.,Patients’ comorbidities, arterial blood gas results, and in-patient interventions were retrieved from their medical records.,Outcomes analyzed included hospital and ICU length of stay (LOS) and mortality.,A total of 305 patients were included.,Mean age was 67.4 years.,A total of 77% of patients required non-invasive ventilation; and 38.7% required invasive mechanical ventilation (IMV) for a median of 127.2 hours (SD =179.5).,Mean ICU LOS was 4.5 days (SD =5.96), and hospital LOS was 11.6 days (SD =13).,In-hospital mortality was 18.7%.,Multivariate analysis revealed that patient age (odds ratio [OR] =1.06; 95% CI: 1.031-1.096), ICU LOS (OR =1.26; 95% CI: 1.017-1.571), Acute Physiology and Chronic Health Evaluation-II score (OR =1.07; 95% CI: 1.012-1.123), and requirement for IMV (OR =4.09; 95% CI: 1.791-9.324) to be significantly associated with in-hospital mortality.,Patient age, requirement for IMV, and illness severity were associated with poor patient outcomes. | 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 |
Chronic bronchitis (CB) is one of the classic phenotypes of COPD.,The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population.,We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE).,CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years.,CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry.,Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls.,Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis.,For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A.,In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7).,We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6).,This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD.,ClinicalTrials.gov NCT00608764, NCT00292552,The online version of this article (doi:10.1186/s12931-014-0113-2) contains supplementary material, which is available to authorized users. | Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease.,Recent studies suggested an association between COPD and polymorphisms in CHRNA coding subunits of nicotinic acetylcholine receptor.,Herein, we performed a meta-analysis to clarify the impact of CHRNA variants on COPD.,We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on CHRNA.,Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.,Among seven reported variants in CHRNA, rs1051730 was finally analyzed with sufficient studies.,Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed.,A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10-5).,At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10-5).,Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).,Our findings suggest that rs1051730 in CHRNA is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction. | 1 |
Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future.,Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes.,We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease (COPD) and clinically relevant disease phenotypes.,Breath samples from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry.,Subjects with COPD also underwent sputum induction.,Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis: 1. principal component analysis; 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis.,Comparing COPD versus healthy controls, principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71% of the variance.,Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69%.,The model had 85% sensitivity, 50% specificity and ROC area under the curve of 0.74.,Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy.,Models were constructed which classified subjects with ≥2% sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95.,Potential biomarkers correlated to clinical variables were identified in each subgroup.,The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinically relevant COPD subgroups.,If these findings are validated in prospective cohorts, they may have diagnostic and management value in this disease. | Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes.,Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes.,To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations.,In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV1 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation.,Sputum total cell counts (9.0 versus 7.9 × 106/mL), eosinophils (0.3 versus 0.2 × 106/mL), neutrophils (6.1 versus 5.8 × 106/mL), and lymphocytes (0.07 versus 0.02 × 106/mL) increased significantly during an exacerbation compared to stable disease.,A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation.,These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-α (TNF-α) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection.,Sputum TNF-α level during an exacerbation had the best test characteristics to predict a bacterial infection.,Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations.,The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways.,Sputum TNF-α is a candidate marker for predicting airway bacterial infection. | 1 |
This study aimed to directly measure pH in the lungs, determine lactate dehydrogenase (LDH), C-reactive protein (CRP), and glucose levels in serum and bronchoalveolar aspirate, and identify bacterial pathogens from bronchoalveolar fluid during acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,We performed an observational, analytical case-control study from February 2015 to March 2017.,We included 84 patients with AECOPD and 42 with stable chronic obstructive pulmonary disease (COPD).,All participants underwent detailed medical anamnesis, a clinical examination, chest radiography, spirometry, an arterial blood gas test, bronchoscopy, bacterial culture, and serum/bronchiolar aspirate laboratory testing.,The mean pH of bronchoalveolar fluid was significantly higher in patients with AECOPD than in patients with stable COPD.,The mean lung pH value, bronchoalveolar and serum LDH levels, and serum CRP levels in patients with isolated bacteria were higher than those in patients without isolated bacteria in the AECOPD patient group.,Lung pH values in patients with AECOPD were significantly correlated with bronchoalveolar LDH and glucose levels.,AECOPD is associated with local cell and tissue injury in the lungs, especially in the presence of bacterial pathogens, which is accompanied by a low systemic inflammatory response. | COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment.,Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation.,We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens.,COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015.,Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured.,Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality.,Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed.,Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined.,A total of 62 COPD patients were enrolled.,These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively.,Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria.,Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively.,Influenza was the most commonly detected viral pathogen.,Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar.,Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation.,Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035).,Increased serum PCT is associated with longer LOS in COPD exacerbation.,However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation. | 1 |
There is a need to identify individuals with COPD at risk for disease progression and mortality.,Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation.,We hypothesized that ECM remodeling was associated with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling.,Biomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort.,Validated immunoassays measuring serological neo-epitopes produced by proteolytic cleavage associated with degradation of collagen type I, III, IV, and VI, elastin, and biglycan, and formation of collagen type VI as well as fibrinogen and C-reactive protein were used.,Multivariate models were used to assess the prognostic value of these biomarkers.,Thirty subjects (3.0 %) died during follow-up.,Non-survivors were older, had reduced exercise capacity, increased dyspnea score, and included fewer current smokers.,All collagen biomarkers were significantly elevated in non-survivors compared to survivors.,Mortality risk was significantly increased for subjects with collagen remodeling biomarkers in the upper quartile, especially for the degradation fragment of collagen type IV C6M (hazard ratio 6.6 [95 % confidence interval 2.9-15.2], P < 0.0001) after adjusting for relevant confounders.,Serological biomarkers of collagen remodeling were strongly associated with mortality in subjects with COPD indicating that assessment of tissue turnover in the parenchyma and small airways may be useful in the prognosis of COPD.,NCT00292552, GSK Study No.,SCO104960.,The online version of this article (doi:10.1186/s12931-016-0440-6) contains supplementary material, which is available to authorized users. | To determine whether a serine protease inhibitor treatment can prevent or minimize emphysema in mice.,C57BL/6 mice were subjected to porcine pancreatic elastase (PPE) nasal instillation to induce emphysema and were treated with a serine protease inhibitor (rBmTI-A) before (Protocol 1) and after (Protocol 2) emphysema development.,In both protocols, we evaluated lung function to evaluate the airway resistance (Raw), tissue damping (Gtis) and tissue elastance (Htis).,The inflammatory profile was analyzed in the bronchoalveolar lavage (BALF) and through the use of morphometry; we measured the mean linear intercept (Lm) (to verify alveolar enlargement), the volume proportion of collagen and elastic fibers, and the numbers of macrophages and metalloprotease 12 (MMP-12) positive cells in the parenchyma.,We showed that at both time points, even after the emphysema was established, the rBmTI-A treatment was sufficient to reverse the loss of elastic recoil measured by Htis, the alveolar enlargement and the increase in the total number of cells in the BALF, with a primary decrease in the number of macrophages.,Although, the treatment did not control the increase in macrophages in the lung parenchyma, it was sufficient to decrease the number of positive cells for MMP-12 and reduce the volume of collagen fibers, which was increased in PPE groups.,These findings attest to the importance of MMP-12 in PPE-induced emphysema and suggest that this metalloprotease could be an effective therapeutic target. | 1 |
A genetic contribution to develop chronic obstructive pulmonary disease (COPD) is well established.,However, the specific genes responsible for enhanced risk or host differences in susceptibility to smoke exposure remain poorly understood.,The goal of this review is to provide a comprehensive literature overview on the genetics of COPD, highlight the most promising findings during the last few years, and ultimately provide an updated COPD gene list.,Candidate gene studies on COPD and related phenotypes indexed in PubMed before January 5, 2012 are tabulated.,An exhaustive list of publications for any given gene was looked for.,This well-documented COPD candidate-gene list is expected to serve many purposes for future replication studies and meta-analyses as well as for reanalyzing collected genomic data in the field.,In addition, this review summarizes recent genetic loci identified by genome-wide association studies on COPD, lung function, and related complications.,Assembling resources, integrative genomic approaches, and large sample sizes of well-phenotyped subjects is part of the path forward to elucidate the genetic basis of this debilitating disease. | 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 |
Mortality from coronavirus disease 2019 (COVID‐19) is increased in patients with chronic obstructive pulmonary disease (COPD).,Furthermore, higher BMI is related to severe disease.,Severe acute respiratory syndrome coronavirus 2 utilizes angiotensin converting enzyme 2 (ACE2) to gain cellular entry.,Whether ACE2 bronchial epithelial expression is increased in COPD patients who have overweight compared with those who do not was investigated by RNA sequencing.,Increased ACE2 expression was observed in patients with COPD with overweight (mean BMI, 29 kg/m2) compared with those without overweight (mean BMI, 21 kg/m2) (P = 0.004).,Increased ACE2 expression may cause increased severe acute respiratory syndrome coronavirus 2 infection of the respiratory tract.,Overweight COPD patients may be at greater risk for developing severe COVID‐19. | Chronic obstructive pulmonary disease (COPD) is a complex chronic disease in which T cell-mediated pulmonary inflammation has been shown to play a key role.,Accumulating evidence shows that COPD has many of the characteristics of an autoimmune response.,An adaptive immune response directed against lung self-antigens, which are released during the initial innate inflammatory response and are triggered by constant exposure to cigarette smoke and epithelial injury, drives the persistent inflammatory response found in smokers.,The development and severity of adaptive inflammation depend on the level of tolerance to self-antigens.,For these reasons, the effect of regulatory T (Treg) cells on adaptive immunity in COPD patients is of particular interest and could be targeted therapeutically.,The disturbance in immune homeostasis caused by changes in the number or function of Treg cells, which is related to cigarette smoke exposure, may be of importance in understanding the development and progression of COPD. | 1 |
The aim of this study was to investigate the association between systemic inflammatory mediators and peripheral muscle mass and strength in COPD patients.,Fifty-five patients (69% male; age: 64±9 years) with mild/very severe COPD (defined as forced expiratory volume in the first second [FEV1] =54%±23%) were evaluated.,We evaluated serum concentrations of IL-8, CRP, and TNF-α.,Peripheral muscle mass was evaluated by computerized tomography (CT); midthigh cross-sectional muscle area (MTCSA) and midarm cross-sectional muscle area (MACSA) were obtained.,Quadriceps, triceps, and biceps strength were assessed through the determination of the one-repetition maximum.,The multiple regression results, adjusted for age, sex, and FEV1%, showed positive significant association between MTCSA and leg extension (0.35 [0.16, 0.55]; P=0.001), between MACSA and triceps pulley (0.45 [0.31, 0.58]; P=0.001), and between MACSA and biceps curl (0.34 [0.22, 0.47]; P=0.001).,Plasma TNF-α was negatively associated with leg extension (−3.09 [−5.99, −0.18]; P=0.04) and triceps pulley (−1.31 [−2.35, −0.28]; P=0.01), while plasma CRP presented negative association with biceps curl (−0.06 [−0.11, −0.01]; P=0.02).,Our results showed negative association between peripheral muscle mass (evaluated by CT) and muscle strength and that systemic inflammation has a negative influence in the strength of specific groups of muscles in individuals with stable COPD.,This is the first study showing association between systemic inflammatory markers and strength in upper limb muscles. | The skeletal muscles play an essential role in life, providing the mechanical basis for respiration and movement.,Skeletal muscle dysfunction is prevalent in all stages of chronic obstructive pulmonary disease (COPD), and significantly influences symptoms, functional capacity, health related quality of life, health resource usage and even mortality.,Furthermore, in contrast to the lungs, the skeletal muscles are potentially remedial with existing therapy, namely exercise-training.,This review summarizes clinical and laboratory observations of the respiratory and peripheral skeletal muscles (in particular the diaphragm and quadriceps), and current understanding of the underlying etiological processes.,As further progress is made in the elucidation of the molecular mechanisms of skeletal muscle dysfunction, new pharmacological therapies are likely to emerge to treat this important extra-pulmonary manifestation of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition sharing risk factors with lung cancer.,Lung cancer screening may provide an opportunity to improve COPD diagnosis.,Using Pan-Canadian Early Detection of Lung Cancer (PanCan) study data, the present study sought to determine the following: 1) What is the prevalence of COPD in a lung cancer screening population?,2) Can a model based on clinical and screening low-dose CT scan data predict the likelihood of COPD?,The single arm PanCan study recruited current or former smokers age 50-75 who had a calculated risk of lung cancer of at least 2% over 6 years.,A baseline health questionnaire, spirometry, and low-dose CT scan were performed.,CT scans were assessed by a radiologist for extent and distribution of emphysema.,With spirometry as the gold standard, logistic regression was used to assess factors associated with COPD.,Among 2514 recruited subjects, 1136 (45.2%) met spirometry criteria for COPD, including 833 of 1987 (41.9%) of those with no prior diagnosis, 53.8% of whom had moderate or worse disease.,In a multivariate model, age, current smoking status, number of pack-years, presence of dyspnea, wheeze, participation in a high-risk occupation, and emphysema extent on LDCT were all statistically associated with COPD, while the overall model had poor discrimination (c-statistic = 0.627 (95% CI of 0.607 to 0.650).,The lowest and the highest risk decile in the model predicted COPD risk of 27.4 and 65.3%.,COPD had a high prevalence in a lung cancer screening population.,While a risk model had poor discrimination, all deciles of risk had a high prevalence of COPD, and spirometry could be considered as an additional test in lung cancer screening programs.,(Clinical Trial Registration: ClinicalTrials.gov, number NCT00751660, registered September 12, 2008),The online version contains supplementary material available at 10.1186/s12890-020-01344-y. | We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | 1 |
Fatigue is the second most common symptom in patients with chronic obstructive pulmonary disease (COPD).,Despite its high prevalence, fatigue is often ignored in daily practice.,For this reason, little is known about the underlying determinants of fatigue in patients with COPD.,The primary objectives of this study are to chart the course of fatigue in patients with COPD, to identify the physical, systemic, psychological and behavioural factors that precipitate and perpetuate fatigue in patients with COPD, to evaluate the impact of exacerbation-related hospitalisations on fatigue and to better understand the association between fatigue and 2-year all-cause hospitalisation and mortality in patients with COPD.,The secondary aim is to identify diurnal differences in fatigue by using ecological momentary assessment (EMA).,This manuscript describes the protocol of the FAntasTIGUE study and gives an overview of the possible strengths, weaknesses and clinical implications.,A 2-year longitudinal, observational study, enrolling 400 patients with clinically stable COPD has been designed.,Fatigue, the primary outcome, will be measured by the subjective fatigue subscale of the Checklist Individual Strength (CIS-Fatigue).,The secondary outcome is the day-to-day/diurnal fatigue, registered in a subsample (n=60) by EMA.,CIS-Fatigue and EMA will be evaluated at baseline, and at 4, 8 and 12 months.,The precipitating and perpetuating factors of fatigue (physical, psychological, behavioural and systemic) will be assessed at baseline and at 12 months.,Additional assessments will be conducted following hospitalisation due to an exacerbation of COPD that occurs between baseline and 12 months.,Finally, at 18 and 24 months the participants will be followed up on their fatigue, number of exacerbations, exacerbation-related hospitalisation and survival.,This protocol was approved by the Medical research Ethics Committees United, Nieuwegein, the Netherlands (NL60484.100.17).,NTR6933; Pre-results. | The morning is the most bothersome period for COPD patients.,Morning symptom severities in different Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages are not well studied.,Furthermore, factors that are associated with morning symptoms, especially the associations with objectively measured physical activity, are also not well described.,The aim of this cross-sectional observational study was to assess morning symptom severity in GOLD A, B, C and D patients, according to the definitions of the GOLD 2015 statement.,Morning symptoms were assessed with the PRO-Morning COPD Symptoms Questionnaire.,Differences in morning symptom severity between different COPD stages were assessed with a one-way analysis of variance followed by post hoc analyses.,The association between dyspnea severity (assessed with the modified Medical Research Council scale), health status, airflow limitation, lung hyperinflation, anxiety and depression, inflammatory parameters, exacerbations, objectively measured physical activity parameters retrieved from accelerometry and morning symptom severity was evaluated using linear regression analysis.,Eighty patients were included (aged 65.6±8.7 years, forced expiratory volume in 1 second [FEV1] % predicted 55.1±16.9).,Mean (±SD) morning symptom score was 19.7 (±11.7).,Morning symptom severity was significantly different between COPD stages: mean (±SD) score in GOLD A was 9.7 (±7.2), in GOLD B 19.8 (±10.7), in GOLD C 8.6 (±9.3) and in GOLD D 23.8 (±11.2) (p<0.001).,Lower health status, more symptoms, increased anxiety and depression, less physical activity (all p<0.001) and lower FEV1 (p=0.03) were associated with an increased morning symptom severity.,Patients with overall more symptomatic COPD have significant higher morning symptom scores.,Morning symptom severity was associated with important clinical outcomes: lower health status, more symptoms, increased anxiety and depression, fewer steps a day, less time in moderate and vigorous physical activity with bouts of at least 10 minutes and lower FEV1.,The data suggest that morning symptoms should be carefully assessed in addition to assessment by general COPD-specific questionnaires, especially in those with more symptomatic COPD.,More research is needed on potential therapies to improve morning symptoms; this study shows potential targets for intervention. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide.,Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations.,Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation.,Long-acting β2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD.,The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects.,Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe.,Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA.,Several other agents are in the late stages of development, most of which offer once-daily dosing.,The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations.,These evolving treatments will provide new opportunities and challenges in the management of COPD. | Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | 1 |
In comparison to genome-wide association studies (GWAS), there has been poor replication of gene expression studies in chronic obstructive pulmonary disease (COPD).,We performed microarray gene expression profiling on a large sample of resected lung tissues from subjects with severe COPD.,Comparing 111 COPD cases and 40 control smokers, 204 genes were differentially expressed; none were at significant GWAS loci.,The top differentially expressed gene was HMGB1, which interacts with AGER, a known COPD GWAS gene.,Differentially expressed genes showed enrichment for putative interactors of the first three identified COPD GWAS genes IREB2, HHIP, and FAM13A, based on gene sets derived from protein and RNA binding studies, RNA-interference, a murine smoking model, and expression quantitative trait locus analyses.,The gene module most highly associated for COPD in Weighted Gene Co-Expression Network Analysis (WGCNA) was enriched for B cell pathways, and shared seventeen genes with a mouse smoking model and twenty genes with previous emphysema studies.,As in other common diseases, genes at COPD GWAS loci were not differentially expressed; however, using a combination of network methods, experimental studies and careful phenotype definition, we found differential expression of putative interactors of these genes, and we replicated previous human and mouse microarray results. | 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. | 1 |
The purpose of this study was to compare the Korean COPD guideline to GOLD consensus report in terms of acute exacerbation.,A total of 361 patients were enrolled in this study, and 16.9% of them experienced acute exacerbation during the follow-up.,A total of 6.3% of patients in GOLD A, 9.5% in GOLD B, 7.7% in GOLD C and 17.0% of GOLD D experienced exacerbation during the first year of follow-up, respectively (P=0.09).,There was no one who experienced exacerbation during the first year of follow-up in the Korean group 'ga'.,The 12-month exacerbation rates of Korean group 'na' and 'da' were 4.5% and 16.0%, respectively (P<0.001).,We explore the experience of exacerbation in patients with change of their risk group after applying Korean COPD guideline.,A total of 16.0% of the patients who were reclassified from GOLD A to Korean group 'da' experienced acute exacerbation,and 15.3% from GOLD B to Korean group 'da' experienced acute exacerbation.,In summary, the Korean COPD guideline is useful to differentiate the high risk from low risk for exacerbation in terms of spirometry.,This indicates that application of Korean COPD guideline is appropriate to treat Korean COPD patients. | As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | 1 |
Physical inactivity is associated with poor outcomes in COPD, and as a result, interventions to improve physical activity (PA) are a current research focus.,However, many trials have been small and inconclusive.,The aim of this systematic review and meta-analysis was to study the effects of randomized controlled trials (RCTs) targeting PA in COPD.,Databases (Physiotherapy Evidence Database [PEDro], Embase, MEDLINE, CINAHL and the Cochrane Central Register for Controlled Trials) were searched using the following keywords: “COPD”, “intervention” and “physical activity” from inception to May 20, 2016; published RCTs that aimed to increase PA in individuals with COPD were included.,The PEDro scale was used to rate study quality.,Standardized mean differences (effect sizes, ESs) with 95% confidence intervals (CIs) were determined.,Effects of included interventions were also measured according to the minimal important difference (MID) in daily steps for COPD (599 daily steps).,A total of 37 RCTs with 4,314 participants (mean forced expiratory volume in one second (FEV1) % predicted 50.5 [SD=10.4]) were identified.,Interventions including exercise training (ET; n=3 studies, 103 participants) significantly increased PA levels in COPD compared to standard care (ES [95% CI]; 0.84 [0.44-1.25]).,The addition of activity counseling to pulmonary rehabilitation (PR; n=4 studies, 140 participants) showed important effects on PA levels compared to PR alone (0.47 [0.02-0.92]), achieving significant increases that exceeded the MID for daily steps in COPD (mean difference [95% CI], 1,452 daily steps [549-2,356]).,Reporting of methodological quality was poor in most included RCTs.,Interventions that included ET and PA counseling during PR were effective strategies to improve PA in COPD. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. | The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | 1 |
The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed.,We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II).,Blood was taken once in Control I and 4 times (every month) in Control II.,In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively.,Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I.,In Control II, the similar differences as compared to Control I were observed throughout the study.,Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E.,COPD is accompanied by oxidative stress.,A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters. | COPD is associated with an increased load on the diaphragm.,Since chronic muscle loading results in changes in antioxidant capacity and formation of reactive oxygen and reactive nitrogen species, we hypothesized that COPD has a similar effect on the diaphragm, which is related to the severity of COPD.,Catalase activity was determined spectrophotometrically.,Levels of 4-hydroxy-2-nonenal (HNE)-protein adducts and 3-nitrotyrosine (NT) formation were measured using western blotting.,Levels of malondialdehyde (MDA) were assessed by high-performance liquid chromatography.,We found that catalase activity was ~89% higher in the diaphragm of severe COPD patients (FEV1 37 ± 5% predicted) compared with non-COPD patients.,MDA levels, a marker for lipid peroxidation, were significantly lower in the diaphragm of COPD patients compared with non-COPD patients, whereas the level of HNE-protein adducts was equal in both groups.,NT formation was not different between groups.,However, increasing hyperinflation and NT formation were inversely correlated.,These results indicate that in COPD the diaphragm adapts to a higher work load by increasing catalase activity, resulting in a reduction in oxidative damage to lipids and tyrosine nitration of proteins. | 1 |
Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance.,Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD).,However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown.,We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC).,βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks.,Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured.,Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles.,Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice.,CS exposure further altered lung function measurements.,We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD. | Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality.,RSV is able to evade antiviral defenses to persist in the lungs of COPD patients.,Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established.,Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice.,RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice.,This infiltration of cells was most pronounced around the vasculature and bronchial airways.,By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure.,Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression.,In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure.,RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity.,This is significant as these phosphatases counter smoke-induced inflammation and protease expression.,Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice.,Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | Objectives To understand the perspectives of people with severe chronic obstructive pulmonary disease (COPD) as their illness progresses, and of their informal and professional carers, to inform provision of care for people living and dying with COPD.,Design Up to four serial qualitative interviews were conducted with each patient and nominated carer over 18 months.,Interviews were transcribed and analysed both thematically and as narratives.,Participants 21 patients, and 13 informal carers (a family member, friend, or neighbour) and 18 professional carers (a key health or social care professional) nominated by the patients.,Setting Primary and secondary care in Lothian, Tayside, and Forth Valley, Scotland, during 2007-9.,Results Eleven patients died during the study period.,Our final dataset comprised 92 interviews (23 conducted with patient and informal carer together).,Severe symptoms that caused major disruption to normal life were described, often in terms implying acceptance of the situation as a “way of life” rather than an “illness.”,Patients and their informal carers adapted to and accepted the debilitating symptoms of a lifelong condition.,Professional carers’ familiarity with the patients’ condition, typically over many years, and prognostic uncertainty contributed to the difficulty of recognising and actively managing end stage disease.,Overall, patients told a “chaos narrative” of their illness that was indistinguishable from their life story, with no clear beginning and an unanticipated end described in terms comparable with attitudes to death in a normal elderly population.,Conclusions Our findings challenge current assumptions underpinning provision of end of life care for people with COPD.,The policy focus on identifying a time point for transition to palliative care has little resonance for people with COPD or their clinicians and is counter productive if it distracts from early phased introduction of supportive care.,Careful assessment of possible supportive and palliative care needs should be triggered at key disease milestones along a lifetime journey with COPD, in particular after hospital admission for an exacerbation. | 1 |
In addition to smoking, dietary habits may contribute to the development of chronic obstructive pulmonary disease (COPD).,This study aimed to examine the association between dietary patterns and lung function in a Korean community cohort.,A total of 5436 participants were included from the Ansan-Ansung cohort study.,To identify the dietary patterns, we performed principal component factor analysis using the results of a semi-quantitative food frequency questionnaire.,The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were measured by spirometry.,Multiple logistic regression models were used to evaluate the association between dietary patterns and lung function after adjusting for confounders.,We identified four major dietary patterns; ‘prudent’, ‘coffee, fat, and sweet’, ‘westernized’, and ‘white rice’.,After adjusting for potential confounders, the ‘coffee, fat, and sweet’ dietary pattern was negatively associated with lung function, particularly the FEV1/FVC ratio.,Participants with high scores for the ‘coffee, fat and sweet’ pattern had a higher risk of COPD among men but not women.,Therefore, these results indicate that the ‘coffee, fat and sweet’ dietary pattern is inversely related to lung function in Korean adults.,Our results indicate that dietary habits may be modifiable risk factors for COPD. | There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course.,Previous studies on this topic did not generate causally-interpretable estimates.,Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients.,Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes.,We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events.,Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics.,35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up.,The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations.,This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event.,The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality.,There was substantial heterogeneity in the individual-specific rate of severe exacerbations.,Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile.,Using robust statistical methodology that controlled for heterogeneity in exacerbation rates among individuals, we demonstrated potential causal associations among past and future severe exacerbations, albeit the magnitude of association was noticeably lower than previously reported.,The prevention of severe exacerbations has the potential to modify the disease trajectory. | 1 |
Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | Systemic inflammatory factors are inconsistently associated with the pathogenesis of chronic obstructive pulmonary disease (COPD).,We conducted a systematic review and meta-analysis to summarize the evidence supporting the association between systemic inflammation and the risk of COPD.,Pertinent studies were retrieved from PubMed, EmBase, and the Cochrane Library until April 2015.,A random-effects model was used to process the data, and the analysis was further stratified by factors affecting these associations.,Sensitivity analyses for publication bias were performed.,We included 24 observational studies reporting data on 10,677 COPD patients and 28,660 controls.,Overall, we noted that COPD was associated with elevated serum CRP (SMD: 1.21; 95%CI: 0.92-1.50; P < 0.001), leukocytes (SMD: 1.07; 95%: 0.25-1.88; P = 0.010), IL-6 (SMD: 0.90; 95%CI: 0.48-1.31; P < 0.001), IL-8 (SMD: 2.34; 95%CI: 0.69-4.00; P = 0.006), and fibrinogen levels (SMD: 0.87; 95%CI: 0.44-1.31; P < 0.001) when compared with control.,However, COPD was not significantly associated with TNF-α levels when compared with control (SMD: 0.60; 95%CI: -0.46 to 1.67; P = 0.266).,Our findings suggested that COPD was associated with elevated serum CRP, leukocytes, IL-6, IL-8, and fibrinogen, without any significant relationship with TNF-α. | 1 |
Many lung diseases are associated with changes in autophagic activity.,The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a key regulatory role in autophagy.,Our aim was to explore the function of PI3K/AKT/mTOR pathway on autophagy in chronic obstructive pulmonary disease (COPD) caused by particulate matter with a diameter <2.5 µm (PM2.5).,Male C57BL/6 mice were randomly divided into sham, model, and PI3K inhibitor groups.,Mice were exposed to PM2.5 for 4 weeks to establish an in vivo COPD model.,Alveolar epithelial cells were stimulated with PM2.5 to establish an in vitro COPD model.,In mice with COPD induced by PM2.5, the PI3K inhibitor PF-04979064 suppressed protein expression of PI3K, p-AKT, and p-mTOR to increase apoptosis of alveolar epithelial cells and reduce autophagy.,Short interfering PI3K suppressed the PI3K/AKT/mTOR pathway to induce apoptosis and reduce autophagy of alveolar epithelial cells in an in vitro model of COPD.,Activation of PI3K induced the PI3K/AKT/mTOR pathway to reduce apoptosis of alveolar epithelial cells in the in vitro model of COPD by promoting autophagy.,These data demonstrate that PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in COPD. | The direct relationship between pulmonary structural changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) is unclear.,We investigated AHR in relation to airway and parenchymal structural changes in a guinea pig model of COPD and in COPD patients.,Precision-cut lung slices (PCLS) were prepared from guinea pigs challenged with lipopolysaccharide or saline two times weekly for 12 wk.,Peripheral PCLS were obtained from patients with mild to moderate COPD and non-COPD controls.,AHR to methacholine was measured in large and small airways using video-assisted microscopy.,Airway smooth muscle mass and alveolar airspace size were determined in the same slices.,A mathematical model was used to identify potential changes in biomechanical properties underlying AHR.,In guinea pigs, lipopolysaccharide increased the sensitivity of large (>150 μm) airways toward methacholine by 4.4-fold and the maximal constriction of small airways (<150 μm) by 1.5-fold.,Similarly increased small airway responsiveness was found in COPD patients.,In both lipopolysaccharide-challenged guinea pigs and patients, airway smooth muscle mass was unaltered, whereas increased alveolar airspace correlated with small airway hyperresponsiveness in guinea pigs.,Fitting the parameters of the model indicated that COPD weakens matrix mechanical properties and enhances stiffness differences between the airway and the parenchyma, in both species.,In conclusion, this study demonstrates small airway hyperresponsiveness in PCLS from COPD patients.,These changes may be related to reduced parenchymal retraction forces and biomechanical changes in the airway wall.,PCLS from lipopolysaccharide-exposed guinea pigs may be useful to study mechanisms of small airway hyperresponsiveness in COPD. | 1 |
The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear.,Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults.,A cross-sectional study was conducted in southern China.,Seven clusters were randomly selected from four cities across Guangdong province.,Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry.,COPD was defined as a post-bronchodilator FEV1/FVC less than 70%.,Atmosphere PM sampling was conducted across the clusters along with our survey.,Of the subjects initially recruited, 84.4% (n=5993) were included for analysis.,COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters.,COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1.,A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI −43 to −9) decrease in FEV1, a 28 mL (−49 to −8) decrease in FVC and a 0.09% decrease (−0.170 to −0.010) in FEV1/FVC ratio.,The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker.,Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function.,ChiCTR-OO-14004264; Post-results. | The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | 1 |
Self-management interventions (SMIs) are recommended for individuals with COPD to help monitor symptoms and optimize health-related quality of life (HRQOL).,However, SMIs vary widely in content, delivery, and intensity, making it unclear which methods and techniques are associated with improved outcomes.,This systematic review aimed to summarize the current evidence base surrounding the effectiveness of SMIs for improving HRQOL in people with COPD.,Systematic reviews that focused upon SMIs were eligible for inclusion.,Intervention descriptions were coded for behavior change techniques (BCTs) that targeted self-management behaviors to address 1) symptoms, 2) physical activity, and 3) mental health.,Meta-analyses and meta-regression were used to explore the association between health behaviors targeted by SMIs, the BCTs used, patient illness severity, and modes of delivery, with the impact on HRQOL and emergency department (ED) visits.,Data related to SMI content were extracted from 26 randomized controlled trials identified from 11 systematic reviews.,Patients receiving SMIs reported improved HRQOL (standardized mean difference =−0.16; 95% confidence interval [CI] =−0.25, −0.07; P=0.001) and made fewer ED visits (standardized mean difference =−0.13; 95% CI =−0.23, −0.03; P=0.02) compared to patients who received usual care.,Patients receiving SMIs targeting mental health alongside symptom management had greater improvement of HRQOL (Q=4.37; P=0.04) and fewer ED visits (Q=5.95; P=0.02) than patients receiving SMIs focused on symptom management alone.,Within-group analyses showed that HRQOL was significantly improved in 1) studies with COPD patients with severe symptoms, 2) single-practitioner based SMIs but not SMIs delivered by a multidisciplinary team, 3) SMIs with multiple sessions but not single session SMIs, and 4) both individual- and group-based SMIs.,SMIs can be effective at improving HRQOL and reducing ED visits, with those targeting mental health being significantly more effective than those targeting symptom management alone. | Self-management is becoming increasingly important in COPD health care although it remains difficult to embed self-management into routine clinical care.,The implementation of self-management is understood as a complex interaction at the level of patient, health care provider (HCP), and health system.,Nonetheless there is still a poor understanding of the barriers and effective facilitators.,Comprehension of these determinants can have significant implications in optimizing self-management implementation and give further directions for the development of self-management interventions.,Data were collected among COPD patients (N=46) and their HCPs (N=11) in three general practices and their collaborating affiliated hospitals.,Mixed methods exploration of the data was conducted and collected by interviews, video-recorded consultations (N=50), and questionnaires on consultation skills.,Influencing determinants were monitored by 1) interaction and communication between the patient and HCP, 2) visible and invisible competencies of both the patient and the HCP, and 3) degree of embedding self-management into the health care system.,Video observations showed little emphasis on effective behavioral change and follow-up of given lifestyle advice during consultation.,A strong presence of COPD assessment and monitoring negatively affects the patient-centered communication.,Both patients and HCPs experience difficulties in defining personalized goals.,The satisfaction of both patients and HCPs concerning patient centeredness during consultation was measured by the patient feedback questionnaire on consultation skills.,The patients scored high (84.3% maximum score) and differed from the HCPs (26.5% maximum score).,Although the patient-centered approach accentuating self-management is one of the dominant paradigms in modern medicine, our observations show several influencing determinants causing difficulties in daily practice implementation.,This research is a first step unravelling the determinants of self-management leading to a better understanding. | 1 |
Vertebral compression fractures (VCF) are common in COPD patients, with osteoporosis being the main cause.,The clinical impact of VCF derives mostly from both pain and chest deformity, which may lead to ventilatory and physical activity limitations.,Surprisingly, the consequences of VCF on the quality outcomes of hospital care are poorly known.,To assess these indicators in patients hospitalized due to a COPD exacerbation (ECOPD) who also have VCF.,Clinical characteristics and quality care indicators were assessed in two one-year periods, one retrospective (exploratory) and one prospective (validation), in all consecutive patients hospitalized for ECOPD.,Diagnosis of VCF was based on the reduction of >20% height of the vertebral body evaluated in standard lateral chest X-ray (three independent observers).,From the 248 patients admitted during the exploratory phase, a third had at least one VCF.,Underdiagnosis rate was 97.6%, and patients with VCF had more admissions (normalized for survival), longer hospital stays, and higher mortality than patients without (4 [25th-75th percentiles, 2-8] vs 3 [1-6] admissions, P<0.01; 12 [6-30] vs 9 [6-18] days, P<0.05; and 50 vs 32.1% deaths, P<0.01, respectively).,The risk of dying in the two following years was also higher in VCF patients (odds ratio: 2.11 [1.2-3.6], P<0.01).,The validation cohort consisted of 250 patients who showed very similar results.,The logistic regression analysis indicated that both VCF and age were factors independently associated with mortality.,Although VCF is frequently underdiagnosed in patients hospitalized for ECOPD, it is strongly associated with a worse prognosis and quality care outcomes. | Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy. | 1 |
Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide.,Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease.,We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors.,Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103).,We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions.,We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice.,HRVs are isolated from nasal and lung fluid from subjects with AE-COPD.,Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection.,HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells.,Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells.,Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD.,HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD.,Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD. | Moraxella catarrhalis causes approximately 10% of exacerbations in chronic obstructive pulmonary disease (COPD) and also colonizes the lower airway in stable patients.,Little is known about the effects of colonization by M. catarrhalis on airway inflammation and protease-antiprotease balance, and how these changes compare to those seen during exacerbations.,Since COPD is a progressive inflammatory disease, elucidating the effects of bacterial colonization and exacerbation on airway inflammation is relevant to understanding disease progression in COPD.,Our aims were (1) Analyze changes in airway inflammation in colonization and exacerbation of COPD due to M. catarrhalis; (2) Explore protease-antiprotease balance in colonization and exacerbation due to M. catarrhalis.,Our hypothesis were (1) Acquisition of a new strain of M. catarrhalis in COPD increases airway inflammation from baseline and alters the protease-antiprotease balance towards a more proteolytic environment; (2) These changes are greater during exacerbations associated with M. catarrhalis as compared to colonization.,Thirty-nine consecutive COPD patients with 76 acquisitions of a new strain of M. catarrhalis over a 6-year period were identified in a prospective study.,Seventy-six pre-acquisition sputum supernatant samples, obtained just before acquisition of M catarrhalis, and 76 acquisition samples (34 were associated with exacerbation, 42 with colonization) were analyzed for IL-8, TNF-α, Neutrophil Elastase (NE) and Secretory leukocyte protease inhibitor (SLPI).,Changes were compared in paired samples from each patient.,IL-8, TNF-α and NE were significantly elevated after acquisition of M. catarrhalis, compared to pre-acquisition samples (p =< 0.001 for all three).,These changes were present in colonization (p = 0.015 for IL-8; p =< 0.001 for TNF-α and NE) as well as in exacerbation (p =< 0.001 for all three), compared to pre-acquisition levels.,SLPI was significantly lower after acquisition (p =< 0.001), in colonization (p =< 0.001) as well as in exacerbation (p = 0.004), compared to pre-acquisition levels.,SLPI levels correlated negatively with NE levels (R2 = 0.07; p = 0.001).,Acquisition of M. catarrhalis in COPD causes increased airway inflammation and worsening protease-antiprotease imbalance during exacerbations and also in colonization, even in the absence of increased symptoms.,These effects could contribute to progression of airway disease in COPD. | 1 |
This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).,Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months.,Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3.,This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.,There were no significant baseline differences between treatment groups.,With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping.,There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.,Six-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression. | Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity.,There are only limited data about its role in airway remodeling in COPD.,We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD).,This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.,Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls.,The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups.,Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3.,Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls.,TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs.,0.0 (0.0-7.0), p<0.05].,Percentage of vessels stained was also increased in these clinical groups.,Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.,Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD. | 1 |
The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 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 |
This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD.,A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa.,The primary endpoint was inspiratory capacity (IC) at peak post-dose.,Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001).,Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001).,Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254).,In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337).,Tiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients.,A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol. | Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | 1 |
To determine the importance of spirometric testing for early detection of chronic obstructive pulmonary disease (COPD).,Spirometric testing has been performed annually on World COPD Day in Sezana from 2003.,Sezana is in a semiurban region of Slovenia, with 12,000 inhabitants.,The investigation was performed between January 2003 and December 2008.,In total, 770 persons were enrolled (414 females and 356 males).,The participants were recruited by mass media appeals.,Smokers aged ≥40 years with a smoking history of ≥10 pack-years were invited to visit the local chest clinic.,The participants completed a questionnaire and had spirometry performed.,Subjects with a postbronchodilator forced expiratory volume in one second/forced vital capacity <0.70 were defined as having COPD, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines.,We identified that 16.2% of subjects had impaired lung function.,Of these, 10.2% had an obstructive pattern of ventilatory impairment and 6% had a restrictive pattern.,We identified 79 individuals with COPD.,Subjects with COPD were >70 years in 40.5% in cases.,The majority of individuals with COPD were men (74.6%), and 90% were smokers.,COPD was mild in 52% of subjects, moderate in 34%, and severe in 14%.,The majority of subjects had a milder stage of the disease, and 92% of those with COPD (72/79) had not been recognized to have COPD previously.,These results suggest that spirometry testing could detect patients with COPD in the earlier stages of the disease. | Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution.,However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far.,Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women.,We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.,In consecutive cross sectional studies conducted between 1985-1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany.,NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data.,Lung function was determined and COPD was defined by using the GOLD criteria.,Chronic respiratory symptoms and possible confounders were defined by questionnaire data.,Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.,The prevalence of COPD (GOLD stages 1-4) was 4.5%.,COPD and pulmonary function were strongest affected by PM10 and traffic related exposure.,A 7 μg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%-7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%-5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03-1.72) for COPD.,Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06-3.02) than for those living farther away.,Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.,Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function. | 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. | The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | 1 |
Monitoring pathological mechano-acoustic signals emanating from the lungs is critical for timely and cost-effective healthcare delivery.,Adventitious lung sounds including crackles, wheezes, rhonchi, bronchial breath sounds, stridor or pleural rub and abnormal breathing patterns function as essential clinical biomarkers for the early identification, accurate diagnosis and monitoring of pulmonary disorders.,Here, we present a wearable sensor module comprising of a hermetically encapsulated, high precision accelerometer contact microphone (ACM) which enables both episodic and longitudinal assessment of lung sounds, breathing patterns and respiratory rates using a single integrated sensor.,This enhanced ACM sensor leverages a nano-gap transduction mechanism to achieve high sensitivity to weak high frequency vibrations occurring on the surface of the skin due to underlying lung pathologies.,The performance of the ACM sensor was compared to recordings from a state-of-art digital stethoscope, and the efficacy of the developed system is demonstrated by conducting an exploratory research study aimed at recording pathological mechano-acoustic signals from hospitalized patients with a chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia, and acute decompensated heart failure.,This unobtrusive wearable system can enable both episodic and longitudinal evaluation of lung sounds that allow for the early detection and/or ongoing monitoring of pulmonary disease. | Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with systemic inflammation and balance impairment.,The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD]) phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation.,We enrolled 41 patients with COPD (22 stable and 19 in AECOPD) and 20 healthy subjects (control group), having no significant differences regarding the anthropometric data.,We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I) questionnaire, Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Single Leg Stance (SLS), 6-minute walking distance (6MWD), isometric knee extension (IKE) between these groups, and also the correlation between these scores and inflammatory biomarkers.,The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001), 6MWD (P<0.001), SLS (P<0.001), and BBS (P<0.001), at the same time noting a significant increase in median TUG score across the studied groups (P<0.001).,The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP) levels (10.60 vs 4.01; P=0.003) and decrease in PaO2 (70.1 vs 59.1; P<0.001).,We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes.,In both COPD groups, we observed that fibrinogen reversely and significantly correlated with the 6MWD, and FES-I questionnaire is correlated positively with TUG test.,Hs-CRP correlated reversely with the walking test and SLS test, while correlating positively with TUG test and FES-I questionnaire.,According to this study, COPD in advanced and acute stages is associated with an increased history of falls, systemic inflammation, balance impairment, and lower extremity muscle weakness. | 1 |
To explore the effects of group singing therapy on depression symptoms and quality of life of patients with stable chronic obstructive pulmonary disease (COPD).,Patients with COPD were randomly allocated to intervention (n = 30) and control groups (n = 30).,The intervention group received group singing therapy once a week for 24 sessions along with routine health education, whereas the control group only received the routine health education.,All patients were administered the Hospital Anxiety and Depression Scale depression subscale (HADS-D) and the Clinical COPD Questionnaire (CCQ).,Data were collected at baseline and at 1, 3, and 6 months.,Fifty-six participants completed this trial.,Significant between-group differences were observed with respect to the main effect of group and time as well as the effect of group × time interaction on HADS-D score.,The HADS-D score was significantly improved 1, 3, 6 months after group singing therapy.,The CCQ total scores were significantly different between the two groups with respect to the main effect of group and time and the group × time interaction effect.,Significantly better CCQ was detected in the intervention group at 3 months and 6 months after intervention.,Group singing therapy reduces depressive symptoms and improves the quality of life of patients with stable COPD. | This study aimed to investigate the effects of weekly singings classes on pulmonary function parameters and quality of life (QoL) of COPD patients.,Forty-three patients were randomized to weekly classes of singing practice, or handcraft work.,They performed spirometry and completed maximal respiratory pressure measurements, evaluations of dyspnea, and the Saint George’s Respiratory Questionnaire, before and after 24 training classes.,A functional evaluation, immediately after 10 minutes of singing practice, was also performed at the end of the study.,Fifteen subjects completed the study in each group.,In comparison to controls the singing group exhibited transitory elevations on the dyspnea Borg scale (p = 0.02), and inspiratory capacity (p = 0.01), and decreases of expiratory reserve volume (p = 0.03), just after a short session of singing.,There was a significant difference on changes of maximal expiratory pressures in the comparison between groups at the end of training.,While the control group showed deterioration of maximal expiratory pressure, the singing group exhibited a small improvement (p = 0.05).,Both groups showed significant improvements of QoL in within group comparisons.,We have concluded that singing classes are a well tolerated activity for selected subjects with COPD.,Regular practice of singing may improve QoL, and preserve the maximal expiratory pressure of these patients. | 1 |
Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time.,Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year.,Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics.,Four subtypes were identified.,Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity.,Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C.,Subtype D had higher rates of hospitalization the previous year, and comorbidities.,After 1 year, all clusters remained stable.,Generally, patients continued in the same subtype but 28% migrated to another cluster.,Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to.,Chronic obstructive pulmonary disease clusters remained stable over 1 year.,Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes. | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Several studies suggest that there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases.,On the other hand, increased sympathetic tone has been described in several respiratory diseases.,Our objective was to determine whether hypertension mediated by sympathetic overactivity is a mechanism that explains the association between COPD and cardiovascular diseases.,Prospective nested case-control observational study; 67 COPD patients were matched 1:1 by sex and age to controls with smoking history. 24 hour-blood pressure monitoring, urinary catecholamines and their metabolites measurement, echocardiography, carotid ultrasound examination, nocturnal oximetry and retinography were performed.,classic cardiovascular risk factors and comorbidities were similarly distributed between cases and controls.,No significant differences for blood pressure variables (difference for mean systolic blood pressure: -0·13 mmHg; 95% CI: -4·48,4·20; p = 0·94; similar results for all blood presssure variables) or catecholamines values were found between both groups.,There was a tendency for lower left ventricle ejection fraction in the COPD cases, that approached statistical significance (64·8 ± 7·4 vs 67·1 ± 6·2, p = 0·05).,There were no differences in the retinal arteriovenous ratio, the carotid intima-media thickness, or the number of carotid plaques, between cases and controls.,Fibrinogen values were higher in the COPD group (378·4 ± 69·6 vs 352·2 ± 45·6 mg/dL, p = 0·01) and mean nocturnal oxygen saturation values were lower for COPD patients (89·0 ± 4·07 vs 92·3 ± 2·2%, p < 0·0001).,Hypertension induced by sympathetic overactivity does not seem to be a mechanism that could explain the association between COPD and cardiovascular disease. | 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 |
Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response.,Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β.,The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations.,While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable.,In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines.,The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor.,Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD.,The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit.,Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either.,Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned.,There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target.,Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond. | Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers.,Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial.,This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.,Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab.,Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109).,Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.,Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins.,This profile was largely independent of smoking status, age, and clinical phenotype.,The majority of these associations of serum analytes with COPD are novel findings.,Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement.,Infliximab did not affect this systemic inflammatory profile.,A robust systemic inflammatory profile was associated with COPD.,This profile was generally independent of disease severity.,Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.,ClinicalTrials.gov, No.: NCT00056264. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users. | As part of the Respiratory Disease Specific Program (DSP) conducted to provide observations of clinical practice from a physician and matched patient viewpoint, this study aimed to establish how patients with COPD are treated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system and to quantify the symptom burden.,Data were obtained from the Respiratory DSP, a cross-sectional survey of patients with a diagnosis of COPD consulting for routine care in France, Germany, Italy, Spain, the UK, and the USA during the third quarter of 2013.,Patients’ exacerbation risk and symptom data were used for classification into GOLD groups A−D based on GOLD 2014 criteria.,Prescribing practices were stratified by physician type and time since patient diagnosis.,A total of 903 physicians participated in the Respiratory DSP, with data from 1,641 patients included in this analysis.,Most patients were classified into GOLD groups B (n=742; 45.2%) and D (n=704; 42.9%).,Patients in groups A and D were most likely to be treated in line with GOLD recommendations (61.5% and 77.5%, respectively), compared with 40.1% for group B.,Patients with a diagnosis within the past 12 months were more likely to be treated according to recommendations.,Inhaled corticosteroids (ICSs) in combination with one or more long-acting bronchodilator were prescribed across all GOLD groups.,Patterns of treatment were, in general, similar for patients treated by a primary care physician or a pulmonologist.,COPD assessment test scores ≥10 indicating a high symptom burden were reported for >80% of patients.,This analysis confirmed a high symptom burden among patients with COPD and indicates some misalignment of prescribing with GOLD recommendations, particularly regarding the role of ICS/long-acting β2-agonist (LABA) and ICS/LABA + long-acting muscarinic antagonist combinations across the different GOLD groups. | 1 |
Admission to hospital with chronic obstructive pulmonary disease (COPD) is associated with deprivation and season.,However, it is not known whether deprivation and seasonality act synergistically to influence the risk of hospital admission with COPD.,To investigate whether the relationship between season/temperature and admission to hospital with COPD differs with deprivation.,All COPD admissions (ICD10 codes J40-J44 and J47) were obtained for the decade 2001-2010 for all Scottish residents by month of admission and 2009 Scottish Index of Multiple Deprivation (SIMD) quintile.,Confidence intervals for rates and absolute differences in rates were calculated and the proportion of risk during winter attributable to main effects and interactions were estimated.,Monthly rates of admission by average daily minimum temperatures were plotted for each quintile of SIMD.,Absolute differences in admission rates between winter and summer increased with greater deprivation.,In the most deprived quintile, in winter 19.4% (95% CI 17.3% to 21.4%) of admissions were attributable to season/deprivation interaction, 61.2% (95% CI 59.5% to 63.0%) to deprivation alone, and 5.2% (95% CI 4.3% to 6.0%) to winter alone.,Lower average daily minimum temperatures over a month were associated with higher admission rates, with stronger associations evident in the more deprived quintiles.,Winter and socioeconomic deprivation-related factors appear to act synergistically, increasing the rate of COPD admissions to hospital more among deprived people than among affluent people in winter than in the summer months.,Similar associations were observed for admission rates and temperatures.,Interventions effective at reducing winter admissions for COPD may have potential for greater benefit if delivered to more deprived groups. | Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed.,A number of studies have evaluated the accuracy of screening tests for COPD, but their findings have not been formally summarised.,We therefore sought to determine and compare the diagnostic accuracy of such screening tests in primary care.,Systematic review and meta-analysis of the diagnostic accuracy of screening tests for COPD confirmed by spirometry in primary care.,We searched MEDLINE, EMBASE and other bibliographic databases from 1997 to 2013 for diagnostic accuracy studies that evaluated 1 or more index tests in primary care among individuals aged ≥35 years with no prior diagnosis of COPD.,Bivariate meta-analysis of sensitivity and specificity was performed where appropriate.,Methodological quality was assessed independently by 2 reviewers using the QUADAS-2 tool.,10 studies were included. 8 assessed screening questionnaires (the COPD Diagnostic Questionnaire (CDQ) was the most evaluated, n=4), 4 assessed handheld flow meters (eg, COPD-6) and 1 assessed their combination.,Among ever smokers, the CDQ (score threshold ≥19.5; n=4) had a pooled sensitivity of 64.5% (95% CI 59.9% to 68.8%) and specificity of 65.2% (52.9% to 75.8%), and handheld flow meters (n=3) had a sensitivity of 79.9% (95% CI 74.2% to 84.7%) and specificity of 84.4% (68.9% to 93.0%).,Inadequate blinding between index tests and spirometry was the main risk of bias.,Handheld flow meters demonstrated higher test accuracy than the CDQ for COPD screening in primary care.,The choice of alternative screening tests within whole screening programmes should now be fully evaluated.,CRD42012002074. | 1 |
Limited accessibility to health care may be a barrier to obtaining good care.,Few studies have investigated the association between access-to-care factors and COPD hospitalizations.,The objective of this study is to estimate the association between access-to-care factors and health care utilization including hospital/emergency department (ED) visits and primary care physician (PCP) office visits among adults with COPD utilizing a nationally representative survey data.,We conducted a pooled cross-sectional analysis based upon a bivariate probit model, utilizing datasets from the 2011-2012 Behavioral Risk Factor Surveillance System linked with the 2014 Area Health Resource Files among adults with COPD.,Dichotomous outcomes were hospital/ED visits and PCP office visits.,Key covariates were county-level access-to-care factors, including the population-weighted numbers of pulmonary care specialists, PCPs, hospitals, rural health centers, and federally qualified health centers.,Among a total of 9,332 observations, proportions of hospital/ED visits and PCP office visits were 16.2% and 44.2%, respectively.,Results demonstrated that access-to-care factors were closely associated with hospital/ED visits.,An additional pulmonary care specialist per 100,000 persons serves to reduce the likelihood of a hospital/ED visit by 0.4 percentage points (pp) (P=0.028).,In contrast, an additional hospital per 100,000 persons increases the likelihood of hospital/ED visit by 0.8 pp (P=0.008).,However, safety net facilities were not related to hospital utilizations.,PCP office visits were not related to access-to-care factors.,Pulmonary care specialist availability was a key factor in reducing hospital utilization among adults with COPD.,The findings of our study implied that an increase in the availability of pulmonary care specialists may reduce hospital utilizations in counties with little or no access to pulmonary care specialists and that since availability of hospitals increases hospital utilization, directing patients with COPD to pulmonary care specialists may decrease hospital utilizations. | Influenza is a disease with global impact that causes enormous morbidity and mortality on an annual basis.,It primarily infects the respiratory tract and causes a broad range of illness ranging from symptomless infection to fulminant primary viral and secondary bacterial pneumonia.,The severity of infection depends on both the virus strain and a number of host factors, primarily age and the presence of comorbid conditions such as cardiopulmonary disease.,The mortality and utilization of healthcare resources associated with influenza is concentrated in the elderly and those with coexisting disease such as chronic obstructive pulmonary disease (COPD).,Increasing use of vaccination and the development of new antiviral drugs hold out hope that the burden of disease associated with influenza can be reduced.,However the constant emergence of new influenza strains and the current risk of avian influenza pandemic serve as warnings that influenza will remain a serious pathogen for the foreseeable future. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | To characterize the distribution of BMI in a population-based sample of COPD patients and to evaluate the impact of obesity on their health status, exercise tolerance, systemic inflammation and comorbidity.,A population-based sample of 3,797 subjects aged 40-80 years from the EPI-SCAN study was selected.,Subjects were categorized according their body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) or obese (BMI≥30.0 kg/m2).,Subjects were evaluated with post-bronchodilator spirometry and 6-minute walk tests.,Smoking habits, respiratory symptoms, generic and specific quality of life, daily physical activities, comorbidities and systemic inflammatory biomarkers were recorded.,The prevalence of obesity or being overweight was higher in the 382 COPD patients than in the subjects without airflow limitation (29.4%, 95%CI 24.8-33.9% vs.,24.3, 95%CI 22.9-25.8; and 44.7%, 95%CI 39.7-49.6% vs.,43.0%, 95%CI 41.3-44.6, respectively; p = 0.020).,In the COPD subgroup, obese subjects presented more dyspnea and less chronic cough, chronic bronchitis or chronic phlegm than normal-weight patients, as well as a worse health status.,Moreover, reduced exercise tolerance and higher plasmatic C-reactive protein levels were found in the obese patients, who also presented a greater prevalence of cardiovascular disease (adjusted odds ratio 4.796, 95%CI 1.806-12.736, p = 0.002).,In a population-based sample, obesity is more prevalent in COPD patients than in subjects without airflow limitation.,Furthermore, obesity affects the clinical manifestations, quality of life and exercise tolerance of COPD patients, and it may contribute to a phenotype characterized by increased systemic inflammation and greater frequency of cardiovascular comorbidity. | 1 |
Exacerbations of COPD represent an important medical and health care problem.,Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis.,The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease.,However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients.,In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care.,This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations. | Smoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix.,This is thought to contribute to airway remodeling and airflow obstruction.,We have previously observed that long-term treatment with inhaled corticosteroids can not only reduce bronchial inflammation, but can also attenuate lung function decline in moderate-severe COPD.,We hypothesized that inhaled corticosteroids and current smoking modulate bronchial extracellular matrix components in COPD.,To compare major extracellular matrix components (elastic fibers; proteoglycans [versican, decorin]; collagens type I and III) in bronchial biopsies 1) after 30-months inhaled steroids treatment or placebo; and 2) between current and ex-smokers with COPD.,We included 64 moderate-severe, steroid-naive COPD patients (24/40 (ex)-smokers, 62±7 years, 46 (31-54) packyears, post-bronchodilator forced expiratory volume in one second (FEV1) 62±9% predicted) at baseline in this randomized, controlled trial. 19 and 13 patients received 30-months treatment with fluticasone or placebo, respectively.,Bronchial biopsies collected at baseline and after 30 months were studied using (immuno)histochemistry to evaluate extracellular matrix content.,Percentage and density of stained area were calculated by digital image analysis.,30-Months inhaled steroids increased the percentage stained area of versican (9.6% [CI 0.9 to 18.3%]; p = 0.03) and collagen III (20.6% [CI 3.8 to 37.4%]; p = 0.02) compared to placebo.,Increased collagen I staining density correlated with increased post-bronchodilator FEV1 after inhaled steroids treatment (Rs = 0.45, p = 0.04).,There were no differences between smokers and ex-smokers with COPD in percentages and densities for all extracellular matrix proteins.,These data show that long-term inhaled corticosteroids treatment partially changes the composition of extracellular matrix in moderate-severe COPD.,This is associated with increased lung function, suggesting that long-term inhaled steroids modulate airway remodeling thereby potentially preventing airway collapse in COPD.,Smoking status is not associated with bronchial extracellular matrix proteins.,ClinicalTrials.gov NCT00158847 | 1 |
Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | Studying the causal and temporal association between past and future exacerbations in COPD is an active area of research.,Standard survival analysis techniques often used in such studies typically produce results that pertain to the overall population, whereas the greatest interest is in the study of associations within individuals.,A factor that can lead to profound discrepancies between population-level and individual-level survival patterns is the between-individual heterogeneity in the rate of exacerbations.,We briefly review two studies that, while reporting valid results for the overall population, drew conclusions at the individual level that could not be supported by the observations.,We caution on the distinction between population and individual-level associations in survival analysis, and recommend accounting for heterogeneity in future studies. | 1 |
The Asp358Ala variant in the interleukin-6 receptor (IL-6R) gene has been implicated in asthma, autoimmune and cardiovascular disorders, but its role in other respiratory conditions such as chronic obstructive pulmonary disease (COPD) has not been investigated.,The aims of this study were to evaluate whether there is an association between Asp358Ala and COPD or asthma risk, and to explore the role of the Asp358Ala variant in sIL-6R shedding from neutrophils and its pro-inflammatory effects in the lung.,We undertook logistic regression using data from the UK Biobank and the ECLIPSE COPD cohort.,Results were meta-analyzed with summary data from a further three COPD cohorts (7,519 total cases and 35,653 total controls), showing no association between Asp358Ala and COPD (OR = 1.02 [95% CI: 0.96, 1.07]).,Data from the UK Biobank showed a positive association between the Asp358Ala variant and atopic asthma (OR = 1.07 [1.01, 1.13]).,In a series of in vitro studies using blood samples from 37 participants, we found that shedding of sIL-6R from neutrophils was greater in carriers of the Asp358Ala minor allele than in non-carriers.,Human pulmonary artery endothelial cells cultured with serum from homozygous carriers showed an increase in MCP-1 release in carriers of the minor allele, with the difference eliminated upon addition of tocilizumab.,In conclusion, there is evidence that neutrophils may be an important source of sIL-6R in the lungs, and the Asp358Ala variant may have pro-inflammatory effects in lung cells.,However, we were unable to identify evidence for an association between Asp358Ala and COPD. | 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 objective of this study was to evaluate the comparative efficacy of indacaterol 75 μg once daily (OD), tiotropium 18 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD) based on individual patient data (IPD) from randomized controlled trials (RCTs) from the indacaterol trial program and aggregate data (AD) identified from a systematic review of RCTs.,22 RCTs were included in the AD analysis that evaluated: indacaterol 75 μg (n = 2 studies), indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg) (n = 5), indacaterol 300 μg (n = 2), tiotropium 18 μg (n = 10), salmeterol 50 μg (n = 7), and formoterol 12 μg (n = 4).,All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol) were placebo controlled.,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and St.,George’s Respiratory Questionnaire (SGRQ) total score at week 12.,The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA) and relative treatment effects between all regimens were obtained.,In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA.,Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials.,All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks.,Indacaterol 75 μg is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses.,In comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09).,In terms of SGRQ total score at 12 weeks, indacaterol 75 μg and formoterol were more efficacious than placebo, whereas for tiotropium and salmeterol the credible intervals included zero for the AD results only (tiotropium: -2.99 points improvement versus placebo; 95%CrI −6.48 to 0.43; salmeterol:-2.52; 95%CrI: -5.34; 0.44).,Both IPD and AD results suggest that indacaterol 75 μg is expected to be comparable to all active treatments.,Based on a synthesis of currently available AD RCT evidence as well as an IPD network meta-analysis of six RCTs, indacaterol 75 μg is expected to be at least as efficacious as formoterol and comparable to tiotropium and salmeterol regarding FEV1.,Furthermore, indacaterol 75 μg shows comparable level of improvement in health-related quality of life to tiotropium, salmeterol, and formoterol, as measured by the SGRQ. | Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD.,The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.,We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD.,All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET).,The end-expiratory lung volume (EELV) was evaluated during the CPET.,Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.,Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%.,Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004).,Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.,The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise.,This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function. | 1 |
An incremental approach using open-triple therapy may improve outcomes in patients with chronic obstructive pulmonary disease (COPD).,However, there is little sufficient, real-world evidence available identifying time to open-triple initiation.,This retrospective study of patients with COPD, newly initiated on long-acting muscarinic antagonist (LAMA) monotherapy or inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination therapy, assessed baseline demographics, clinical characteristics, and exacerbations during 12 months prior to first LAMA or ICS/LABA use.,Time to initiation of open-triple therapy was assessed for 12 months post-index date.,Post hoc analyses were performed to assess the subsets of patients with pulmonary-function test (PFT) information and patients with and without comorbid asthma.,Demographics and clinical characteristics were similar between cohorts in the pre-specified and post hoc analyses.,In total, 283 (19.3%) and 160 (10.9%) patients had moderate and severe exacerbations at baseline, respectively, in the LAMA cohort, compared with 482 (21.3%) and 289 (12.8%) patients in the ICS/LABA cohort.,Significantly more patients initiated open-triple therapy in the LAMA cohort compared with the ICS/LABA cohort (226 [15.4%] versus 174 [7.7%]; P<0.001); results were similar in the post hoc analyses.,Mean (standard deviation) time to open-triple therapy was 79.8 (89.0) days in the LAMA cohort and 122.9 (105.4) days in the ICS/LABA cohort (P<0.001).,This trend was also observed in the post hoc analyses, though the difference between cohorts was nonsignificant in the subset of patients with PFT information.,In this population, patients with COPD are more likely to initiate open-triple therapy following LAMA therapy, compared with ICS/LABA therapy.,Further research is required to identify factors associated with the need for treatment augmentation among patients with COPD. | Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines.,This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD.,Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis.,Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997-2001; (2) 2002-2006; and (3) 2007-2010.,Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression.,The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment.,Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis.,Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors.,In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens.,Predictors of initial therapy were identified. | 1 |
Background and objectives: Exertional desaturation (ED) is often overlooked in chronic obstructive pulmonary disease (COPD).,We aim to investigate the impact of ED on mortality and the predictors of ED in COPD.,Materials and methods: A cohort of COPD patients with clinically stable, widely ranging severities were enrolled.,ED is defined as oxyhemoglobin saturation by pulse oximetry (SpO2) < 90% or a drop of ΔSpO2 ≥ 4% during a six-minute walk test (6MWT).,Cox regression analysis is used to estimate the hazard ratio (HR) for three-year mortality.,Results: A total of 113 patients were studied, including ED (N = 34) and non-ED (N = 79) groups.,FVC (% of predicted value), FEV1/FVC (%), FEV1 (% of predicted value), DLCO (%), maximal inspiratory pressure, SpO2 during the 6MWT, GOLD stage, and COPD severity were significantly different between the ED and non-ED groups in univariate analysis.,Low minimal SpO2 (p < 0.001) and high maximal heart rate (p = 0.04) during the 6MWT were significantly related to ED in multivariate analysis.,After adjusting for age, gender, body mass index, 6MWD, FEV1, mMRC, GOLD staging, exacerbation, hs-CRP, and fibrinogen, the mortality rate of the ED group was higher than that of the non-ED group (p = 0.012; HR = 4.12; 95% CI 1.37-12.39).,For deaths, the average survival time of ED was shorter than that of the non-ED group (856.4 days vs.,933.8 days, p = 0.033).,Conclusions: ED has higher mortality than non-ED in COPD.,COPD should be assessed for ED, especially in patients with low minimal SpO2 and high maximal HR during the 6MWT. | Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death worldwide, is characterized by irreversible airflow limitation based on obstructive bronchiolitis, emphysema, and chronic pulmonary inflammation.,Inhaled toxic gases and particles, e.g., cigarette smoke, are major etiologic factors for COPD, while the pathogenesis of the disease is only partially understood.,Over the past decade, an increasing body of evidence has been accumulated for a link between COPD and autoimmunity.,Studies with clinical samples have demonstrated that autoantibodies are present in sera of COPD patients and some of these antibodies correlate with specific disease phenotypes.,Furthermore, evidence from animal models of COPD has shown that autoimmunity against pulmonary antigens occur during disease development and is capable of mediating COPD-like symptoms.,The idea that autoimmunity could contribute to the development of COPD provides a new angle to understand the pathogenesis of the disease.,In this review article, we provide an advanced overview in this field and critically discuss the role of autoantibodies in the pathogenesis of COPD. | 1 |
To determine if there is a correlation between the BODE Index and variables assessed during the Activities of Daily Living assessment, performance on lower limber tests, and peripheral muscle impairment of the upper limb in patients with chronic obstructive pulmonary disease.,Ten men (aged 58 to 80 years old) with moderate to very severe obstruction were evaluated and classified by the BODE Index.,They were evaluated by pulmonary ventilation (V̇E), oxygen consumption (V̇O2), and carbonic gas production (V̇CO2) on the ADL assessment; Distance Walking (DW) in the Six Minute Walking Test (6MWT) and the Six Minute Walking Test on Treadmill (6MWTT); number of repetitions in the Sit-to-Stand Test; and the Hand Grip Strength Test.,Correlations were evaluated between the classification and the tests performed (Pearson and Spearman test, p<0.05).,The mean of the total score for the BODE Index was 2.80 (±1.03), with three patients scoring in the first quartile (Q1) and seven scoring in the second quartile (Q2).,This Index showed a negative correlation with the 6MWTT (r=−0.86), the Sit-to-Stand Test (r=−0.66), and the Hand Grip Strength Test (r=−0.83).,Our results show that there is no correlation between the BODE Index and the ventilatory and metabolic responses in the Activities of Daily Living assessment.,On the other hand, a correlation was observed between the BODE Index and the variables assessed in the 6MWTT, Sit-to-Stand Test, and Hand Grip Strength Test in moderate to very severe Chronic Obstructive Pulmonary Disease patients.,This suggests that these tests can be employed as predictors of physical exercise capacity, perhaps as complementary tests to the BODE Index. | To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD, using St.George’s Respiratory questionnaire (SGRQ), the 6-minutes walking test (6-MWT) and BODE index as the primary outcome measures.,A prospective, parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD (67 men and 13 women; mean age 64.8 ± 10.6 years; FEV1, 42.8% ± 7.6% of the predicted value.,The active group (n = 40) took part in a 14-week rehabilitation program [3 h/wk, 1.5 h of education and exercise and 1.5 h of cycling].,The control group (n = 40) was reviewed routinely as medical outpatients.,The following evaluations were carried out at study entry and after14 weeks: (1) pulmonary function studies; (2) 6-minutes walking test 6MWT; (3) quality of life; and (4) BODE index.,The following patients completed the study: 35 patients (87.5%) from the active group (mean age, 63.7 ± 11.9 years; mean forced expiratory volume in one second (FEV1), 41.9 ± 2.6% of the predicted value); and 36 patients (88%) from the control group (mean age, 65.9 ± 10.3 years; mean FEV1, 43.33 ± 3.6% of the predicted value).,We found no changes in pulmonary function parameters in the active group and the control one at 14weeks.,On the other hand, there were significant changes within the components of the SGRQ (12.3 for the score total) for the patients of the active group but not for the patients of the control one (only 1.5 for the score total), we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one, and finally a decrease of two points (from 6 to 4) was noted in the score of the active group’s BODE index without any change in the control group’s one.,An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD, and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index. | 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 assessment of symptoms of chronic obstructive pulmonary disease (COPD) is important for monitoring and managing the disease and for evaluating outcomes of interventions.,COPD patients experience symptoms during the day and night, and symptoms experienced at night often disturb sleep.,The aim of this paper is to describe methods used to develop a patient-reported outcome (PRO) instrument for evaluating nighttime symptoms of COPD, and to document evidence for the content validity of the instrument.,Literature review and clinician interviews were conducted to inform discussion guides to explore patients’ nighttime COPD symptom experience.,Data from focus groups with COPD patients was used to develop a conceptual framework and the content of a new PRO instrument.,Patient understanding of the new instrument was assessed via cognitive interviews with COPD patients.,The literature review confirmed that there is no instrument with evidence of content validity currently available to assess nighttime symptoms of COPD.,Additionally, the literature review and clinician interviews suggested the need to understand patients’ experience of specific symptoms in order to evaluate nighttime symptoms of COPD.,Analyses of patient focus group data (N = 27) supported saturation of concepts and aided in development of a conceptual framework.,Items were generated using patients’ terminology to collect data on concepts in the framework including the occurrence and severity of COPD symptoms, use of rescue medication at night, and nocturnal awakening.,Response options were chosen to reflect concepts that were salient to patients.,Subsequent cognitive interviewing with ten COPD patients demonstrated that the items, response options, recall period, and instructions were understandable, relevant, and interpreted as intended.,A new PRO instrument, the Nighttime Symptoms of COPD Instrument (NiSCI), was developed with documented evidence of content validity.,The NiSCI is ready for empirical testing, including item reduction and evaluation of psychometric properties. | 1 |
Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations.,However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available.,Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow.,A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed.,The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate.,Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible.,The usefulness of formally scheduled regular follow-up visits was assessed.,Two different databases (resources and clinical database) were constructed.,Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes.,Exacerbations and survival served as the main endpoints.,This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting.,Results from such audits can guide health information systems development and implementation in real-world settings. | AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines.,The present study describes hospital resources, hospital factors related to case recruitment variability, patients’ characteristics, and adherence to guidelines.,An organisational database was completed by all participant hospitals recording resources and organisation.,Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified.,At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population.,Audited patients were reassessed 90 days after admission for survival and readmission rates.,A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death.,Median inpatient mortality was 5% (across-hospital range 0-35%).,Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%).,The overall mortality rate was 11.6% (0-50%).,Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment.,Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles.,The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes.,The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement. | 1 |
Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines.,This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD.,Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis.,Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997-2001; (2) 2002-2006; and (3) 2007-2010.,Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression.,The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment.,Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis.,Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors.,In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens.,Predictors of initial therapy were identified. | This study aimed to characterize patients with chronic obstructive pulmonary disease (COPD) newly prescribed a long-acting bronchodilator (LABD), and to assess changes in medication over 24 months.,A cohort of patients with COPD aged ≥40 years newly prescribed an LABD between January 1, 2007 and December 31, 2009 were identified from the Truven Marketscan® Commercial Database (Truven Health Analytics, Ann Arbor, MI, USA) and followed for 24 months.,Inclusion criteria included no prior prescription for an LABD or inhaled corticosteroids for 12 months prior to the LABD index date (baseline).,Patient characteristics were examined.,As LABDs were mainly long-acting muscarinic antagonists (LAMAs), additions, switches, discontinuation, adherence to (medication possession ratio), and persistence (proportion of days covered) with LAMA monotherapy were assessed for 24 months following the index date.,Adherence and persistence with long-acting β2-agonists (LABAs) were also assessed.,A cohort of 3,268 patients aged 40-65 years was identified (mean age 55.8 years, 48% male).,LAMA monotherapy was prescribed to 93% of patients who received an LABD.,During the 24-month follow-up, 16% of these patients added COPD medication, 10% switched to an inhaled corticosteroid-containing medication, and 25% discontinued after one LAMA prescription at baseline.,Over 12 and 24 months, adherence to LAMA was 40% and 33%, respectively, and adherence to LABA was 29% and 24%, respectively.,Over the same time periods, persistence with LAMA monotherapy was 19% and 15%, respectively, and persistence with LABA was 9% and 7%, respectively.,Adherence to newly initiated LAMA monotherapy was low, with one in four patients adding to or switching from LAMA and many patients discontinuing therapy.,Adherence to LABA was also low.,These results suggest that additional medication to a single LABD may be required in some patients with COPD to achieve optimal disease control. | 1 |
Functional respiratory imaging (FRI) is a quantitative postprocessing imaging technique used to assess changes in the respiratory system.,Using FRI, we characterized the effects of the long-acting muscarinic antagonist (LAMA), glycopyrrolate metered dose inhaler (GP MDI), and the long-acting β2-agonist (LABA), formoterol fumarate metered dose inhaler (FF MDI), on airway volume and resistance in patients with moderate-to-severe chronic obstructive pulmonary disease.,Patients in this phase IIIb, randomized, double-blind crossover study received twice-daily GP MDI (18 μg) and FF MDI (9.6 μg).,Primary endpoints were specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and specific image-based airway resistance (siRaw), measured using FRI.,Secondary and other endpoints included additional FRI, spirometry, and body plethysmography parameters.,Postdose efficacy assessments were performed within 60-150 min of dosing on day 15.,A total of 23 patients were randomized and 19 completed both treatment periods.,GP MDI and FF MDI both achieved significant improvements from baseline to day 15 in siVaw [11% (p = 0.0187) and 23% (p < 0.0001) increases, respectively] and siRaw [25% (p = 0.0219) and 44% (p < 0.0001) reductions, respectively].,Although, on average, improvements were larger for FF MDI than GP MDI, some individuals displayed greater responses with each of the two treatments.,These within-patient differences increased with airway generation number.,Spirometry and body plethysmography endpoints showed significant improvements from baseline in inspiratory capacity for both treatments, and numeric improvements for other endpoints.,Both GP MDI and FF MDI significantly improved siRaw and siVaw at day 15 versus baseline.,FRI endpoints demonstrated increased sensitivity relative to spirometry and body plethysmography in detecting differences between treatments in a small number of patients.,Intra-patient differences in treatment response between the LAMA and the LABA provide further support for the benefit of dual bronchodilator therapies.,NCT02937584,The reviews of this paper are available via the supplemental material section. | Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD).,However, their bronchodilating effect has not yet been compared in the central and distal airways.,Functional imaging using computational fluid dynamics offers the possibility of making such a comparison.,The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.,Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments.,Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging.,Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.,Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product.,On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways.,Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient.,Salbutamol was more effective in the other patients.,This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics. | 1 |
The mechanisms underlying altered susceptibility and propensity to severe Coronavirus disease 2019 (COVID-19) disease in at-risk groups such as patients with chronic obstructive pulmonary disease (COPD) are poorly understood.,Inhaled corticosteroids (ICSs) are widely used in COPD, but the extent to which these therapies protect or expose patients to risk of severe COVID-19 is unknown.,The aim of this study was to evaluate the effect of ICSs following pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme-2 (ACE2).,We evaluated the effect of ICS administration on pulmonary ACE2 expression in vitro in human airway epithelial cell cultures and in vivo in mouse models of ICS administration.,Mice deficient in the type I IFN-α/β receptor (Ifnar1−/−) and administration of exogenous IFN-β were used to study the functional role of type-I interferon signaling in ACE2 expression.,We compared sputum ACE2 expression in patients with COPD stratified according to use or nonuse of ICS.,ICS administration attenuated ACE2 expression in mice, an effect that was reversed by exogenous IFN-β administration, and Ifnar1−/− mice had reduced ACE2 expression, indicating that type I interferon contributes mechanistically to this effect.,ICS administration attenuated expression of ACE2 in airway epithelial cell cultures from patients with COPD and in mice with elastase-induced COPD-like changes.,Compared with ICS nonusers, patients with COPD who were taking ICSs also had reduced sputum expression of ACE2.,ICS therapies in COPD reduce expression of the SARS-CoV-2 entry receptor ACE2.,This effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
Chronic obstructive pulmonary disease (COPD) is an inflammatory airways disease with limited therapeutic options.,We have previously shown that mesenchymal stromal cell (MSC) infusions are well tolerated in patients with COPD and reduce circulatory biomarkers associated with systemic inflammation and oxidative stress.,This study aimed to delineate the underlying mechanisms further by characterizing the transcriptional networks in these patients and to explore the role of MSC‐derived paracrine factors in regulating these pathways.,Allogeneic, bone marrow‐derived MSCs were systemically administered into patients with stable COPD (n = 9).,Gene expression profiles from peripheral blood mononuclear cells (PBMCs) were analyzed across the first week after infusion.,Paracrine mechanisms associated with these transcriptional changes were explored further by culturing patient PBMCs with MSC‐conditioned medium (MSC‐CM) or post‐MSC infusion (PI) plasma to measure the regulatory effects of soluble factors that may be derived from MSCs.,MSC‐CM and PI‐plasma were characterized further to identify potential immunoregulatory candidates.,MSC infusion elicited a strong but transient transcriptional response in patient PBMCs that was sustained up to 7 days.,MSC infusion strongly downregulated transcriptional pathways related to interleukin (IL)‐8 and IL‐1β, which were also significantly inhibited in vitro following co‐culture of PBMCs with MSC‐CM and PI‐plasma.,MSC‐derived soluble tumor necrosis factor receptor‐1, transforming growth factor‐β1, and extracellular vesicle‐associated microRNAs were identified as potential mechanisms promoting these changes, but depletion of these individual candidates revealed inconsistent results.,MSC‐derived paracrine factors modulate important inflammatory pathways that are relevant to COPD pathogenesis.,These data strengthen the hypothesis that therapies using MSCs and their secreted products may be beneficial to patients with COPD.,Mesenchymal stromal cells (MSC) are potent immunomodulators that have shown promise in treating chronic obstructive pulmonary disease (COPD).,Using transcriptomics, we have demonstrated that MSC infusions elicit a strong, yet transient (<7 days) transcriptional response in circulating mononuclear cells of COPD patients, attenuating key pro‐inflammatory pathways.,These responses are likely mediated by soluble factors and/or products of MSC breakdown. | Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD.,Fibroblast-derived WNT-5A inhibits canonical WNT-β-catenin-driven alveolar epithelial cell-mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.,Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide.,One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined.,Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated.,Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis.,We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens.,WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence.,Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro.,Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo.,Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD.,We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy. | 1 |
To validate a Portuguese-language version of the COPD assessment test (CAT) for use in Brazil and to assess the reproducibility of this version.,This was multicenter study involving patients with stable COPD at two teaching hospitals in the city of Fortaleza, Brazil.,Two independent observers (twice in one day) administered the Portuguese-language version of the CAT to 50 patients with COPD.,One of those observers again administered the scale to the same patients one week later.,At baseline, the patients were submitted to pulmonary function testing and the six-minute walk test (6MWT), as well as completing the previously validated Portuguese-language versions of the Saint George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (MMRC) dyspnea scale, and hospital anxiety and depression scale (HADS).,Inter-rater and intra-rater reliability was excellent (intraclass correlation coefficient [ICC] = 0.96; 95% CI: 0.93-0.97; p < 0.001; and ICC = 0.98; 95% CI: 0.96-0.98; p < 0.001, respectively).,Bland Altman plots showed good test-retest reliability.,The CAT total score correlated significantly with spirometry results, 6MWT distance, SGRQ scores, MMRC dyspnea scale scores, and HADS-depression scores.,The Portuguese-language version of the CAT is a valid, reproducible, and reliable instrument for evaluating patients with COPD in Brazil.,Realizar a validação e verificar a reprodutibilidade da versão em português do Brasil do COPD Assessment Test (CAT).,Estudo multicêntrico, no qual foram selecionados pacientes com DPOC estável em dois hospitais de ensino na cidade de Fortaleza, CE.,A versão do CAT foi aplicada duas vezes a 50 pacientes com DPOC por dois observadores independentes no mesmo dia.,Após uma semana, esse mesmo questionário foi aplicado novamente aos mesmos pacientes por um dos observadores.,No primeiro dia, os pacientes foram submetidos à prova de função pulmonar e ao teste de caminhada de seis minutos (TC6) e responderam as versões validadas de qualidade de vida relacionada à saúde (QVRS).,(SGRQ), escala de dispneia Modified Medical Research Council (MMRC) e hospital anxiety and depression scale (HADS).,As reprodutibilidades interobservador e intraobservador foram excelentes (coeficiente de correlação intraclasse [CCI] = 0,96; IC95%: 0,93-0,97; p < 0,001; e CCI = 0,98; IC95%: 0,96-0,98; p < 0,001, respectivamente).,As disposições gráficas de Bland Altman demonstraram boa confiabilidade teste-reteste.,Houve correlações significativas do escore total do CAT com os resultados de espirometria, TC6, SGRQ, escala de dispneia MMRC e HADS-depressão.,A versão brasileira do CAT é um instrumento válido, reprodutível e confiável para a avaliação dos pacientes com DPOC na população brasileira. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
The lung is composed of airways and lung parenchyma, and the extracellular matrix (ECM) contains the main building blocks of both components.,The ECM provides physical support and stability to the lung, and as such it has in the past been regarded as an inert structure.,More recent research has provided novel insights revealing that the ECM is also a bioactive environment that orchestrates the cellular responses in its environs.,Changes in the ECM in the airway or parenchymal tissues are now recognized in the pathological profiles of many respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF).,Only recently have we begun to investigate whether these ECM changes result from the disease process, or whether they constitute a driving factor that orchestrates the pathological outcomes.,This review summarizes our current knowledge of the alterations in the ECM in asthma, COPD, and IPF, and the contributions of these alterations to the pathologies.,Emerging data suggest that alterations in the composition, folding or rigidity of ECM proteins may alter the functional responses of cells within their environs, and in so doing change the pathological outcomes.,These characteristics highlight potential avenues for targeting lung pathologies in the future.,This may ultimately contribute to a better understanding of chronic lung diseases, and novel approaches for finding therapeutic solutions.,© 2016 The Authors.,The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. | : To verify the accordance of functional and morphometric parameters during the development of emphysema.,: BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days.,Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed.,To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma.,: We only observed decreases in tissue elastance and tissue damping on the 28th day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema.,However, only the mean linear intercept values remained increased until the 40th day.,The volume proportion of collagen fibers was increased from the 15th day to the 40th day, whereas the volume proportion of elastic fibers was only increased on the 40th day.,The number of macrophages increased beginning on the 1st day.,The expression of metalloproteinase 12 was increased from the 3rd day until the 40th day.,However, 8-isoprostane expression was only increased on the 1st and 3rd days.,: In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics.,Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process. | 1 |
Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes.,Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment).,Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF25-75).,Measures of symptom burden (COPD Assessment Test) and functional impairment (six-minute walk distance) also associate with disparate lung microbiota composition.,Drivers of these relationships include members of the Streptococcus, Prevotella, Veillonella, Staphylococcus, and Pseudomonas genera.,Thus, lung microbiota differences may contribute to airway dysfunction and airway disease in milder COPD. | There is now convincing evidence that the airway epithelium drives the pathogenesis of COPD.,A major aspect of this is the disease-related reduction in barrier function that is potentiated by dysregulation of tight junction (TJ) protein complexes.,However, a significant number of studies using in vitro smoke exposure models have not observed alterations in barrier permeability.,We have previously shown that zinc (Zn) is an influential cytoprotective factor for the airway epithelium, and its depletion by cigarette smoke produces disease-related modifications consistent with inflammatory changes in COPD.,We hypothesized that Zn deficiency is a significant co-stimulus with cigarette smoke extract (CSE) for potentiating the leaky barrier phenotype exhibited in COPD.,We employed an ex vivo model of differentiated human airway epithelium exposed to Zn depletion and CSE to determine the contribution of Zn in maintaining normal epithelial permeability.,Western blot analysis demonstrated a significant downregulation of the TJ proteins such as ZO-1 (−1.93-fold, P<0.05) and Claudin-1 (−3.37-fold, P<0.01) with the combination exposure.,Assessment of barrier function via paracellular ionic conductance and tracer permeability also showed that Zn depletion was an important factor, which potentiated an increase in epithelial permeability (P<0.001 for both) compared to Zn depletion or CSE exposures in isolation.,Visual inspection of the epithelium using transmission electron microscopy revealed a marked reduction in junction complexes between the adjacent airway epithelial cells treated with a combination of Zn depletion and CSE.,These observations identify Zn deficiency as a significant codeterminant with CSE as a factor leading to an increase in airway epithelial permeability.,Hence, as Zn dyshomeostasis has been reported in the airway epithelium exposed to chronic cigarette smoke and inflammation, targeting these phenomena may represent a promising strategy to ameliorate the leaky barrier phenotype that is synonymous with COPD. | 1 |
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. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. | Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD).,In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP).,The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs) 8 and 9 and prolyl endopeptidase (PE).,Here we investigated whether cigarette smoke extract (CSE) stimulates human PMNs to breakdown whole matrix collagen leading to the generation of the chemotactic collagen fragment N-ac-PGP.,Incubating PMNs with CSE led to the release of chemo-attractant CXCL8 and proteases MMP8 and MMP9.,PMNs constitutively expressed PE activity as well as PE protein.,Incubating CSE-primed PMNs with collagen resulted in collagen breakdown and in N-ac-PGP generation.,Incubation of PMNs with the tripeptide N-ac-PGP resulted in the release of CXCL8, MMP8 and MMP9.,Moreover, we tested whether PMNs from COPD patients are different from PMNs from healthy donors.,Here we show that the intracellular basal PE activity of PMNs from COPD patients increased 25-fold compared to PMNs from healthy donors.,Immunohistological staining of human lung tissue for PE showed that besides neutrophils, macrophages and epithelial cells express PE.,This study indicates that neutrophils activated by cigarette smoke extract can breakdown collagen into N-ac-PGP and that this collagen fragment itself can activate neutrophils, which may lead in vivo to a self-propagating cycle of neutrophil infiltration, chronic inflammation and lung emphysema.,MMP-, PE- or PGP-inhibitors can serve as an attractive therapeutic target and may open new avenues towards effective treatment of COPD. | 1 |
This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.,Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied.,The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls.,Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001].,The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.,The characteristics of Rbm remodelling are quite different in asthma and COPD. | Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD).,We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls.,This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.,To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.,Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable.,The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects.,Rbm fragmentation correlated with smoking history in COPD but not with age.,There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05).,The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004).,In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).,Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall.,Rbm fragmentation was also present to as great an extent in ex-smokers with COPD.,These characteristics may have potential physiological consequences. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease with exacerbations causing hospitalizations, morbidity, and mortality.,COPD exacerbation causes a substantial health impact, and its subtypes might differ in prognosis and treatment response.,This study evaluated the factors of COPD exacerbations and explored the probabilities of frequent severe COPD exacerbations.,Categorical and continuous variables between groups were compared.,The hazard ratio (HR) and the probability of no hospital readmission were also estimated.,A total of 617 COPD patients were enrolled and comprised the frequent exacerbator (N = 226) and the non-frequent exacerbator (N = 391) groups.,The frequent exacerbator group significantly displayed a higher eosinophil count (EC; p=0.004), a higher percentage of the frequent severe acute exacerbation history before the index hospitalization (IH; p < 0.001), a lower FEV1 value (p=0.001), and a higher triple combination inhaler prior and following the IH (p < 0.001 and p=0.002) than the non-frequent exacerbator one.,Increasing age (aOR of 1.02), higher EC (aOR of 1.09), and lower FEV1 value (aOR of 0.72) were significantly associated with an increased hospital readmission risk.,The readmission rate and risk were higher in patients with a history of frequent severe acute exacerbation (aHR of 3.38) than those without severe acute exacerbation.,Cases treated with the triple combination inhaler before the IH had a higher readmission rate and risk than non-users.,Patients with EC ≥2%, FEV1 <50%, or frequent severe acute exacerbation history before the IH have a higher risk of being diagnosed with a frequent exacerbator phenotype.,Besides, higher age, triple combination inhaler before the IH, and smoking might be independently correlated with the frequent readmission risk within 1-year post-exacerbation.,A better comprehension of the COPD exacerbation mechanism may further identify the best course of preventative strategy and lead to novel interventions. | COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited.,This study aimed to identify the factors associated with acute exacerbation leading to hospitalization.,This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria) hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE) group, while the others were grouped into the infrequent exacerbation (IE) group.,The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups.,Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25-75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04).,According to generations of bronchi, the percentage of the wall area (%WA) of lobes was found to be higher in the FE group.,Emphysema index (EI), mean emphysema density (MED)whole and MEDleft lung in the FE group were significantly worse than in the IE group (P<0.05).,Using logistic regression, exacerbation hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1-34.0, P<0.001) and EI >10% (OR 2.9, 95% CI 1.2-7.1, P=0.02) were independently associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.,Exacerbation hospitalizations in the past year and imaging features of emphysema (EI) were independently associated with FE hospitalization. | 1 |
Readmission after hospital discharge is common in patients with acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD).,Although frailty predicts hospital readmission in patients with chronic nonpulmonary diseases, no multidimensional frailty measures have been validated to stratify the risk for patients with COPD.,The aim of this study was to explore multidimensional frailty as a potential risk factor for readmission due to a new exacerbation episode during the 90 days after hospitalization for AE-COPD and to test whether frailty could improve the identification of patients at high risk of readmission.,We hypothesized that patients with moderate-to-severe frailty would be at greater risk for readmission within that period of follow up.,A secondary aim was to test whether frailty could improve the accuracy with which to discriminate patients with a high risk of readmission.,Our investigation was part of a wider study protocol with additional aims on the same study population.,Frailty, demographics, and disease-related factors were measured prospectively in 102 patients during hospitalization for AE-COPD.,Some of the baseline data reported were collected as part of a previously study.,Readmission data were obtained on the basis of the discharge summary from patients’ electronic files by a researcher blinded to the measurements made in the previous hospitalization.,The association between frailty and readmission was assessed using bivariate analyses and multivariate logistic regression models.,Whether frailty better identifies patients at high risk for readmission was evaluated by area under the receiver operator curve (AUC).,Severely frail patients were much more likely to be readmitted than nonfrail patients (45% versus 18%).,After adjusting for age and relevant disease-related factors in a final multivariate model, severe frailty remained an independent risk factor for 90-day readmission (odds ratio = 5.19; 95% confidence interval: 1.26-21.50).,Age, number of hospitalizations for exacerbations in the previous year and length of stay were also significant in this model.,Additionally, frailty improved the predictive accuracy of readmission by improving the AUC.,Multidimensional frailty predicts the risk of early hospital readmission in patients hospitalized for AE-COPD.,Frailty improved the accuracy of discriminating patients at high risk for readmission.,Identifying patients with frailty for targeted interventions may reduce early readmission rates. | Employment rates among those with chronic obstructive pulmonary disease (COPD) are lower than those without COPD, but little is known about the factors that affect COPD patients’ ability to work.,Multivariable analysis of the Birmingham COPD Cohort Study baseline data was used to assess the associations between lifestyle, clinical, and occupational characteristics and likelihood of being in paid employment among working-age COPD patients.,In total, 608 of 1,889 COPD participants were of working age, of whom 248 (40.8%) were in work.,Older age (60-64 years vs 30-49 years: odds ratio [OR] =0.28; 95% confidence interval [CI] =0.12-0.65), lower educational level (no formal qualification vs degree/higher level: OR =0.43; 95% CI =0.19-0.97), poorer prognostic score (highest vs lowest quartile of modified body mass index, airflow obstruction, dyspnea, and exercise (BODE) score: OR =0.10; 95% CI =0.03-0.33), and history of high occupational exposure to vapors, gases, dusts, or fumes (VGDF; high VGDF vs no VGDF exposure: OR =0.32; 95% CI =0.12-0.85) were associated with a lower probability of being employed.,Only the degree of breathlessness of BODE was significantly associated with employment.,This is the first study to comprehensively assess the characteristics associated with employment in a community sample of people with COPD.,Future interventions should focus on managing breathlessness and reducing occupational exposures to VGDF to improve the work capability among those with COPD. | 1 |
This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation.,ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014.,These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population.,A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population.,A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs.,30.7%).,Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001).,Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients.,Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke.,The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001).,The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.,Co-existing conditions should be taken into consideration when treating patients with chronic lung disease to ensure coherent and cost-effective disease management.,In a large-scale study of the Swedish population, Björn Ställberg at Uppsala University and co-workers analyzed electronic medical records spanning fourteen years for 17,479 patients with chronic obstructive pulmonary disease (COPD) and compared their health status with 84,514 age-, sex- and comorbidity-matched non-COPD members of the population.,Patients with COPD were significantly more likely to suffer from co-morbidities two years after initial diagnosis than their non-COPD counterparts, with cardiovascular diseases being the most common comorbidities.,Lung cancer, hypertension, depression and sleep disorders were among other comorbidities more prevalent in the COPD population.,These data support the need for fully integrated, targeted healthcare to reduce mortality and the economic burden associated with COPD. | AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines.,The present study describes hospital resources, hospital factors related to case recruitment variability, patients’ characteristics, and adherence to guidelines.,An organisational database was completed by all participant hospitals recording resources and organisation.,Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified.,At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population.,Audited patients were reassessed 90 days after admission for survival and readmission rates.,A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death.,Median inpatient mortality was 5% (across-hospital range 0-35%).,Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%).,The overall mortality rate was 11.6% (0-50%).,Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment.,Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles.,The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes.,The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement. | 1 |
Sarcopenia prevalence and its clinical impact are reportedly variable in chronic obstructive pulmonary disease (COPD) due partly to definition criteria.,This review aimed to identify the criteria used to diagnose sarcopenia and the prevalence and impact of sarcopenia on health outcomes in people with COPD.,This review was registered in PROSPERO (CRD42018092576).,Five electronic databases were searched to August 2018 to identify studies related to sarcopenia and COPD.,Study quality was assessed using validated instruments matched to study designs.,Sarcopenia prevalence was determined using authors' definitions.,Comparisons were made between people who did and did not have sarcopenia for pulmonary function, exercise capacity, quality of life, muscle strength, gait speed, physical activity levels, inflammation/oxidative stress, and mortality.,Twenty‐three studies (70% cross‐sectional) from Europe (10), Asia (9), and North and South America (4) involving 9637 participants aged ≥40 years were included (69.5% men).,Sarcopenia criteria were typically concordant with recommendations of hEuropean and Asian consensus bodies.,Overall sarcopenia prevalence varied from 15.5% [95% confidence interval (CI) 11.8-19.1; combined muscle mass, strength, and/or physical performance criteria] to 34% (95%CI 20.6-47.3; muscle mass criteria alone) (P = 0.009 between subgroups) and was greater in people with more severe [37.6% (95%CI 24.8-50.4)] versus less severe [19.1% (95%CI 10.2-28.0)] lung disease (P = 0.020), but similar between men [41.0% (95%CI 26.2-55.9%)] and women [31.9% (95%CI 7.0-56.8%)] (P = 0.538).,People with sarcopenia had lower predicted forced expiratory volume in the first second (mean difference −7.1%; 95%CI −9.0 to −5.1%) and poorer exercise tolerance (standardized mean difference −0.8; 95%CI −1.4 to −0.2) and quality of life (standardized mean difference 0.26; 95%CI 0.2-0.4) compared with those who did not (P < 0.001 for all).,No clear relationship was observed between sarcopenia and inflammatory or oxidative stress biomarkers.,Incident mortality was unreported in the literature.,Sarcopenia is prevalent in a significant proportion of people with COPD and negatively impacts upon important clinical outcomes.,Opportunities exist to optimize its early detection and management and to evaluate its impact on mortality in this patient group. | 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 |
Hospitalizations for persons with chronic obstructive pulmonary disease (COPD) result in significant health care resource use and excess expenditures.,Despite well-documented sociodemographic disparities in COPD outcomes, no study has characterized geographic variations in COPD hospitalization across the US.,Almost 3.8 million COPD hospitalization records were extracted from Medicare claims for 1995-2006, and the total population of eligible Medicare beneficiaries was extracted from the Medicare enrollment records to calculate COPD hospitalization rates by Health Service Area (HSA), (n = 949).,Spatial cluster analysis and Bayesian hierarchical spatial modeling were used to characterize the geography of COPD hospitalizations.,The overall COPD hospitalization rate was 11.30 per 1,000 beneficiaries for the aggregated period 1995-2006.,HSA-level COPD hospitalization rates had a median of 11.7 and a range of 3.0 (Cache, UT) to 76.3 (Pike, KY).,Excessive hospitalization risk was concentrated in Appalachia, the southern Great Lakes, the Mississippi Delta, the Deep South, and west Texas.,In the Bayesian spatial mixture model, 73% of variability of COPD hospitalization relative risk was attributed to unidentified regional social and physical environments shared by HSAs rather than to unique local HSA factors (27%).,We discovered distinct geographic patterns in COPD hospitalization rates and risks attributed to both regionally-shared environmental risk factors and HSA-unique environmental contexts.,The correlates of these geographic patterns remain to be determined.,Geographic comparisons of COPD hospitalization risk provide insights for better public health practice, policies, and programs for COPD prevention. | The American Lung Association of Minnesota (ALAMN) was granted access to a 2004 administrative claims data from an upper mid-Western, independent practice association model health plan.,Claims information, including demographics, prevalence, medication and oxygen therapy, and health care utilization, was extracted for 7,782 patients with COPD who were 40 years of age and older.,In addition, ALAMN conducted a survey of 1,911 patients from Minnesota diagnosed with COPD.,The survey queried the patients about demographics, treatment, medications, limitations, wants, and needs.,This article compares and contrasts the information gained through the health plan administrative claims database with the findings from the COPD patient survey in areas of age, gender, types of provider primarily responsible for COPD care, spirometry use, medication therapy, pulmonary rehabilitation, oxygen therapy, and health care utilization.,Primary care practitioners provided a majority of the COPD-related care.,The claims evidence of spirometry use was 16%-62% of COPD patients had claims evidence of COPD-related medications. 25% of patients reported, and 23% of patients had claims evidence of, a hospitalization during the observation year. 16% of patients reported using pulmonary rehabilitation programs.,The results indicate there is an opportunity to improve COPD diagnosis and management. | 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. | Introduction: Inhaled corticosteroids (ICS) (in fixed combinations with long-acting β2-agonists [LABAs]) are frequently prescribed for patients with chronic obstructive pulmonary disease (COPD), outside their labeled indications and recommended treatment strategies and guidelines, despite having the potential to cause significant side effects.,Areas covered: Although the existence of asthma in patients with asthma-COPD overlap syndrome (ACOS) clearly supports the use of anti-inflammatory treatment (typically an ICS/LABA combination, as ICS monotherapy is usually not indicated for COPD), the current level of ICS/LABA use is not consistent with the prevalence of ACOS in the COPD population.,Data have recently become available showing the comparative efficacy of fixed bronchodilator combinations (long-acting muscarinic antagonist [LAMA]/LABA with ICS/LABA combinations).,Additionally, new information has emerged on ICS withdrawal without increased risk of exacerbations, under cover of effective bronchodilation.,Expert opinion: For patients with COPD who do not have ACOS, a LAMA/LABA combination may be an appropriate starting therapy, apart from those with mild disease who can be managed with a single long-acting bronchodilator.,Patients who remain symptomatic or present with exacerbations despite effectively delivered LAMA/LABA treatment may require additional drug therapy, such as ICS or phosphodiesterase-4 inhibitors.,When prescribing an ICS/LABA, the risk:benefit ratio should be considered in individual patients. | 1 |
Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce.,Our aim was to develop and validate a new model to predict exacerbations in patients with COPD.,The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months.,The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over.,Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization.,Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting.,The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics.,The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up.,The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69-0.82).,Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61-0.71]).,Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
Exacerbations, a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD), affect the quality of life and prognosis.,Treatment recommendations as provided in the evidence-based guidelines are not consistently followed, partly due to absence of simplified task-oriented approach to care.,In this study, we describe the development and implementation of a clinical pathway (CP) and evaluate its effectiveness in the management of COPD exacerbation.,We developed a CP and evaluated its effectiveness in a non-randomized prospective study with historical controls on patients admitted for exacerbation of COPD to Universiti Kebangsaan Malaysia Medical Centre (UKMMC).,Consecutive patients who were admitted between June 2009 and December 2010 were prospectively recruited into the CP group.,Non-CP historical controls were obtained from case records of patients admitted between January 2008 and January 2009.,Clinical outcomes were evaluated by comparing the length of stay (LOS), complication rates, readmissions, and mortality rates.,Ninety-five patients were recruited in the CP group and 98 patients were included in the non-CP historical group.,Both groups were comparable with no significant differences in age, sex and severity of COPD (p = 0.641).,For clinical outcome measures, patients in the CP group had shorter length of stay than the non-CP group (median (IQR): 5 (4-7) days versus 7 (7-9) days, p < 0.001) and 24.1% less complications (14.7% versus 38.8%, p < 0.001).,We did not find any significant differences in readmission and mortality rates.,The implementation of CP -reduced the length of stay and complication rates of patients hospitalized for acute exacerbation of COPD. | 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. | 1 |
Recent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e.,GOLD groups C and D.,However, it is known that ICS is frequently prescribed for patients with less severe COPD.,Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use.,The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen.,Linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used.,For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy.,Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms.,Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing.,Treatment acquisition costs were not assessed.,Results showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group.,Rate ratios favoured the non-ICS group for eight of nine outcomes assessed.,Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV1 < 50% predicted), one prior exacerbation or elevated blood eosinophils.,These data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use.,The online version of this article (10.1186/s12931-018-0767-2) contains supplementary material, which is available to authorized users. | Recent studies that assessed the relevance of the blood eosinophil count as a biomarker in patients with COPD may have overestimated it because they included patients with asthma-COPD overlap syndrome (ACOS).,We investigated the clinical implications of the blood eosinophil count in patients with non-ACOS COPD.,From a Korean COPD Subtype Study (KOCOSS) cohort, we selected patients with non-ACOS COPD after excluding ACOS patients according to Spanish criteria.,Clinical characteristics and the incidence of moderate-to-severe exacerbation were compared among the four groups stratified according to the quartiles of blood eosinophil percent and count.,Of the KOCOSS cohort of 1,132 patients with COPD, 467 non-ACOS COPD patients (41.2%) with data of blood eosinophil count remained after excluding those with ACOS based on the Spanish definition.,There was no difference in clinical characteristics among groups classified according to the quartiles of eosinophil percent and count.,On multivariate logistic regression, eosinophil quartiles in percent and absolute count were not associated with the incidence of moderate-to-severe acute exacerbations of COPD (AECOPD).,The eosinophil count did not affect the risk of AECOPD or forced expiratory volume in 1 second (FEV1) changes according to exposure to inhaled corticosteroid (ICS).,However, by increasing the cutoff value for the eosinophil count from 200/μL to 600/μL, the odds ratio for risk of exacerbation increased serially from 0.82 to 2.96 on trend analysis.,In patients with non-ACOS COPD, the blood eosinophil count and percent were not associated with FEV1 changes, quality of life (QoL), AECOPD frequency, or response to ICS.,The clinical implication of the blood eosinophil count should not be overestimated in patients with non-ACOS COPD. | 1 |
The objective of this study was to evaluate the comparative efficacy of indacaterol 75 μg once daily (OD), tiotropium 18 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD) based on individual patient data (IPD) from randomized controlled trials (RCTs) from the indacaterol trial program and aggregate data (AD) identified from a systematic review of RCTs.,22 RCTs were included in the AD analysis that evaluated: indacaterol 75 μg (n = 2 studies), indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg) (n = 5), indacaterol 300 μg (n = 2), tiotropium 18 μg (n = 10), salmeterol 50 μg (n = 7), and formoterol 12 μg (n = 4).,All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol) were placebo controlled.,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and St.,George’s Respiratory Questionnaire (SGRQ) total score at week 12.,The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA) and relative treatment effects between all regimens were obtained.,In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA.,Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials.,All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks.,Indacaterol 75 μg is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses.,In comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09).,In terms of SGRQ total score at 12 weeks, indacaterol 75 μg and formoterol were more efficacious than placebo, whereas for tiotropium and salmeterol the credible intervals included zero for the AD results only (tiotropium: -2.99 points improvement versus placebo; 95%CrI −6.48 to 0.43; salmeterol:-2.52; 95%CrI: -5.34; 0.44).,Both IPD and AD results suggest that indacaterol 75 μg is expected to be comparable to all active treatments.,Based on a synthesis of currently available AD RCT evidence as well as an IPD network meta-analysis of six RCTs, indacaterol 75 μg is expected to be at least as efficacious as formoterol and comparable to tiotropium and salmeterol regarding FEV1.,Furthermore, indacaterol 75 μg shows comparable level of improvement in health-related quality of life to tiotropium, salmeterol, and formoterol, as measured by the SGRQ. | Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD).,This randomized, double-blind study compared the bronchodilator efficacy of indacaterol with that of placebo and tiotropium in patients with moderate-to-severe COPD.,In an incomplete-block, multi-dose, three-period, crossover design, patients received three of the following four treatments: indacaterol 150 μg, indacaterol 300 μg, tiotropium 18 μg and placebo, each once-daily for 14 days.,Each treatment period was separated by a 14-day washout.,Study drug was supplied daily by blinded, third party study personnel to maintain blinding of patients and investigators.,The primary efficacy variable was trough forced expiratory volume in one second (FEV1) at 24 h post-dose after 14 days.,The study was powered to demonstrate non-inferiority of indacaterol to tiotropium for this variable.,A total of 169 patients were randomized (mean age 65 years); 153 (90.5%) completed.,Trough FEV1 after 14 days with indacaterol 150 μg and 300 μg was statistically and clinically superior to placebo, with differences (95% CI) of 170 (120-220) and 150 (100-200) mL respectively (both p < 0.001).,For this endpoint, both doses of indacaterol not only met the criterion for non-inferiority compared with tiotropium, but also achieved numerically higher values, with differences versus tiotropium of 40 and 30 mL for indacaterol 150 and 300 μg, respectively.,At 5 min post-dose on Day 1, the mean FEV1 for both indacaterol doses was significantly higher than placebo (by 120 and 130 mL for indacaterol 150 and 300 μg, respectively; p < 0.001) and tiotropium (by 80 mL for both doses; p < 0.001).,Adverse events were reported by similar proportions of patients: 31.4%, 29.5%, 28.3% and 28.5% for indacaterol 150 μg and 300 μg, tiotropium and placebo treatments, respectively.,Once-daily indacaterol provided clinically and statistically significant 24-h bronchodilation.,Indacaterol was at least as effective as tiotropium, with a faster onset of action (within 5 min) on the first day of dosing.,Indacaterol should prove useful in patients with moderate-to-severe COPD, for whom treatment with one or more classes of long-acting bronchodilator is recommended.,ClinicalTrials.gov: NCT00615459, EudraCT number: 2007-004071-19 | 1 |
The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) show systemic consequences, such as chronic systemic inflammation leading to changes in the airway, airway penetrability, and endothelial function.,Endothelial dysfunction is characterized by a list of alterations of endothelium towards reduced vasodilation, proinflammatory state, detachment and apoptosis of endothelial cells, and development of atherosclerosis.,COPD-induced endothelial dysfunction is associated with elevated cardiovascular risk.,The increment of physical activities such as pulmonary rehabilitation (PR) training have a significant effect on COPD, thus, PR can be an integrative part of COPD treatment.,In this narrative review the focus is on the function of endothelial inflammatory mediators [cytokines, chemokines, and cellular proteases] and pulmonary endothelial cells and endothelial dysfunction in COPD as well as the effects of dysfunction of the endothelium may play in COPD-related pulmonary hypertension.,The relationship between smoking and endothelial dysfunction is also discussed.,The connection between different pulmonary rehabilitation programs, arterial stiffness and pulse wave velocity (PWV) is presented.,Endothelial dysfunction is a significant prognostic factor of COPD, which can be characterized by PWV.,We discuss future considerations, like training programs, as an important part of the treatment that has a favorable impact on the endothelial function. | The Notch signaling pathway plays critical role for determining cell fate by controlling proliferation, differentiation, and apoptosis.,In the current study, we investigated the roles of the Notch signaling pathway in cigarette smoke (CS)-induced endothelial apoptosis in chronic obstructive pulmonary disease (COPD).,We obtained surgical specimens from 10 patients with COPD and 10 control participants.,Notch1, 2, and 4 express in endothelial cells, whereas Notch3 mainly localizes in smooth muscle cells.,Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE).,Overexpression of Notch1 with N1ICD in HPMECs markedly alleviated the cell apoptosis induced by CSE.,The ERK signaling pathway was significantly activated by CSE, which correlated with CSE-induced apoptosis.,However, this activation can be abolished by N1ICD overexpression.,Furthermore, treatment of PD98059 (ERK inhibitor) significantly alleviated CSE-induced apoptosis, as well as reduced the methylation of mitochondrial transcription factor A (mtTFA) promoter, which was correlated with CS-induced endothelial apoptosis.,These results suggest that CS alters Notch signaling in pulmonary endothelial cells.,Notch1 protects against CS-induced endothelial apoptosis in COPD through inhibiting the ERK pathway, while the ERK pathway further regulates the methylation of mtTFA promotor. | 1 |
Chronic bronchitis (CB) is one of the conditions that contribute to chronic obstructive pulmonary disease (COPD).,Despite its widespread prevalence among patients with COPD and overall negative impact on treatment outcomes, the effect of CB on the efficacy of bronchodilator therapy has not been evaluated.,The objective of this post hoc analysis is to assess the effect of nebulized glycopyrrolate (GLY) on lung function and health-related quality of life outcomes in patients with St George’s Respiratory Questionnaire (SGRQ)-defined CB at baseline.,Pooled data from the replicate, 12-week GOLDEN 3 and 4 studies (N=861) were grouped by CB status at baseline.,The endpoints reported are changes from baseline in trough forced expiratory volume in 1 second (FEV1), SGRQ and EXAcerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (EXACT-RS) scores.,Safety of GLY was evaluated by monitoring the incidence of adverse events (AEs).,Following 12 weeks of treatment, GLY 25 μg twice-daily (BID) resulted in placebo-adjusted improvements from baseline in FEV1 of 77.1 mL and 124.4 mL in the CB and non-CB groups, respectively (p<0.0001 vs placebo in both groups).,Significant improvements in SGRQ total scores were observed with GLY 25 μg BID compared with placebo, regardless of baseline CB status.,Although EXACT-RS improvements were noted in both CB and non-CB groups, significant improvements were observed only in the CB group.,GLY 25 μg BID was generally well tolerated through 12 weeks of treatment, with a low incidence of AEs.,Treatment with nebulized GLY 25 μg BID for 12 weeks resulted in significant improvements in lung function and SGRQ total scores, compared with placebo.,Significant improvements in EXACT-RS total scores were observed only in the CB group.,Together, these results support the use of GLY 25 μg BID in patients with COPD, regardless of their CB status. | In the upcoming years, the proportion of elderly patients with chronic obstructive pulmonary disease (COPD) will increase, according to the progressively aging population and the increased efficacy of the pharmacological treatments, especially considering the management of chronic comorbidities.,The issue to prescribe an appropriate inhalation therapy to COPD patients with significant handling or coordination difficulties represents a common clinical experience; in the latter case, the choice of an inadequate inhalation device may jeopardize the adherence to the treatment and eventually lead to its ineffectiveness.,Treatment options that do not require particular timing for coordination between activation and/or inhalation or require high flow thresholds to be activated should represent the best treatment option for these patients.,Nebulized bronchodilators, usually used only in acute conditions such as COPD exacerbations, could fulfill this gap, enabling an adequate drug administration during tidal breathing and without the need for patients’ cooperation.,However, so far, only short-acting muscarinic antagonists have been available for nebulization.,Recently, a nebulized formulation of the inhaled long-acting muscarinic antagonist glycopyrrolate, delivered by means of a novel proprietary vibrating mesh nebulizer closed system (SUN-101/eFlow®), has progressed to Phase III trials and is currently in late-stage development as an option for maintenance treatment in COPD.,The present critical review describes the current knowledge about the novel nebulizer technology, the efficacy, safety, and critical role of nebulized glycopyrrolate in patients with COPD.,To this end, PubMed, ClinicalTrials.gov, Embase, and Cochrane Library have been searched for relevant papers.,According to the available results, the efficacy and tolerability profile of nebulized glycopyrrolate may represent a valuable and dynamic treatment option for the chronic pharmacological management of patients with COPD. | 1 |
Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination.,This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).,In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks.,Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT).,Safety evaluations included adverse events (AEs).,Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001).,Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2-0.0]; P≤0.05).,More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01).,Improvements in SGRQ and CAT scores were similar between treatments.,The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).,UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations.,Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of “clinically important deterioration” (CID) has therefore been developed.,We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies.,The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE).,All studies recruited patients with symptomatic COPD, FEV1 <50%, and an exacerbation history.,We measured the time to first CID and to sustained CID, an endpoint combining FEV1, St George’s Respiratory Questionnaire (SGRQ), moderate-to-severe exacerbations, and death.,The time to first CID was based on the first occurrence of any of the following: a decrease of ≥100 mL from baseline in FEV1, an increase of ≥4 units from baseline in SGRQ total score, the occurrence of a moderate/severe COPD exacerbation, or death.,The time to sustained CID was defined as: a CID in FEV1 and/or SGRQ total score maintained at all subsequent visits, an exacerbation, or death.,Extrafine BDP/FF/G significantly extended the time to first CID vs BDP/FF (HR 0.61, P<0.001), tiotropium (0.72, P<0.001), and IND/GLY (0.82, P<0.001), and significantly extended the time to sustained CID vs BDP/FF (HR 0.64, P<0.001) and tiotropium (0.80, P<0.001), with a numerical extension vs IND/GLY.,In patients with symptomatic COPD, FEV1 <50%, and an exacerbation history, extrafine BDP/FF/G delayed disease deterioration compared with BDP/FF, tiotropium, and IND/GLY.,The studies are registered in ClinicalTrials.gov: TRILOGY, NCT01917331; TRINITY, NCT01911364; TRIBUTE, NCT02579850. | We studied if pre-bronchodilator FEV1/FEV6 determinations with microspirometers by GPs improve the diagnostic process for COPD in a 6-8 month clustered randomised controlled trial in Dutch general practices (http://www.trialregister.nl: NTR4041).,GPs allocated to microspirometry (MI) used COPD-6® microspirometers in patients ≥50 years old with a smoking history and respiratory complaints that could indicate undiagnosed COPD and ask to refer patients for full spirometry if MI was positive (FEV1/FEV6 <0.73).,Introduction of the COPD-6® was postponed in the usual care (UC) group.,GPs of both study arms were asked to list all patients that fulfilled study criteria and at the end of the study we screened the electronic medical record system for number of patients that fulfilled study criteria and visited their GP within the study period.,Main end point was a documented diagnostic conclusion of COPD within 3 months after the patient’s visit.,We used multilevel logistic regression with correction for relevant covariates.,Next, we described the process of care. 21 practices (88 GPs) participated and 416 possible undiagnosed COPD patient visited these practices in the study period. 78 (of 192 visiting) subjects were listed by MI GPs and diagnostic conclusions were documented in 77%, compared to 61 listed (of 224 visiting) subjects and 44% with documented diagnostic conclusions by UC GPs (Odds Ratio: OR: 4.3, 95%CI: 1.6-11.5).,Microspirometry improved the diagnostic process for possible underlying COPD in patients who consulted their GP with respiratory symptoms, but the majority of possible undiagnosed COPD patients remained unrecognised by GPs.,A quick, simple test that can be used by family doctors may help identify patients suffering from chronic obstructive pulmonary disease (COPD).,The small, inexpensive microspirometry (MI) kit enables doctors conducting routine appointments to measure the volume of air expelled from patients’ lungs.,Lisette van den Bemt at Radboud University Medical Center, the Netherlands, and co-workers worked with two groups of doctors in local practices.,Both groups were asked to identify patients over 50 with a smoking history, respiratory problems and no diagnose of asthma and COPD, and start a diagnostic process for COPD.,One group was given microspirometers to aid diagnoses.,Of 192 patients visiting the MI doctors, 78 were identified and 77 per cent were later listed as COPD or COPD was ruled out.,In the other group, 61 out of 224 patients were identified with only 44 per cent listed. | 1 |
There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population.,The study examined COPD patients with moderate COPD exacerbations.,COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation.,This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation.,A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period.,A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs.,COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009).,COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution.,21,524 patients with a moderate COPD exacerbation were identified.,Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation.,Annual costs averaged $594 per patient.,A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis.,The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04).,After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91).,The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort.,However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05).,Total monthly COPD-related costs, as a result, did not differ between cohorts.,Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy.,Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC. | Few estimates of health care costs related to chronic obstructive pulmonary disease (COPD) are available regarding commercially insured patients in the United States.,The aims of this retrospective observational analysis of administrative data were to describe and compare health care resource use and costs related to COPD in the United States for patients with commercial insurance or Medicare Advantage with Part D benefits, and to assess cost trends over time.,Patient-level and visit-level health care costs in the calendar years 2006, 2007, 2008, and 2009 were assessed for patients with evidence of COPD.,Generalized linear models adjusting for sex, age category, and geographic region were used to investigate cost trends over time for patients with Medicare or commercial insurance.,Medical costs, which ranged from an annual mean of US$2382 (Medicare 2007) to US$3339 (commercial 2009) per patient, comprised the majority of total costs in all years for patients with either type of insurance.,COPD-related costs were less for Medicare than commercial cohorts.,In the multivariate analysis, total costs increased by approximately 6% per year for commercial insurance patients (cost ratio 1.06; 95% confidence interval [CI] 1.04-1.07; P < 0.001) and 5% per year for Medicare patients (cost ratio 1.05; 95% CI 1.03-1.07; P < 0.001).,Costs for outpatient and emergency department visits increased significantly over time in both populations.,Standard admission costs increased significantly for Medicare patients (cost ratio 1.03; 95% CI 1.00-1.05; P = 0.03), but not commercial patients, and costs for intensive care unit visits remained stable for both populations.,COPD imposed a substantial economic burden on patients and the health care system, with costs increasing significantly in both the Medicare and commercial populations. | 1 |
Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD).,The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear.,In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I-IV) and 18 controls without lung disease.,In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle-brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined.,The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction.,A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD.,GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis.,The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level.,PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations. | Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke than those without COPD.,This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design.,The study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort.,Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long-acting muscarinic antagonists, short-acting β-agonists (SABAs), long-acting β-agonists (LABAs), and LABA plus inhaled corticosteroid (ICS), on the risk after adjustment for patient demographic characteristics and comorbid disorders.,Of the 52,065 sampled patients, 2,689 (5.2%) developed stroke during follow-up, including 727 (7.0%) from the COPD cohort and 1,962 (4.7%) from the comparison cohort (p < 0.001).,Treatment with SABA was associated with 1.67-fold (95% CI 1.45-1.91; p < 0.001) increased risk of stroke in COPD patients.,By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60-0.94, p = 0.014).,Among COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction.,Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD. | 1 |
The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes.,Whether they are associated with emphysema is not known.,Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people.,The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined.,Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001).,Among the 12 examined SNPs, only rs975278 in the SERPINE2 gene was positively associated with emphysema.,Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002).,SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers. | For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis').,Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases.,We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD).,Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion.,We found a weak association of the 249Ser allele with childhood asthma (p = 0.03).,Yet, significance was lost after Bonferroni correction.,No association was evident for AD or COPD.,Variation in TLR6 might play a role in the pathogenesis of childhood asthma. | 1 |
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