a stringlengths 138 8.15k | b stringlengths 138 8.15k | label int64 1 1 |
|---|---|---|
Background and objective: There are few data on the short‐term natural history of airway inflammation during severe episodes of acute exacerbation of COPD (AECOPD).,An observational study was performed to determine how rapidly conventional treatment improves airway inflammation in patients admitted to hospital with AECOPD.,Methods: Twenty‐four consecutive patients with AECOPD were recruited and changes in sputum inflammatory indices were assessed after 2 and 4 days of treatment.,The primary end‐points included presence of bacteria and viruses, changes in sputum total cell counts (TCC) and polymorphonuclear leukocyte (PMN) differential counts, and levels of secretory leukocyte protease inhibitor (SLPI), IL‐8 and TNF‐α.,Results: All patients received oral corticosteroids and 17 (71%) were also treated with oral antibiotics.,A bacterial or viral pathogen was isolated from 12 patients (50%), and Aspergillus fumigatus was isolated from one.,A positive bacterial culture was associated with increased sputum TCC and PMN count (P < 0.05), as well as higher levels of IL‐8 and TNF‐α (P < 0.05), and a trend towards lower sputum SLPI levels (P = 0.06).,Sputum PMN numbers fell by 70% within the first 48 h of admission (P < 0.05), accompanied by an increase in sputum SLPI (P < 0.001) and reductions in the levels of TNF‐α (P < 0.005) and IL‐8 (P = 0.06), with no further significant change at 4 days.,Conclusions: Conventional treatment for severe AECOPD is associated with rapid reduction of neutrophilic inflammation and improvement in anti‐protease defences. | Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD).,However, little is known about viral etiology related to AECOPD in Asia.,We aimed to study the viral etiology of AECOPD in Hong Kong.,Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005.,Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture.,Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge.,There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 ± 7.7 years [± SD]; 160 men).,Mean FEV1 was 39.6 ± 18.9% of predicted normal, and FEV1/FVC ratio was 58.0 ± 15.2%.,Fifty-eight episodes (22.1%) yielded positive viral PCR results.,The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%).,The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture.,The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV1 ≥ 50%, ≥ 30 to 50%, and < 30% of predicted normal.,Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year,Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong.,These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD. | 1 |
Combinations of long-acting bronchodilators are recommended to reduce the rate of COPD exacerbations.,Evidence from the DYNAGITO trial showed that the fixed-dose combination of tiotropium + olodaterol reduced the annual rate of total exacerbations (P<0.05) compared with tiotropium monotherapy.,This study aimed to estimate the cost-effectiveness of the fixed-dose combination of tiotropium + olodaterol vs tiotropium monotherapy in COPD patients in the French setting.,A recently developed COPD patient-level simulation model was used to simulate the lifetime effects and costs for 15,000 patients receiving either tiotropium + olodaterol or tiotropium monotherapy by applying the reduction in annual exacerbation rate as observed in the DYNAGITO trial.,The model was adapted to the French setting by including French unit costs for treatment medication, COPD maintenance treatment, COPD exacerbations (moderate or severe), and pneumonia.,The main outcomes were the annual (severe) exacerbation rate, the number of quality-adjusted life-years (QALYs), and total lifetime costs.,The number of QALYs for treatment with tiotropium + olodaterol was 0.042 higher compared with tiotropium monotherapy.,Using a societal perspective, tiotropium + olodaterol resulted in a cost increase of +€123 and an incremental cost-effectiveness ratio (ICER) of €2,900 per QALY compared with tiotropium monotherapy.,From a French National Sickness Fund perspective, total lifetime costs were reduced by €272 with tiotropium + olodaterol, resulting in tiotropium + olodaterol being the dominant treatment option, that is, more effects with less costs.,Sensitivity analyses showed that reducing the cost of exacerbations by 34% increased the ICER to €15,400, which could still be considered cost-effective in the French setting.,Treatment with tiotropium + olodaterol resulted in a gain in QALYs and savings in costs compared with tiotropium monotherapy using a National Sickness Fund perspective in France.,From the societal perspective, tiotropium + olodaterol was found to be cost-effective with a low cost per QALY. | The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.,While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model.,Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage.,Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT.,Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data.,Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included.,A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.,Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC.,The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium.,Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.,Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. | 1 |
The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
A low body mass index (BMI) is associated with increased mortality and low health-related quality of life in patients with COPD.,The Asia-Pacific classification of BMI has a lower cutoff for overweight and obese categories compared to the World Health Organization (WHO) classification.,The present study assessed patients with COPD among different BMI categories according to two BMI classification systems: WHO and Asia-Pacific.,Patients with COPD aged 40 years or older from the Korean COPD Subtype Study cohort were selected for evaluation.,We enrolled 1,462 patients.,Medical history including age, sex, St George’s Respiratory Questionnaire (SGRQ-C), the modified Medical Research Council (mMRC) dyspnea scale, and post-bronchodilator forced expiratory volume in 1 second (FEV1) were evaluated.,Patients were categorized into different BMI groups according to the two BMI classification systems.,FEV1 and the diffusing capacity of the lung for carbon monoxide (DLCO) percentage revealed an inverse “U”-shaped pattern as the BMI groups changed from underweight to obese when WHO cutoffs were applied.,When Asia-Pacific cutoffs were applied, FEV1 and DLCO (%) exhibited a linearly ascending relationship as the BMI increased, and the percentage of patients in the overweight and obese groups linearly decreased with increasing severity of the Global Initiative for Chronic Obstructive Lung Disease criteria.,From the underweight to the overweight groups, SGRQ-C and mMRC had a decreasing relationship in both the WHO and Asia-Pacific classifications.,The prevalence of comorbidities in the different BMI groups showed similar trends in both BMI classifications systems.,The present study demonstrated that patients with COPD who have a high BMI have better pulmonary function and health-related quality of life and reduced dyspnea symptoms.,Furthermore, the Asia-Pacific BMI classification more appropriately reflects the correlation of obesity and disease manifestation in Asian COPD patients than the WHO classification. | How well the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification prognosticates for Asian patients with COPD is unknown.,The authors aimed to study the predictive utility of the GOLD 2011 classification for exacerbations and mortality as compared with other multidimensional tools in an Asian population.,In all, 1,110 COPD patients were prospectively followed between March 2008 and March 2013.,They were classified using the 2011 and 2007 GOLD guidelines, modified Medical Research Council score, St.,George’s Respiratory Questionnaire (SGRQ), and Body mass index, Obstruction, Dyspnea (BOD) index.,Outcome measures were exacerbations and mortality.,Multivariable survival analyses and receiver operating characteristic (ROC) curves were used to assess the different classification systems.,Time-to-event analyses demonstrated earlier exacerbations in 2011’s GOLD D when compared with GOLD A (hazard ratio [HR] 0.54, 95% confidence interval [CI]: 0.31-0.95, P=0.032) and GOLD B (HR 0.62, 95% CI: 0.45-0.85, P=0.003) and higher mortality when compared with GOLD A (HR 0.37, 95% CI: 0.16-0.88, P=0.025) and GOLD B (HR 0.46, 95% CI: 0.31-0.70, P<0.001).,The areas under the ROC curve for GOLD 2011, GOLD 2007, modified Medical Research Council, St.,George’s Respiratory Questionnaire, and BOD index were 0.62, 0.59, 0.61, 0.60, and 0.61, respectively, for the prediction of exacerbations and 0.71, 0.70, 0.71, 0.71, and 0.72, respectively, for the prediction of mortality (ROC comparator, P>0.05).,The 2011 GOLD classification predicts exacerbations and mortality moderately well in Asian COPD patients.,Its prognostic utility is similar to that of other multidimensional systems. | 1 |
We have used impulse oscillometry to identify COPD patients with tidal expiratory flow limitation (EFL), which is a measurement related to small airway disease.,We report that 37.4% of COPD patients had EFL; these patients had multiple clinical characteristics of more severe disease including lower forced expiratory volume in 1 second values, greater hyperinflation, reduced exercise performance, and increased small airway impairment.,We highlight that EFL can be used to identify a subgroup of COPD patients with distinct characteristics associated with small airway disease. | Spirometry is commonly accepted as the gold standard for the diagnosis of COPD, but the reality remains that quality assured spirometry is not or cannot be provided universally around the globe.,Adding PEF measurement to a screening questionnaire may rule out airflow limitation compatible with COPD rationalizing spirometry testing.,We conducted a cross-sectional survey in a sample of individuals 40-80 yrs. old in Dubai, UAE.,They were invited to answer a short socio-demographic questionnaire including a report on current, past history of smoking, and had PEF measured, then they conducted spirometry to identify airflow limitation compatible with COPD.,Overall, 525 (91.0%) participants performed PEF and spirometry (68% male, with a mean age of 59 years, 17% UAE Nationals), 24% reported smoking of different sorts.,Overall, 68 participants (12.9%, 95% C.I.,10.3% to 16.1%) had airflow limitation compatible with COPD.,PEFR alone identified 141participants with airflow limitation compatible with COPD, with specificity of 80% and sensitivity of 73.5%.,PEFR could be an easy, cheap, and non-biased tool to assist with the case-finding of COPD before confirmation with spirometry. | 1 |
Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression.,We aimed to assess this in a prospective observational study.,The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD).,Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline.,Effect modification by blood eosinophils was studied through interaction terms.,Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS.,In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001).,This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS.,Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS.,More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function. | The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown.,We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.,A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database.,Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009).,Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale.,Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations.,Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011.,The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%).,The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively.,General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.,Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly. | 1 |
Some COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype.,To define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death.,We analyzed baseline data from a multi-center observational study (SPIROMICS).,This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls).,We defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire <5; 6-minute walking distance <250 m; St George’s Respiratory Questionnaire activity domain >60; COPD Assessment Test >20; fatigue (FACIT-F Trial Outcome Index) <50; SF-12 <20.,Using these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female).,Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%.,Compared with others, participants with disability had more emphysema (13.2 vs.,6.6%) and air-trapping (37.0 vs.,21.6%) on HRCT (P<0.0001).,Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point −1.0 reliably identified disability.,This disability score independently predicted future exacerbations (ß=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001).,Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability.,Our novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers.,The disability score also proved to be an independent predictor of future exacerbations and death.,These findings validate disability as an important phenotype in the spectrum of COPD. | Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | 1 |
One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients.,However, local inflammation may result and can contribute to worsening of clinical status in these patients.,We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients.,This initial study sought to investigate the safety of this approach.,For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used.,Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs.,Patients were evaluated 1, 7, 30, and 90 days after therapy.,All patients completed the study protocol and 90‐day follow‐up.,MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death.,No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease.,Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes.,However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV.,EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores.,Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy.,Stem Cells Translational Medicine 2017;6:962-969 | The 6-minute walk test (6MWT) in a regular hallway is commonly used to assess functional exercise capacity in patients with chronic obstructive pulmonary disease (COPD).,However, treadmill walking might provide additional advantages over overground walking, especially if virtual reality and self-paced treadmill walking are combined.,Therefore, this study aimed to assess the reproducibility and validity of the 6MWT using the Gait Real-time Analysis Interactive Lab (GRAIL) in patients with COPD and healthy elderly.,Sixty-one patients with COPD and 48 healthy elderly performed two 6MWTs on the GRAIL.,Patients performed two overground 6MWTs and healthy elderly performed one overground test.,Differences between consecutive 6MWTs and the test conditions (GRAIL vs. overground) were analysed.,Patients walked further in the second overground test (24.8 m, 95% CI 15.2-34.4 m, p<0.001) and in the second GRAIL test (26.8 m, 95% CI 13.9-39.6 m).,Healthy elderly improved their second GRAIL test (49.6 m, 95% CI 37.0-62.3 m).,The GRAIL 6MWT was reproducible (intra-class coefficients = 0.65-0.80).,The best GRAIL 6-minute walk distance (6MWD) in patients was shorter than the best overground 6MWD (-27.3 ± 49.1 m, p<0.001).,Healthy elderly walked further on the GRAIL than in the overground condition (23.6 ± 41.4 m, p<0.001).,Validity of the GRAIL 6MWT was assessed and intra-class coefficient values ranging from 0.74-0.77 were found.,The GRAIL is a promising system to assess the 6MWD in patients with COPD and healthy elderly.,The GRAIL 6MWD seems to be more comparable to the 6MWDs assessed overground than previous studies on treadmills have reported.,Furthermore, good construct validity and reproducibility were established in assessing the 6MWD using the GRAIL in patients with COPD and healthy elderly. | 1 |
In recent years, the pleiotropic roles of vitamin D have been highlighted in various diseases.,However, the association between serum vitamin D and COPD is not well studied.,This updated systematic review and meta-analysis aimed to assess the relationship between vitamin D and the risk, severity, and exacerbation of COPD.,A systematic literature search was conducted in PubMed, Medline, EMBASE, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases.,The pooled risk estimates were standardized mean difference (SMD) with 95% confidence interval (CI) for vitamin D levels and odds ratio (OR) with 95% CI for vitamin D deficiency.,Meta-regression and subgroup analyses were performed on latitude, body mass index, and assay method.,A total of 21 studies, including 4,818 COPD patients and 7,175 controls, were included.,Meta-analysis showed that lower serum vitamin D levels were found in COPD patients than in controls (SMD: −0.69, 95% CI: −1.00, −0.38, P<0.001), especially in severe COPD (SMD: −0.87, 95% CI: −1.51, −0.22, P=0.001) and COPD exacerbation (SMD: −0.43, 95% CI: −0.70, −0.15, P=0.002).,Vitamin D deficiency was associated with increased risk of COPD (OR: 1.77, 95% CI: 1.18, 2.64, P=0.006) and with COPD severity (OR: 2.83, 95% CI: 2.00, 4.00, P<0.001) but not with COPD exacerbation (OR: 1.17, 95% CI: 0.86, 1.59, P=0.326).,Assay methods had significant influence on the heterogeneity of vitamin D deficiency and COPD risk.,Serum vitamin D levels were inversely associated with COPD risk, severity, and exacerbation.,Vitamin D deficiency is associated with increased risk of COPD and severe COPD but not with COPD exacerbation.,It is worth considering assay methods in the heterogeneity sources analysis of association between vitamin D deficiency and COPD. | Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD.,The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms.,Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy.,A systematic literature review was performed on the association of vitamins and COPD.,The role of vitamin supplements in COPD was then evaluated.,The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function.,High vitamin intake would probably reduce the annual decline of FEV1.,There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function. | 1 |
COPD is associated with a relevant burden of disease and a high mortality worldwide.,Only recently, the importance of comorbidities of COPD has been recognized.,Studies postulated an association with inflammatory conditions potentially sharing pathogenic pathways and worsening overall prognosis.,More evidence is required to estimate the role of comorbidities of COPD.,Our aim was to investigate the prevalence and clustering of comorbidities associated with COPD, and to estimate their impact on clinically relevant outcomes.,In this population-based case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2010 (n = 12′888′075) was analyzed using MySQL and R statistical software.,Statistical methods included non-parametric hypothesis testing by means of Fisher’s exact test and Wilcoxon rank sum test, as well as linear models with generalized estimating equation to account for intra-patient variability.,Exploratory multivariate approaches were also used for the identification of clusters of comorbidities in COPD patients.,In 2.6% (6.3% in patients aged >70 years) of all hospitalization cases an active diagnosis of COPD was recorded.,In 21% of these cases, COPD was the main reason for hospitalization.,Patients with a diagnosis of COPD had more comorbidities (7 [IQR 4-9] vs.,3 [IQR 1-6]; ), were more frequently rehospitalized (annual hospitalization rate 0.33 [IQR 0.20-0.67] vs.,0.25 [IQR 0.14-0.43]/year; ), had a longer hospital stay (9 [IQR 4-15] vs.,5 [IQR 2-11] days; ), and had higher in-hospital mortality (5.9% [95% CI 5.8%-5.9%] vs.,3.4% [95% CI 3.3%-3.5%]; ) compared to matched controls.,A set of comorbidities was associated with worse outcome.,We could identify COPD-related clusters of COPD-comorbidities. | 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 |
Respiratory inhalers, which directly deliver medication to the airway, are important for controlling symptoms and preventing exacerbations of chronic obstructive pulmonary disease (COPD).,The inhaler misuse rate of patients with COPD in Taiwan is unclear.,In this study, the inhaler techniques and patient characteristics associated with incorrect inhaler techniques among patients with COPD were evaluated.,This cross-sectional study enrolled 298 patients with COPD (mean age 72.10 years) who used at least one inhaler device.,The following five types of inhalers were included: metered-dose inhaler (MDI) with spacer, Diskus®, Turbuhaler®, Respimat®, and Breezhaler®.,The inhaler technique was evaluated step by step.,Misuse of an individual inhaler was defined as an error in at least one step.,The sociodemographic characteristics, vision, hearing ability, type and number of inhalers, and inhaler-related knowledge of these patients were recorded.,The misuse rates of the five types of inhalers ranged from 65.00% to 87.89%.,The Respimat inhaler was the most likely to be assembled incorrectly.,The steps that were most commonly performed incorrectly were “breathing out fully” and “holding breath”.,In the logistic regression analysis, poor hearing was related to misuse of the MDI with spacer (adjusted odds ratio [aOR] 9.85; 95% CI 1.40-69.30); the number of acute exacerbations was related to misuse of Breezhaler (aOR 4.07; 95% CI 1.50-11.08).,Incorrect inhaler-related knowledge was significantly associated with misuse in handling the MDI with spacer (aOR 9.58; 95% CI 2.14-42.80), Respimat (aOR 5.14; 95% CI 2.07-12.76), and Breezhaler (aOR 6.98; 95% CI 1.95-25.08).,The misuse rates were high for all five types of inhaler.,Poor hearing and the number of acute exacerbations were device-specific factors related to the misuse of inhalers.,Inhaler-related knowledge was significantly associated with misuse, emphasizing the importance of inhaler education. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven. | 1 |
Chronic obstructive pulmonary disease (COPD) is recognized as a multisystemic inflammatory disease associated with extrapulmonary comorbidities, including respiratory muscle weakness and cardiovascular and cardiac autonomic regulation disorders.,We investigated whether alterations in respiratory muscle strength (RMS) would affect cardiac autonomic modulation in COPD patients.,This study was a cross-sectional study done in ten COPD patients affected by moderate to very severe disease.,The heart rate variability (HRV) signal was recorded using a Polar cardiofrequencimeter at rest in the sitting position (10 minutes) and during a respiratory sinus arrhythmia maneuver (RSA-M; 4 minutes).,Linear analysis in the time and frequency domains and nonlinear analysis were performed on the recorded signals.,RMS was assessed using a digital manometer, which provided the maximum inspiratory pressure (PImax) and the maximum expiratory pressure (PEmax).,During the RSA-M, patients presented an HRV power increase in the low-frequency band (LFnu) (46.9±23.7 vs 75.8±27.2; P=0.01) and a decrease in the high-frequency band (HFnu) (52.8±23.5 vs 24.0±27.0; P=0.01) when compared to the resting condition.,Significant associations were found between RMS and HRV spectral indices: PImax and LFnu (r=−0.74; P=0.01); PImax and HFnu (r=0.74; P=0.01); PEmax and LFnu (r=−0.66; P=0.01); PEmax and HFnu (r=0.66; P=0.03); between PEmax and sample entropy (r=0.83; P<0.01) and between PEmax and approximate entropy (r=0.74; P=0.01).,Using a linear regression model, we found that PImax explained 44% of LFnu behavior during the RSA-M.,COPD patients with impaired RMS presented altered cardiac autonomic control, characterized by marked sympathetic modulation and a reduced parasympathetic response; reduced HRV complexity was observed during the RSA-M. | In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses.,We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD.,Sixteen sedentary males with COPD were enrolled in this study.,Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured.,The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA).,Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated.,HF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio.,Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=−0.53 (P<0.05).,Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=−0.77, r2=0.43, P<0.05).,Responses of HRV indices were more prominent during M-RSA in moderate to severe COPD.,Moreover, greater lung function impairment was related to poorer heart rate dynamics.,Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients. | 1 |
The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments.,The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention.,ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy.,In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations.,We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS.,In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA. | Guidelines recommend inhaled corticosteroids (ICS) for patients with severe chronic obstructive pulmonary disease (COPD).,Most COPD patients are managed in primary care and receive ICS long-term and irrespective of severity.,The effect of withdrawing ICS from COPD patients in primary care is unknown.,In a pragmatic randomised, double-blind, placebo-controlled trial in 31 practices, 260 COPD patients stopped their usual ICS (median duration of use 8 years) and were allocated to 500 mcg fluticasone propionate twice daily (n = 128), or placebo (n = 132).,Follow-up assessments took place at three monthly intervals for a year at the patients' practice.,Our primary outcome was COPD exacerbation frequency.,Secondary outcomes were time to first COPD exacerbation, reported symptoms, peak expiratory flow rate and reliever inhaler use, and lung function and health related quality of life.,In patients randomised to placebo, COPD exacerbation risk over one year was RR: 1.11 (CI: 0.91-1.36).,Patients taking placebo were more likely to return to their usual ICS following exacerbation, placebo: 61/128 (48%); fluticasone: 34/132 (26%), OR: 2.35 (CI: 1.38-4.05).,Exacerbation risk whilst taking randomised treatment was significantly raised in the placebo group 1.48 (CI: 1.17-1.86).,Patients taking placebo exacerbated earlier (median time to first exacerbation: placebo (days): 44 (CI: 29-59); fluticasone: 63 (CI: 53-74), log rank 3.81, P = 0.05) and reported increased wheeze.,In a post-hoc analysis, patients with mild COPD taking placebo had increased exacerbation risk RR: 1.94 (CI: 1.20-3.14).,Withdrawal of long-term ICS in COPD patients in primary care increases risk of exacerbation shortens time to exacerbation and causes symptom deterioration.,Patients with mild COPD may be at increased risk of exacerbation after withdrawal.,ClinicalTrials.gov NCT00440687 | 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. | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
The obesity paradox in COPD describes protective effects of obesity on lung pathology and inflammation.,However, the underlying relationships between obesity, diet and disease outcomes in COPD are not fully understood.,In this study we measured the response to dietary fatty acids upon markers of inflammation and remodelling in human lung cells from people with and without COPD.,Pulmonary fibroblasts were challenged with ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, saturated fatty acids (SFAs) or the obesity-associated cytokine TNFα.,After 48-72 h release of the pro-inflammatory cytokines interleukin (IL)-6 and CXCL8 was measured using ELISA and mRNA expression and deposition of the extracellular matrix (ECM) proteins fibronectin, type I collagen, tenascin and perlecan were measured using qPCR or ECM ELISA, respectively.,Challenge with the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, resulted in increased IL-6 and CXCL8 release from fibroblasts, however IL-6 and CXCL8 release was reduced in COPD (n = 19) compared to non-COPD (n = 36).,AA-induced cytokine release was partially mediated by downstream mediators of cyclooxygenase (COX)-2 in both COPD and non-COPD.,In comparison, TNFα-induced IL-6 and CXCL8 release was similar in COPD and non-COPD, indicating a specific interaction of AA in COPD.,In patients with or without COPD, regression analysis revealed no relationship between BMI and cytokine release.,In addition, AA, but not SFAs or ω-3 PUFAs reduced the basal deposition of fibronectin, type I collagen, tenascin and perlecan into the ECM in COPD fibroblasts.,In non-COPD fibroblasts, AA-challenge decreased basal deposition of type I collagen and perlecan, but not fibronectin and tenascin.,This study shows that AA has disease-specific effects on inflammation and ECM protein deposition.,The impaired response to AA in COPD might in part explain why obesity appears to have less detrimental effects in COPD, compared to other lung diseases.,The online version of this article (10.1186/s12931-018-0919-4) contains supplementary material, which is available to authorized users. | Sphingolipid bioactivities in the respiratory airways and the roles of the proteins that handle them have been extensively investigated.,Gas or inhaled particles or microorganisms come into contact with mucus components, epithelial cells, blood barrier, and immune surveillance within the airways.,Lung structure and functionality rely on a complex interplay of polar and hydrophobic structures forming the surfactant layer and governing external-internal exchanges, such as glycerol-phospholipids sphingolipids and proteins.,Sphingolipids act as important signaling mediators involved in the control of cell survival and stress response, as well as secreted molecules endowed with inflammation-regulatory activities.,Most successful respiratory infection and injuries evolve in the alveolar compartment, the critical lung functional unit involved in gas exchange.,Sphingolipid altered metabolism in this compartment is closely related to inflammatory reaction and ceramide increase, in particular, favors the switch to pathological hyperinflammation.,This short review explores a few mechanisms underlying sphingolipid involvement in the healthy lung (surfactant production and endothelial barrier maintenance) and in a selection of lung pathologies in which the impact of sphingolipid synthesis and metabolism is most apparent, such as acute lung injury, or chronic pathologies such as cystic fibrosis and chronic obstructive pulmonary disease. | 1 |
Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene, whereas chronic obstructive pulmonary disease (COPD) is mainly caused by environmental factors (mostly cigarette smoking) on a genetically susceptible background.,Although the etiology and pathogenesis of these diseases are different, both are associated with progressive airflow obstruction, airway neutrophilic inflammation, and recurrent exacerbations, suggesting common mechanisms.,The airway epithelium plays a crucial role in maintaining normal airway functions.,Major molecular and morphologic changes occur in the airway epithelium in both CF and COPD, and growing evidence suggests that airway epithelial dysfunction is involved in disease initiation and progression in both diseases.,Structural and functional abnormalities in both airway and alveolar epithelium have a relevant impact on alteration of host defences, immune/inflammatory response, and the repair process leading to progressive lung damage and impaired lung function.,In this review, we address the evidence for a critical role of dysfunctional airway epithelial cells in chronic airway inflammation and remodelling in CF and COPD, highlighting the common mechanisms involved in the epithelial dysfunction as well as the similarities and differences of the two diseases. | β2-agonists were introduced in the 1940s as bronchodilators to be used in obstructive respiratory diseases.,Long-acting β2-agonists have been a mainstay of bronchodilating treatment for decades.,Recently, agents extending their effect to 24 hours and thus allowing the once-daily administration were introduced, defined as very-long-acting β2-agonists.,Olodaterol is a new very-long-acting β2-agonist that has been shown, in controlled trials, to improve lung function as well as clinical outcomes and quality of life.,Most of these trials included patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD).,Olodaterol has a rapid onset of action (comparable to formoterol) and provides bronchodilation over 24 hours.,In controlled trials, olodaterol was shown to be as effective as formoterol twice daily, but significantly superior in terms of quality of life in patients with COPD.,The safety profile of olodaterol was very good, with a rate of adverse events, including the cardiac events that are particularly important for β2-agonists, comparable to placebo.,Also, the efficiency of the Respimat® device concurs to the effectiveness of treatment. | 1 |
COPD patients with community-acquired pneumonia (CAP) have worse clinical outcomes, as compared to those without COPD.,Cardiovascular disease (CVD) is a common comorbidity for COPD patients.,Whether COPD with comorbid CVD will increase the risk of CAP is not well investigated.,The incidence and factors associated with CAP in COPD patients with and without CVD were analyzed.,The medical records of patients with newly diagnosed COPD between 2007 and 2010 were reviewed.,The patients’ characteristics, medical history of CVD, occurrence of CAP, and type of medication were recorded.,Kaplan-Meier curves were used to assess the differences in cumulative incidence of CAP.,Cox’s proportional hazards regression model was used to determine the adjusted hazard ratios with 95% confidence intervals in relation to factors associated with CAP in COPD patients with and without CVD.,Among 2,440 patients, 475 patients (19.5%) developed CAP during the follow-up period.,COPD patients who developed CAP were significantly older, had lower forced expiratory volume in 1 second, frequent severe exacerbation and comorbid CVD, as well as received inhaled corticosteroid (ICS)-containing therapy than those without CAP.,The cumulative incidence of CAP was higher in COPD patients with CVD compared to those without CVD.,Patients who received ICS-containing therapy had significantly increased risk of developing CAP compared to those who did not.,For patients with COPD, comorbid CVD is an independent risk factor for developing CAP.,ICS-containing therapy may increase the risk of CAP among COPD patients. | Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | 1 |
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. | Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction.,Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies.,Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD.,Participants were recruited from all 48 contiguous U.S. states by random digit dialing.,Lifetime ETS exposure was ascertained by structured telephone interview.,We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD.,Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD.,The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21).,The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84).,The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure.,ETS exposure may be an important cause of COPD.,Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure. | 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. | Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms.,Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections.,Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.,Exogenous interferon-β reverses these effects.,FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways.,Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection.,This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production.,Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.,Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia.,Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ. | 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. | Dyspnea is a complex, prevalent, and distressing symptom of chronic obstructive pulmonary disease (COPD) associated with decreased quality of life, significant disability, and increased mortality.,It is a major reason for referral to pulmonary rehabilitation.,We reviewed 23 COPD studies to examine the evidence for the effectiveness of cognitive-behavioral strategies for relieving dyspnea in COPD.,Preliminary evidence from randomized controlled trials exists to support cognitive- behavioral strategies, used with or without exercise, for relieving sensory and affective components of dyspnea in COPD.,Small to moderate treatment effects for relieving dyspnea were noted for psychotherapy (effect size [ES] = 0.08-0.25 for intensity; 0.26-0.65 for mastery) and distractive auditory stimuli (ES = 0.08-0.33 for intensity; 0.09 to −0.61 for functional burden).,Small to large dyspnea improvements resulted from yoga (ES = 0.2-1.21 for intensity; 0.67 for distress; 0.07 for mastery; and −8.37 for functional burden); dyspnea self-management education with exercise (ES = −0.14 to −1.15 for intensity; −0.62 to −0.69 for distress; 1.04 for mastery; 0.14-0.35 for self-efficacy); and slow-breathing exercises (ES = −0.34 to −0.83 for intensity; −0.61 to −0.80 for distress; and 0.62 for self-efficacy).,Cognitive-behavioral interventions may relieve dyspnea in COPD by (1) decreasing sympathetic nerve activity, dynamic hyperinflation, and comorbid anxiety, and (2) promoting arterial oxygen saturation, myelinated vagus nerve activity, a greater exercise training effect, and neuroplasticity.,While evidence is increasing, additional randomized controlled trials are needed to evaluate the effectiveness of psychosocial and self-management interventions in relieving dyspnea, in order to make them more available to patients and to endorse them in official COPD, dyspnea, and pulmonary rehabilitation practice guidelines.,By relieving dyspnea and related anxiety, such interventions may promote adherence to exercise programs and adaptive lifestyle change. | 1 |
Comorbidities are associated with the severity of coronavirus disease 2019 (COVID‐19).,This meta‐analysis aimed to explore the risk of severe COVID‐19 in patients with pre‐existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history.,A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases.,The languages of literature included English and Chinese.,The point prevalence of severe COVID‐19 in patients with pre‐existing COPD and those with ongoing smoking was evaluated with this meta‐analysis.,Overall 11 case series, published either in Chinese or English language with a total of 2002 cases, were included in this study.,The pooled OR of COPD and the development of severe COVID‐19 was 4.38 (fixed‐effects model; 95% CI: 2.34‐8.20), while the OR of ongoing smoking was 1.98 (fixed‐effects model; 95% CI: 1.29‐3.05).,There was no publication bias as examined by the funnel plot and Egger's test (P = not significant).,The heterogeneity of included studies was moderate for both COPD and ongoing smoking history on the severity of COVID‐19.,COPD and ongoing smoking history attribute to the worse progression and outcome of COVID‐19. | The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function. | 1 |
Lung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling.,Abnormal repair and remodeling has been observed in lung diseases like COPD.,As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function.,We investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays.,TGF-β1-induced miRNA expression changes were validated and replicated in an independent set of lung fibroblasts composted of 10 controls and 15 COPD patients using qRT-PCR.,Ago2-immunoprecipitation followed by mRNA expression profiling was used to identify the miRNA-targetomes of unstimulated and TGF-β1-stimulated primary lung fibroblasts (n = 2).,The genes affected by TGF-β1-modulated miRNAs were identified by comparing the miRNA targetomes of unstimulated and TGF-β1-stimulated fibroblasts.,Twenty-nine miRNAs were significantly differentially expressed after TGF-β1 stimulation (FDR<0.05).,The TGF-β1-induced miR-455-3p and miR-21-3p expression changes were validated and replicated, with in addition, lower miR-455-3p levels in COPD (p<0.05).,We identified 964 and 945 genes in the miRNA-targetomes of unstimulated and TGF-β1-stimulated lung fibroblasts, respectively.,The TGF-β and Wnt pathways were significantly enriched among the Ago2-IP enriched and predicted targets of miR-455-3p and miR-21-3p.,The miR-455-3p target genes HN1, NGF, STRADB, DLD and ANO3 and the miR-21-3p target genes HHEX, CHORDC1 and ZBTB49 were consistently more enriched after TGF-β1 stimulation.,Two miRNAs, miR-455-3p and miR-21-3p, were induced by TGF-β1 in lung fibroblasts.,The significant Ago2-IP enrichment of targets of these miRNAs related to the TGF-β and/or Wnt pathways (NGF, DLD, HHEX) in TGF-β1-stimulated fibroblasts suggest a role for these miRNAs in lung diseases by affecting lung fibroblast function. | Small airway remodeling is an important cause of the airflow limitation in chronic obstructive pulmonary disease (COPD).,A large population of patients with COPD also have pulmonary hypertension.,Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor that contributes to tissue remodeling in cardiovascular diseases.,Here, we evaluate the possible involvement of KLF5 in the remodeling of small airways and pulmonary vessels in COPD.,Lung tissues were obtained from 23 control never-smokers, 17 control ex-smokers and 24 ex-smokers with COPD.,The expression of KLF5 in the lung tissues was investigated by immunohistochemistry.,We investigated whether oxidative/nitrosative stress, which is a major cause of the pathogenesis in COPD, could augment the production of KLF5.,We examined the role of KLF5 in the stress-mediated tissue remodeling responses.,We also investigated the susceptibility of KLF5 expression to nitrosative stress using bronchial fibroblasts isolated from the lung tissues.,The expression of KLF5 was up-regulated in the small airways and pulmonary vessels of the COPD patients and it was mainly expressed in bronchial fibroblasts and cells of the pulmonary vessels.,The extent of the KLF5 expression in the small airway of the COPD group had a significant correlation with the severity of the airflow limitation.,Oxidative/nitrosative stress augmented the production of KLF5 in lung fibroblasts as well as the translocation of KLF5 into the nuclei.,Silencing of KLF5 suppressed the stress-augmented differentiation into myofibroblasts, the release of collagens and metalloproteinases.,Bronchial fibroblasts from the patients with COPD highly expressed KLF5 compared to those from the control subjects under basal condition and were more susceptible to the induction of KLF5 expression by nitrosative stress compared to those from the control subjects.,We provide the first evidence that the expression of KLF5 is up-regulated in small airways and pulmonary vessels of patients with COPD and may be involved in the tissue remodeling of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. | COPD exacerbations have a negative impact on lung function, decrease quality of life (QoL) and increase the risk of death.,The objective of this study was to assess the course of health status after an outpatient or inpatient exacerbation in patients with COPD.,This is an epidemiological, prospective, multicentre study that was conducted in 79 hospitals and primary care centres in Spain.,Four hundred seventy-six COPD patients completed COPD assessment test (CAT) and Clinical COPD Questionnaire (CCQ) questionnaires during the 24 hours after presenting at hospital or primary care centres with symptoms of an exacerbation, and also at weeks 4-6.,The scores from the CAT and CCQ were evaluated and compared at baseline and after recovery from the exacerbation.,A total of 164 outpatients (33.7%) and 322 inpatients (66.3%) were included in the study.,The majority were men (88.2%), the mean age was 69.4 years (SD = 9.5) and the mean FEV1 (%) was 47.7% (17.4%).,During the exacerbation, patients presented high scores in the CAT: [mean: 22.0 (SD = 7.0)] and the CCQ: [mean: 4.4 (SD = 1.2)].,After recovery there was a significant reduction in the scores of both questionnaires [CAT: mean: -9.9 (SD = 5.1) and CCQ: mean: -3.1 (SD = 1.1)].,Both questionnaires showed a strong correlation during and after the exacerbation and the best predictor of the magnitude of improvement in the scores was the severity of each score at onset.,Due to their good correlation, CAT and CCQ can be useful tools to measure health status during an exacerbation and to evaluate recovery.,However, new studies are necessary in order to identify which factors are influencing the course of the recovery of health status after a COPD exacerbation. | 1 |
The extent of the survival benefit of augmentation therapy for alpha-1 antitrypsin deficiency (AATD) in individuals with advanced COPD is difficult to define.,We performed a retrospective analysis using all available data from the observational registry of individuals with severe deficiency of alpha-1 antitrypsin (AAT) conducted by the NHLBI investigators.,Individuals (N=1129) with severe deficiency of AAT were evaluated for mortality using all data sources and stratified by 10% increments of baseline forced expiratory volume in 1 second (FEV1) percent predicted and by augmentation therapy status (ever receiving versus never receiving).,Kaplan-Meier survival curves were constructed for each of the deciles comparing survival in treated vs non-treated groups.,A multivariable model was performed to define the correlates of survival in individuals with FEV1 <30% predicted.,Amongst all subjects, augmentation was associated with improved survival (p<0.0001).,Among the individuals ever receiving augmentation therapy, survival was better than for those not receiving augmentation at all 10% increments of FEV1% predicted from 10% to 60% (P values <0.05 in all deciles).,In subgroups of participants with hyperinflation defined as residual volume (RV)>120% predicted and in subgroups of participants with reduced diffusing capacity for carbon monoxide (DLCO) <70% predicted, there was significantly better survival for those ever receiving augmentation therapy than for those who never received augmentation (p<0.001).,A multivariable analysis showed that mortality benefit is influenced by age, DLCO % predicted, and augmentation therapy.,There is a survival benefit from augmentation therapy in AATD between FEV1 values in the 10-60% predicted range.,Screening and treatment of AATD patients should therefore not be limited by the severity of illness as defined by FEV1. | The rising disease burden from chronic obstructive pulmonary disease (COPD) requires new approaches.,We suggest an approach based around three elements: inflammometry and multidimensional assessment to identify therapeutic targets and case management to design and implement an individualised treatment programme based on these assessments.,This tailored approach to treatment would maximise efficacy, limit cost and permit a better risk-benefit ratio of treatment.,The advantages include the ability to add up the benefits of individual therapies leading to a cumulative therapeutic benefit that is greater than each individual therapy alone.,We can now design a multifaceted inflammometry intervention for airway diseases based on targeting eosinophilic inflammation, non-eosinophilic pathways and systemic inflammation.,COPD is a complex and challenging disease.,The use of inflammometry and multidimensional assessment is necessary to identify relevant treatment targets and maximise the scope of therapy while limiting unnecessary use of drugs.,An individualised programme of management can be designed and coordinated by using a case manager.,This new approach may provide tangible benefits to people with COPD. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | This study assessed the effects of ursolic acid (UA) on airway-vessel remodeling and muscle atrophy in cigarette smoke (CS)-induced emphysema rats and investigated potential underlying mechanisms.,Emphysema was induced in a rat model with 3 months of CS exposure.,Histology and immunohistochemistry (IHC) stains were used to assess airway-vessel remodeling and muscle atrophy-associated changes.,Levels of cleaved-caspase3, 8-OHdG, and S100A4 were measured in airways and associated vessels to evaluate cell apoptosis, oxidant stress, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT)-associated factors.,Western blot and/or IHC analyses were performed to measure transforming growth factor-beta 1(TGF-β1)/Smad2.3, alpha-smooth muscle actin (α-SMA), and insulin-like growth factor 1 (IGF1) expression.,We also gave cultured HBE and HUVEC cells Cigarette Smoke Extract (CSE) administration and UA intervention.,Using Western blot method to measure TGF-β1/Smad2.3, α-SMA, S100A4, and IGF1 molecules expression.,UA decreased oxidant stress and cell apoptosis in airway and accompanying vascular walls of cigarette smoke-induced emphysema model rats.,UA alleviated EMT, EndMT, changes associated with airway-vessel remodeling and muscle atrophy.,The UA effects were associated with IGF1 and TGF-β1/Smad2.3 pathways.,UA reduced EMT, EndMT, airway-vessel remodeling, and musculi soleus atrophy in CS-induced emphysema model rats at least partly through IGF1 and TGF-β1/Smad2.3 signaling pathways. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that reduces lung and respiratory function, with a high mortality rate.,Severe and acute deterioration of COPD can easily lead to respiratory failure, resulting in personal, social, and medical burden.,Recent studies have shown a high correlation between the gut microbiota and lung inflammation.,In this study, we investigated the relationship between gut microbiota and COPD severity.,A total of 60 COPD patients with varying severity according to GOLD guidelines were enrolled in this study.,DNA was extracted from patients’ stool and 16S rRNA data analysis conducted using high-throughput sequencing followed by bioinformatics analysis.,The richness of the gut microbiota was not associated with COPD severity.,The gut microbiome is more similar in stage 1 and 2 COPD than stage 3+4 COPD.,Fusobacterium and Aerococcus were more abundant in stage 3+4 COPD.,Ruminococcaceae NK4A214 group and Lachnoclostridium were less abundant in stage 2-4, and Tyzzerella 4 and Dialister were less abundant in stage 1.,However, the abundance of a Bacteroides was associated with blood eosinophils and lung function.,This study suggests that no distinctive gut microbiota pattern is associated with the severity of COPD.,The gut microbiome could affect COPD by gut inflammation shaping the host immune system. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
Across Europe, COPD affects 23 million people leading to annual health care costs of ~€25.1 billion.,This burden is particularly severe during winter months in association with the peak incidence of exacerbation events.,Seasonal variation in the health status of patients with COPD places additional and often critical pressure on already strained health care resources.,COPD exacerbations are characterized by worsening day-to-day symptoms of an individual and often triggered by respiratory infections, but the process by which this occurs in a seasonal fashion is likely to be multifactorial.,In this review, we discuss recent population studies that highlight the impact of seasonality in COPD and review the proposed biological mechanisms underlying this.,An appraisal of the role of the host susceptibility and response, environmental triggers and the biology of respiratory pathogens is detailed.,The impact of each aspect is considered, and an integrated model of the context for the whole individual and society in general is explored. | Although COPD exacerbations are known to occur more frequently in winter, there is little information on hospitalizations and cause-specific mortality.,This study aimed to examine seasonal variations in mortality and exacerbations in patients with COPD during the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial.,TIOSPIR was a large-scale, multicenter trial, which assessed the safety and efficacy of tiotropium delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ (2.5 or 5 μg once daily) inhaler in patients with COPD.,Patients were aged ≥40 years, with a smoking history ≥10 pack-years, and post-bronchodilator forced expiratory volume in 1 second ≤70% and forced expiratory volume in 1 second/forced vital capacity ≤0.70.,COPD exacerbations and deaths were monitored throughout the trial.,The data were pooled to examine seasonal patterns.,Southern hemisphere data were shifted by 6 months to align with northern hemisphere seasons.,TIOSPIR was conducted in 43 northern (n=15,968) and 7 southern (n=1,148) hemisphere (n=1,148) countries.,The median duration of treatment was 835 days, with a mean follow-up of 2.3 years.,Among 19,494 exacerbations, there were clear seasonal differences (winter, 6,646 [34.1%]; spring, 4,515 [23.2%]; summer, 3,198 [16.4%]; autumn, 5,135 [26.3%]).,Exacerbations peaked in early winter (December in the northern hemisphere and June in the southern hemisphere), respiratory hospitalizations in midwinter, and respiratory deaths in early spring.,Although winter poses a 2-fold hazard for COPD exacerbations vs summer, respiratory deaths peak in early spring.,These data suggest that seasonal intensification of preventive treatments may impact COPD morbidity and mortality.,NCT01126437. | 1 |
Patients with COPD experience respiratory symptoms, impairments of daily living and recurrent exacerbations.,The aim of integrated disease management (IDM) is to establish a programme of different components of care (ie, self-management, exercise, nutrition) in which several healthcare providers (ie, nurses, general practitioners, physiotherapists, pulmonologists) collaborate to provide efficient and good quality of care.,The aim of this Cochrane systematic review was to evaluate the effectiveness of IDM on quality of life, exercise tolerance and exacerbation related outcomes.,Searches for all available evidence were carried out in various databases.,Included randomised controlled trials (RCTs) consisted of interventions with multidisciplinary (≥2 healthcare providers) and multitreatment (≥2 components) IDM interventions with duration of at least 3 months.,Two reviewers independently searched, assessed and extracted data of all RCTs.,A total of 26 RCTs were included, involving 2997 patients from 11 different countries with a follow-up varying from 3 to 24 months.,In all 68% of the patients were men, with a mean age of 68 years and a mean forced expiratory volume in 1 s (FEV1) predicted value of 44.3%.,Patients treated with an IDM programme improved significantly on quality of life scores and reported a clinically relevant improvement of 44 m on 6 min walking distance, compared to controls.,Furthermore, the number of patients with ≥1 respiratory related hospital admission reduced from 27 to 20 per 100 patients.,Duration of hospitalisation decreased significantly by nearly 4 days. | Favorable effects of formal pulmonary rehabilitation in selected moderate to severe COPD patients are well established.,Few data are available on the effects and costs of integrated disease management (IDM) programs on quality of care and health status of COPD patients in primary care, representing a much larger group of COPD patients.,Therefore, the RECODE trial assesses the long-term clinical and cost-effectiveness of IDM in primary care.,RECODE is a cluster randomized trial with two years of follow-up, during which 40 clusters of primary care teams (including 1086 COPD patients) are randomized to IDM or usual care.,The intervention started with a 2-day multidisciplinary course in which healthcare providers are trained as a team in essential components of effective COPD IDM in primary care.,During the course, the team redesigns the care process and defines responsibilities of different caregivers.,They are trained in how to use feedback on process and outcome data to guide implement guideline-driven integrated healthcare.,Practice-tailored feedback reports are provided at baseline, and at 6 and 12 months.,The team learns the details of an ICT program that supports recording of process and outcome measures.,Afterwards, the team designs a time-contingent individual practice plan, agreeing on steps to be taken in order to integrate a COPD IDM program into daily practice.,After 6 and 12 months, there is a refresher course for all teams simultaneously to enable them to learn from each other’s experience.,Health status of patients at 12 months is the primary outcome, measured by the Clinical COPD Questionnaire (CCQ).,Secondary outcomes include effects on quality of care, disease-specific and generic health-related quality of life, COPD exacerbations, dyspnea, costs of healthcare utilization, and productivity loss.,This article presents the protocol and baseline results of the RECODE trial.,This study will allow to evaluate whether IDM implemented in primary care can positively influence quality of life and quality of care in mild to moderate COPD patients, thereby making the benefits of multidisciplinary rehabilitation applicable to a substantial part of the COPD population.,Netherlands Trial Register (NTR): NTR2268 | 1 |
It is unclear whether cell culture methodology affects the corticosteroid sensitivity of chronic obstructive pulmonary disease (COPD) alveolar macrophages.,We compared the effect of a short and a long isolation procedure on corticosteroid inhibition of lipopolysaccharide (LPS) stimulated cytokine release from COPD alveolar macrophages.,We also investigated signalling pathways associated with macrophage activation during cell isolation.,Macrophages cultured using a short isolation protocol released higher unstimulated levels of tumour necrosis factor (TNF)-α and chemokine C-X-C motif ligand (CXCL) 8; these macrophages were less sensitive to corticosteroid inhibition of LPS stimulated TNF-α and CXCL8 release when compared to a long isolation procedure.,This was associated with increased p38 mitogen activated kinase (MAPK) activation.,The p38 MAPK inhibitor, BIRB-796, significantly reduced unstimulated cytokine release.,A key finding of this study was that both cell culture methods showed no difference in the corticosteroid sensitivity between COPD and control macrophages.,We conclude that the culture of alveolar macrophages using a short isolation procedure alters cytokine production through p38 MAPK activation; this is associated with a change in corticosteroid sensitivity. | Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily.,In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases.,Of the various pulmonary diseases, TNFα is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).,In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFα in the cytotoxicity.,Thus, pharmacological agents that can either suppress the production of TNFα or block its biological actions may have potential therapeutic value against a wide variety of diseases.,Despite some immunological side effects, anti-TNFα therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death. | 1 |
More than one third of individuals with chronic obstructive pulmonary disease (COPD) experience comorbid symptoms of depression and anxiety.,This review aims to provide an overview of the burden of depression and anxiety in those with COPD and to outline the contemporary advances and challenges in the management of depression and anxiety in COPD.,Symptoms of depression and anxiety in COPD lead to worse health outcomes, including impaired health-related quality of life and increased mortality risk.,Depression and anxiety also increase health care utilization rates and costs.,Although the quality of the data varies considerably, the cumulative evidence shows that complex interventions consisting of pulmonary rehabilitation interventions with or without psychological components improve symptoms of depression and anxiety in COPD.,Cognitive behavioral therapy is also an effective intervention for managing depression in COPD, but treatment effects are small.,Cognitive behavioral therapy could potentially lead to greater benefits in depression and anxiety in people with COPD if embedded in multidisciplinary collaborative care frameworks, but this hypothesis has not yet been empirically assessed.,Mindfulness-based treatments are an alternative option for the management of depression and anxiety in people with long-term conditions, but their efficacy is unproven in COPD.,Beyond pulmonary rehabilitation, the evidence about optimal approaches for managing depression and anxiety in COPD remains unclear and largely speculative.,Future research to evaluate the effectiveness of novel and integrated care approaches for the management of depression and anxiety in COPD is warranted. | Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD).,However, limited data are available regarding the longitudinal change in dyspnea, and it remains unknown which of relevant measurements might be used for following dyspnea.,We previously consecutively recruited 137 male outpatients with moderate to very severe COPD, and followed them every 6 months for 5 years.,We then reviewed and reanalyzed the data focusing on the relationships between the change in dyspnea and the changes in other clinical measurements of lung function, exercise tolerance tests and psychological status.,Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ) and the St.,George’s Respiratory Questionnaire (SGRQ) were also used.,Dyspnea at the end of exercise tolerance tests was measured using the Borg scale.,The mMRC, CRQ dyspnea and SGRQ activity significantly worsened over time (p < 0.001), but the OCD did not (p = 0.097).,Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV1) (correlation of determination (r2) = 0.05-0.19), diffusing capacity for carbon monoxide (r2 = 0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r2 = 0.14-0.17), although these correlations were weak.,Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements.,Dyspnea worsened over time in patients with COPD.,However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements.,Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status.,Changes in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements. | 1 |
COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | COPD (chronic obstructive pulmonary disease) is a major incurable global health burden and will become the third largest cause of death in the world by 2020.,It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, causes progressive airflow limitation.,This inflammation, where macrophages, neutrophils and T-cells are prominent, leads to oxidative stress, emphysema, small airways fibrosis and mucus hypersecretion.,The mechanisms and mediators that drive the induction and progression of chronic inflammation, emphysema and altered lung function are poorly understood.,Current treatments have limited efficacy in inhibiting chronic inflammation, do not reverse the pathology of disease and fail to modify the factors that initiate and drive the long-term progression of disease.,Therefore there is a clear need for new therapies that can prevent the induction and progression of COPD.,Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies.,The present review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and whether they can be used to predict the efficacy of new therapeutics for COPD. | 1 |
Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors.,Genome-wide association studies (GWAS) of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability.,In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function.,We used a pooled sequencing approach, with 12 pools of 25 individuals each, enabling high depth (30x) coverage per sample to be achieved.,This pooled design maximised sample size and therefore power, but led to challenges during variant-calling since sequencing error rates and minor allele frequencies for rare variants can be very similar.,For this reason we employed a rigorous quality control pipeline for variant detection which included the use of 3 independent calling algorithms.,In order to avoid false positive associations we also developed tests to detect variants with potential batch effects and removed them before undertaking association testing.,We tested for the effects of single variants and the combined effect of rare variants within a locus.,We followed up the top signals with data available (only 67% of collapsing methods signals) in 4,249 COPD cases and 11,916 smoking controls from UK Biobank.,We provide suggestive evidence for the combined effect of rare variants on COPD risk in TNXB and in sliding windows within MECOM and upstream of HHIP.,These findings can lead to an improved understanding of the molecular pathways involved in the development of COPD. | Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality.,Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties.,Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.,We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs.,The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.,Nine RCTs comprising 1666 patients met the inclusion criteria.,Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01).,Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective.,Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates.,The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups.,A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).,Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD.,However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance.,A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages. | 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. | 1 |
To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score.,In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days.,A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL.,The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT.,We evaluated 40 COPD patients and 40 controls.,In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs.,105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs.,6.4 ± 3.2 km/day; p < 0.001).,The COPD patients also walked fewer steps/day.,The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower.,The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results.,Patients with COPD are less active than are healthy adults of a comparable age.,Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures. | Quadriceps muscle dysfunction is well confirmed in chronic obstructive pulmonary disease (COPD) and reported to be related to a higher risk of mortality.,Factors contributing to quadriceps dysfunction have been postulated, while not one alone could fully explain it and there are few reports on it in China.,This study was aimed to investigate the severity of quadriceps dysfunction in patients with COPD, and to compare quadriceps muscle function in COPD and the healthy elderly.,Quadriceps strength and endurance capabilities were investigated in 71 COPD patients and 60 age-matched controls; predicted values for quadriceps strength and endurance were calculated using regression equations (incorporating age, gender, anthropometric measurements and physical activities), based on the data from controls.,Potential parameters related to quadriceps dysfunction in COPD were identified by stepwise regression analysis.,Mean values of quadriceps strength was 46% and endurance was 38% lower, in patients with COPD relative to controls.,Gender, physical activities and anthropometric measurements were predictors to quadriceps function in the controls.,While in COPD, forced expiratory volume in 1 second percentage of predicted value (FEV1% pred), nutritional depletion, gender and physical inactivity were identified as independent factors to quadriceps strength (R2 = 0.72); FEV1%pred, thigh muscle mass, serum levels of tumor necrosis factor-alpha (TNF-α) and gender were correlated to quadriceps endurance variance, with each p<0.05.,Quadriceps strength and endurance capabilities are both substantially impaired in Chinese COPD patients, with strength most affected.,For the controls, physical activity is most important for quadriceps function.,While for COPD patients, quadriceps dysfunction is related to multiple factors, with airflow limitation, malnutrition and muscle disuse being the main ones. | 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. | Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disorder characterized by the progressive obstruction of airflow and is currently the fourth leading cause of death in the world.,The pathogenesis of COPD is thought to involve bacterial infections and inflammations.,Owing to advancement in sequencing technology, evidence is emerging that supports an association between the lung microbiome and COPD.,However, few studies have looked into the expression profile of the bacterial communities in the COPD lungs.,In this study, we analyzed the sputum microbiome of four moderate and four severe COPD male patients both at the DNA and RNA level, using next generation sequencing technology.,We found that bacterial composition determined by 16S rRNA gene sequencing may not directly translate to the set of actively expressing bacteria as defined by transcriptome sequencing.,The two sequencing data agreed on Prevotella, Rothia, Neisseria, Porphyromonas, Veillonella, Fusobacterium and Streptococcus being among the most differentially abundant genera between the moderate and severe COPD samples, supporting their association with COPD severity.,However, the two sequencing analyses disagreed on the relative abundance of these bacteria in the two COPD groups, implicating the importance of studying the actively expressing bacteria for enriching our understanding of COPD.,Though we have described the metatranscriptome profiles of the lung microbiome in moderate and severe COPD, further investigations are required to determine the functional basis underlying the relationship between the microbial species in the lungs and pathogenesis of COPD. | 1 |
COPD self-management is a complex behavior influenced by many factors.,Despite scientific evidence that better disease outcomes can be achieved by enhancing self-management, many COPD patients do not respond to self-management interventions.,To move toward more effective self-management interventions, knowledge of characteristics associated with activation for self-management is needed.,The purpose of this study was to identify key patient and disease characteristics of activation for self-management.,An explorative cross-sectional study was conducted in primary and secondary care in patients with COPD.,Data were collected through questionnaires and chart reviews.,The main outcome was activation for self-management, measured with the 13-item Patient Activation Measure (PAM).,Independent variables were sociodemographic variables, self-reported health status, depression, anxiety, illness perception, social support, disease severity, and comorbidities.,A total of 290 participants (age: 67.2±10.3; forced expiratory volume in 1 second predicted: 63.6±19.2) were eligible for analysis.,While poor activation for self-management (PAM-1) was observed in 23% of the participants, only 15% was activated for self-management (PAM-4).,Multiple linear regression analysis revealed six explanatory determinants of activation for self-management (P<0.2): anxiety (β: −0.35; −0.6 to −0.1), illness perception (β: −0.2; −0.3 to −0.1), body mass index (BMI) (β: −0.4; −0.7 to −0.2), age (β: −0.1; −0.3 to −0.01), Global Initiative for Chronic Obstructive Lung Disease stage (2 vs 1 β: −3.2; −5.8 to −0.5; 3 vs 1 β: −3.4; −7.1 to 0.3), and comorbidities (β: 0.8; −0.2 to 1.8), explaining 17% of the variance.,This study showed that only a minority of COPD patients is activated for self-management.,Although only a limited part of the variance could be explained, anxiety, illness perception, BMI, age, disease severity, and comorbidities were identified as key determinants of activation for self-management.,This knowledge enables health care professionals to identify patients at risk of inadequate self-management, which is essential to move toward targeting and tailoring of self-management interventions.,Future studies are needed to understand the complex causal mechanisms toward change in self-management. | In this narrative review, we put self-management in the context of a 50-year history of research about how patients with COPD respond to their illness.,We review a definition of self-management, and emphasize that self-management should be combined with disease management and the chronic care model in order to be effective.,Reviewing the empirical status of self-management in COPD, we conclude that self-management is part and parcel of modern, patient-oriented biopsychosocial care.,In pulmonary rehabilitation programs, self-management is instrumental in improving patients’ functional status and quality of life.,We conclude by emphasizing how studying the way persons with COPD make sense of their illness helps in refining self-management, and thereby patient-reported outcomes in COPD. | 1 |
In Denmark, general practitioners (GPs) have the main responsibility for chronic obstructive pulmonary disease (COPD) management.,Internationally, COPD appears to be significantly under-treated, which could be explained by ‘therapeutic nihilism’ or lack of knowledge.,To investigate: (1) To what extent COPD management provided by GPs includes the core elements of pharmacological treatment, smoking cessation and physical activity, and (2) To what extent GPs need educational support and consulting with a specialist in pulmonary medicine.,A national cross-sectional web-based survey conducted in April-June 2019.,The survey included items on COPD management and educational support needs.,Danish general practice.,A population of approximately 3400 GPs (all GPs in Denmark).,We received response from 470 GPs (14% response rate).,Overall, the respondents reported that they offered COPD management including all relevant treatment elements.,Smoking cessation was supported in 58% and physical activity was supported in 23% of the respondents.,Future consultations on smoking cessation were planned by 35% and physical activity by 15% respondents.,GPs responded to ‘needing educational support in COPD management’ to a ‘high degree’ in 8% and to ‘some degree’ in 43%.,The survey suggested that COPD maintenance support provided by GPs seemed to be inadequate regarding smoking cessation and physical activity.,Moreover, some GPs expressed a need for educational support in COPD management.,More research is needed to understand the potential barriers to evidence-based delivery of COPD-management.Key pointsIn Denmark, general practitioners (GPs) have the main responsibility for the management of chronic obstructive pulmonary disease (COPD).,The present study shows that non-pharmacological interventions such as supporting smoking cessation and particularly promoting physical activity received less attention than pharmacological treatment.The study suggests a need for educational support of the GPs in COPD management.,In Denmark, general practitioners (GPs) have the main responsibility for the management of chronic obstructive pulmonary disease (COPD).,The present study shows that non-pharmacological interventions such as supporting smoking cessation and particularly promoting physical activity received less attention than pharmacological treatment.,The study suggests a need for educational support of the GPs in COPD management. | Patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) seem to have several symptoms in common that impact health.,However, methodological differences make this difficult to compare.,Comparisons of symptoms, impact of symptoms on function and health between patients with COPD and CHF in primary health care (PHC).,The study is cross sectional, including patients with COPD (n=437) and CHF (n=388), registered in the patient administrative systems of PHC.,The patients received specific questionnaires - the Memorial Symptom Assessment Scale, the Medical Research Council dyspnea scale, and the Fatigue Impact Scale - by mail and additional questions about psychological and physical health.,The mean age was 70±10 years and 78±10 years for patients with COPD and CHF respectively (P=0.001).,Patients with COPD (n=273) experienced more symptoms (11±7.5) than the CHF patients (n=211) (10±7.6).,The most prevalent symptoms for patients with COPD were dyspnea, cough, and lack of energy.,For patients with CHF, the most prevalent symptoms were dyspnea, lack of energy, and difficulty sleeping.,Experience of dyspnea, cough, dry mouth, feeling irritable, worrying, and problems with sexual interest or activity were more common in patients with COPD while the experience of swelling of arms or legs was more common among patients with CHF.,When controlling for background characteristics, there were no differences regarding feeling irritable, worrying, and sexual problems.,There were no differences in impact of symptoms or health.,Patients with COPD and CHF seem to experience similar symptoms.,There were no differences in how the patients perceived their functioning according to their cardinal symptoms; dyspnea and fatigue, and health.,An intervention for both groups of patients to optimize the management of symptoms and improve function is probably more relevant in PHC than focusing on separate diagnosis groups. | 1 |
Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world, and its associated health burdens and costs are mounting.,Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively fruitless effort, since treatments other than already ubiquitous smoking-cessation efforts were unlikely to alter its course.,However, there is strong evidence to suggest that the majority of patients with objective COPD are not aware of their condition, and this leads to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment.,Novel methods of diagnostic testing, community health programs, and primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages - where recent evidence suggests a rapid decline in lung function occurs and may be prevented if acted upon.,This review explores the evidence to support the efforts to justify programs aimed at early diagnosis, alternative diagnostic strategies that may augment traditional spirometry, therapeutic modalities that could potentially be used in the future to alter early lung-function decline, and emphasizes the necessary cooperative role that physicians, patients, communities, and governments need to play to realize the significant health impact that stands to be gained. | COPD is a complex disease with multiple pathological components, which we unfortunately tend to ignore when spirometry is used as the only method to evaluate the disorder.,Additional measures are needed to allow a more complete and clinically relevant assessment of COPD.,The earliest potential risk factors of disease in COPD are variations in the genetic background.,Genetic variations are present from conception and can determine lifelong changes in enzyme activities and protein concentrations.,In contrast, measurements in blood, sputum, exhaled breath, broncho-alveolar lavage, and lung biopsies may vary substantially over time.,This review explores potential markers of early disease and prognosis in COPD by examining genetic markers in the α1-antitrypsin, cystic fibrosis transmembrane conductance regulator (CFTR), and MBL-2 genes, and by examining the biochemical markers fibrinogen and C-reactive protein (CRP), which correlate with degree of pulmonary inflammation during stable conditions of COPD.,Chronic lung inflammation appears to contribute to the pathogenesis of COPD, and markers of this process have promising predictive value in COPD.,To implement markers for COPD in clinical practice, besides those already established for the α1-antitrypsin gene, further research and validation studies are needed. | 1 |
Oscillometry is a tool to measure respiratory impedance that requires minimal patients’ effort.,In patients with chronic obstructive pulmonary disease (COPD), the correlation of respiratory impedance at rest with exertional ventilatory parameters, including exercise tolerance, has scarcely been reported.,In addition, the utility of oscillometric parameters might differ between the inspiratory and expiratory phases due to airflow obstruction during expiration, but the hypothesis had not been validated.,The aim of the present study was to investigate whether oscillometric parameters are associated with exertional ventilatory parameters in patients with COPD.,Fifty-five subjects with COPD who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center performed spirometry, oscillometry, and cardiopulmonary exercise testing (CPET) within 2 weeks.,The correlations between parameters of spirometry, oscillometry, and CPET were analyzed using Spearman’s rank correlation coefficient, univariate, and multivariate analyses.,Respiratory reactance had better correlations with the CPET parameters than respiratory resistance.,Moreover, inspiratory reactance at rest correlated with the CPET parameters stronger than expiratory reactance.,In particular, inspiratory resonant frequency (Fres-ins) correlated with peak oxygen uptake (rS=−0.549, p<0.01) and dead space to tidal volume ratio at peak exercise (rS=0.677, p<0.01) and the best predicted expiratory tidal volume (VT ex) at peak exercise of all the oscillometric parameters (rS=−0.679, p<0.01).,However, the correlation between Fres-ins and VT ex at peak exercise became weak in subjects with severe and very severe COPD during exercise.,Measurement of respiratory reactance is useful for the effortless evaluation of not only exertional ventilatory parameters but exercise tolerance in patients with COPD.,The correlation of respiratory impedance with exertional ventilatory parameters can become weak in patients with advanced COPD; thus, the measurement of oscillometry might not be appropriate for evaluating exertional ventilatory parameters of patients with advanced COPD. | To develop reference equations for the Glittre Activities of Daily Living test (Glittre ADL-test) on the basis of anthropometric and demographic variables in apparently healthy individuals.,A secondary objective was to determine the reliability of the equations in a sample of COPD patients.,This was a cross-sectional study including 190 apparently healthy individuals (95 males; median age, 54.5 years [range, 42-65]; median FEV1 = 97% [range, 91-105.2]; and median FVC = 96% [range, 88.5-102]) recruited from the general community and 74 COPD patients (55 males; mean age, 65 ± 8 years; body mass index [BMI] = 25.9 ± 4.7 kg/m2; FEV1 = 36.1 ± 14.1%; and FVC = 62.7 ± 16.1%) recruited from a pulmonary rehabilitation center.,The mean time to complete the Glittre ADL-test was 2.84 ± 0.45 min.,In the stepwise multiple linear regression analysis, age and height were selected as Glittre ADL-test performance predictors, explaining 32.1% (p < 0.01) of the total variance.,Equation 1 was as follows: Glittre ADL-testpredicted = 3.049 + (0.015 × ageyears) + (−0.006 × heightcm).,Equation 2 included age and BMI and explained 32.3% of the variance in the test, the equation being as follows: Glittre ADL-testpredicted = 1.558 + (0.018 × BMI) + (0.016 × ageyears).,The reference equations for the time to complete the Glittre ADL-test were based on age, BMI, and height as independent variables and can be useful for predicting the performance of adult individuals.,The predicted values appear to be reliable when applied to COPD patients. | 1 |
Goblet cell hyperplasia is a classic but variable pathologic finding in COPD.,Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described.,We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.,We recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers.,Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue.,Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane.,Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.,Healthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects.,COPD subjects had a greater GCD than nonsmokers.,When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD.,When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD.,This finding was also seen in those with CB in the COPD group alone.,In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates.,All other covariates were not significant predictors of GCD or MVD.,Current smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction.,This provides clinical and pathologic correlation for smokers with and without COPD. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
Growing evidence suggests that endothelial injury is involved in the pathophysiology of chronic obstructive pulmonary disease (COPD).,Circulating endothelial microparticles (EMPs) increase in patients with COPD because of the presence of endothelial injury.,We examined the relationship between EMP number and changes in forced expiratory volume in 1 s (FEV1) in patients with COPD.,Prospective study.,One hospital in Japan.,A total 48 outpatients with stable COPD coming to the hospital from September 2010 to September 2011.,Blood samples were collected and vascular endothelial (VE)-cadherin EMPs (CD144+ EMPs), E-selectin EMPs (CD62E+ EMPs) and platelet endothelial cell adhesion molecule EMPs (CD31+/CD41− EMPs) were measured using fluorescence-activated cell sorting.,Annual FEV1 changes were evaluated using FEV1 data acquired a year before and a year after sample collection.,The number of E-selectin and VE-cadherin EMPs showed significant negative correlations with annual FEV1 changes (rs=−0.65, p<0.001, rs=−0.43, p=0.003, respectively).,Leucocyte counts tended to be correlated with annual FEV1 changes, but this correlation was not significant (rs=−0.28, p=0.057).,There were significant differences in annual FEV1 changes between with and without history of frequent exacerbation (p=0.006), and among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (p=0.009).,Multiple linear regression analysis revealed E-selectin EMP to be the only significant parameter associated with annual FEV1 changes, independent of VE-cadherin EMP, GOLD stages, leucocyte counts, and history of frequent exacerbation.,Receiver operating characteristic curves showed the optimum E-selectin EMP cut-off level for prediction of rapid FEV1 decline (>66 mL/year) to be 153.0/µL (areas under curve 0.78 (95% CI 0.60 to 0.89); sensitivity, 67%; specificity, 81%).,The high E-selectin EMP levels in stable patients with COPD are predictive of rapid FEV1 decline.,UMIN000005168. | 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 |
Guidelines are critical for facilitating cost-effective COPD care.,Development and implementation in low-and middle-income countries (LMICs) is challenging.,To guide future strategy, an overview of current global COPD guidelines is required.,We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation.,Scoping review of national COPD management guidelines.,We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards.,LMICs guidelines were compared with those from high-income countries (HICs).,Of the 61 national COPD guidelines identified, 30 were from LMICs.,Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines.,Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities.,More than 90% of all guidelines included smoking cessation advice.,Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%).,LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05).,LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05).,Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation.,Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated.,Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources. | Geographic clusters in prevalence and hospitalizations for COPD have been identified at national, state, and county levels.,The study objective is to identify county-level geographic accessibility to pulmonologists for adults with COPD.,Service locations of 12,392 practicing pulmonologists and 248,160 primary care physicians were identified from the 2013 National Provider Identifier Registry and weighted by census block-level populations within a series of circular distance buffer zones.,Model-based county-level population counts of US adults ≥ 18 years of age with COPD were estimated from the 2013 Behavioral Risk Factor Surveillance System.,The percentages of all estimated adults with potential access to at least one provider type and the county-level ratio of adults with COPD per pulmonologist were estimated for selected distances.,Most US adults (100% in urbanized areas, 99.5% in urban clusters, and 91.7% in rural areas) had geographic access to a primary care physician within a 10-mile buffer distance; almost all (≥ 99.9%) had access to a primary care physician within 50 miles.,At least one pulmonologist within 10 miles was available for 97.5% of US adults living in urbanized areas, but only for 38.3% in urban clusters and 34.5% in rural areas.,When distance increased to 50 miles, at least one pulmonologist was available for 100% in urbanized areas, 93.2% in urban clusters, and 95.2% in rural areas.,County-level ratios of adults with COPD per pulmonologist varied greatly across the United States, with residents in many counties in the Midwest having no pulmonologist within 50 miles.,County-level geographic variations in pulmonologist access for adults with COPD suggest that those adults with limited access will have to depend on care from primary care physicians. | 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. | 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 |
The aim of the present study was to characterize and quantify the numbers and expression levels of cells markers associated with dendritic cell (DC) maturation in small airways in current smokers and non-smokers with or without chronic obstructive pulmonary disease (COPD).,Lung tissues from the following 32 patients were obtained during resection for lung cancer: Eight smokers with COPD, eight non-smokers with COPD, eight current smokers without COPD and eight non-smokers without COPD, serving as a control.,The tissue sections were immunostained for cluster of differentiation (CD)83+ and CD1a+ to delineate mature and immature DCs, and chemokine receptor type 7 (CCR7+) to detect DC migratory ability.,Myeloid DCs were collected from the lung tissues, and subsequently the CD83+ and CCR7+ expression levels in the lung myeloid DCs were detected using flow cytometry.,The expression levels of CD83+, CD1a+ and CCR7+ mRNA in total lung RNA were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).,Evident chronic bronchitis and emphysema pathological changes were observed in the lung tissues of patients with COPD.,The results revealed that the numbers of CD83+ and CCR7+ DCs were reduced but the numbers of CD1a+ DCs were significantly increased in the COPD group as compared with the control group (P<0.05, respectively).,Using RT-qPCR, the expression levels of CCR7+ and CD83+ mRNA were found to be reduced in the smokers with COPD as compared with the non-smokers without COPD group (P<0.05, respectively).,Excessive local adaptive immune responses are key elements in the pathogenesis of COPD.,Cigarette smoke may stimulate immune responses by impairing the homing of airway DCs to the lymph nodes and reduce the migratory potential of DCs.,The present study revealed that COPD is associated with reduced numbers of mature CD83+ DCs and lower CCR7+ expression levels in small airways. | 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. | 1 |
Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD.,The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms.,Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy.,A systematic literature review was performed on the association of vitamins and COPD.,The role of vitamin supplements in COPD was then evaluated.,The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function.,High vitamin intake would probably reduce the annual decline of FEV1.,There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function. | Chronic obstructive pulmonary disease is a varied condition when examined from a number of different perspectives including factors which influence disease development, pathological process and clinical features.,There may be a complex interaction between the degree by which each of these processes influences the development of COPD and the subsequent clinical phenotype with which the patient presents.,The varied host response and subsequent clinical phenotype has generated much interest in recent years.,It is possible that failure of treatment to impact on mortality and reverse the disease process is because of the heterogeneous nature of the condition.,Identification and targeted treatment of clinical and pathological phenotypes within the broad spectrum of COPD may therefore improve outcome.,This article will review previous work which has attempted to phenotype COPD and identify if specific treatment for these phenotypes has been shown to be of benefit.,It will examine the work on pathological processes and clinical manifestations, both pulmonary and systemic, and will focus on pharmacological therapies. | 1 |
According to the Fletcher-Peto curve, rate of decline in forced expiratory volume in 1-second (FEV1) accelerates as age increases.,However, recent studies have not demonstrated that the rate of FEV1 decline accelerates with age among COPD patients.,The objective of the study is to evaluate annual rate of FEV1 decline as age increases among COPD patients.,In this retrospective cohort study, we enrolled COPD patients who were followed up at two tertiary care university hospitals from January 2000 to August 2013.,COPD was defined as post-bronchodilator (BD) FEV1/forced vital capacity (FVC) of <0.7.,All participants had more than two spirometries, including BD response.,Age groups were categorized as follows: below versus above median age or four quartiles.,A total of 518 participants (94.2% male; median age, 67 years; range, 42-90 years) were included.,Mean absolute and predictive values of post-BD FEV1 were 1.57±0.62 L and 52.53%±18.29%, respectively.,Distribution of Global initiative for Chronic Obstructive Lung Disease groups did not show statistical differences between age groups categorized by two different criteria.,After grouping the population by age quartiles, the rate of FEV1 decline was faster among older patients than younger ones whether expressed as absolute value (−10.60±5.57 mL/year, −15.84±6.01 mL/year, −18.63±5.53 mL/year, 32.94±6.01 mL/year, respectively; P=0.048) or predicted value (−0.34%±0.19%/year, −0.53%±0.21%/year, −0.62%±0.19%/year, −1.26%±0.21%/year, respectively, P=0.010).,As suggested conceptually by the Fletcher−Peto curve, annual FEV1 decline among COPD patients is accelerated among older patients than younger ones. | Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | 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. | Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU).,Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population.,We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006.,Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses.,PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay.,Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission.,The median [25%-75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours.,The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively.,Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients.,Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L.,The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L.,The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80).,The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics.,Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.,The online version of this article (doi:10.1186/1471-2334-8-145) contains supplementary material, which is available to authorized users. | 1 |
Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies.,Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.,Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts.,A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients.,Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.,Odds ratios (ORs) were pooled by random effects models.,Fourteen observational studies were eligible for the study.,Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29-3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16-7.82), severe airway obstruction (1.31, 95% CI, 1.09-1.58) and mortality (1.96, 95% CI, 1.04-3.70).,The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. | Allergy and Aspergillus hypersensitivity (AH) were shown to be associated with severe symptoms or worse lung function in COPD patients.,The prevalence of elevated total IgE (T-IgE) and its association with clinical symptoms and lung function in COPD have not been studied.,The prevalence of AH and its correlation with clinical characteristics in a COPD cohort of larger sample size is also lacking.,273 patients with COPD were evaluated by respiratory symptoms, blood test, chest HRCT, lung function, serum detection of T-IgE and Aspergillus specific IgE.,Patients with T-IgE ≥ 1000 KU/L were further investigated for allergic bronchopulmonary aspergillosis (ABPA).,The prevalence of elevated T-IgE and AH in patients with COPD was 47.3% and 15.0%, respectively.,Eight patients (2.9%) met the diagnostic criteria for ABPA.,Compared with the normal T-IgE group, patients with elevated T-IgE had a longer history of dyspnea (p < 0.01), an earlier onset of dyspnea after chronic cough/expectoration (p < 0.01), and were more likely to wheeze (p < 0.01).,They also showed worse lung functions and more severe GOLD staging (p < 0.01).,Analysis of the clinical data in male patients with smoking as the risk factor showed the same results.,To evaluate the clinical characteristics of COPD with AH, patients with elevated T-IgE were further divided into subgroups with and without AH.,When compared with the normal T-IgE group, both the two subgroups showed longer history of dyspnea (p < 0.01), an earlier onset of dyspnea (p < 0.01) and a worse status of lung function (p < 0.05).,Correlation analysis demonstrated that T-IgE was correlated positively with the time length of dyspnea (r = 0.401, p < 0.001), and the ratio of duration of dyspnea to that of chronic cough/expectoration (r = 0.59, p < 0.001), but negatively with FEV1/FVC% (r = −0.194, p = 0.001), and FEV1%predicted (r = −0.219, p < 0.001).,There was a high prevalence of elevated serum T-IgE and AH in patients with COPD.,Serum T-IgE level was correlated with symptoms such as dyspnea and impairment of lung function.,Allergens other than Aspergillus may have similar effects on disease expression or progression of COPD. | 1 |
The aim of this study was to estimate the prevalence of concurrent diagnoses of asthma/COPD and examine its full spectrum of comorbid disorders in Germany.,We used nationwide outpatient claims data comprising diagnoses of all statutory health insurees (40+ years) in 2017 (N = 40,477,745).,The ICD-10 codes J44 (COPD) and J45 (asthma) were used to identify patients.,The odds of 1,060 comorbid disorders were examined in a case-control study design.,Of all insurees, 4,632,295 (11%) were diagnosed with either asthma or COPD.,Of them, 43% had asthma only, 44% COPD only and 13% both diseases.,The prevalence of concurrent asthma/COPD was 1.5% with a slightly higher estimate among females than males (1.6% vs.,1.4%) and constant increase by age in both sexes.,Comorbid disorders were very common among these patients. 31 disorders were associated with a strong effect size (odds ratio > 10), including other respiratory diseases, but also bacterial (e.g., mycobacteria, including tuberculosis) and fungal infections (e.g., sporotrichosis and aspergillosis).,Patients with concurrent asthma/COPD suffer from comorbid disorders involving various body systems, which points to the need of a multidisciplinary care approach.,Regular screening for common comorbid disorders may result in better clinical course and prognosis as well as improvement of patients’ quality of life. | 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. | 1 |
Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity. | 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 |
Polypharmacy of respiratory medications is commonly observed in patients with chronic obstructive pulmonary disease (COPD).,The aims of this study were to investigate determinants of polypharmacy and to study the consistency of actual respiratory drug use with current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in pulmonary rehabilitation candidates with COPD.,Data were extracted from the records of all patients with a diagnosis of COPD referred for pulmonary rehabilitation to CIRO+ between 2005 and 2009.,Use of respiratory medications, self-reported COPD exacerbations, lung function, blood gases, exercise capacity, Medical Research Council (MRC) dyspnea grade, and St George’s Respiratory Questionnaire (SGRQ) were recorded as part of assessment of health status.,In total, 1859 COPD patients of mean age (± standard deviation) 64.3 ± 9.7 years and with a forced expiratory volume in one second (FEV1) of 44.7% ± 18.2% were included.,On average, patients used 3.5 ± 1.5 respiratory medications; this number increased with increasing GOLD stage, MRC score, and SGRQ scores.,FEV1 (% predicted), SGRQ, and number of recent exacerbations were independent determinants of polypharmacy.,Use of long-acting bronchodilators and inhaled corticosteroids was substantial and comparable in all GOLD stages.,Use of corticosteroids was not restricted to patients with frequent exacerbations.,Polypharmacy of respiratory medications is common in COPD patients with persistent symptoms.,In addition to severity of disease, health status is an independent predictor of polypharmacy.,Actual drug use in COPD patients referred for pulmonary rehabilitation is partially inconsistent with current GOLD guidelines. | Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | 1 |
Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease.,We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort.,We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter.,Patients were dichotomized as frequent (≥2 AECOPD/year) or infrequent exacerbators.,Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline.,The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95 % CI, 1.24-7.14, p = 0.01).,The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]).,Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum.,However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test).,In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival.,The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989.,The online version of this article (doi:10.1186/s12931-015-0306-3) contains supplementary material, which is available to authorized users. | We have previously established that a defect in the ability of alveolar macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is a potential therapeutic target in COPD.,We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic function) were reduced in the airways but not circulation of COPD patients.,We hypothesized that increased oxidative stress in the airway could be a cause for such disturbances.,We therefore studied the effects of oxidation on the structure of the MBL molecule and its functional interactions with macrophages.,Oligomeric structure of plasma derived MBL (pdMBL) before and after oxidation (oxMBL) with 2,2′-azobis(2-methylpropionamidine)dihydrochroride (AAPH) was investigated by blue native PAGE.,Macrophage function in the presence of pd/oxMBL was assessed by measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae (NTHi) and expression of macrophage scavenger receptors.,Oxidation disrupted higher order MBL oligomers.,This was associated with changed macrophage function evident by a significantly reduced capacity to phagocytose apoptotic cells and NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively).,Interestingly, oxidation of MBL significantly reduced macrophage phagocytic ability to below control levels.,Flow cytometry and immunofluorescence revealed a significant increase in expression of macrophage scavenger receptor (SRA1) in the presence of pdMBL that was abrogated in the presence of oxMBL.,We show the pulmonary macrophage dysfunction in COPD may at least partially result from an oxidative stress-induced effect on MBL, and identify a further potential therapeutic strategy for this debilitating disease. | 1 |
To evaluate the effectiveness of long-term treatment of statins for chronic obstructive pulmonary disease (COPD), and to answer which one is better.,General meta-analysis was performed to produce polled estimates of the effect of mortality, inflammatory factors, and lung function index in COPD patients by the search of PubMed, Web of Science, Embase, and China National Knowledge Infrastructure for eligible studies.,A network meta-analysis was performed to synthetically compare the effectiveness of using different statins in COPD patients.,General meta-analysis showed that using statins reduced the risk of all-cause mortality, heart disease-related mortality and COPD acute exacerbation (AECOPD) in COPD patients, the RR (95% CI) were 0.72 (0.63,0.84), 0.72 (0.53,0.98) and 0.84 (0.79,0.89), respectively.,And using statins reduced C-reactive protein (CRP) and pulmonary hypertension (PH) in COPD patients, the SMD (95% CI) were − 0.62 (− 0.52,-0.72) and − 0.71 (− 0.85,-0.57), respectively.,Network meta-analysis showed that Fluvastatin (97.7%), Atorvastatin (68.0%) and Rosuvastatin (49.3%) had higher cumulative probability than other statins in reducing CRP in COPD patients.,Fluvastatin (76.0%) and Atorvastatin (75.4%) had higher cumulative probability than other satins in reducing PH in COPD patients.,Using statins can reduce the risk of mortality, the level of CRP and PH in COPD patients.,In addition, Fluvastatin and Atorvastatin are more effective in reducing CRP and PH in COPD patients.,The online version of this article (10.1186/s12931-019-0984-3) contains supplementary material, which is available to authorized users. | 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 |
This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity.,A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study.,Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups.,We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores.,Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment.,This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients. | Asthma-COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease.,However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized.,To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected.,This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma.,The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS.,Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90) of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135).,The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves.,Only sputum NGAL levels could differentiate ACOS from asthma (P<0.001 and P<0.001) and COPD (P<0.05 and P=0.002) in the discovery and replication cohorts, respectively.,Sputum NGAL levels were independently correlated with the percentage of pre-bronchodilator forced expiratory volume in 1 second predicted in multivariate analysis in the discovery and replication cohorts (P=0.001 and P=0.002, respectively).,In conclusion, sputum biomarkers reflecting both airway inflammation and remodeling of the tissue show potential in differentiation between asthma, COPD, and ACOS. | 1 |
CD8+ T-lymphocytes, natural killer T-like cells (NKT-like cells, CD56+CD3+) and natural killer cells (NK cells, CD56+CD3−) are the three main classes of human killer cells and they are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Activation of these cells can initiate immune responses by virtue of their production of inflammatory cytokines and chemokines that cause lung tissue damage, mucus hypersecretion and emphysema.,The objective of the current study was to investigate the activation levels of human killer cells in healthy non-smokers, healthy smokers, ex-smokers with COPD and current smokers with COPD, in both peripheral blood and induced sputum.,After informed consent, 124 participants were recruited into the study and peripheral blood or induced sputum was taken.,The activation states and receptor expression of killer cells were measured by flow cytometry.,In peripheral blood, current smokers, regardless of disease state, have the highest proportion of activated CD8+ T-lymphocytes, NKT-like cells and NK cells compared with ex-smokers with COPD and healthy non-smokers.,Furthermore, CD8+ T-lymphocyte and NK cell activation is positively correlated with the number of cigarettes currently smoked.,Conversely, in induced sputum, the proportion of activated killer cells was related to disease state rather than current smoking status, with current and ex-smokers with COPD having significantly higher rates of activation than healthy smokers and healthy non-smokers.,A differential effect in systemic and lung activation of killer cells in COPD is evident.,Systemic activation appears to be related to current smoking whereas lung activation is related to the presence or absence of COPD, irrespective of current smoking status.,These findings suggest that modulating killer cell activation may be a new target for the treatment of COPD. | There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD.,We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3-) cells and NKT-like (CD56+CD3+) cells.,Peripheral blood mononuclear cells (PBMCs) were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry.,Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies.,The proportion of peripheral blood NKT-like (CD56+CD3+) cells in smokers with COPD (COPD subjects) was significantly lower (0.6%) than in healthy smokers (smokers) (2.8%, p < 0.001) and non-smoking healthy participants (HNS) (3.3%, p < 0.001).,NK (CD56+CD3-) cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p < 0.001) as were NKT-like (CD56+CD3+) cells (16.7% vs 52.4% specific lysis, p < 0.001).,Both cell types had lower proportions expressing both perforin and granzyme B.,Blocking the action of perforin and granzyme B reduced the cytotoxic activity of NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells from smokers and HNS.,In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells in COPD subjects are reduced and that their cytotoxic effector function is defective. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airway obstruction and inflammation but also accompanied by several extrapulmonary consequences, such as skeletal muscle weakness and osteoporosis.,Skeletal muscle weakness is of major concern, since it leads to poor functional capacity, impaired health status, increased healthcare utilization, and even mortality, independently of lung function.,Osteoporosis leads to fractures and is associated with increased mortality, functional decline, loss of quality of life, and need for institutionalization.,Therefore, the presence of the combination of these comorbidities will have a negative impact on daily life in patients with COPD.,In this review, we will focus on these two comorbidities, their prevalence in COPD, combined risk factors, and pathogenesis.,We will try to prove the clustering of these comorbidities and discuss possible preventive or therapeutic strategies. | 1 |
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
COPD symptoms show a diurnal variability.,However, morning and night variability has generally not been taken into consideration in disease management plans.,The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status.,A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology.,We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service.,Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1).,A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0).,Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers (P<0.0001).,Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect.,Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%).,Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors (n=346, OR:4.13, CI: 2.45−6.95, P<0.000).,Morning symptoms increased the odds of poor health status at follow-up (n=346, OR:12.22, CI:4.76−31.39, P<0.000).,Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations.,Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ.,Severe morning symptoms predicted worsening of COPD health status. | Chronic obstructive pulmonary disease (COPD) is a widespread disease.,It produces some night symptoms such as nighttime cough and dyspnea.,Then subjective and objective changes in sleep pattern are expected.,Present study was conducted to determine frequency of sleepiness and quality of sleep in patients with COPD.,Present case-control study has been performed on 120 patients with diagnosis of COPD who had been referred to pulmonary disease clinic in a University teaching hospital.,One hundred twenty age- and sex- matched healthy individuals were recruited in the study and served as control.,Spirometry (PFT) was performed for all patients.,Patients were categorized under 3 groups in relation to their PFT as follow: mild COPD (FEV1/FVC<70% and FEV1≥80%), moderate COPD (FEV1/FVC<70% and 50%≤FEV1<80%), and severe COPD (FEV1/FVC<70% and FEV1<50%).,Pittsburgh Sleep Quality questionnaire (PSQI) and Epworth Sleepiness Scale (ESS) were used to estimate quality of sleep and daytime sleepiness in the patients and control group.,The collected data were analyzed using version 16 SPSS software.,Student’s T- test, Chi- square and multiple logistic regressions were used as appropriated.,120 patients with COPD (79 males and 41 females) and 120 normal individuals responded to the questionnaires.,Mean scores of quality of sleep were 8.03±3.66 and 4.2±2.8 in COPD patients and control group respectively.,32.1% of the patients had good sleep quality (PSQI score less than 5) and 67.9% had poor sleep quality.,Daytime sleepiness (ESS≥ 10) was present in 34.8% of the patients and 15% of control people.,Multiple logistic regressions showed that the patients reported significantly worse sleep quality and more daytime sleepiness than control group [OR=2.9; 95% CI (1.6-3.7) & OR=3.5; 95% CI (2.5-4.3) respectively].,Results of present study confirmed that COPD is associated with daytime sleepiness and poor quality of sleep, possibly attributable to nighttime respiratory difficulties and concomitant sleep apnea.,Assessment of the patients for symptoms of sleep apnea, daytime sleepiness should be a part of regular follow up visits of patients with COPD. | 1 |
Pulmonary vascular disease, especially pulmonary hypertension, is an important complication of COPD.,Bronchiectasis is considered not only a comorbidity of COPD, but also a risk factor for vascular diseases.,The main pulmonary artery to aorta diameter ratio (PA:A ratio) has been found to be a reliable indicator of pulmonary vascular disease.,It is hypothesized that the co-existence of COPD and bronchiectasis may be associated with relative pulmonary artery enlargement (PA:A ratio >1).,This retrospective study enrolled COPD patients from 2012 through 2016.,Demographic and clinical data were collected.,Bhalla score was used to determine the severity of bronchiectasis.,Patient characteristics were analyzed in two ways: the high (PA:A >1) and low (PA:A ≤1) ratio groups; and COPD with and without bronchiectasis groups.,Logistic regression analysis was used to assess risk factors for high PA:A ratios.,In this study, 480 COPD patients were included, of whom 168 had radiographic bronchiectasis.,Patients with pulmonary artery enlargement presented with poorer nutrition (albumin, 35.6±5.1 vs 38.3±4.9, P<0.001), lower oxygen partial pressure (74.4±34.5 vs 81.3±25.4, P<0.001), more severe airflow obstruction (FEV1.0, 0.9±0.5 vs 1.1±0.6, P=0.004), and a higher frequency of bronchiectasis (60% vs 28.8%, P<0.001) than patients in the low ratio group.,Patients with both COPD and bronchiectasis had higher levels of systemic inflammation (erythrocyte sedimentation rate, P<0.001 and fibrinogen, P=0.006) and PA:A ratios (P<0.001).,A higher PA:A ratio was significantly closely correlated with a higher Bhalla score (r=0.412, P<0.001).,Patients with both COPD and bronchiectasis with high ratios presented higher levels of NT-proBNP (P<0.001) and systolic pulmonary artery pressure (P<0.001).,Multiple logistic analyses have indicated that bronchiectasis is an independent risk factor for high PA:A ratios in COPD patients (OR =3.707; 95% CI =1.888-7.278; P<0.001).,Bronchiectasis in COPD has been demonstrated to be independently associated with relative pulmonary artery enlargement. | Pulmonary rehabilitation is effective in all stages of COPD.,The availability and utilization of pulmonary rehabilitation resources, and the characteristics of COPD patients receiving rehabilitation, were investigated in primary and secondary care in central Sweden.,Data on available pulmonary rehabilitation resources were collected using questionnaires, to 14 hospitals and 54 primary health care centers, and information on utilization of different rehabilitation professionals was obtained from questionnaires completed by 1,329 COPD patients from the same centers.,Multivariable logistic regression examined associations with having received rehabilitation in the previous year.,In primary care, nurse-based asthma/COPD clinics were common (87%), with additional separate access to other rehabilitation professionals.,In secondary care, rehabilitation was more often offered as part of a multidisciplinary teamwork (71%).,In total, 36% of the patients met an asthma/COPD nurse in the previous year.,Utilization was lower in primary than in secondary care for physiotherapists (7% vs 16%), occupational therapists (3% vs 10%), nutritionists (5% vs 13%), and counselors (1% vs 4%).,A higher COPD Assessment Test score and frequent exacerbations were associated with higher utilization of all rehabilitation professionals.,Pulmonary rehabilitation resources are available but underutilized, and receiving rehabilitation is more common in severe COPD.,Treatment recommendations need to be better implemented, especially in mild and moderate COPD. | 1 |
Little is known about whether there is any sex effect on chronic obstructive lung disease (COPD) exacerbations.,This study is intended to describe the possible sex-associated differences in exacerbation profile in COPD patients.,A total of 384 COPD patients who were hospitalized due to exacerbation were evaluated retrospectively for their demographics and previous and current exacerbation characteristics.,The study was conducted on 109 (28%) female patients and 275 (72%) male patients.,The mean age was 68.30±10.46 years.,Although females had better forced expiratory volume in 1 second and near-normal forced vital capacity, they had much impaired arterial blood gas levels (partial oxygen pressure [PO2] was 36.28 mmHg vs 57.93 mmHg; partial carbon dioxide pressure [PCO2] was 45.97 mmHg vs 42.49 mmHg; P=0.001), indicating severe exacerbation with respiratory failure.,More females had two exacerbations and two hospitalizations, while more men had one exacerbation and one hospitalization.,Low adherence to treatment and pulmonary embolism were more frequent in females.,Females had longer time from the onset of symptoms till the admission and longer hospitalization duration than males.,Comorbidities were less in number and different in women (P<0.05).,Women were undertreated and using more oral corticosteroids.,Current data showed that female COPD patients might be more prone to have severe exacerbations, a higher number of hospitalizations, and prolonged length of stay for hospitalization.,They have a different comorbidity profile and might be undertreated for COPD. | Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary.,Strong epidemiological evidence suggests that exposure to particulate matter (PM) air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD) resulting in increased morbidity and mortality.,However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD.,The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces.,Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease.,This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death world-wide, where chronic inflammation accelerates lung function decline.,Pathological inflammation is worsened by chronic bacterial lung infections and susceptibility to recurrent acute exacerbations of COPD (AECOPD), typically caused by viral and/or bacterial respiratory pathogens.,Despite ongoing efforts to reduce AECOPD rates with inhaled corticosteroids, COPD patients remain at heightened risk of developing serious lung infections/AECOPD, frequently leading to hospitalization and infection-dependent delirium.,Here, we review emerging mechanisms into why COPD patients are susceptible to chronic bacterial infections and highlight dysregulated inflammation and production of reactive oxygen species (ROS) as central causes.,This underlying chronic infection leaves COPD patients particularly vulnerable to acute viral infections, which further destabilize host immunity to bacteria.,The pathogeneses of bacterial and viral exacerbations are significant as clinical symptoms are more severe and there is a marked increase in neutrophilic inflammation and tissue damage.,AECOPD triggered by a bacterial and viral co-infection increases circulating levels of the systemic inflammatory marker, serum amyloid A (SAA).,SAA is a functional agonist for formyl peptide receptor 2 (FPR2/ALX), where it promotes chemotaxis and survival of neutrophils.,Excessive levels of SAA can antagonize the protective actions of FPR2/ALX that involve engagement of specialized pro-resolving mediators, such as resolvin-D1.,We propose that the anti-microbial and anti-inflammatory actions of specialized pro-resolving mediators, such as resolvin-D1 should be harnessed for the treatment of AECOPD that are complicated by the co-pathogenesis of viruses and bacteria. | The interaction between influenza and pneumococcus is important for understanding how coinfection may exacerbate pneumonia.,Secondary pneumococcal pneumonia associated with influenza infection is more likely to increase respiratory morbidity and mortality.,This study aimed to assess exacerbated inflammatory effects posed by secondary pneumococcal pneumonia, given prior influenza infection.,A well-derived mathematical within-host dynamic model of coinfection with influenza A virus and Streptococcus pneumoniae (SP) integrated with dose-response relationships composed of previously published mouse experimental data and clinical studies was implemented to study potentially exacerbated inflammatory responses in pneumonia based on a probabilistic approach.,We found that TNFα is likely to be the most sensitive biomarker reflecting inflammatory response during coinfection among three explored cytokines.,We showed that the worst inflammatory effects would occur at day 7 SP coinfection, with risk probability of 50% (likely) to develop severe inflammatory responses.,Our model also showed that the day of secondary SP infection had much more impact on the severity of inflammatory responses in pneumonia compared to the effects caused by initial virus titers and bacteria loads.,People and health care workers should be wary of secondary SP infection on day 7 post-influenza infection for prompt and proper control-measure implementation.,Our quantitative risk-assessment framework can provide new insights into improvements in respiratory health especially, predominantly due to chronic obstructive pulmonary disease (COPD). | 1 |
COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | Influenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD.,Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD.,Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days.,On day 5, mice were infected with 1 × 104.5 PFUs of the IAV Mem71 (H3N1).,BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection.,IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non-smoking mice.,This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice.,Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro-inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice.,Targeting oxidative stress using apocynin and ebselen reduces IAV-induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD. | 1 |
The human small airway epithelium (SAE) plays a central role in the early events in the pathogenesis of most inherited and acquired lung disorders.,Little is known about the molecular phenotypes of the specific cell populations comprising the SAE in humans, and the contribution of SAE specific cell populations to the risk for lung diseases.,Drop-seq single-cell RNA-sequencing was used to characterize the transcriptome of single cells from human SAE of nonsmokers and smokers by bronchoscopic brushing.,Eleven distinct cell populations were identified, including major and rare epithelial cells, and immune/inflammatory cells.,There was cell type-specific expression of genes relevant to the risk of the inherited pulmonary disorders, genes associated with risk of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis and (non-mutated) driver genes for lung cancers.,Cigarette smoking significantly altered the cell type-specific transcriptomes and disease risk-related genes.,This data provides new insights into the possible contribution of specific lung cells to the pathogenesis of lung disorders. | Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | 1 |
To analyze symptoms at different times of day in patients with COPD.,This was a multicenter, cross-sectional observational study conducted at eight centers in Brazil.,We evaluated morning, daytime, and nighttime symptoms in patients with stable COPD.,We included 593 patients under regular treatment, of whom 309 (52.1%) were male and 92 (15.5%) were active smokers.,The mean age was 67.7 years, and the mean FEV1 was 49.4% of the predicted value.,In comparison with the patients who had mild or moderate symptoms, the 183 (30.8%) with severe symptoms were less physically active (p = 0.002), had greater airflow limitation (p < 0.001), had more outpatient exacerbations (p = 0.002) and more inpatient exacerbations (p = 0.043), as well as scoring worse on specific instruments.,The most common morning and nighttime symptoms were dyspnea (in 45.2% and 33.1%, respectively), cough (in 37.5% and 33.3%, respectively), and wheezing (in 24.4% and 27.0%, respectively).,The intensity of daytime symptoms correlated strongly with that of morning symptoms (r = 0.65, p < 0.001) and that of nighttime symptoms (r = 0.60, p < 0.001), as well as with the COPD Assessment Test score (r = 0.62; p < 0.001), although it showed only a weak correlation with FEV1 (r = −0.205; p < 0.001).,Dyspnea was more common in the morning than at night.,Having morning or nighttime symptoms was associated with greater daytime symptom severity.,Symptom intensity was strongly associated with poor quality of life and with the frequency of exacerbations, although it was weakly associated with airflow limitation. | To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score.,In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days.,A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL.,The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT.,We evaluated 40 COPD patients and 40 controls.,In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs.,105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs.,6.4 ± 3.2 km/day; p < 0.001).,The COPD patients also walked fewer steps/day.,The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower.,The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results.,Patients with COPD are less active than are healthy adults of a comparable age.,Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures. | 1 |
Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis.,Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer’s and Parkinson’s diseases, but little is known about iron accumulation in COPD.,We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction.,Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects.,Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay.,Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)).,The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues.,Futhermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity.,The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively).,In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction.,These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress. | 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. | 1 |
Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented.,However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited.,Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons.,We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002).,Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects.,No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA.,Co-occurrence analysis suggests the presence of networks of co-occurring bacteria.,Four communities of positively correlated bacteria were revealed.,The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype.,Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells.,This might result in a changed interplay with the host immune system. | The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined.,Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation.,COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa.,Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing.,Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa.,Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364).,In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations.,An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples.,These increases were not identified by culture in 5 out of 13 participants (38.5 %).,Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions.,Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.,The online version of this article (doi:10.1007/s10096-013-2044-0) contains supplementary material, which is available to authorized users. | 1 |
Increased iron availability modifies cardiorespiratory function in healthy volunteers and improves exercise capacity and quality of life in patients with heart failure or pulmonary hypertension.,We hypothesised that intravenous iron would produce improvements in oxygenation, exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD).,We performed a randomised, placebo-controlled, double-blind trial in 48 participants with COPD (mean±SD: age 69±8 years, haemoglobin 144.8±13.2 g/L, ferritin 97.1±70.0 µg/L, transferrin saturation 31.3%±15.2%; GOLD grades II-IV), each of whom received a single dose of intravenous ferric carboxymaltose (FCM; 15 mg/kg bodyweight) or saline placebo.,The primary endpoint was peripheral oxygen saturation (SpO2) at rest after 1 week.,The secondary endpoints included daily SpO2, overnight SpO2, exercise SpO2, 6 min walk distance, symptom and quality of life scores, serum iron indices, spirometry, echocardiographic measures, and exacerbation frequency.,SpO2 was unchanged 1 week after FCM administration (difference between groups 0.8%, 95% CI −0.2% to 1.7%).,However, in secondary analyses, exercise capacity increased significantly after FCM administration, compared with placebo, with a mean difference in 6 min walk distance of 12.6 m (95% CI 1.6 to 23.5 m).,Improvements of ≥40 m were observed in 29.2% of iron-treated and 0% of placebo-treated participants after 1 week (p=0.009).,Modified MRC Dyspnoea Scale score was also significantly lower after FCM, and fewer participants reported scores ≥2 in the FCM group, compared with placebo (33.3% vs 66.7%, p=0.02).,No significant differences were observed in other secondary endpoints.,Adverse event rates were similar between groups, except for hypophosphataemia, which occurred more frequently after FCM (91.7% vs 8.3%, p<0.001).,FCM did not improve oxygenation over 8 weeks in patients with COPD.,However, this treatment was well tolerated and produced improvements in exercise capacity and functional limitation caused by breathlessness.,These effects on secondary endpoints require confirmation in future studies.,ISRCTN09143837. | Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and an accumulation of apoptotic epithelial cells in the bronchioles of the mice.,Normally, apoptotic cells are rapidly cleared by macrophage efferocytosis, limiting any secondary necrosis and inflammation.,We therefore hypothesized that zinc deficiency is not only pro-apoptotic but also impairs macrophage efferocytosis.,Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD), cigarette-smoking and other lung inflammatory diseases.,We now show that zinc is a factor in impaired macrophage efferocytosis in COPD.,Concentrations of zinc were significantly reduced in the supernatant of bronchoalveolar lavage fluid of patients with COPD who were current smokers, compared to healthy controls, smokers or COPD patients not actively smoking.,Lavage zinc was positively correlated with AM efferocytosis and there was decreased efferocytosis in macrophages depleted of Zn in vitro by treatment with the membrane-permeable zinc chelator TPEN.,Organ and cell Zn homeostasis are mediated by two families of membrane ZIP and ZnT proteins.,Macrophages of mice null for ZIP1 had significantly lower intracellular zinc and efferocytosis capability, suggesting ZIP1 may play an important role.,We investigated further using the human THP-1 derived macrophage cell line, with and without zinc chelation by TPEN to mimic zinc deficiency.,There was no change in ZIP1 mRNA levels by TPEN but a significant 3-fold increase in expression of another influx transporter ZIP2, consistent with a role for ZIP2 in maintaining macrophage Zn levels.,Both ZIP1 and ZIP2 proteins were localized to the plasma membrane and cytoplasm in normal human lung alveolar macrophages.,We propose that zinc homeostasis in macrophages involves the coordinated action of ZIP1 and ZIP2 transporters responding differently to zinc deficiency signals and that these play important roles in macrophage efferocytosis. | 1 |
Chronic obstructive pulmonary disease (COPD), lung cancer, and tuberculosis are three leading causes of death in China, where prevalences of smoking and solid-fuel use are also high.,We aimed to predict the effects of risk-factor trends on COPD, lung cancer, and tuberculosis.,We used representative data sources to estimate past trends in smoking and household solid-fuel use and to construct a range of future scenarios.,We obtained the aetiological effects of risk factors on diseases from meta-analyses of epidemiological studies and from large studies in China.,We modelled future COPD and lung cancer mortality and tuberculosis incidence, taking into account the accumulation of hazardous effects of risk factors on COPD and lung cancer over time, and dependency of the risk of tuberculosis infection on the prevalence of disease.,We quantified the sensitivity of our results to methods and data choices.,If smoking and solid-fuel use remain at current levels between 2003 and 2033, 65 million deaths from COPD and 18 million deaths from lung cancer are predicted in China; 82% of COPD deaths and 75% of lung cancer deaths will be attributable to the combined effects of smoking and solid-fuel use.,Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 million deaths from COPD and 6·3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6-31% (COPD) and 8-26% (lung cancer).,Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence in 2033 by 14-52% if 80% DOTS coverage is sustained, 27-62% if 50% coverage is sustained, or 33-71% if 20% coverage is sustained.,Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China.,International Union Against Tuberculosis and Lung Disease. | Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ. | 1 |
Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties.,Vitamin D deficiency is a common problem in patients with COPD.,Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients.,However, subgroup analyses suggested protective effects in vitamin D deficient patients.,Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients.,We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study.,The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L).,Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year.,Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period.,Visits will be performed at baseline, at 6 months and at 12 months after randomisation.,Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure.,Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken.,The primary outcome will be exacerbation rate.,This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients.,Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation.,Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied.,Finally, the effects on physical functioning will be examined.,This trial is registered in ClinicalTrials.gov, ID number NCT02122627.,Date of Registration April 2014. | Chronic obstructive pulmonary disease (COPD) is characterized by excessive inflammation and disturbed bacterial clearance in the airways.,Although cigarette smoke (CS) exposure poses a major risk, vitamin D deficiency could potentially contribute to COPD progression.,Many in vitro studies demonstrate important anti-inflammatory and antibacterial effects of vitamin D, but a direct contribution of vitamin D deficiency to COPD onset and disease progression has not been explored.,In the current study, we used a murine experimental model to investigate the combined effect of vitamin D deficiency and CS exposure on the development of COPD-like characteristics.,Therefore, vitamin D deficient or control mice were exposed to CS or ambient air for a period of 6 (subacute) or 12 weeks (chronic).,Besides lung function and structure measurements, we performed an in depth analysis of the size and composition of the cellular infiltrate in the airways and lung parenchyma and tested the ex vivo phagocytic and oxidative burst capacity of alveolar macrophages.,Vitamin D deficient mice exhibited an accelerated lung function decline following CS exposure compared to control mice.,Furthermore, early signs of emphysema were only observed in CS-exposed vitamin D deficient mice, which was accompanied by elevated levels of MMP-12 in the lung.,Vitamin D deficient mice showed exacerbated infiltration of inflammatory cells in the airways and lung parenchyma after both subacute and chronic CS exposure compared to control mice.,Furthermore, elevated levels of typical proinflammatory cytokines and chemokines could be detected in the bronchoalveolar lavage fluid (KC and TNF-α) and lung tissue (IP-10, MCP-1, IL-12) of CS-exposed vitamin D deficient mice compared to control mice.,Finally, although CS greatly impaired the ex vivo phagocytic and oxidative burst function of alveolar macrophages, vitamin D deficient mice did not feature an additional defect.,Our data demonstrate that vitamin D deficiency both accelerates and aggravates the development of characteristic disease features of COPD.,As vitamin D deficiency is highly prevalent, large randomized trials exploring effects of vitamin D supplementation on lung function decline and COPD onset are needed.,The online version of this article (doi:10.1186/s12931-015-0271-x) contains supplementary material, which is available to authorized users. | 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. | Dysregulated lipid metabolism plays crucial roles in various diseases, including diabetes mellitus, cancer, and neurodegeneration.,Recent studies suggest that alterations in major lipid metabolic pathways contribute to pathogenesis of lung diseases, including chronic obstructive pulmonary disease (COPD).,These changes allow lung tissue to meet the energy needs and trigger anabolic pathways that initiate the synthesis of active molecules directly involved in the inflammation.,In this review, we summarize the changes of catabolism and anabolism of lipids, lipid molecules including lipid mediators, lipid synthesis transcription factors, cholesterol, and phospholipids, and how those lipid molecules participate in the initiation and resolution of inflammation in COPD. | 1 |
Pulmonary hypertension (PH) is a frequent complication in patients with COPD.,To determine if, in patients with COPD, the presence of PH decreases exercise tolerance.,We included studies that analysed exercise tolerance using a cardiopulmonary exercise test (CPET) in patients with COPD with PH (COPD-PH) and without PH (COPD-nonPH).,Two independent reviewers analysed the studies, extracted the data and assessed the quality of the evidence.,Of the 4915 articles initially identified, seven reported 257 patients with COPD-PH and 404 patients with COPD-nonPH.,The COPD-PH group showed differences in peak oxygen consumption (V′O2peak), −3.09 mL·kg−1·min−1 (95% CI −4.74 to −1.43, p=0.0003); maximum workload (Wmax), −20.5 W (95% CI −34.4 to −6.5, p=0.004); and oxygen pulse (O2 pulse), −1.24 mL·beat−1 (95% CI −2.40 to −0.09, p=0.03), in comparison to the group with COPD-nonPH.,If we excluded studies with lung transplant candidates, the sensitivity analyses showed even bigger differences: V′O2, −4.26 mL·min−1·kg−1 (95% CI −5.50 to −3.02 mL·kg−1·min−1, p<0.00001); Wmax, −26.6 W (95% CI −32.1 to −21.1 W, p<0.00001); and O2 pulse, −2.04 mL·beat−1 (95% CI −2.92 to −1.15 mL·beat−1, p<0.0001).,Exercise tolerance was significantly lower in patients with COPD-PH than in patients with COPD-nonPH, particularly in nontransplant candidates.,The V′O2peak, Wmax and O2 pulse values were significantly lower in patients with COPD-PH than in patients with COPD-nonPH, particularly in nontransplant candidateshttps://bit.ly/3s5dtJ9 | A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression.,Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time.,33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects.,A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months.,In COPD, compared to no-COPD, we found a faster lung function decline at follow-up.,Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced.,Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD.,The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001).,Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = − 0.587, p < 0.01) and with baseline smoking history (r = − 0.39, p < 0.03).,No correlation was found between ΔFEV1, ΔCRP and ΔWBCs.,By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance.,Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression.,Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease. | 1 |
Autophagy plays essential roles in the development of COPD.,We aim to identify and validate the potential autophagy-related genes of COPD through bioinformatics analysis and experiment validation.,The mRNA expression profile dataset GSE38974 was obtained from GEO database.,The potential differentially expressed autophagy-related genes of COPD were screened by R software.,Then, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed autophagy-related genes.,Finally, RNA expression of top five differentially expressed autophagy-related genes was validated in blood samples from COPD patients and healthy controls by qRT-PCR.,A total of 40 differentially expressed autophagy-related genes (14 up-regulated genes and 26 down-regulated genes) were identified between 23 COPD patients and 9 healthy controls.,The PPI results demonstrated that these autophagy-related genes interacted with each other.,The GO and KEGG enrichment analysis of differentially expressed autophagy-related genes indicated several enriched terms related to autophagy and mitophagy.,The results of qRT-PCR showed that the expression levels of HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 in COPD patients and healthy controls were consistent with the bioinformatics analysis results from mRNA microarray.,We identified 40 potential autophagy-related genes of COPD through bioinformatics analysis.,HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 may affect the development of COPD by regulating autophagy.,These results may expand our understanding of COPD and might be useful in the treatment of COPD. | 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. | 1 |
The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD) patients has been well documented, but less is known about the role played by the large airways.,Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients.,The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM) area and the extracellular matrix (ECM) protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes.,Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin.,ECM protein deposition was measured at both subepithelial, and ASM layers.,The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects.,An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity.,A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls.,These findings indicate that airway remodeling also affects the large airways in COPD patients who have greater deposition of ECM proteins in the subepithelial layer and a larger smooth muscle area than control smoker subjects.,These changes may contribute to chronic airflow obstruction in COPD patients. | During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype.,One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment.,Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12).,Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels.,The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p < 0.001) and (p < 0.01), respectively.,Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p < 0.01).,The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients.,ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients.,Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity.,This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD. | 1 |
There is evidence that bacterial colonisation in chronic obstructive pulmonary disease (COPD) is associated with increased neutrophilic airway inflammation.,This study tested the hypothesis that different bacterial phyla and species cause different inflammatory profiles in COPD patients.,Sputum was analysed by quantitative polymerase chain reaction (qPCR) to quantify bacterial load and 16S rRNA gene sequencing to identify taxonomic composition.,Sputum differential cell counts (DCC) and blood DCC were obtained at baseline and 6 months.,Patients were categorised into five groups based on bacterial load defined by genome copies/ml of ≥ 1 × 104, no colonisation and colonisation by Haemophilus influenzae (H. influenzae), Moraxella catarrhalis (M. catarrhalis), Streptococcus pneumoniae (S. pneumoniae), or > 1 potentially pathogenic microorganism (PPM).,We observed an increase in sputum neutrophil (%), blood neutrophil (%) and neutrophil-lymphocyte ratio (NLR) in patients colonised with H. influenzae (82.6, 67.1, and 3.29 respectively) compared to those without PPM colonisation at baseline (69.5, 63.51 and 2.56 respectively) (p < 0.05 for all analyses), with similar findings at 6 months.,The bacterial load of H. influenzae and Haemophilus determined by qPCR and 16s rRNA gene sequencing respectively, and sputum neutrophil % were positively correlated between baseline and 6 months visits (p < 0.0001, 0.0150 and 0.0002 with r = 0.53, 0.33 and 0.44 respectively).,These results demonstrate a subgroup of COPD patients with persistent H. influenzae colonisation that is associated with increased airway and systemic neutrophilic airway inflammation, and less eosinophilic airway inflammation. | Macrophages have been implicated in the pathogenesis of COPD.,M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties.,We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD.,Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.,114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months).,BAL was collected from 71 patients.,CD163+ macrophages were quantified in BAL and sputum cytospins.,Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.,Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×104/ml, p = 0.001 respectively).,The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001).,BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003).,No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.,Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide.,Identifying COPD-associated DNA methylation marks in African-Americans may contribute to our understanding of racial disparities in COPD susceptibility.,We determined differentially methylated genes and co-methylation network modules associated with COPD in African-Americans recruited during exacerbations of COPD and smoking controls from the Pennsylvania Study of Chronic Obstructive Pulmonary Exacerbations (PA-SCOPE) cohort.,We assessed DNA methylation from whole blood samples in 362 African-American smokers in the PA-SCOPE cohort using the Illumina Infinium HumanMethylation27 BeadChip Array.,Final analysis included 19302 CpG probes annotated to the nearest gene transcript after quality control.,We tested methylation associations with COPD case-control status using mixed linear models.,Weighted gene comethylation networks were constructed using weighted gene coexpression network analysis (WGCNA) and network modules were analyzed for association with COPD.,There were five differentially methylated CpG probes significantly associated with COPD among African-Americans at an FDR less than 5 %, and seven additional probes that approached significance at an FDR less than 10 %.,The top ranked gene association was MAML1, which has been shown to affect NOTCH-dependent angiogenesis in murine lung.,Network modeling yielded the “yellow” and “blue” comethylation modules which were significantly associated with COPD (p-value 4 × 10-10 and 4 × 10-9, respectively).,The yellow module was enriched for gene sets related to inflammatory pathways known to be relevant to COPD.,The blue module contained the top ranked genes in the concurrent differential methylation analysis (FXYD1/LGI4, gene significance p-value 1.2 × 10-26; MAML1, p-value 2.0 × 10-26; CD72, p-value 2.1 × 10-25; and LPO, p-value 7.2 × 10-25), and was significantly associated with lung development processes in Gene Ontology gene-set enrichment analysis.,We identified 12 differentially methylated CpG sites associated with COPD that mapped to biologically plausible genes.,Network module comethylation patterns have identified candidate genes that may be contributing to racial differences in COPD susceptibility and severity.,COPD-associated comethylation modules contained genes previously associated with lung disease and inflammation and recapitulated known COPD-associated genes.,The genes implicated by differential methylation and WGCNA analysis may provide mechanistic targets contributing to COPD susceptibility, exacerbations, and outcomes among African-Americans.,Trial Registration: NCT00774176, Registry: ClinicalTrials.gov, URL: www.clinicaltrials.gov, Date of Enrollment of First Participant: June 2004, Date Registered: 04 January 2008 (retrospectively registered).,The online version of this article (doi:10.1186/s12931-016-0459-8) contains supplementary material, which is available to authorized users. | To investigate the gene-expression profile of chronic obstructive pulmonary disease (COPD) patients and explore the possible therapeutic targets.,The microarray raw dataset GSE29133, including three COPD samples and three normal samples, was obtained from Gene Expression Omnibus.,After data preprocessing with the Affy package, Student’s t-test was employed to identify the differentially expressed genes (DEGs).,The up- and downregulated DEGs were then pooled for gene-ontology and pathway-enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID).,The upstream regulatory elements of these DEGs were also explored by using Whole-Genome rVISTA.,Furthermore, we constructed a protein-protein interaction (PPI) network for DEGs.,The surfactant protein D (SP-D) serum level and HLA-A gene frequency in COPD patients and healthy controls were also measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction, respectively.,A total of 39 up- and 15 downregulated DEGs were screened.,Most of the upregulated genes were involved in the immune response process, while the downregulated genes were involved in the steroid metabolic process.,Moreover, we also found that HLA-A has the highest degree in the PPI network.,The SP-D serum level and HLA-A gene frequency in COPD patients were significantly higher than those in healthy controls (13.62±2.09 ng/mL vs 10.28±2.86 ng/mL; 62.5% vs 12.5%; P<0.05).,Our results may help further the understanding of the mechanisms of COPD.,The identified DEGs, especially HLA-A, may serve as diagnosis markers for COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status. | 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 |
The role of interleukins in the severity and clinical profile of chronic obstructive pulmonary disease (COPD) is not known, but evidence supports the contribution of systemic inflammation to disease pathophysiology.,This study evaluated the relationship of serum biomarkers to the severity and clinical parameters of COPD.,Serum levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in 50 patients with stable COPD and in 16 controls.,The levels of these biomarkers were compared with parameters of severity, such as the grading of flow obstruction using the recommendations of the Global initiative for chronic Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea, exercise capacity (health index) index, the number of exacerbations within the last year, and peripheral oxygen saturation after the six-minute walk test, and with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the number of associated comorbidities, and the smoking burden.,COPD patients exhibited higher levels of IL-6 and IL-8 compared to the control group.,Higher levels of IL-6 occurred in COPD groups with body mass index <21 kg/m2, with more than two exacerbations in the past year, with a higher smoking burden, and with bronchitis.,The increase in serum IL-8 was found only in the group with the highest number of exacerbations within the previous year.,Increased IL-6 was mainly associated with smoking burden, in patients who had smoked for more than 30 pack-years and exhibited a bronchitis phenotype.,No direct association was observed for both IL-6 and IL-8 blood levels with the severity of COPD in ex-smokers. | There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD.,We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3-) cells and NKT-like (CD56+CD3+) cells.,Peripheral blood mononuclear cells (PBMCs) were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry.,Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies.,The proportion of peripheral blood NKT-like (CD56+CD3+) cells in smokers with COPD (COPD subjects) was significantly lower (0.6%) than in healthy smokers (smokers) (2.8%, p < 0.001) and non-smoking healthy participants (HNS) (3.3%, p < 0.001).,NK (CD56+CD3-) cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p < 0.001) as were NKT-like (CD56+CD3+) cells (16.7% vs 52.4% specific lysis, p < 0.001).,Both cell types had lower proportions expressing both perforin and granzyme B.,Blocking the action of perforin and granzyme B reduced the cytotoxic activity of NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells from smokers and HNS.,In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells in COPD subjects are reduced and that their cytotoxic effector function is defective. | 1 |
Chronic bronchitis and previous exacerbations are both well-known risk factors for new exacerbations, impaired health-related quality of life, and increased mortality in COPD.,The aim of the study was to characterize the phenotype of concurrent chronic bronchitis and frequent exacerbation in severe COPD.,Information on patient characteristics, comorbidity, and exacerbations from the previous year (total number and number requiring hospitalization) was collected from 373 patients with stage III and IV COPD attending 27 secondary care respiratory units in Sweden.,Logistic regression used chronic bronchitis and frequent exacerbations (≥2 exacerbations or ≥1 hospitalized exacerbations in the previous year) as response variables.,Stratification and interaction analyses examined effect modification by sex.,Chronic bronchitis was associated with current smoking (adjusted odds ratio [OR] [95% CI], 2.75 [1.54-4.91]; P=0.001), frequent exacerbations (OR [95% CI], 1.93 [1.24-3.01]; P=0.004), and musculoskeletal symptoms (OR [95% CI], 1.74 [1.05-2.86]; P=0.031), while frequent exacerbations were associated with lung function (forced expiratory volume in 1 second as a percentage of predicted value [FEV1% pred]) (OR [95% CI] 0.96 [0.94-0.98]; P=0.001) and chronic bronchitis (OR [95% CI] 1.73 [1.11-2.68]; P=0.015).,The phenotype with both chronic bronchitis and frequent exacerbations was associated with FEV1% pred (OR [95% CI] 0.95 [0.92-0.98]; P=0.002) and musculoskeletal symptoms (OR [95% CI] 2.55 [1.31-4.99]; P=0.006).,The association of smoking with the phenotype of chronic bronchitis and exacerbations was stronger in women than in men (interaction, P=0.040).,Musculoskeletal symptoms and low lung function are associated with the phenotype of combined chronic bronchitis and frequent exacerbations in severe COPD.,In women, current smoking is of specific importance for this phenotype.,This should be considered in clinical COPD care. | Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).,There are differences in serum biomarker levels between women and men with COPD.,Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.,We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction.,We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life.,We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD.,The plasma biomarkers level explored were similar in men and women without COPD.,In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men.,Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels.,There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes.,In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables.,Further studies should confirm our findings. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation.,Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes.,Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.,This post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies.,Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study.,Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.,Exacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150-300 cells/μL and 20.1% with > 300 cells/μL.,The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count.,When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150-300 cells/μL and 0.44 for > 300 cells/μL respectively).,A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively.,For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150-300 cells/μL) and 1.07 (> 300 cells/μL).,Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).,We found no clinically important relationship between baseline blood eosinophil count and exacerbation rate.,Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.,ClinicalTrials.gov Identifiers: NCT00168844, NCT00168831, NCT00387088, NCT00782210, NCT00782509, NCT00793624, NCT00796653, NCT01431274, NCT01431287, NCT02296138 and NCT00975195. | It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | 1 |
Current pharmacological treatments for chronic obstructive pulmonary disease (COPD) are mostly limited to inhaled bronchodilators and corticosteroids.,Azithromycin can contribute to exacerbation prevention.,Roflumilast, a phosphodiesterase (PDE) 4 inhibitor administered orally, also prevents exacerbations in selected patients with chronic bronchitis, recurrent exacerbations, severe airflow limitation and concomitant therapy with long-acting inhaled bronchodilators.,This outcome likely results from anti-inflammatory effects since PDE4 is expressed by all inflammatory cell types involved in COPD.,The use of this agent is, however, limited by side-effects, particularly nausea and diarrhea.,To address remaining unmet needs and enrich therapeutic options for patients with COPD, inhaled dual PDE3/4 inhibitors have been developed, with the aim of enhancing bronchodilation through PDE3 inhibition and modulating inflammation and mucus production though PDE4 inhibition, thus producing a potentially synergistic effect on airway calibre.,Experimental preclinical data confirmed these effects in vitro and in animal models.,At present, RPL554/ensifentrine is the only agent of this family in clinical development.,It decreases sputum markers of both neutrophilic and eosinophilic inflammation in patients with COPD.,Clinical Phase II trials confirmed its bronchodilator effect and demonstrated clinically meaningful symptom relief and quality of life improvements in these patients.,The safety profile appears satisfactory, with less effects on heart rate and blood pressure than salbutamol and no other side effect.,Altogether, these data suggest that ensifentrine could have a role in COPD management, especially in addition to inhaled long-acting bronchodilators with or without corticosteroids since experimental studies suggest potentiation of ensifentrine effects by these agents.,However, results from ongoing and future Phase III studies are needed to confirm both beneficial effects and favourable safety profile on a larger scale and assess other outcomes including exacerbations, lung function decline, comorbidities and mortality. | This study evaluated the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ (PI3Kδ) inhibitor, in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD).,In this double-blind, placebo-controlled study, 126 patients (40-80 years with a post-bronchodilator forced expiratory volume in 1 sec (FEV1) ≤80% of predicted (previously documented)) were randomized 1:1 to once daily inhaled nemiralisib (1 mg) or placebo for 84 days, added to standard of care.,The primary endpoint was specific imaging airway volume (siVaw) after 28 treatment days and was analyzed using a Bayesian repeated measures model (clintrials.gov: NCT02294734).,A total of 126 patients were randomized to treatment; 55 on active treatment and 49 on placebo completed the study.,When comparing nemiralisib and placebo-treated patients, an 18% placebo-corrected increase from baseline in distal siVaw (95% credible intervals (Cr I) (−1%, 42%)) was observed on Day 28.,The probability that the true treatment ratio was >0% (Pr(θ>0)) was 96%, suggestive of a real treatment effect.,Improvements were observed across all lung lobes.,Patients treated with nemiralisib experienced a 107.3 mL improvement in posterior median FEV1 (change from baseline, 95% Cr I (−2.1, 215.5)) at day 84, compared with placebo.,Adverse events were reported by 41 patients on placebo and 49 on nemiralisib, the most common being post-inhalation cough on nemiralisib (35%) vs placebo (3%).,These data show that addition of nemiralisib to usual care delivers more effective recovery from an acute exacerbation and improves lung function parameters including siVaw and FEV1.,Although post-inhalation cough was identified, nemiralisib was otherwise well tolerated, providing a promising novel therapy for this acutely ill patient group. | 1 |
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) aggravates the overall severity in COPD patients, resulting in severe morbidity and mortality.,However, there are no objective biomarkers currently available to predict the development of AECOPD.,Several studies have indicated that galectin-3 (Gal-3) is involved in diseases characterized by excessive inflammatory response and fibrosis.,The objective of this study was to examine the dynamic changes of Gal-3 in acute exacerbation and convalescence phases of COPD.,Serum levels of Gal-3, high sensitivity C-reactive protein (hsCRP), and prohormone of brain natriuretic peptide (pro-BNP) were determined using multiplex enzyme-linked immunosorbent assay kits.,Serum levels of Gal-3 in 44 patients with COPD were further analyzed and correlated with the parameters of lung function and the biomarkers of systemic inflammation.,The mean level of serum Gal-3 was significantly higher in acute exacerbation of COPD compared with the level in COPD convalescence phase (32.10±9.83 versus 29.02±8.68 ng/mL, p<0.01).,Serum levels of Gal-3 positively correlated with hsCRP (r=0.354, p=0.018 for total patients) and pro-BNP (r=0.319, p=0.035 for total patients) in AECOPD.,In addition, the level of Gal-3 was the highest in the current smoker group, and the lowest in the never-smoker group in either the acute exacerbation phase (33.91±3.55 versus 29.12±11.73 ng/mL, p=0.036) or the convalescence phase (30.94±3.40 versus 27.76±9.68 ng/mL, p=0.045) of COPD.,Our results indicated that serum Gal-3 is increased in AECOPD patients, which is also positively associated with systemic inflammation and smoking in patients with COPD, suggesting that Gal-3 might be a valuable biomarker for AECOPD. | Numerous studies have investigated the association between eosinophilia and clinical outcome of patients with chronic obstructive pulmonary disease (COPD) but the evidence is conflicting.,We conducted a pooled analysis of outcome measures comparing eosinophilic and non-eosinophilic COPD patients.,We searched articles indexed in four databases using Medical Subject Heading or Title and Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from inception to December 2016.,Observational studies and randomized controlled trials with parallel groups comparing COPD patients with and without eosinophilia were included.,Comparing to the non-eosinophilic group, those with eosinophilic COPD had a similar risk for exacerbation in 12 months [Odds ratio = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55] and in-hospital mortality [OR = 0.52, 95% CI 0.25-1.07].,Eosinophilia was associated with reduced length of hospital stay (P = 0.04).,Subsequent to therapeutic interventions, eosinophilic outpatients performed better in pulmonary function tests [Mean Difference = 1.64, 95% CI 0.05-3.23, P < 0.001].,Inclusion of hospitalized patients nullified the effect.,Improvement of quality of life was observed in eosinophilic subjects [Standardized Mean Difference = 1.83, 95% CI 0.02-3.64, P = 0.05], independent of hospitalization status.,In conclusion, blood eosinophilia may be predictive of favorable response to steroidal and bronchodilator therapies in patients with stable COPD. | 1 |
Self-Management Support (SMS), refers to the actions taken by individuals to recognise and manage their own health.,It is increasingly recognised that individuals with chronic obstructive pulmonary disease (COPD) require additional support with their Self-management.,Emerging evidence suggests that the use of a social network intervention can improve health outcomes and increase quality of life.,In order to understand the potential benefits of SMS in COPD, the GENIE (Generating Engagement in Network Support) SMS tool was implemented and evaluated in a COPD primary care context.,The GENIE intervention is a social networking tool that consists of 3 parts; a concentric circle modelling to map existing social networks; a questions sections to elicit preferences for activities; a map of selected resources is then produced, aligned with the user’s interests and suggestions for connections to existing network members and to new resources.,A pilot, parallel, single blind, block randomised controlled trial.,Patients with COPD ranging from mild-very severe were recruited.,Participants provided written consent and were then randomised to either the intervention or usual care.,The primary aim was to understand the clinical benefit through the analysis of health status, symptom burden and quality of life.,The secondary outcome measure was health utilisation.,NHS cost differences were reported between groups using the GENIE intervention over usual care.,The GENIE pilot results demonstrate maintenance in health status and clinical symptoms with a decrease in anxiety.,An overall increase in quality of life was observed, these findings did not reach significance.,A cost reduction was demonstrated in inpatient stay with no difference in primary care costs.,Overall a cost reduction in NHS service utilisation was indicated in the intervention group.,This pilot study indicated that using a social network intervention can encourage the development of new social connections and extend existing support networks for COPD patients.,Increasing network support in this population is of benefit to both patients and NHS providers in terms of cost reductions and enhancing wellbeing.,This broadens the understanding of possible new approaches to SMS in community COPD patients, which could now be investigated in a larger population over a longer period.,Clinical Trials.gov PRS National Library of Medicine.,Protocol ID number: 19175, Clinical Trial ID: NCT02935452. | Understanding the breadth of patients’ support needs is important for the delivery of person-centered care, particularly in progressive long-term conditions such as chronic obstructive pulmonary disease (COPD).,Existing reviews identify important aspects of managing life with COPD with which patients may need support (support needs); however, none of these comprehensively outlines the full range of support needs that patients can experience.,We therefore sought to systematically determine the full range of support needs for patients with COPD to inform development of an evidence-based tool to enable person-centered care.,We conducted a systematic search and narrative review of the literature.,Medline (Ovid), EMBASE, PsycINFO, Cochrane Library, and CINAHL were systematically searched for papers which included data addressing key aspects of support need, as identified by patients with COPD.,Relevant data were extracted, and a narrative analysis was conducted.,Thirty-one papers were included in the review, and the following 13 domains (broad areas) of support need were identified: 1) understanding COPD, 2) managing symptoms and medication, 3) healthy lifestyle, 4) managing feelings and worries, 5) living positively with COPD, 6) thinking about the future, 7) anxiety and depression, 8) practical support, 9) finance work and housing, 10) families and close relationships, 11) social and recreational life, 12) independence, and 13) navigating services.,These 13 domains of support need were mapped to three of the four overarching categories of need commonly used in relevant national strategy documents (ie, physical, psychological, and social); however, support needs related to the fourth category (spiritual) were notably absent.,This review systematically identifies the comprehensive set of domains of support need for patients with COPD.,The findings provide the evidence base for a tool to help patients identify and express their support needs, which underpins a proposed intervention to enable the delivery of person-centered care: the Support Needs Approach for Patients (SNAP). | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung.,Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways.,Bacterial variety diminishes with increasing COPD severity.,Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections.,In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD.,In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial-viral infections and related immune response in COPD phenotypes need to be better clarified.,Our paper would address these points that we consider of great importance for the clinical management of COPD. | 1 |
Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs.,Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases.,Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells.,These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease.,Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1.,MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1.,Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16INK4a, p21Waf1, and p27Kip1), thereby restoring cellular growth by allowing progression through the cell cycle.,MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6).,Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.-Baker, J.,R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P.,S., Donnelly, L.,E., Ito, K., Barnes, P.,J.,MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. | Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis.,In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release.,Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined.,The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD.,Primary adult lung fibroblasts were isolated from patients with or without COPD.,MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without inflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α.,MiR-503 expression was decreased in COPD lung fibroblasts.,The expression of miR-503 was positively correlated with %FVC, %FEV1, and %DLco as well as IL-6, -8, PGE2, HGF, KGF, and VEGF in the absence or presence of IL-1ß/TNF-α.,In addition, IL-8 and VEGF release from COPD lung fibroblasts were increased compared to those from control.,Exogenous miR-503 inhibited VEGF release from primary adult and fetal lung fibroblasts but not IL-8 release.,As expected, COPD fibroblasts proliferated more slowly than control fibroblasts.,MiR-503 did not affect proliferation of either control or COPD lung fibroblasts.,MiR-503 inhibition of VEGF protein production and mRNA was mediated by direct binding to the 3’ untranslated region of VEGF mRNA.,Endogenous miR-503 was differently regulated by exogenous stimulants associated with COPD pathogenesis, including IL-1ß/TNF-α, TGF-ß1 and PGE2.,Endogenous miR-503 inhibition augmented VEGF release by IL-1ß/TNF-α and TGF-ß1 but not by PGE2, demonstrating selectivity of miR-503 regulation of VEGF.,In conclusions, reduced miR-503 augments VEGF release from lung fibroblasts from patients with COPD.,Since VEGF contributes to disturbed vasculature in COPD, altered miR-503 production might play a role in modulating fibroblast-mediated vascular homeostasis in COPD. | 1 |
The ability of a long-acting muscarinic antagonist (LAMA) and long-acting beta 2 agonists (LABAs; long-acting bronchodilators, LABDs) with or without inhaled corticosteroids (ICSs) to reduce early readmission in hospitalized patients with COPD is unknown.,We studied a 5% sample of Medicare beneficiaries enrolled in Medicare parts A, B and D and hospitalized for COPD in 2011.,We examined prescriptions filled for LABDs with or without ICSs (LABDs±ICSs) within 90 days prior to and 30 days after hospitalization.,Primary outcome was the 30-day readmission rate between “users” and “nonusers” of LABDs±ICSs.,Propensity score matching and sensitivity analysis were performed by limiting analysis to patients hospitalized for acute exacerbation of COPD (AECOPD).,Among 6,066 patients hospitalized for COPD, 3,747 (61.8%) used LABDs±ICSs during the specified period.,The “user” and “nonuser” groups had similar rates of all-cause emergency room (ER) visits and readmissions within 30 days of discharge date (22.4% vs 20.7%, P-value 0.11; 18.0% vs 17.8%, P-value 0.85, respectively).,However, the “users” had higher rates of COPD-related ER visits (5.3% vs 3.4%, P-value 0.0006), higher adjusted odds ratio (aOR) 1.47 (95% CI, 1.11-1.93) and readmission (7.8% vs 5.0%, P-value <0.0001 and aOR 1.48 [95% CI, 1.18-1.86]) than “nonusers”.,After propensity score matching, the aOR of COPD-related ER visits was 1.45 (95% CI, 1.07-1.96) and that of readmission was 1.34 (95% CI, 1.04-1.73).,The results were similar when restricted to patients hospitalized for AECOPD.,Use of LABDs±ICSs did not reduce 30-day readmissions in patients hospitalized for COPD. | The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system. | 1 |
COPD is concomitantly present in ~30% of patients with heart failure.,Here, we investigated the pulmonary function test parameters for left ventricular (LV) diastolic dysfunction and the relationship between pulmonary function and LV diastolic function in patients with COPD.,Overall, 822 patients who underwent a pulmonary function test and echocardiography simultaneously between January 2011 and December 2012 were evaluated.,Finally, 115 patients with COPD and 115 age- and sex-matched control patients with an LV ejection fraction of ≥50% were enrolled.,The mean age of the patients was 74.4±10.4 years, and 72.3% were men.,No significant differences were found between the two groups regarding comorbidities, such as hypertension, diabetes mellitus, and anemia.,The index of LV diastolic function (E/e′) and the proportion of patients with high E/e′ (defined as E/e′ ≥15) were significantly higher in patients with COPD than in control patients (10.5% vs 9.1%, P=0.009; 11.3% vs 4.3%, P=0.046).,E/e′ was significantly correlated with the residual volume/total lung capacity ratio.,Univariate and multivariate analyses revealed severe COPD (Global Initiative for Chronic Obstructive Lung Disease III or IV) to be a significant predictive factor for high E/e′ (odds ratio [OR] 5.81, 95% confidence interval [CI] 2.13-15.89, P=0.001 and OR 6.00, 95% CI 2.08-17.35, P=0.001, respectively).,Our data suggest that LV diastolic dysfunction as a complication of COPD may be associated with mechanical exclusion of the heart by pulmonary overinflation. | The prevalence of electrocardiographic and echocardiographic abnormalities in chronic obstructive pulmonary disease according to disease severity has not yet been established.,The aim of this study was to assess the prevalence of electrocardiographic and echocardiographic abnormalities in chronic obstructive pulmonary disease patients according to disease severity.,The study included 25 mild/moderate chronic obstructive pulmonary disease patients and 25 severe/very severe chronic obstructive pulmonary disease patients.,All participants underwent clinical evaluation, spirometry and electrocardiography/echocardiography.,Electrocardiography and echocardiography showed Q-wave alterations and segmental contractility in five (10%) patients.,The most frequent echocardiographic finding was mild left diastolic dysfunction (88%), independent of chronic obstructive pulmonary disease stage.,The proportion of right ventricular overload (p<0.05) and blockage of the anterosuperior division of the left bundle branch were higher in patients with greater obstruction.,In an echocardiographic analysis, mild/moderate chronic obstructive pulmonary disease patients showed more abnormalities in segmental contractility (p<0.05), whereas severe/very severe chronic obstructive pulmonary disease patients showed a higher prevalence of right ventricular overload (p<0.05), increased right cardiac chamber (p<0.05) and higher values of E-wave deceleration time (p<0.05).,Age, sex, systemic arterial hypertension, C-reactive protein and disease were included as independent variables in a multiple linear regression; only disease severity was predictive of the E-wave deceleration time [r2 = 0.26, p = 0.01].,Chronic obstructive pulmonary disease patients have a high prevalence of left ventricular diastolic dysfunction, which is associated with disease severity.,Because of this association, it is important to exclude decompensated heart failure during chronic obstructive pulmonary disease exacerbation. | 1 |
We previously reported satisfactory results with the Karakoca resector balloon in 10 patients with stage IV chronic obstructive pulmonary disease (COPD) who did not respond to medical treatment.,In this article, we present the outcomes of the Karakoca resector balloon dilatation and curettage technique in a larger case series (n = 188).,A total of 188 COPD patients [mean age (SD): 69.2 (8.0) years; 46 females] classified as stage III to IV by the Global Initiative for Obstructive Lung Disease criteria underwent balloon desobstruction for segmental and subsegmental bronchi by therapeutic bronchoscopy.,None of the patients could have achieved symptom relief even under high-dose inhaled bronchodilators and corticosteroids, oral corticosteroids, or oxygen and noninvasive mechanical ventilation therapy before the intervention.,Forced expiratory volume in 1 s (FEV1) and oxygen saturation (SpO2) were measured, and modified Borg dyspnea scale (MBS) scores were determined before and 1 week and 1 month after the intervention.,All patients were active smokers and 80% had concomitant chronic diseases.,After the intervention, there was a notable reduction in the oxygen need of the patients.,Comparison of lung function tests 1 week after the procedure with results before the procedure showed significant improvements in FEV1, MBS, and SpO2 levels (P < 0.001 for each), and the improvements were maintained for the entire postprocedural month (P < 0.001 for each).,Except for 4 males, all patients were free of symptoms.,These results confirmed our early observations that balloon dilatation and curettage is a safe and successful technique for medical treatment-resistant COPD. | Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation.,The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure.,This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1] 30%-60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators.,The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year.,Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life.,Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up.,A total of 15 patients (47% male, age 63.2±4.0 years) underwent TLD with a total procedure time of 89±16 min, and the total fluoroscopy time was 2.5±2.7 min.,Primary safety end point of freedom from worsening of COPD was 100%.,There were no procedural complications reported.,Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD.,Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy.,TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years. | 1 |
The association between TNF-α −308 G/A polymorphism and COPD remains controversial due to insufficiently strict study designs and small group sizes among different studies.,In the present study, a meta-analysis update which followed a stricter procedure was performed to obtain a clearer understanding of this association.,A comprehensive database search was conducted to identify the case-control studies published up to July 2015 which reported an association between the TNF-α −308 G/A polymorphism and COPD risk.,Data were extracted to calculate pooled odds ratios with 95% confidence intervals under the most appropriate genetic and allelic models.,Sensitivity was analyzed, and heterogeneity as well as publication bias was assessed.,Thirty-eight eligible studies, comprising 3,951 COPD cases and 5,110 controls, were included in this study, among which 22 studies comprising 2,067 COPD cases and 2,167 controls were performed in Asians, and 16 studies comprising 1,884 COPD cases and 2,943 controls were in non-Asians.,The overall result showed that TNF-α −308 G/A polymorphisms were significantly associated with increased COPD risk in both the codominant genetic and allelic models.,Individuals with the GA or AA genotype were more susceptible to COPD development than those with the GG genotype.,In addition, individuals with the AA genotype were more susceptible to developing COPD than those with the GA genotype.,The subgroup analysis stratified by ethnicity supported the results in Asians but not in non-Asians.,However, no association was found between TNF-α −308 G/A polymorphisms and COPD susceptibility either in Asians or in non-Asians in the meta-analysis conducted with restriction to former/current smokers.,The present meta-analysis suggested that the TNF-α −308 G/A polymorphism was associated with an increased risk of COPD among Asians but not in non-Asians.,Furthermore, individuals with the AA genotype of TNF-α −308 were more susceptible to developing COPD. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
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. | Although Th2 driven inflammation is present in COPD, it is not clearly elucidated which COPD patients are affected.,Since periostin is associated with Th2 driven inflammation and inhaled corticosteroid (ICS)-response in asthma, it could function as a biomarker in COPD.,The aim of this study was to analyze if serum periostin is elevated in COPD compared to healthy controls, if it is affected by smoking status, if it is linked to inflammatory cell counts in blood, sputum and endobronchial biopsies, and if periostin can predict ICS-response in COPD patients.,Serum periostin levels were measured using Elecsys Periostin immunoassay.,Correlations between periostin and inflammatory cell count in blood, sputum and endobronchial biopsies were analyzed.,Additionally, the correlation between serum periostin levels and treatment responsiveness after 6 and 30 months was assessed using i.e.,ΔFEV1% predicted, ΔCCQ score and ΔRV/TLC ratio.,Forty-five COPD smokers, 25 COPD past-smokers, 22 healthy smokers and 23 healthy never-smokers were included.,Linear regression analysis of serum periostin showed positive correlations age (B = 0.02, 95%CI 0.01-0.03) and FEV1% predicted (B = 0.01, 95%CI 0.01-0.02) in healthy smokers, but not in COPD patients In conclusion, COPD -smokers and -past-smokers have significantly higher periostin levels compared to healthy smokers, yet periostin is not suitable as a biomarker for Th2-driven inflammation or ICS-responsiveness in COPD.,The online version of this article (10.1186/s12931-018-0818-8) contains supplementary material, which is available to authorized users. | 1 |
We aimed to assess the effects of comorbidities on COPD costs and to investigate the relationship between comorbidities and clinical variables.,All patients hospitalized with a diagnosis of COPD exacerbation between January 1, 2014, and December 31, 2014, at all state hospitals of Aydın province, a city located in the western part of Turkey, were included in this study.,The costs examined in the study pertained to medications, laboratory tests, hospital stays, and other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees.,A total of 3,095 patients with 5,237 exacerbations (mean age, 71.9±10.5 years; 2,434 males and 661 females) were evaluated.,For 880 of the patients (28.9%), or 3,852 of the exacerbations (73.1%), at least one comorbid disease was recorded.,The mean cost of each exacerbation was $808.5±1,586, including $325.1±879.9 (40.7%) for hospital stays, $223.1±1,300.9 (27.6%) for medications, $46.3±49.6 (0.9%) for laboratory expenditures, and $214±1,068 (26.5%) for other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees.,The cost of each exacerbation was $1,014.9 in patients with at least one comorbidity, whereas it was $233.6 in patients without comorbidity (P<0.001).,Age >65 years, female gender, hospitalization in an intensive care unit, invasive or noninvasive mechanical ventilation, and a long duration of hospitalization were all found to be significant factors in increasing total costs during the exacerbations requiring hospitalization (P<0.05 for all).,Comorbidities have an important role in the total costs of acute exacerbations of COPD.,Strategies for the prevention, diagnosis, and effective management of comorbidities would decrease the overall financial burden associated with acute exacerbations of COPD. | The role of vitamin D (VitD) in calcium and bone homeostasis is well described.,In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair.,VitD deficiency appears to be frequent in industrialized countries.,Especially patients with lung diseases have often low VitD serum levels.,Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases.,Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer.,The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells.,This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status. | 1 |
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in the United States.,Exacerbations- acute worsening of COPD symptoms-can be mild to severe in nature.,Increased healthcare resource use is common among patients with frequent exacerbations, and exacerbations are a major cause of the high 30-day hospital readmission rates associated with COPD.,This review provides a concise overview of the literature regarding the impact of COPD exacerbations on both the patient and the healthcare system, the recommendations for pharmacologic management of COPD, and the strategies employed to improve patient care and reduce hospitalizations and readmissions.,COPD exacerbations significantly impact patients’ health-related quality of life and disease progression; healthcare costs associated with severe exacerbation-related hospitalization range from $7,000 to $39,200.,Timely and appropriate maintenance pharmacotherapy, particularly dual bronchodilators for maximizing bronchodilation, can significantly reduce exacerbations in patients with COPD.,Additionally, multidisciplinary disease-management programs include pulmonary rehabilitation, follow-up appointments, aftercare, inhaler training, and patient education that can reduce hospitalizations and readmissions for patients with COPD.,Maximizing bronchodilation by the appropriate use of maintenance therapy, together with multidisciplinary disease-management and patient education programs, offers opportunities to reduce exacerbations, hospitalizations, and readmissions for patients with COPD. | Background: Blood eosinophils may predict response to inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) where ICS is recommended in patients at high risk of exacerbations.,The proportion of patients who may benefit the most from ICS-based therapy was quantified in a real-world population.,Materials and methods: European data from the Adelphi Real World Respiratory Disease Specific Programme™ 2017 survey were collected from consecutive COPD patients by participating physicians.,Overall, 1,528 patients were assessable for Global Initiative for COPD (GOLD) 2017 status and were included in the analysis.,Results: More GOLD D patients had elevated eosinophil counts compared with GOLD B.,The proportions of GOLD D patients with a history of ≥2 exacerbations and eosinophil counts of ≥150, ≥300, and ≥400 cells/µL were 81.2%, 39.4%, and 24.6%, respectively.,In total, 10.6% of the patients had ≥300 eosinophils/µL and a history of ≥2 exacerbations.,ICS-based therapy was received by 41.5% of GOLD B and 68.0% of GOLD D patients.,Conclusion: There was no apparent relation between ICS use and eosinophil blood count.,There are differences in the distributions of patients with frequent exacerbations and/or high blood eosinophil counts and the use of ICS in COPD.,These data may provide information for the implementation of future treatment recommendations. | 1 |
COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA).,MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders.,Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD.,miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats.,The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay.,Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene.,Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells.,Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed.,COPD rat model was successfully induced by smoke inhalation.,Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene.,In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2.,In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition.,Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients. | To evaluate the effect of a single nucleotide polymorphism (rs2910164) in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2 (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from smokers with chronic obstructive pulmonary disease, as well as the lung function and disease stages from the same patient population.,One-hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary disease were recruited.,The patients were genotyped for rs2910164 polymorphism using Sanger sequencing, and their lung function/disease stages were evaluated following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a and COX2 as well as PGE2 production were determined in 66 lung tissue samples collected in the patients who received surgical treatment.,We confirmed that COX2 is a validated target of miR-146a in human fibroblast cells, and identified the differential expression patterns of miR-146a and COX2 in each rs2910164 genotype group.,We observed a significant association between rs2910164 in miR-146a and the levels of either COX2 or PGE2 using real-time polymerase chain reaction and Western blot.,Consistently, we were able to demonstrate that the rs2910164 single nucleotide polymorphism has a functional effect on the baseline lung function in the study population.,In the present study, the rs2910164 CC and GC genotype was found to be associated with an improved lung function and milder disease stages, at least partially, mediated by its ability to increase in COX2 expression and PGE2 production. | 1 |
Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are increasingly frequent in Asia and commonly coexist in patients.,However, the prevalence of COPD among Asian patients with HF and its impact on HF treatment are unclear.,We compared clinical characteristics and treatment approaches between patients with or without a history of COPD, before and after 1:2 propensity matching (for age, sex, geographical region, income level, and ethnic group) in 5232 prospectively recruited patients with HF and reduced ejection fraction (HFrEF, <40%) from 11 Asian regions (Northeast Asia: South Korea, Japan, Taiwan, Hong Kong, and China; South Asia: India; Southeast Asia: Thailand, Malaysia, Philippines, Indonesia, and Singapore).,Among the 5232 patients with HFrEF, a history of COPD was present in 8.3% (n = 434), with significant variation in geography (11.0% in Northeast Asia vs.,4.7% in South Asia), regional income level (9.7% in high income vs.,5.8% in low income), and ethnicity (17.0% in Filipinos vs.,5.2% in Indians) (all P < 0.05).,Use of mineralocorticoid receptor antagonists and diuretics was similar between groups, while usage of all β‐blockers was lower in the COPD group than in the non‐COPD group in the overall (66.3% vs.,79.9%) and propensity‐matched cohorts (66.3% vs.,81.7%) (all P < 0.05).,A striking exception was the Japanese cohort in which β‐blocker use was high in COPD and non‐COPD patients (95.2% vs.,91.2%).,The prevalence of COPD in HFrEF varied across Asia and was related to underuse of β‐blockers, except in Japan. | Although β-blockers are an established therapy in heart failure (HF) guidelines, including for patients with chronic obstructive pulmonary disease (COPD), there remain concerns regarding bronchoconstriction even with cardioselective β-blockers.,We wished to assess the real-life use of β-blockers for patients with HF and comorbid COPD.,We evaluated data from the Optimum Patient Care Research Database over a period of 1 year for co-prescribing of β-blockers with either an ACE inhibitor (ACEI) or angiotensin-2 receptor blocker (ARB) in patients with HF alone versus HF+COPD.,Association with inhaler therapy was also evaluated.,We identified 89 861 patients with COPD, 24 237 with HF and 10 853 with both conditions.,In patients with HF+COPD, the mean age was 79 years; 60% were male, and 27% had prior myocardial infarction.,Of patients with HF+COPD, 22% were taking a β-blocker in conjunction with either ACEI/ARB (n=2416) compared with 41% of patients with HF only (n=10 002) (adjusted OR 0.54, 95% CI 0.51 to 0.58, p<0.001).,Among HF+COPD patients taking inhaled corticosteroid (ICS) with long-acting β-agonist (LABA) and long-acting muscarinic antagonist, 27% of patients were taking an ACEI/ARB with β-blockers (n=778) versus 46% taking an ACEI/ARB without β-blockers (n=1316).,Corresponding figures for those patients taking ICS/LABA were 20% (n=583) versus 48% (n=1367), respectively.,These data indicate a substantial unmet need for patients with COPD who should be prescribed β-blockers more often for concomitant HF. | 1 |
Heterogeneous nature of Chronic Obstructive Pulmonary Disease (COPD) must be comprehensively addressed.,It is unclear if integrative multidisciplinary disease management (IMDM) can optimize clinical outcomes of patients with COPD.,A single-center, retrospective cohort observational study with a historical intervention was conducted in a clinic specialized for COPD care.,Patients with a confirmed diagnosis of COPD were administered IMDM with measurement of BODE score on initial and follow-up visits.,Primary outcomes were dynamic changes in BODE quartiles after receiving IMDM.,Of 124 patients, 21% were misdiagnosed with COPD.,Patients with a confirmed diagnosis of COPD were 50% female, median age 64 years (IQR 57-70), 43% actively smoking and initial visit median BODE quartile 2 (IQR 1-3).,Three subgroups were identified based on the changes in BODE quartiles: worsened (21%), unchanged (55%) and improved (24%).,At baseline, mMRC (median [IQR]) was higher in improved subgroup vs worsened and unchanged subgroup (3 [3, 4] vs 2 [1, 2] vs 2 [1, 3], p value 0.002) respectively.,Drop in all components of BODE score was noted in worsened group, but significant improvement in mMRC with preservation of spirometry values was noted in the improved group.,The incidence of smoking cigarettes changed from 39% to 26% during follow-up.,Our study demonstrates that IMDM can be potentially effective in a subgroup of COPD patients.,In others precipitous drop in lung function, activity tolerance, and subjective symptoms seems inevitable with worsening BODE quartiles. | The purpose of this study was to assess the prevalence of COPD phenotypes at a national level and to determine their geographic distribution among different autonomous communities in Spain.,A total of 1,610 patients (82% men, median age 67 years) recruited in primary care centers and pneumology services participated in an observational, cross-sectional, and multicenter study.,Phenotypes evaluated were the non-exacerbator phenotype, the asthma-COPD overlap syndrome (ACOS), the exacerbator phenotype with emphysema, and the exacerbator phenotype with chronic bronchitis.,The non-exacerbator phenotype was the most common (46.7%) followed by exacerbator with chronic bronchitis (22.4%) and exacerbator with emphysema (16.4%).,The ACOS phenotype accounted for the lowest rate (14.5%).,For each phenotype, the highest prevalence rates were concentrated in two or three autonomous communities, with relatively similar rates for the remaining regions.,Overall prevalence rates were higher for the non-exacerbator and the exacerbator with chronic bronchitis phenotypes than for ACOS and the exacerbator with chronic bronchitis phenotypes.,Differences in the distribution of COPD phenotypes according to gender, age, physician specialty, smoking habit, number of comorbidities, quality of life assessed with the COPD Assessment Test, and BODEx index (body mass index, airflow obstruction, dyspnea, and exacerbations) were all statistically significant.,Differences in the prevalence rates of COPD phenotypes among the Spanish autonomous communities have been documented.,Mapping the distribution of COPD phenotypes is useful to highlight regional differences as starting point for comparisons across time.,This geographic analysis provides health-care planners a valuable platform to assess changes in COPD burden at nationwide and regional levels. | 1 |
Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.,Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting.,The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria.,Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.,3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma-COPD overlap.,Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma-COPD cohort.,There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.,The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.,Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatmenthttp://ow.ly/oMZI307ndr5 | Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists.,EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics.,We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.,This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics.,The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.,A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated.,Of the 5,726 patients selected, 4,508 (78.7%) were eligible.,Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria.,Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units.,There was insufficient implementation of clinical guidelines in preventive and educational matters.,In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed.,Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%.,The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses.,This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. | 1 |
The high prevalence of COPD in the Russian Federation has been demonstrated in several epidemiological studies.,However, there are still no data on the clinical characteristics of these patients according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups and phenotypes, which could provide additional understanding of the burden of COPD, routine clinical practice, and ways to improve the treatment of patients with COPD in Russia.,SUPPORT was an observational multicenter study designed to obtain data about the distribution of patients with previously diagnosed COPD according to the severity of bronchial obstruction, symptom severity, risk of exacerbation, COPD phenotypes, and treatment of COPD.,We included patients with a previous diagnosis of COPD who visited one of 33 primary-care centers for any reason in 23 cities in Russia.,Among the 1,505 patients with a previous diagnosis of COPD who attended the primary-care centers and were screened for the study, 1,111 had a spirometry-confirmed diagnosis and were included in the analysis.,Up to 53% of the patients had severe or very severe COPD (GOLD stages III-IV), and 74.3% belonged to the GOLD D group.,The majority of patients were frequent exacerbators (exacerbators with chronic bronchitis [37.3%], exacerbators without chronic bronchitis [14%]), while 35.8% were nonexacerbators and 12.9% had asthma-COPD overlap.,Among the GOLD D group patients, >20% were treated with only short-acting bronchodilators.,COPD is still misdiagnosed in primary care in Russia.,COPD patients in primary care are usually GOLD D with frequent exacerbations and are often treated with only short-acting bronchodilators. | Randomized interventional trials generally recruit highly selected patients.,In contrast, long-term, noninterventional studies can reflect standard of care of real-life populations.,DACCORD (Die ambulante Versorgung mit langwirksamen Bronchodilatatoren: COPD-Register in Deutschland [Outpatient Care With Long-Acting Bronchodilators: COPD Registry in Germany]) is an ongoing observational study, conducted in primary and secondary care in Germany, aiming to describe the impact of disease and treatments on real-life patients with chronic obstructive pulmonary disease (COPD).,Patients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years, and were initiating or changing COPD maintenance medication.,The only exclusion criteria were asthma and participation in a randomized clinical trial.,Exacerbation data were collected every 3 months.,COPD medication, COPD Assessment Test, and forced expiratory volume in 1 second (FEV1) were recorded at the end of the 1 year period.,In the 6 months prior to baseline, 26.5% of the 3,974 patients experienced ≥1 exacerbation, compared with 26.1% over the 1-year follow-up (annualized rate 0.384).,Importantly, only previous exacerbations and not poor lung function alone predicted an increased exacerbation risk.,There was a general shift to lower disease severity from baseline to 1 year, predominantly as a consequence of a lower proportion of patients considered at high risk due to exacerbations.,COPD Assessment Test mean change from baseline was −1.9, with 48.9% of patients reporting a clinically relevant improvement.,Overall persistence to medication was high, with 77.2% of patients still receiving the same class of medication at 1 year.,DACCORD suggests that in clinical practice, the large majority of COPD patients are symptomatic but seldom exacerbate and that widely used tools and treatment recommendations do not reflect this fully. | 1 |
Corticosteroids (CS) have limited efficacy in the treatment of chronic obstructive pulmonary disease (COPD). p38 mitogen-activated protein kinase (MAPK) activation is increased in lung macrophages of COPD.,We investigated whether p38 MAPK inhibition can modulate CS insensitivity of peripheral blood mononuclear cells (PBMCs) from patients with COPD.,PBMCs from patients with COPD (n=8) or healthy smokers (n=8) were exposed to lipopolysaccharide (LPS) with a selective p38 MAPK inhibitor (GW856553; 10−10-10−6 M), with dexamethasone (10−10-10−6 M), or with both.,Phosphorylated glucocorticoid receptor (GR) was measured by Western blot.,Baseline (P<0.01) and LPS-induced (P<0.05) CXCL8 release was greater in PBMCs from COPD compared to healthy smokers.,Inhibition of LPS-induced CXCL8 release by dexamethasone (10−6 M) was reduced, and baseline and LPS-induced p38 MAPK activation increased in PBMCs of COPD.,GW856553 (10−9 and 10−10 M) synergistically increased the inhibitory effect of dexamethasone (10−8 and 10−6 M) on LPS-induced CXCL8 release in COPD.,Similar results were obtained for IL-6 release.,GW856553 inhibited dexamethasone- and LPS-activated phosphorylation of serine 211 on GR.,CS insensitivity in COPD PBMCs is reversed by inhibition of p38 MAPK activity, partly by preventing phosphorylation of GR at serine 211.,p38 MAPK inhibition may be beneficial in COPD by restoring CS sensitivity. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
Corticosteroids (CS) have limited efficacy in the treatment of chronic obstructive pulmonary disease (COPD). p38 mitogen-activated protein kinase (MAPK) activation is increased in lung macrophages of COPD.,We investigated whether p38 MAPK inhibition can modulate CS insensitivity of peripheral blood mononuclear cells (PBMCs) from patients with COPD.,PBMCs from patients with COPD (n=8) or healthy smokers (n=8) were exposed to lipopolysaccharide (LPS) with a selective p38 MAPK inhibitor (GW856553; 10−10-10−6 M), with dexamethasone (10−10-10−6 M), or with both.,Phosphorylated glucocorticoid receptor (GR) was measured by Western blot.,Baseline (P<0.01) and LPS-induced (P<0.05) CXCL8 release was greater in PBMCs from COPD compared to healthy smokers.,Inhibition of LPS-induced CXCL8 release by dexamethasone (10−6 M) was reduced, and baseline and LPS-induced p38 MAPK activation increased in PBMCs of COPD.,GW856553 (10−9 and 10−10 M) synergistically increased the inhibitory effect of dexamethasone (10−8 and 10−6 M) on LPS-induced CXCL8 release in COPD.,Similar results were obtained for IL-6 release.,GW856553 inhibited dexamethasone- and LPS-activated phosphorylation of serine 211 on GR.,CS insensitivity in COPD PBMCs is reversed by inhibition of p38 MAPK activity, partly by preventing phosphorylation of GR at serine 211.,p38 MAPK inhibition may be beneficial in COPD by restoring CS sensitivity. | We have previously reported that the lungs of patients with very severe chronic obstructive pulmonary disease (COPD) contain significantly higher numbers of alveolar macrophages than those of non-smokers or smokers.,M1 and M2 macrophages represent pro- and anti-inflammatory populations, respectively.,However, the roles of M1 and M2 alveolar macrophages in COPD remain unclear.,Immunohistochemical techniques were used to examine CD163, CD204 and CD206, as M2 markers, expressed on alveolar macrophages in the lungs of patients with mild to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (mild) n = 11, II (moderate) n = 9, III (severe) n = 2, and IV (very severe) n = 16).,Fifteen smokers and 10 non-smokers were also examined for comparison.,There were significantly higher numbers of alveolar macrophages in COPD patients than in smokers and non-smokers.,The numbers and percentages of CD163+, CD204+ or CD206+ alveolar macrophages in patients with COPD at GOLD stages III and IV were significantly higher than in those at GOLD stages I and II, and those in smokers and non-smokers.,In patients with COPD, there was a significant negative correlation between the number of CD163+, CD204+ or CD206+ alveolar macrophages and the predicted forced expiratory volume in one second.,Overexpression of CD163, CD204 and CD206 on lung alveolar macrophages may be involved in the pathogenesis of COPD. | 1 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.