Chronic Obstructive Pulmonary Disease Disease Severity Research Articles

Cell-free DNA levels associate with COPD exacerbations and mortality

The question addressed by the studyGood biological indicators capable of predicting chronic obstructive pulmonary disease (COPD) phenotypes and clinical trajectories are lacking. Because nuclear and mitochondrial genomes are damaged and released by cigarette smoke exposure, plasma cell-free mitochondrial and nuclear DNA (cf-mtDNA and cf-nDNA) levels could potentially integrate disease physiology and clinical phenotypes in COPD. This study aimed to determine whether plasma cf-mtDNA and cf-nDNA levels are associated with COPD disease severity, exacerbations, and mortality risk.Materials and methodsWe quantified mtDNA and nDNA copy numbers in plasma from participants enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE, n = 2,702) study and determined associations with relevant clinical parameters.ResultsOf the 2,128 participants with COPD, 65% were male and the median age was 64 (interquartile range, 59–69) years. During the baseline visit, cf-mtDNA levels positively correlated with future exacerbation rates in subjects with mild/moderate and severe disease (Global Initiative for Obstructive Lung Disease [GOLD] I/II and III, respectively) or with high eosinophil count (≥ 300). cf-nDNA positively associated with an increased mortality risk (hazard ratio, 1.33 [95% confidence interval, 1.01–1.74] per each natural log of cf-nDNA copy number). Additional analysis revealed that individuals with low cf-mtDNA and high cf-nDNA abundance further increased the mortality risk (hazard ratio, 1.62 [95% confidence interval, 1.16–2.25] per each natural log of cf-nDNA copy number).Answer to the questionPlasma cf-mtDNA and cf-nDNA, when integrated into quantitative clinical measurements, may aid in improving COPD severity and progression assessment.

Relationship Between Platelet Parameters and Eosinophils with Disease Severity, CRP and Treatment in Stable COPD.

Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition that primarily impairs respiration but can also affect hemostasis. This study aimed to determine differences in platelet-related parameters and eosinophil between COPD patients and healthy controls. We included 149 patients with stable COPD and 30 healthy controls who were recruited from the outpatient department of Chest Diseases. Complete blood count, including platelet count (Plt), and C-reactive protein were measured. Other platelet-related parameters were determined, including mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (Pct), their ratios (MPV/Plt, MPV/Pct, PDW/Plt, PDW/Pct), and platelet to lymphocyte ratio (PLR). COPD patients and controls did not show significant differences in platelet parameters (Plt, Pct, PDW, MPV, PDW/Pct, MPV/Pct). PLR was significantly higher in the patient groups than in the control group (p=0.009). Correlation between platelet count and PLR (p=0.047; p=0.05) showed borderline significance. However, we found no correlation between the patients' CRP levels, Pct, PDW, PDW/Pct, MPV/Pct and MPV values. There were no significant differences in platelet parameters in patients using and not using long-acting muscarinic antagonists (LAMA). We did not find differences in eosinophil levels among COPD severity grades. In our study, we found that PLR is elevated in COPD. PLR could be a useful and easily accessible parameter to evaluate ongoing inflammation in stable COPD. Large-scale studies are warranted to further investigate the role of platelet and eosinophil parameters in COPD.

Long-Term Safety of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease, a Multinational Observational Database Cohort Study.

This study evaluated the long-term safety of roflumilast in patients with chronic obstructive pulmonary disease or chronic bronchitis using electronic healthcare databases from Germany, Norway, Sweden, and the United States (US). The study population consisted of patients aged ≥40 years who had been exposed to roflumilast and a matched cohort unexposed to roflumilast. The matching was based on sex, age, calendar year of cohort entry date (2010-2011, 2012, or 2013), and a propensity score that included variables such as demographics, markers of chronic obstructive pulmonary disease (COPD) severity and morbidity, and comorbidities. In comparison to the unexposed matched cohort (never use), three exposure definitions were used for the exposed matched cohort: ever use, use status (current, recent, past use), and cumulative duration of use. The main outcome was 5-year all-cause mortality. Cox regression models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CI). 112,541 unexposed and 23,239 exposed patients across countries were included. Some variables remained unbalanced after matching, indicating higher COPD disease severity among the exposed patients. Adjusted HRs of 5-year all-cause mortality for "ever use" of roflumilast, compared to "never use", were 1.12 (95% CI, 1.08-1.17) in Germany, 1.00 (95% CI, 0.92-1.08) in Norway, 0.98 (95% CI, 0.92-1.04) in Sweden, and 1.16 (95% CI, 1.12-1.20) in the US. Compared to never users, there was a decrease in 5-year mortality risk observed among "current users" in Germany (HR: 0.93, 95% CI: 0.88-0.98), Norway (HR: 0.77, 95% CI: 0.67-0.87), and Sweden (HR: 0.80, 95% CI: 0.73-0.88). There was no observed increase in 5-year mortality risk with the use of roflumilast in Sweden or Norway. A small increase in 5-year mortality risk was observed in Germany and the US in the ever versus never comparison, likely due to residual confounding by indication.

Urine Albumin/Creatinine Ratio and Serum Uric Acid as Predictors of Severity in Patients with Chronic Obstructive Pulmonary Disease

Background and Objective: As a global healthcare issue, Chronic Obstructive Pulmonary Disease (COPD) is mainly associated with smoking. Nonetheless, environmental and occupational issues are also linked to its development. The present study aimed to assess the urine albumin-to-creatinine ratio (ACR) and serum uric acid (SUA) levels as predictors of disease severity in COPD patients. Materials and Methods: This cross-sectional study was conducted on 67 patients diagnosed with COPD using the Global Initiative for Obstructive Lung Disease diagnostic criteria. The participants were patients who were either referred to the subspecialty clinic of the pulmonology and spirometry unit of Hamadan Shahid Beheshti Hospital or were hospitalized in the pulmonology ward. Blood and urine samples were taken from the COPD patients, and the serum uric acid, urine albumin, and urine creatinine levels were assessed and recorded in a checklist. The data were analyzed in SPSS software (version 23) at a significance level of 0.05. Results: In terms of gender, 5.7% of the participants were male and 34.3% were female. The mean age of patients was 61.77 years. The stages of disease severity in the patients were as follows: 20.89%, 22.38%, 5.73%, and 2.98% of cases had very severe, severe, moderate, and mild COPD, respectively. The regression analysis results demonstrated that SUA levels could significantly predict the FEV1 in COPD patients; nonetheless, urine ACR could not predict the FEV1 scores. Conclusion: As evidenced by the result of the present study, the FEV1 in COPD patients and disease severity could be predicted by the SUA levels. Therefore, it is recommended to consider monitoring and assessing non-pulmonary factors, especially SUA levels, in the treatment of COPD patients.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Baseline dependent minimally important differences for clinical outcomes of pulmonary rehabilitation in people with COPD

IntroductionMinimally important differences (MIDs) for common outcomes of pulmonary rehabilitation are well documented for people with chronic obstructive pulmonary disease (COPD). It is not known whether MIDs differ based on COPD disease characteristics. This study aimed to estimate MIDs for clinical outcomes of pulmonary rehabilitation dependent upon baseline characteristics. MethodsA database containing 2791 people with COPD was split into derivation (n=2245; age 66±9 years; 50% males; FEV1 47±20% predicted) and comparator (n=546; age 66±9 years; 47% males; FEV1 46±21% predicted) cohorts. MIDs were estimated using 0.5 x SD (symmetrically distributed) or 0.5 x IQR (non-symmetrically distributed) for: 6-minute walk test (6MWT), constant work rate test (CWRT), COPD assessment test (CAT), St. George's respiratory questionnaire (SGRQ), hospital anxiety and depression scale (HADS), and fat-free mass index (FFMI). MIDs were estimated based on baseline outcome scores, lung function, modified medical research council (mMRC) grade and FFMI. ResultsMID estimates were comparable to previously reported values. MIDs for SGRQ domains (Symptom=8.7 points, Activity=7.1 points, Impact=8.1 points) and FFMI were produced (0.36kg/m2). There was greater variation of change in 6MWT, SGRQ-activity, SGRQ-impact, HADS and FFMI on which the MIDs were determined when categorising for baseline values (all, p<0.05). Greater variation of change in 6MWT on which the MIDs were determined was evident with COPD disease severity grouping (p<0.05). The magnitude of change in 6MWT, CAT, CWRT, SGRQ-activity, and FFMI with baseline mMRC score categorisation resulted in greater variation on which the MIDs were determined (all, p<0.05). Baseline stratification for FFMI resulted in greater variation of change in CWRT (p<0.001) and HADS-depression (p = 0.043) on which MIDs were determined. DiscussionFindings suggest that baseline presentation should be considered for people with COPD when assessing the efficacy of pulmonary rehabilitation. However, clinical significance of the variation underpinning MIDs is yet to be determined.

Modified MRC assessment and FEV1.0 can predict frequent acute exacerbation of COPD: An observational prospective cohort study at a single-center in Japan

IntroductionAcute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) is a fatal event, leading to poor outcomes among COPD patients. However, exact frequency and poor prognostic factors are not well known in Japan. Methodsand patients, To assess the frequency and risk factors of AE, we performed this prospective cohort study at the Kameda Medical Center in Japan between during 2011 and 2013. AE was defined as an acute worsening of respiratory symptoms according to the GOLD guideline. Furthermore, we compared the exacerbation-free time between the groups. ResultsA total of 330 patients (230 COPD patients and 100 smoking controls) were enrolled in the study. The mean age in the study was 73 years, and 94% of the patients were male. As for the frequency of AE, 0.17 times/patients/year was found in all patients. The frequency of AE increased as the COPD disease severity (p = 0.042 by Jonch-Heere terpla test). GOLD I patients had longer exacerbation-free time than GOLD II, and GOLD II grade COPD patients had longer exacerbation-free time than GOLD III grade COPD patients. In terms of risk factors for AE, logistic regression analysis showed that Modified Medical Research Council (mMRC) scale ≥3 and FEV1.0% <50% were independent poor prognostic factors for moderate grade of AE events, and mMRC scale ≥3 was independent poor prognostic factor for severe AE events. ConclusionThe frequency of AE increases as the disease severity becomes more severe. We found mMRC scale >3 and FEV1 <50% were risk factors for AE-COPD.

Role of C-reactive Protein and Mean Platelet Volume in Predicting COPD Severity and its Association with Cardiac Abnormalities among the Southern Indian Population: A Cross-sectional Study

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of disease and mortality worldwide. In individuals with mild-to-moderate COPD, serum C-reactive Protein (CRP) corresponds with disease severity and poor health outcomes. Mean Platelet Volume (MPV) is also linked to an elevated degree of inflammation in the body, as well as the severity and acute exacerbation of COPD. Aim: To evaluate the relationship between serum CRP levels and MPV and its association with COPD disease severity and the patient’s cardiac abnormality. Materials and Methods: A cross-sectional study was conducted in the Department of Respiratory Medicine, Chettinad Hospital and Research Institute, Chennai, Tamil Nadu, India, between January 2015 and January 2016. Study was carried out among 55 patients who were diagnosed with COPD in accordance with Global Initiative for Chronic Obstructive Lung Disease 2014 (GOLD) and who were within the age range of 40-70 years were included in the investigation. Severity of airflow obstruction was confirmed by Spirometry using True Flow Easy on PC sensor Pulmonary Function Test (PFT) machine with bronchodilator reversibility testing, as per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2014 and abnormality was evaluated by clinical and radiological assessment. A 3 mL of blood was collected into a clot vial and sent for analysis of CRP using an immunoassay system based on antigen-antibody reaction and fluorescence technology and MPV using the impedance count technique. Receiver Operating Characteristic (ROC) curve was used to find out the sensitivity and specificity of MPV and CRP levels with cardiac abnormality. The study was statistically analysed by Pearson’s Chi-square test. Results: Out of total sample, majority (n=25, 45.5%) were between 51-60 years age group and, there were 35 (63.63%) males and 20 (36.37%) females. The mean CRP levels of mild COPD patients were found to be 6.980±0.7328 mg/dL, moderate and severe COPD patients were found to be 7.243±0.5324 mg/ dL and 7.550±0.4950 mg/dL, respectively and it was statistically significant (p-value &lt;0.0001). In the present study, the mean CRP levels and mean MPV were found to be significantly higher in patients with cardiac abnormality than the patients without cardiac abnormality (p-value &lt;0.0001). Conclusion: Finally, it was concluded that systemic inflammation is common in COPD patients and that CRP and MPV are significant COPD biomarkers for assessing disease severity, predicting cardiac abnormalities, and predicting patient prognosis.

Diaphragmatic Movement at Rest and After Exertion: A Non-Invasive and Easy to Obtain Prognostic Marker in COPD.

IntroductionDiaphragmatic dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the prognostic significance of impaired diaphragmatic movement at rest and after exercise.MethodsThis was a prospective study of patients with stable COPD. Diaphragmatic movements were examined at rest and after a 6-minute walking test (6MWT) with a convex transducer with a frequency of 3.5-5-7.5 MHz. Maximal movement of the diaphragm was measured in both right and left diaphragm, and the side with higher amplitude was selected for further analysis. Measurements obtained were evaluated for their prognostic value for a composite endpoint of moderate and severe COPD exacerbations and death in 1 year time period was assessed. In addition, postbronchodilator spirometry, symptoms, quality of life, and demographic and clinical information were collected.ResultsA total of 96 patients were analyzed (62.5% male, mean age 65.1 years (standard deviation (SD): 8.1), mean FEV1 (% predicted): 55.8%, SD: 18.3%, mean CAT: 15.6 units, SD: 9.2). Sixty-four patients (67%) presented the composite endpoint. In the multivariate Cox analysis, FVC (HR = 0.944, p = 0.005), CAT score (HR = 1.133, p = 0.011), previous severe exacerbations (HR = 5.446, p = 0.004) and diaphragmatic movement at rest (HR = 0.932, p = 0.033) were found to be predictors of the composite endpoint. This model correctly classified 86.5% (83/96) of the patients.ConclusionNon-invasive assessment of diaphragmatic movement by ultrasound measurement both at rest and after exercise could contribute to the assessment of disease severity and prognosis of COPD.

Evaluation of diaphragm thickness and function with ultrasound technique and comparison with spirometry in stable chronic obstructive pulmonary disease.

Although the pathophysiological mechanisms involved in the development of dyspnea and poor exercise tolerance in chronic obstructive pulmonary disease (COPD) patients are complex, diaphragmatic dysfunction plays a significant role. The purpose of this study was to compare the diaphragm thicknesses and diaphragm excursion values measured by M-mode and B-mode ultrasonography with COPD patients and healthy volunteers and to evaluate the contribution of ultrasound use in determining disease severity in COPD. Sixty-seven COPD patients and 53 healthy volunteers were included in the study. Diaphragm thickness and mobility measurements were conducted and recorded with B mode and M mode ultrasound. It was determined that the diaphragm thickness measured by B mode ultrasound in deep inspiration and deep expiration was significantly reduced in patients with COPD, compared to the ones without (p= 0.004, p= 0.00). Diaphragm excursion assessed by M mode ultrasound was significantly less in the COPD group. In this study, we concluded that the patients with COPD develop diaphragmatic dysfunction with reduced diaphragm thickness and mobility. The use of ultrasound in COPD may contribute to clinical practice, yet further studies are needed.

Dysregulated circulating microRNA-126 in chronic obstructive pulmonary disease: linkage with acute exacerbation risk, severity degree, and inflammatory cytokines.

BackgroundMicroRNA‐126 (miR‐126) is engaged in respiratory diseases via regulating airway tissue injury and pulmonary inflammation, while its relation with chronic obstructive pulmonary disease (COPD) is not reported. The study aimed to evaluate the value of miR‐126 for estimating COPD acute exacerbation risk and its relation to disease severity and inflammatory cytokines in COPD patients.MethodsThis study was a case–control study. Seventy acute exacerbation COPD (AECOPD) patients, 70 stable COPD (SCOPD) patients, and 70 healthy controls (HCs) were consecutively recruited. Plasma miR‐126 expression was detected by reverse transcription quantitative polymerase chain reaction. Plasma tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and interleukin‐17 (IL‐17) in COPD patients were further determined by enzyme‐linked immunosorbent assay.ResultsMiR‐126 was higher in AECOPD patients compared to SCOPD patients and HCs (both P adj < 0.001). Receiver operating characteristic curves revealed miR‐126 distinguished AECOPD patients from SCOPD patients (area under curve (AUC): 0.805, 95%CI: 0.733–0.877) and HCs (AUC: 0.884, 95%CI: 0.829–0.939) and also distinguished SCOPD from HCs (AUC = 0.656, 95%CI: 0.566–0.747). MiR‐126 positively related to GOLD stage in both AECOPD patients (p < 0.001) and SCOPD patients (p < 0.001). Furthermore, miR‐126 positively linked with TNF‐α (p < 0.001), IL‐1β (p = 0.002), IL‐6 (p = 0.009), and IL‐17 (p < 0.001) levels in AECOPD patients; but miR‐126 only positively related to TNF‐α and IL‐17 levels (all p < 0.050), instead of IL‐1β or IL‐6 level (all p > 0.050) in SCOPD patients and HCs.ConclusionDysregulated circulating miR‐126 not only relates to COPD susceptibility and its acute exacerbation risk but also links with disease severity and inflammatory cytokines in COPD patients.

Patterns and Predictors of Air Cleaner Adherence Among Adults with COPD.

Poor indoor air quality has been associated with worse chronic obstructive pulmonary disease (COPD) morbidity. In-home portable air cleaners reduce indoor pollutants and could improve respiratory health. Factors associated with air cleaner adherence among adults with COPD remains unknown. In a 6-month trial of former smokers with COPD, participants (n=116) received active or sham portable air cleaners. Air cleaner adherence was measured by electronic monitors. Potential baseline predictors of adherence included individual factors (demographics, socioeconomic status, smoking history, psychological well-being), COPD disease severity, and housing characteristics. Time and season were also considered. Stepwise logistic regression and longitudinal fixed effect analysis were performed to assess independent predictors of adherence. A total of 109 participants had an objective measure of adherence, and 76.1% used at least 1 air cleaner 80% of the time (defined a priori as adherent). Higher annual household income ≥$35,000 (odds ratio [OR]=4.4, 95% confidence interval [CI], 1.1-18.0) and use of heat pump/electricity (versus gas) for heating (OR=6.1, 95%CI, 1.7-22.4) were associated with higher odds of adherence. Further, poor quality of life (St George's Respiratory Questionnaire, per 10-point increase) and prior year exacerbations were associated with lower odds of adherence (OR=0.65, 95%CI, 0.4-1.0) and (OR=0.26, 95%CI, 0.1-0.9), respectively. Adherence was highest during the first month and lower during winter compared to other seasons. These findings suggest that cold weather season, use of gas for home heating, and lower annual income negatively impact adherence. Poor quality of life and worse disease control may also decrease adherence. Addressing factors associated with air cleaner adherence should be considered when designing future environmental studies.

To Study the Correlation of Chronic Obstructive Pulmonary Disease (COPD) Assessment Test, Clinical COPD Questionnaire, and BODE Index in Patients of Stable COPD

Background: Chronic obstructive pulmonary disease (COPD) assessment has emerged as one of the most important parts of COPD treatment. Therefore, a thorough assessment of symptoms is necessary rather than just a measure of dyspnea. Objective: The aim of this study is to assess the disease severity and health status in stable patients of COPD using COPD assessment test (CAT), clinical COPD questionnaire (CCQ) scores, and BODE index and to correlate these indices. Materials and Methods: The study included 100 stable patients suffering from COPD attending outpatient department subjected to CAT, CCQ, and BODE index. Results: CAT and CCQ score correlated significantly (r = 0.52, P &lt; 0.001) and both with the BODE index (r = 0.68; CAT and r = 0.64; CCQ, P &lt; 0.001). COPD severity status and BODE component and forced expiratory volume 1% (FEV1%)-predicted values correlated significantly with individual scores (r = −0.24, CAT; r = −0.41, CCQ; r = −0.72, BODE). Conclusion: An evident negative correlation of FEV1% predicted by CAT and CCQ among study subjects proved both questionnaires as sensitive, simple, and reliable tools not only for early recognition and assessing health status in COPD patients but also for planning appropriate treatment. The BODE index is more objective to assess the disease severity in COPD.

The Arabic version of the Lower Extremity Functional Scale is a reliable and valid measure of activity limitation in people with chronic obstructive pulmonary disease

Purpose To examine the psychometric properties of the Arabic version of the Lower Extremity Functional Scale (LEFS-Ar) in people with chronic obstructive pulmonary disease (COPD). Materials and methods Stable individuals with COPD (N = 70) confirmed by spirometry were asked to complete the LEFS-Ar, St George’s Respiratory Questionnaire (SGRQ) and performed the Six-Minute Walk Test (6MWT). Participants were also asked to complete LEFS-Ar for the second time within 10 days. The LEFS-Ar floor and ceiling effects, internal consistency, test–retest reliability, measurement error, and construct validity were examined. Results The LEFS-Ar had excellent internal consistency with Cronbach’s alpha of 0.95 and excellent test–retest reliability (ICCagreement=0.91) with no floor and ceiling issues. Standard error of measurement was 4.78 points while the minimal detectable change at 90% confidence was 11.15 points. Consistent with our hypotheses, the LEFS-Ar scores correlated significantly with 6MWT (r= −0.66, p < 0.001), activity domain of the SGRQ (r = 0.55, p < 0.001), and were significantly different according to COPD disease severity (p= 0.02). Conclusions In people with COPD, the LEFS-Ar has excellent reliability with no floor or ceiling effects. The LEFS-Ar demonstrated evidence supporting its validity as a measure of activity limitation that can be used in clinical practice and in research studies. Implications for rehabilitation The Arabic version of the Lower Extremity Functional Scale (LEFS-Ar) is a reliable measure in people with chronic obstructive pulmonary disease (COPD). Rehabilitation specialists can use the LEFS-Ar to validly measure activity limitation in people with COPD.

A Correlational study on quality of life and disease severity among Chronic Obstructive Pulmonary Disease (COPD) clients attending a pulmonary Medicine OPD of a Tertiary care hospital, Kolkata

Chronic obstructive pulmonary disease (COPD) is recently the most common chronic lung disease and presents a serious medical, economic, and social problem for people. A correlational survey research was adopted to identify relationship between quality of life and disease severity among Chronic Obstructive Pulmonary Disease (COPD) clients attending Pulmonary Medicine OPD in a selected hospital, Kolkata with the objectives to assess the quality of life of Chronic Obstructive Pulmonary Disease (COPD) clients and to find out correlation between disease severity and quality of life among Chronic Obstructive Pulmonary Disease (COPD) clients. Purposive sampling technique was adapted to select 138 Chronic Obstructive Pulmonary Disease (COPD) clients attending Pulmonary Medicine OPD in a tertiary care hospital, Kolkata. The structured interview schedule was used to collect on demographic data and standardized WHO QOL BREF tool was used to assess Quality of Life. Standardized GOLD criteria were used to assess disease severity of COPD clients. Reliability of the demographic data collection tool was established by inter- rater method and r was 0.77. All the tools were tried out before final data collection. The finding of the study revealed statistically non-significant relationship between all the domain of QOL and disease severity of COPD patients. Total Quality of Life score is also not significantly related with COPD Disease severity score. The study results also showed that QOL is not associated with sociodemographic characteristics. The study concluded that, there is no correlation between quality of life and disease severity.

Circulating Extracellular Vesicles Are Associated with Disease Severity and Interleukin-6 Levels in COPD: A Pilot Study.

Chronic obstructive pulmonary disease (COPD) is a complex condition in which systemic inflammation plays a role in extrapulmonary manifestations, including cardiovascular diseases: interleukin (IL)-6 has a role in both COPD and atherogenesis. The 2011 GOLD document classified patients according to FEV1, symptoms, and exacerbations history, creating four groups, from A (less symptoms/low risk) to D (more symptoms/high risk). Extracellular vesicles (EV) represent potential markers in COPD: nevertheless, no studies have explored their value in association to both disease severity and inflammation. We conducted a pilot study to analyze circulating endothelial-(E) and monocyte-derived (M) EV levels in 35 COPD patients, who were grouped according to the 2011 GOLD document; the relationship between EV and plasmatic markers of inflammation was analyzed. We found a statistically significant trend for increasing EEV, MEV, IL-6, from group A to D, and a significant correlation between EEV and IL-6. The associations between both EEV and MEV and disease severity, and between EEV and IL-6, suggest a significant interplay between pulmonary disease and inflammation, with non-respiratory cells (endothelial cells and monocytes) involvement, along with the progression of the disease. Thus, EV might help identify a high-risk population for extrapulmonary events, especially in the most severe patients.

Spatial Dependence of CT Emphysema in Chronic Obstructive Pulmonary Disease Quantified by Using Join-Count Statistics.

Background Existing CT emphysema measurements quantify the extent or clustering of emphysema voxels in chronic obstructive pulmonary disease (COPD); however, these measurements do not quantify how those voxels are clustered. Purpose To develop a CT measurement to quantify the "compactness" of emphysema voxels, called the normalized join count (NJC), and to determine whether the NJC measurement differentiates COPD disease severity and correlates with lung function and visual emphysema scores. Materials and Methods In this secondary analysis of a prospective study, lung function and CT images were obtained from the Canadian Cohort Obstructive Lung Disease study visit 1 from 2009 to 2013. Participants were categorized as never-smokers, at risk, mild COPD, or moderate-severe COPD. Diffusion capacity for carbon monoxide/alveolar volume was measured. CT emphysema was scored visually by radiologists. CT measurements included the percentage low-attenuation area with attenuation less than -950 HU (%LAA-950insp), low-attenuation cluster (LAC), and lowest 15th percentile point of the CT lung density histogram. NJC was developed to measure compactness of CT emphysema voxels. An analysis of variance determined differences between groups. Multivariable ridge regression determined association between CT measurements with lung function and radiologist scores. Results A total of 1294 participants (750 men; mean age, 67 years ± 10) were analyzed (277 never-smokers, 306 at risk, 427 mild COPD, and 284 moderate-severe COPD). NJC, %LAA-950insp, and LAC measurements were higher in moderate-severe COPD than in never-smokers and at-risk participants (P < .05 for all comparisons), but only NJC was different between mild and ;moderate-severe COPD (mean, 1.98% ± 3.61 vs 1.44% ± 2.14; P < .05). In multivariable regression analysis, among all CT measurements NJC had the greatest relative contribution to diffusion capacity for carbon monoxide/alveolar volume (P = .002) and visual emphysema score (P < .001). Conclusion The relationship of normalized join count with severity of chronic obstructive pulmonary disease may indicate that the assessment of this disease is dependent on the number of low attenuating voxels or the size of clusters and the spatial arrangement of such voxels. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.

The airway microbiome in COPD, bronchiectasis and bronchiectasis-COPD overlap.

To review the airway microbiome in chronic obstructive pulmonary disease (COPD), bronchiectasis and bronchiectasis-COPD overlap (BCO). Relevant studies were selected from PubMed, Google scholar, EMBASE and Web of Science. All studies involving human microbiomes, published in the English language, and using the search terms "COPD", "Chronic Obstructive Pulmonary Disease", "Bronchiectasis", "BCO" or "Bronchiectasis and COPD overlap", AND "microbiome", "mycobiome" or "metagenomics" were included. Despite variability in sampling methods and specimen types used, microbiome composition remains relatively comparable in COPD and bronchiectasis with prominence of Proteobacteria, Firmicutes and Bacteroidetes. Alterations to airway microbiomes occur in association to disease severity and/or exacerbations in COPD and bronchiectasis. Decreased alpha diversity and Haemophilus-predominant microbiomes are associated with poorer survival in COPD, while, in bronchiectasis, Pseudomonas-predominant microbiomes demonstrate high exacerbation frequency and greater symptom burden while Aspergillus-dominant mycobiome profiles associate with exacerbations. The role of the microbiome in BCO remains understudied. Use of next-generation sequencing has revolutionised our detection and understanding of the airway microbiome in chronic respiratory diseases such as COPD and bronchiectasis. Targeted amplicon sequencing reveals important associations between the respiratory microbiome and disease outcome while metagenomics may elucidate functional pathways. How best to apply this information into patient care, monitoring and treatment, however, remains challenging and necessitates further study.

Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD.

Despite advances in the pathophysiology of chronic obstructive pulmonary disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD, but their association to COPD disease severity remains unknown. We analyzed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from 62 patients with mild to very severe COPD (51% male; mean age: 65.9 yr). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, and exercise testing), and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF [leukocyte, polymorphonuclear leukocyte (PMN; i.e., neutrophil), monocyte, epithelial, and platelet MVs] and plasma (leukocyte, PMN, monocyte, and endothelial MVs) and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including forced expiratory volume in 1 s, modified Medical Research Council dyspnea score, 6-min walk test, hyperinflation, and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically relevant disease severity indexes. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome.

Revisiting matrix metalloproteinase 12: its role in pathophysiology of asthma and related pulmonary diseases.

Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent proteases with different biological and pathological activities, and many have been implicated in several diseases. Although nonselective MMP inhibitors are known to induce serious side-effects, targeting individual MMPs may offer a safer therapeutic potential for several diseases. Hence, we provide a concise overview on MMP-12, given its association with pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and other progressive pulmonary fibrosis (PPF), which may also occur in coronavirus disease 2019. In asthma, COPD, and PPF, increased MMP-12 levels have been associated with inflammation and/or structural changes within the lungs and negatively correlated with functional parameters. Increased pulmonary MMP-12 levels and MMP-12 gene expression have been related to disease severity in asthma and COPD. Targeting MMP-12 showed potential in animal models of pulmonary diseases but human data are still very scarce. Although there may be a potential role of MMP-12 in asthma, COPD and PPF, several pathophysiological aspects await elucidation. Targeting MMP-12 may provide further insights into MMP-12 related mechanisms and how this translates into clinical outcomes; this warrants further research.