From pre-COPD to COPD: a Simple, Low cost and easy to IMplement (SLIM) risk calculator.

BACKGROUND: The lifetime risk of developing clinical COPD among smokers ranges from 13% to 22%. Identifying at-risk individuals who will develop overt disease in a reasonable timeframe may allow for early intervention. We hypothesised that readily available clinical and physiological variables could help identify ever-smokers at higher risk of developing chronic airflow limitation (CAL). METHODS: Among 2273 Lovelace Smokers' Cohort (LSC) participants, we included 677 (mean age 54 years) with normal spirometry at baseline and a minimum of three spirometries, each 1 year apart. Repeated spirometric measurements were used to determine incident CAL. Using logistic regression, demographics, anthropometrics, smoking history, modified Medical Research Council dyspnoea scale, St George's Respiratory Questionnaire, comorbidities and spirometry, we related variables obtained at baseline to incident CAL as defined by the Global Initiative for Chronic Obstructive Lung Disease and lower limit of normal criteria. The predictive model derived from the LSC was validated in subjects from the COPDGene study. RESULTS: Over 6.3 years, the incidence of CAL was 26 cases per 1000 person-years. The strongest independent predictors were forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.75, having smoked ≥30 pack-years, body mass index (BMI) ≤25 kg·m2 and symptoms of chronic bronchitis. Having all four predictors increased the risk of developing CAL over 6 years to 85% (area under the receiver operating characteristic curve (AUC ROC) 0.84, 95% CI 0.81-0.89). The prediction model showed similar results when applied to subjects in the COPDGene study with a follow-up period of 10 years (AUC ROC 0.77, 95% CI 0.72-0.81). CONCLUSION: In middle-aged ever-smokers, a simple predictive model with FEV1/FVC, smoking history, BMI and chronic bronchitis helps identify subjects at high risk of developing CAL.

Clinical features and 1-year outcomes of chronic bronchitis in participants with normal spirometry: results from the ECOPD study in China.

BACKGROUND: Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population. METHODS: We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB. RESULTS: NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p<0.05), but there was no significant difference in lung function. Never-smokers with NOCB had higher rates of emphysema than those without NOCB, but airway resistance was similar. Ever-smokers with NOCB had greater airway resistance than those without NOCB, but emphysema rates were similar. During 1-year follow-up, participants with NOCB had a significantly increased risk of acute respiratory events compared with participants who did not have NOCB, after adjustment for confounders (risk ratio 2.10, 95% CI 1.32 to 3.33; p=0.002). These results were robust in never-smokers and ever-smokers. CONCLUSIONS: Never-smokers and ever-smokers with NOCB had more chronic obstructive pulmonary disease-related risk factors, evidence of airway disease and greater risk of acute respiratory events than those without NOCB. Our findings support expanding the criteria defining pre-COPD to include NOCB.

Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype. Methods: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor's diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex. Results: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30-9.92]), stage 2 (3.42 [2.13-5.51]) and stage 3 (2.38 [1.46-3.88]) compared with stage 4, and with CAT score <10 (3.35 [2.34-4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28-0.79]) and (0.68 [0.48-0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030). Conclusion: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.

Association between asthma, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, and lung cancer in the US population.

Lung cancer is one of the primary causes of death with poor life expectancy after diagnosis. History of past respiratory diseases such as asthma, chronic obstructive lung disease (COPD), emphysema, and chronic bronchitis can increase the risk of lung cancer. Very few studies are available to simultaneously assess multiple respiratory diseases and lung cancer. The objective of this study was to investigate correlations between asthma, emphysema, chronic bronchitis, and chronic obstructive lung disease with lung cancer in the US adult population. This was a cross-sectional study using data from a total of 23,523 adult participants from the National Health Examination and Nutrition Survey (NHANES) datasets for seven cycles ranging from 2003-2004 to 2015-2016. To analyze the data, specialized weighted complex survey logit regressions were conducted. Linear logit regression models using only main-effects were constructed first to assess the correlation between the selected demographic and lifestyle variables and asthma, emphysema, chronic bronchitis, and COPD. A second set of linear, main-effects logit regression models were constructed to examine the correlation between lung cancer and asthma, emphysema, chronic bronchitis, COPD when corrected for the selected covariates. The study identified positive correlations between emphysema, chronic bronchitis, COPD, and lung cancer. No correlation between asthma and lung cancer was established. Of the covariates studied, race/ethnicity, marital status, highest educational level, age, family income to poverty ratio, and lifetime smoking were also found to be correlated with the presence of lung cancer. Correlations between the covariates gender, body mass index, alcohol consumption, and country of birth and lung cancer were not found. The study established statistically significant correlations between lung cancer and the lung diseases emphysema, chronic bronchitis, and COPD. The lack of association between asthma and lung cancer may arise from the timeline of diagnosis asthma or type of lung cancer. The study also established significant correlations between lung cancer and several of the covariates included in the analysis. It also established correlations between the covariates and the lung diseases asthma, emphysema, chronic bronchitis, and COPD.

Prevalence of Chronic Obstructive Pulmonary Disease and Chronic Bronchitis Among Predominantly Smoking Workers in the Seafood Industry in Greenland.

Introduction: For decades, the prevalence of smoking has been high in Greenland. Even so, the prevalence of chronic obstructive pulmonary disease (COPD), a smoking-related disease, remains largely unexplored. This cross-sectional study aimed to estimate the prevalence of COPD and chronic bronchitis (CB) among Inuit workers in the seafood industry in Greenland. Methods: A total of 355 participants, 254 males and 101 females, met the inclusion criteria. Participants had a mean age of 38 years (standard deviation 13.5; range 17-68 years). COPD was diagnosed based on post-bronchodilator ratio between forced expiratory volume within one second and forced vital capacity (FEV1/FVC) below the lower limit of normal (LLN) according to the Global Lung Function Initiative. Participants completed a questionnaire aiming to diagnose CB. Results: The overall prevalence was 9.9% for COPD; 7.4% for CB. Participants were predominantly smokers; 73.2% active smokers, 91.8% active or former smokers. The prevalence of COPD was high, especially among those under 40 years of age. Both COPD and CB were associated with smoking status. Discussion: This study among Greenlandic seafood workers found that smoking was a risk factor for COPD and CB among Greenlanders of Inuit origin. The high prevalence of COPD and the high prevalence of smoking underlines the importance of further initiatives to reduce smoking in Greenland.

Comparison of clinical characteristics between chronic bronchitis and non-chronic bronchitis in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores. METHODS: This study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB. RESULTS: Among the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB. CONCLUSIONS: CB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

Association of Nonobstructive Chronic Bronchitis With All-Cause Mortality: A Systematic Literature Review and Meta-analysis.

BACKGROUND: The effect of nonobstructive chronic bronchitis (CB) on mortality is unclear. RESEARCH QUESTION: Is nonobstructive CB associated with increased all-cause mortality? STUDY DESIGN AND METHODS: We conducted a systematic literature review and meta-analysis to assess the association of nonobstructive CB and all-cause mortality. We searched for articles that included both CB and mortality in the title, abstract, or both in PubMed and EMBASE. We excluded studies in which participants demonstrated obstructive spirometry findings and studies in which CB and mortality were not defined. We used the Newcastle-Ottawa Quality Assessment Scale to assess study quality. We pooled adjusted hazard ratios (HRs) using the random effects model and inverse variance weighting. We conducted stratified analysis by the definition of CB and smoking status. We used Cochran's Q and I2 to assess for heterogeneity. We assessed publication bias by visual inspection of a funnel plot. RESULTS: Of 5,014 titles identified, eight fulfilled the inclusion and exclusion criteria. Overall nonobstructive CB was associated with all-cause mortality (HR, 1.37; 95% CI, 1.26-1.50) with no statistically significant heterogeneity (P = .14; I2 = 29%). Nonobstructive CB was associated with increased mortality in studies that defined CB as any respiratory symptoms (broad definition; HR, 1.28; 95% CI, 1.10-1.48; I2 = 0%) as well as in the rest of the studies (HR, 1.40; 95% CI, 1.26-1.56; I2 = 37%). Nonobstructive CB was associated with increased mortality in ever smokers (HR, 1.49; 95% CI, 1.35-1.64; I2 = 0%), but was not associated with increased mortality in never smokers (HR, 1.22; 95% CI, 0.90-1.66), and moderate heterogeneity was found (P = .10; I2 = 49%). The funnel plot did not indicate evidence of a publication bias because it showed symmetrical distribution of studies. INTERPRETATION: Nonobstructive CB is associated with increased all-cause mortality, and this association seems to be present only in current and former smokers. Further research should investigate whether this high-risk population may benefit from early therapeutic intervention. TRIAL REGISTRY: PROSPERO; No.: CRD42021253596; URL: www.crd.york.ac.uk/prospero.

Clinical Impact of the Bronchiectasis with Chronic Bronchitis Symptoms in COPD: Analysis of a Longitudinal Cohort.

PURPOSE: Bronchiectasis (BE) is a poor prognostic factor in COPD. However, it is not clear whether the poor prognosis is a result of BE alone or accompanying chronic bronchitis symptoms. Therefore, we investigated the effect of chronic bronchitis symptoms on clinical outcomes in COPD patients with BE. PATIENTS AND METHODS: We analyzed data of COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. The presence of BE was verified by chest computed tomography. Chronic bronchitis symptoms were determined using items in the symptomatic domain of the SGRQ, which is also used as an alternative definition of chronic bronchitis (CB). Patients were divided into four groups according to the presence of BE and CB symptoms: BE/CB, BE-only, CB-only, and no BE/CB. Demographic features and clinical outcomes were compared among these groups. RESULTS: In total, 389 COPD patients were included in the analysis. BE was present in 148 (38%) patients and CB symptoms were found in 123 patients (33.2%). The patients were divided according to BE and CB symptoms, and the numbers and percentages of each group were as follows: BE/CB, 52 (13.4%); BE-only, 96 (24.7%); CB-only, 77 (19.8%); no BE/CB, 164 (42.2%). No significant differences were observed in baseline characteristics of lung function, radiological findings, and inflammatory markers among the four groups. The proportion of annual exacerbators was higher in the BE/CB and CB-only groups than the other two groups. After adjusting other parameters, the BE/CB group was significantly associated with acute exacerbation of COPD (AE-COPD) (OR = 2.110, p = 0.045). CONCLUSION: BE accompanying CB symptoms is associated with AE-COPD, while BE alone was not significantly associated. This finding suggests that it is more important to examine chronic bronchitis symptoms of BE to predict acute exacerbation than simply to identify BE in COPD patients.

Clinical Evolution and Quality of Life in Clinically Based COPD Chronic Bronchitic and Emphysematous Phenotypes: Results from the 1-Year Follow-Up of the STORICO Italian Observational Study.

Introduction: Understanding clinical evolution of chronic obstructive pulmonary disease (COPD) is crucial for improving disease management. Materials and Methods: STORICO (NCT03105999), an Italian, multicenter, non-interventional, observational study conducted in 40 pulmonology centers, aimed to describe the 1-year clinical evolution and health status of clinicallbased phenotypes. Baseline and follow-up data of COPD subjects with a chronic bronchitis (CB) or emphysema (EM) phenotype were collected. The frequency of COPD symptoms during the 24 hours (gathered via the night-time, morning and day-time symptoms of COPD questionnaire) and the anxiety and depression levels (via the HADS Scale) were recorded at each visit. Results: A total of 261 CB and 159 EM patients were analyzed. CB patients with ≥1 night-time symptom seemed to be more frequent (51.7%, 41.8% and 41.4% at baseline, 6-month and 12-month follow-up, respectively) than EM (37.7%, 32.1% and 30.2% at study visits) even if no statistical differences were observed at time points between phenotypes (chi-square test p-values presence/absence of night-time symptoms in CB vs EM at study visits >0.0007). In the first 6 months, the frequency of patients with ≥1 night-time symptom decreased of 9.9% in CB and of 5.6% in EM. A clinically relevant decline of DLCO % predicted over 1 year in EM was observed, the mean (SD) being 61.5 (20.8) % at baseline and 59.1 (17.4) % at 12-month follow-up. EM had higher levels of anxiety and depression than CB (median (25th-75th percentile) HADS total score in CB: 7.0 (4.0-13.0) and 7.0 (3.0-12.0), in EM: 9.0 (3.0-14.0) and 9.5 (3.0-14.0) both at baseline and at 6-month follow-up, respectively), considering 1.17 as minimally clinical important difference (MCID) for the total score. Conclusion: EM patients, evaluated in a real-world setting, seem to suffer from a worse clinical condition and health status compared to CB patients, appearing to have "more treatable" traits.

Effect of SGRQ-Defined Chronic Bronchitis at Baseline on Treatment Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate.

BACKGROUND: Chronic bronchitis (CB) is one of the conditions that contribute to chronic obstructive pulmonary disease (COPD). Despite its widespread prevalence among patients with COPD and overall negative impact on treatment outcomes, the effect of CB on the efficacy of bronchodilator therapy has not been evaluated. The objective of this post hoc analysis is to assess the effect of nebulized glycopyrrolate (GLY) on lung function and health-related quality of life outcomes in patients with St George's Respiratory Questionnaire (SGRQ)-defined CB at baseline. METHODS: Pooled data from the replicate, 12-week GOLDEN 3 and 4 studies (N=861) were grouped by CB status at baseline. The endpoints reported are changes from baseline in trough forced expiratory volume in 1 second (FEV1), SGRQ and EXAcerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (EXACT-RS) scores. Safety of GLY was evaluated by monitoring the incidence of adverse events (AEs). RESULTS: Following 12 weeks of treatment, GLY 25 µg twice-daily (BID) resulted in placebo-adjusted improvements from baseline in FEV1 of 77.1 mL and 124.4 mL in the CB and non-CB groups, respectively (p<0.0001 vs placebo in both groups). Significant improvements in SGRQ total scores were observed with GLY 25 µg BID compared with placebo, regardless of baseline CB status. Although EXACT-RS improvements were noted in both CB and non-CB groups, significant improvements were observed only in the CB group. GLY 25 µg BID was generally well tolerated through 12 weeks of treatment, with a low incidence of AEs. CONCLUSION: Treatment with nebulized GLY 25 µg BID for 12 weeks resulted in significant improvements in lung function and SGRQ total scores, compared with placebo. Significant improvements in EXACT-RS total scores were observed only in the CB group. Together, these results support the use of GLY 25 µg BID in patients with COPD, regardless of their CB status.

Association of Triglyceride-Glucose Index and Lung Health: A Population-Based Study.

BACKGROUND: Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown. RESEARCH QUESTION: What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function? STUDY DESIGN AND METHODS: This study analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2012. Participants included fasting adults age ≥ 40 years (N = 6,893) with lung function measurements in a subset (n = 3,383). Associations of TyG with respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), and lung function (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated, adjusting for sociodemographic variables, comorbidities, and smoking. TyG was compared vs insulin resistance, represented by the homeostatic model assessment of insulin resistance (HOMA-IR), and vs the metabolic syndrome. RESULTS: TyG was moderately correlated with HOMA-IR (Spearman ρ = 0.51) and had good discrimination for metabolic syndrome (area under the receiver-operating characteristic curve, 0.80). A one-unit increase in TyG was associated with higher odds of cough (adjusted OR [aOR], 1.28; 95% CI, 1.06-1.54), phlegm production (aOR, 1.20; 95% CI, 1.01-1.43), wheeze (aOR, 1.18; 95% CI, 1.03-1.35), exertional dyspnea (aOR, 1.21; 95% CI, 1.07-1.38), and a diagnosis of chronic bronchitis (aOR, 1.21; 95% CI, 1.02-1.43). TyG was associated with higher relative risk of a restrictive spirometry pattern (adjusted relative risk ratio, 1.45; 95% CI, 1.11-1.90). Many associations were maintained with additional adjustment for HOMA-IR or metabolic syndrome. INTERPRETATION: TyG was associated with respiratory symptoms, chronic bronchitis, and a restrictive spirometry pattern. Associations were not fully explained by insulin resistance or metabolic syndrome. TyG is a satisfactory measure of metabolic dysfunction with relevance to pulmonary outcomes. Prospective study to define TyG as a biomarker for impaired lung health is warranted.

Systemic Galectin-3 in Smokers with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis: The Impact of Exacerbations.

PURPOSE: The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations. PATIENTS AND METHODS: The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth. RESULTS: When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with HNS or LTS. Nor did this level of Galectin-3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations. CONCLUSION: Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting.

New bronchoscopic treatment modalities for patients with chronic bronchitis.

Chronic bronchitis is a chronic, progressive disease that is difficult to treat. Despite much effort, patients remain highly symptomatic. Currently, a number of innovative bronchoscopic treatments for this disease are under investigation. Liquid nitrogen metered cryospray, bronchial rheoplasty and balloon desobstruction all aim to destroy the hyperplastic goblet cells and excess submucous glands using different strategies. These therapies are in an early phase of clinical research and larger randomised controlled trials are needed to confirm the pilot data available and to evaluate the treatment durability. The fourth technique, targeted lung denervation (TLD), aims to decrease the release of acetylcholine, which regulates smooth muscle tone and mucus production by ablating the parasympathetic nerves running alongside the main bronchi. Evaluation of this treatment is at a more advanced stage and promising effects on exacerbation frequency have been shown. However, confirmation of the benefit in improvement in chronic bronchitis symptoms is still needed.

Defining Chronic Mucus Hypersecretion Using the CAT in the SPIROMICS Cohort.

Background: Chronic cough and phlegm are frequently reported chronic obstructive pulmonary disease (COPD) symptoms. Prior research classified chronic mucus hypersecretion (CMH) based on the presence of these symptoms for ≥3 months, called chronic bronchitis (CB) if respiratory infection symptoms were present for 1-2 years (Medical Research Council [MRC] definition). We explored whether the COPD Assessment Test (CAT), a simple measure developed for routine clinical use, captures CMH populations and outcomes similarly to MRC and St. George's Respiratory Questionnaire (SGRQ) definitions. Methods: We identified CMH in the SPIROMICS COPD cohort using (a) MRC definitions, (b) SGRQ questions for cough and phlegm (both as most/several days a week), and (c) CAT cough and phlegm questions. We determined optimal cut-points for CAT items and described exacerbation frequencies for different CMH definitions. Moderate exacerbations required a new prescription for antibiotics/oral corticosteroids or emergency department visit; severe exacerbations required hospitalization. Results were stratified by smoking status. Results: In a population of 1431 participants (57% male; mean FEV1% predicted 61%), 47% and 49% of evaluable participants had SGRQ- or CAT-defined CMH, respectively. A cut-point of ≥2 for cough and phlegm items defined CMH in CAT. Among SGRQ-CMH+ participants, 80% were also defined as CMH+ by the CAT. CMH+ participants were more likely to be current smokers. A higher exacerbation frequency was observed for presence of CMH+ versus CMH- in the year prior to baseline for all CMH definitions; this trend continued across 3 years of follow-up, regardless of smoking status. Conclusion: Items from the CAT identified SGRQ-defined CMH, a frequent COPD trait that correlated with exacerbation frequency. The CAT is a short, simple questionnaire and a potentially valuable tool for telemedicine or real-world trials. CAT-based CMH is a novel approach for identifying clinically important characteristics in COPD that can be ascertained in these settings.

Impact of Oscillating Positive Expiratory Pressure Device Use on Post-Discharge Hospitalizations: A Retrospective Cohort Study Comparing Patients with COPD or Chronic Bronchitis Using the Aerobika® and Acapella® Devices.

Purpose: Managing and preventing disease exacerbations are key goals of COPD care. Oscillating positive expiratory pressure (OPEP) devices have been shown to improve clinical outcomes when added to COPD standard of care. This retrospective database study compared real-world resource use and disease exacerbation among patients with COPD or chronic bronchitis prescribed either of two commonly used OPEP devices. Patients and methods: Patients using the Aerobika® (Trudell Medical International, London, ON, Canada) or Acapella® (Smiths Medical, Wampsville, New York, USA) OPEP device for COPD or chronic bronchitis were identified from hospital claims linked to medical and prescription claims between September 2013 and April 2018; the index date was the first hospital visit with an OPEP device. Severe disease exacerbation, defined as an inpatient visit with a COPD or chronic bronchitis diagnosis, and all-cause healthcare resource utilization over 30 days and 12 months post-discharge were compared in propensity score (PS)-matched Aerobika device and Acapella device users. Results: In total, 619 Aerobika device and 1857 Acapella device users remained after PS matching. After discharge from the index visit, Aerobika device users were less likely to have ≥1 severe exacerbation within 30 days (12.0% vs 17.4%, p=0.01) and/or 12 months (39.6% vs 45.3%, p=0.01) and had fewer 12-month severe exacerbations (mean, 0.7 vs 0.9 per patient per year, p=0.01), with significantly longer time to first severe exacerbation than Acapella users (log-rank p=0.01). Aerobika device users were also less likely to have ≥1 all-cause inpatient visit within 30 days (13.9% vs 20.3%, p<0.001) and 12 months (44.9% vs 51.8%, p=0.003) than Acapella users. Conclusion: Patients receiving the Aerobika OPEP device, compared to the Acapella device, had lower rates of subsequent severe disease exacerbation and all-cause inpatient admission. This suggests that Aerobika OPEP device may be a beneficial add-on to usual care and that OPEP devices may vary in clinical effectiveness.

Documento de consenso sobre el diagnóstico y tratamiento de la infección bronquial crónica en la enfermedad pulmonar obstructiva crónica / Consensus document on the diagnosis and treatment of chronic bronchial infection in chronic obstructive pulmonary disease

A pesar de que es conocido que la presencia crónica de microorganismos en las vías aéreas de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) en fase de estabilidad conlleva una evolución desfavorable, ninguna guía de manejo de la enfermedad establece pautas sobre cómo diagnosticar y tratar este tipo de casos. Con la intención de orientar a los profesionales, desde la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) se ha elaborado un documento que pretende aportar respuestas clínicas sobre el manejo de pacientes con EPOC en los que se aíslan microorganismos de forma puntual o persistente. Dado que la heterogeneidad de las evidencias científicas disponibles no permite crear una Guía de Práctica Clínica, se ha elaborado un documento basado en la literatura científica existente y/o en la propia experiencia clínica que aborda tanto la definición de las diferentes situaciones clínicas como su diagnóstico y manejo. El texto ha sido consensuado entre un amplio número de neumólogos con gran experiencia clínica y científica en este ámbito. Este documento cuenta con el aval del Comité Científico de SEPAR

Although the chronic presence of microorganisms in the airways of patients with stable chronic obstructive pulmonary disease (COPD) confers a poor outcome, no recommendations have been established in disease management guidelines on how to diagnose and treat these cases. In order to guide professionals, the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has prepared a document which aims to answer questions on the clinical management of COPD patients in whom microorganisms are occasionally or habitually isolated. Since the available scientific evidence is too heterogeneous to use in the creation of a clinical practice guideline, we have drawn up a document based on existing scientific literature and clinical experience, addressing the definition of different clinical situations and their diagnosis and management. The text was drawn up by consensus and approved by a large group of respiratory medicine experts with extensive clinical and scientific experience in the field, and has been endorsed by the SEPAR Scientific Committee

Clinical phenotypes and heath-related quality of life of COPD patients in a rural setting in Malaysia - a cross-sectional study.

BACKGROUND: The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients' health-related quality of life (HRQoL) according to their COPD phenotypes. METHODS: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c). RESULTS: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p <  0.001). There were significantly more patients with mMRC 2-4 among AE (68.6%) (p <  0.001), compared to those with ACO (38.5%) and NON-AE (16.7%). AE patients had significantly higher total CAT (p = 0.003; p <  0.001) and SGRQ-c (both p <  0.001) scores than those with ACO and NON-AE. Patients with ACO had significantly higher total CAT and SGRQ-c (both p <  0.001) scores than those with NON-AE. AE patients had significantly higher score in each item of CAT and component of SGRQ-c compared to those with NON-AE (all p <  0.001), and ACO [(p = 0.003-0.016; p = < 0.001-0.005) except CAT 1, 2 and 7. ACO patients had significantly higher score in each item of CAT and component of SGRQ-c (p = < 0.001-0.040; p <  0.001) except CAT 2 and activity components of SGRQ-c. CONCLUSIONS: The HRQoL of COPD patients was significantly different across different COPD phenotypes. HRQoL was worst in AE, followed by ACO and NON-AE. This study supports phenotyping COPD patients based on their exacerbation frequency and COPD subtypes. The treatment of COPD should be personalised according to these two factors.

Elevated chronic bronchitis diagnosis risk among women in a local emergency department patient population associated with the 2012 heatwave and drought in Douglas county, NE USA.

BACKGROUND: Concerns about global climate change force local public health agencies to assess potential local disease risk. OBJECTIVE: Determine if risk of an emergency department chronic bronchitis diagnosis in Douglas County, NE, was higher during the 2012 heatwave compared to the same calendar period in 2011. METHODS: Retrospective, observational, case-control design selecting subjects from 2011 and 2012 emergency department (ED) admissions. Risk was estimated by conditional logistic regression. RESULTS: The odds of an ED chronic bronchitis diagnosis among females was 3.77 (95% CI =1.37-10.21) times higher during the 2012 risk period compared to females admitted to the ED during the 2011 risk period. Chronic bronchitis ED diagnosis odds were 1.05 (95%CI=1.04 - 1.06) times higher for each year of age. ED, gender, and race modified the risk (i.e., effect). The overall chronic bronchitis ED risk estimate was 1.61 (95%CI=0.81 - 3.21) times higher during the 2012 risk period compared to the 2011 risk period. The mean ambient absolute humidity upon admission was 11.44 gr/m3 (95%CI; 10.40 - 12.47) among chronic bronchitis cases and 12.67 gr/m3 (95%CI; 12.63 - 12.71) among controls. CONCLUSION: The odds of ED chronic bronchitis diagnosis was higher among female subjects admitted during the 2012 risk period compared to females admitted during the 2011 risk period.  Age also increased chronic bronchitis ED diagnosis risk among 2012 risk period admissions compared to 2011 risk period admissions.

Elevated Circulating CD4+CD25+CD127-/low Regulatory T Cells in Patients with Non-asthmatic Eosinophilic Bronchitis.

PURPOSE: Non-asthmatic eosinophilic bronchitis (NAEB) is a common cause of chronic cough. It is characterized by sputum eosinophilia like asthma but lacks airway hyperresponsiveness. Regulatory T cells (Tregs) are recognized as immune suppressors and are involved in the pathogenesis of asthma. However, the relationship between Tregs and NAEB remains unknown. This study aimed to preliminarily explore the role of Tregs in NAEB by comparing circulating Tregs levels to asthma and healthy controls. METHODS: Fractional exhaled nitric oxide (FeNO), spirometry with bronchial provocation test, sputum induction and blood routine test were performed in all subjects. Peripheral blood mononuclear cells were used to detect the Tregs (CD4+CD25+CD127-/low) by flow cytometry. Relationship between the levels of circulating Tregs and clinical indexes was also observed. RESULTS: A total of 15 patients with NAEB, 20 patients with asthma and 11 healthy controls were included. The absolute numbers of circulating Tregs in the NAEB group (49.8 ± 18.9 × 103 cells/ml) and asthma group (53.3 ± 18.7 × 103 cells/ml) were higher than that in healthy control group (32.7 ± 11.6 × 103 cells/ml) (both P < 0.01). In total, the level of circulating Tregs showed positive correlation with FeNO (r = 0.30, P < 0.05). CONCLUSION: Tregs may play a key role not only in asthmatic patients, but also in patients with NAEB, as reflected by the elevated Tregs in peripheral blood.