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Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive disease resulting in a range of symptoms including breathlessness. "Symptom burden" describes the severity and impact of multiple symptoms in an individual and is best quantified using validated symptom instruments but is not routinely measured in clinical practice. Therefore, we wanted to assess overall symptom burden in patients with moderate-to-severe COPD and find associated independent predictors., Patients and Methods: A single-centre cross-sectional study of patients with COPD who attended the Westmead Breathlessness Service between March 2017 and May 2022 was conducted. We obtained baseline demographic data, lung function, assessed quality of life (CAT), anxiety/depression (HADS), and measured symptom burden (CMSAS). We compared variables between men and women using unpaired t tests or Mann-Whitney tests for continuous variables, and Fisher's exact tests for categorical variables. We used multiple regression to look for independent predictors of overall symptom burden. Data were analysed using Stata/IC 15.1., Results: Eighty-nine patients with COPD, mean age 72.6 years, 55% male, mean FEV 1 32% predicted, reported an average of 8.9 symptoms including 6.9 physical and 1.6 psychological symptoms. The most common physical symptoms were shortness of breath (100%) and lack of energy (80%), and the most common psychological symptoms were worrying (65%) and feeling anxious (61%). Median CMSAS total score was higher in women than men (1.34 versus 1.04, respectively; p =0.03) with more women experiencing nervousness ( p =0.011) and anxiety ( p =0.005). Female sex ( p =0.003), HADS-Anxiety ( p =0.0001), and HADS-Depression ( p =0.0001) were independently associated with total CMSAS score in a multiple linear regression model and explained 63% of total CMSAS variability., Conclusion: Very high physical and psychological symptom burden exists among patients with severe COPD. Anxiety, depression, and female sex were independently associated with increasing symptom burden. Identifying and understanding sex differences for COPD symptoms, and interventions targeting anxiety and depression may help to reduce overall symptom burden within this population., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Roberts et al.)

Purpose: The Phenotypes of COPD in Central and Eastern Europe (POPE) study assessed the prevalence and clinical characteristics of four clinical COPD phenotypes, but not mortality. This retrospective analysis of the POPE study (RETRO-POPE) investigated the relationship between all-cause mortality and patient characteristics using two grouping methods: clinical phenotyping (as in POPE) and Burgel clustering, to better identify high-risk patients., Patients and Methods: The two largest POPE study patient cohorts (Czech Republic and Serbia) were categorized into one of four clinical phenotypes (acute exacerbators [with/without chronic bronchitis], non-exacerbators, asthma-COPD overlap), and one of five Burgel clusters based on comorbidities, lung function, age, body mass index (BMI) and dyspnea (very severe comorbid, very severe respiratory, moderate-to-severe respiratory, moderate-to-severe comorbid/obese, and mild respiratory). Patients were followed-up for approximately 7 years for survival status., Results: Overall, 801 of 1,003 screened patients had sufficient data for analysis. Of these, 440 patients (54.9%) were alive and 361 (45.1%) had died at the end of follow-up. Analysis of survival by clinical phenotype showed no significant differences between the phenotypes (P=0.211). However, Burgel clustering demonstrated significant differences in survival between clusters (P<0.001), with patients in the "very severe comorbid" and "very severe respiratory" clusters most likely to die. Overall survival was not significantly different between Serbia and the Czech Republic after adjustment for age, BMI, comorbidities and forced expiratory volume in 1 second (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65-0.99; P=0.036 [unadjusted]; HR 0.88, 95% CI 0.7-1.1; P=0.257 [adjusted]). The most common causes of death were respiratory-related (36.8%), followed by cardiovascular (25.2%) then neoplasm (15.2%)., Conclusion: Patient clusters based on comorbidities, lung function, age, BMI and dyspnea were more likely to show differences in COPD mortality risk than phenotypes defined by exacerbation history and presence/absence of chronic bronchitis and/or asthmatic features., Competing Interests: VK reports non-financial support from Meditech Media, UK, Boehringer Ingelheim RCV Vienna, AUT, Charles University, Czechia, and Ministry of the Health, Czechia, during the conduct of the study. He gave presentations at symposia and sponsored and received fees for advisory board participation and travel grants from Angelini, AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi and Menarini. He received research grants from Angelini, AstraZeneca, Boehringer Ingelheim and Chiesi. BM has received honoraria for consulting and presenting from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim and Novartis. BM also reports grants from Company Providens, Serbia, non-financial support for Advisory Board for COPD from AstraZeneca, Serbia and Boehringer Ingelheim, outside the submitted work; and President of Respiratory Society of Serbia and President of Republic Expert Commission for Pulmonology (by Ministry of Health Republic of Serbia). MS, JK, SH, VZ, MI, JJank and JJark have nothing to disclose. VC has received honoraria for consulting and presenting from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim and Teva. BP is an employee of Boehringer Ingelheim Serbia d.o.o Beograd. AV has received speaker and/or consultancy fees, as well as research grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini and Novartis., (© 2023 Koblizek et al.)

Background: Patients with chronic obstructive pulmonary disease (COPD) are more inclined to have a high level of social vulnerability due to their physical and psychological burden. However, to date, there have been no study on social frailty in patients with COPD. This study aimed to investigate the prevalence, characteristics, and impact of social frailty in patients with COPD., Methods: Social frailty was assessed using five items in a questionnaire. A patient was diagnosed with social frailty if responses to two or more items were positive. Four hundred and five patients with COPD were assessed for social frailty, dyspnea, and appetite. We also prospectively examined the number of acute exacerbation and unexpected hospitalization for 1 year., Results: Thirty-six percent of patients with COPD had social frailty. They had reduced appetite and more severe dyspnea [Simplified Nutritional Appetite Questionnaire score: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.69‒0.95, p < 0.01; modified Medical Research Council score: OR 1.42, 95% CI 1.05‒1.93, P = 0.02] than patients without social frailty. Social frailty was not a risk factor for moderate acute exacerbation of COPD but a risk factor for severe acute exacerbation and all-cause unexpected hospitalization (severe acute exacerbation: β , standardized regression coefficient: 0.13, 95% CI 0.01‒0.25, P = 0.04, unexpected hospitalization: β 0.17, 95% CI 0.05‒0.29, P = 0.01)., Conclusion: The prevalence of social frailty is 36%; however, social frailty has a marked clinical impact in patients with COPD., Competing Interests: KH reports personal fees from AstraZeneca, Boehringer Ingelheim, Kracie Pharma, Ltd., and GlaxoSmithKline outside of the submitted work. AT reports personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, KYORIN Pharmaceutical, and Sanofi outside of the submitted work. NO reports personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, KYORIN Pharmaceutical, Novartis, and Sanofi outside of the submitted work. TH reports personal fees from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline outside of the submitted work. SS reports personal fees from AstraZeneca, GlaxoSmithKline, KYORIN Pharmaceutical, Sanofi, and Tanabe-Mitsubishi outside of the submitted work. HS reports personal fees from AstraZeneca, Boehringer Ingelheim, Kyorin Pharmaceutical, GlaxoSmithKline, Novartis, Kracie Pharma, Ltd., Gilead Sciences, Tsumura and Co, MSD K.K., and Sanofi outside of the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Hirai et al.)

Background: Chronic heart failure (CHF) is a common comorbidity among patients with chronic obstructive pulmonary disease (COPD). Both exacerbations of COPD (ECOPDs) and exacerbations of CHF (ECHFs) display worsening of breathlessness at rest (BaR) and breathlessness at physical activity (BaPA). Comorbid CHF may have an impact on the vital signs assessed, when the Rome proposal (adopted by GOLD 2023) is applied on ECOPDs. Thus, the aim of the present study was to investigate the impact of comorbid CHF on ECOPDs severity, particularly focusing on the influence of comorbid CHF on BaR and BaPA., Methods: We analysed data on COPD symptoms collected from the telehealth study The eHealth Diary. Patients with COPD (n = 43) and patients with CHF (n = 41) were asked to daily monitor BaR and BaPA, employing a digital pen and scales for BaR and BaPA (from 0 to 10). Twenty-eight patients of the COPD patients presented with comorbid CHF. Totally, 125 exacerbations were analysed., Results: Exacerbations in the group with COPD patients and comorbid CHF were compared to the group with COPD patients without comorbid CHF and the group with CHF patients. Compared with GOLD 2022, the GOLD 2023 (the Rome proposal) significantly downgraded the ECOPD severity. Comorbid CHF did not interfere significantly on the observed difference. Comorbid CHF did not worsen BaR scores, assessed at inclusion and at the symptom peak of the exacerbations., Conclusion: In the present study, we find no evidence that comorbid CHF would interfere significantly with the parameters included in the Rome proposal (GOLD 2023). We conclude that the Rome proposal can be safely applied even on COPD patients with very advanced comorbid CHF., Competing Interests: PKJ reports honoraria for lectures from Chiesi. HLP reports honoraria for advisory boards/lectures from AstraZeneca, Boehringer Ingelheim, GlaxoSmithCline, Intermune, Roche and the Swedish Medical Products Agency. The authors report no other conflicts of interest in this work., (© 2023 Jacobson et al.)

Purpose: The presence of pain can be associated with an exaggerated negative cognitive and emotional response, leading to worsening of existing symptoms. This study aimed to describe the multifaceted impact of chronic pain on cognition, emotional and physical health in people with chronic obstructive pulmonary diseases (COPD) and to explore the clinical impact of pain., Patients and Methods: A prospective, cross-sectional multicenter study was carried out in 68 people with COPD (COPD group) and 65 community-dwelling age-matched participants (control group). Participants were assessed for the presence of chronic pain, pain location, intensity and catastrophizing, pain-related fear (kinesiophobia), anxiety and depression, physical activity, and sleep duration. The COPD group also completed assessments of dyspnea, exercise tolerance (6-minute walk distance [6MWD]), and activities of daily living (ADL)., Results: The prevalence of pain was higher in the COPD group (85% vs 51%, p<0.001). The COPD group reported pain located in neck/shoulder, upper back, thorax and upper limbs, while the control group had more pain in the lower back. Pain catastrophizing and kinesiophobia were reported by 28% and 67% vs 9% and 42%, in the COPD and control groups respectively (both p<0.05). People with COPD and pain (n=58) reported greater dyspnea (p<0.001), and impairment in ADL (p<0.05), and lower 6MWD and physical activity (both p<0.01) compared to COPD participants without pain (n=10)., Conclusion: This study demonstrated that, compared to community-dwelling participants, there is a higher prevalence of chronic pain in people with COPD. Pain combined with dyspnea may impact adversely on cognitive function and lead to anxiety and depression, as well as greater impairment in exercise tolerance, physical activity, and ADL. These results suggested that it is necessary to assess the symptoms of chronic pain and inflect in chronic pain coping strategies., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Tanaka et al.)

Purpose: Previous research has indicated that female and male patients may experience different levels of symptoms. However, no studies of chronic obstructive pulmonary disease (COPD) patients have compared the number and types of symptom clusters identified in male and female patients. Therefore, the purpose of this study was to investigate gender differences in symptom clusters among COPD patients., Patients and Methods: A total of 371 eligible patients were enrolled in the study. We assessed nine COPD symptoms, namely, dyspnea, cough, sputum, chest tightness, sleep quality, fatigue, frailty, anxiety, and depression. Exploratory factor analyses were used to explore the underlying clusters of the COPD symptoms., Results: Underlying the nine symptoms, female patients had 2 clusters, and male patients had 3 clusters. Specifically, the three general symptoms poor sleep, fatigue, and frailty loaded on the same symptom cluster with anxiety and depression in female patients, while the same 3 general symptoms loaded on the same symptom cluster with chest tightness and dyspnea in male patients. Moreover, cough and sputum not only were more common in male patients but also loaded together on a separate symptom cluster., Conclusion: Our findings suggest that in order to improve fatigue, frailty, and poor sleep quality, symptom management strategies should more closely address anxiety and depression in female patients as well as chest tightness and dyspnea in male patients. Smoking cessation is particularly important in male COPD patients because they account for a much higher proportion of smokers and are more likely to have cough and sputum. These findings signify the importance of identifying and implementing gender-tailored symptom management strategies to relieve symptom burden in COPD patients to enhance their quality of life., Competing Interests: The authors report no conflicts of interest with regard to this work., (© 2021 Zhang et al.)

Purpose: This cross-sectional study aimed to describe personal growth and to analyze its associated factors among patients with chronic obstructive pulmonary disease (COPD) in China., Patients and Methods: A total of 364 Chinese COPD hospitalized patients were included in the study between November 2016 and April 2018. Participants provided demographic information and completed the Growth Through Uncertainty Scale (GTUS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the modified Medical Research Council dyspnoea scale (mMRC)., Results: The mean total score on the GTUS was 142.34 ( SD = 7.61). The multiple linear regression analysis showed that factors including educational level, average monthly income, social support, and breathlessness can influence personal growth ( R 2 = 0.427, F = 44.420, p < 0.001), explaining 42.7% of the variance., Conclusion: COPD patients tend to report a moderate level of personal growth in China. Educational level, average monthly income, social support, and breathlessness were significant factors associated with personal growth. Medical workers should be aware of the level of personal growth among COPD patients and make tailored interventions to facilitate COPD patients' personal growth, such as increasing social support and decrease breathlessness., Competing Interests: The authors declare no conflicts of interest., (© 2020 Zhao et al.)

Purpose: Many older adults with a history of smoking and asthma develop clinical features of both asthma and COPD, an entity sometimes called asthma-COPD overlap (ACO). Patients with ACO may be at higher risk of poor health outcomes than those with asthma or COPD alone. However, understanding of ACO is limited in the primary care setting and more information is needed to better inform patient management. We aimed to compare the characteristics of patients with ACO or COPD in Australian general practices., Patients and Methods: Data were from the RADICALS (Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers) trial, an intervention study of an interdisciplinary community-based model of care. Baseline demographic and clinical characteristics, pre- and post-bronchodilator spirometry, dyspnoea and St. George's Respiratory Questionnaire scores were compared between 60 ACO patients and 212 with COPD alone., Results: Pre-bronchodilator Forced Expiratory Volume in 1 second (mean±SD 58.4±14.3 vs 67.5±20.1% predicted) and Forced Vital Capacity (mean 82.1±16.9 v 91.9±17.2% predicted) were significantly lower in the ACO group (p<0.001), but no difference was found in post-bronchodilator spirometry. Demographic and clinical characteristics, dyspnoea, quality of life, comorbidities and treatment prescribed did not differ significantly between groups., Conclusion: This is the first study describing the clinical characteristics of ACO patients in Australian general practices. Our finding of lower pre-bronchodilator lung function in the ACO group compared to those with COPD reinforces the importance of spirometry in primary care to inform management., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12614001155684., Competing Interests: Michael J Abramson holds an investigator-initiated grant from Pfizer for unrelated research. He has also conducted an unrelated consultancy for Sanofi and reports grants from Boehringer-Ingelheim, during the conduct of the study. Johnson George has held investigator-initiated grants from Pfizer for unrelated research and has received cash and in-kind contributions from Boehringer Ingelheim (BI) Pty Ltd for an unrelated project. He has received an honorarium from GSK for consultancy. He also received non-financial support from the Lung Foundation Australia, grants from the National Health and Medical Research Council, non-financial support from the Inner East Melbourne Primary Health Network, during the conduct of the study and grants and personal fees from GSK and grants from Pfizer, outside the submitted work. Professor Anne E Holland reports grants from the National Health and Medical Research Council, grants from Boehringer Ingelheim, non-financial support from Lung Foundation Australia, and non-financial support from Eastern Melbourne PHN, during the conduct of the study. Ms Jenifer Liang reports grants and non-financial support from Boehringer Ingelheim, non-financial support from the Lung Foundation Australia, non-financial support from Eastern Melbourne PHN, and grants from National Health and Medical Research Council (Australia), during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2019 Izbicki et al.)

Background: A seven-item prescreening questionnaire (gender, age, pack-years smoking, dyspnea, sputum, cough, previous spirometry data) was developed for COPD detection in the primary care setting (PUMA Study) of four Latin America countries., Objectives: To validate the PUMA prescreening COPD questionnaire externally in two different populations (primary care and general)., Methods: The PUMA prescreening COPD questionnaire score was applied to subjects from the Hospital Maciel, Montevideo (primary care), case-finding program and the PLATINO population (general) using PUMA study inclusion criteria. Post-bronchodilator FEV 1 /FVC <0.70 and lower limit of normal (LLN) criteria were used to define COPD. Area under the received operator curve (ROC AUC ), sensitivity, specificity, predictive positive and negative values (PNV), number needed to treat (NNT), and best cut-points of the score were calculated., Results: 974 individuals from Hospital Maciel and 2512 from the PLATINO population were eligible, using post-bronchodilator FEV 1 /FVC <0.70, 45.1% and 18.7% had COPD, respectively, and using LLN 38.4% and 15.4% had COPD, respectively. From Hospital Maciel (post-bronchodilator FEV 1 /FVC <0.70), the best cut-point of ≥6 had moderate discriminatory power (ROC AUC 0.70), sensitivity 69.9%, specificity 62.1%, PNV 70.9%, and NNT of 3. The discriminatory power was 0.73 (ROC AUC ) in the PLATINO population with three potential cut-points (Youden's index): ≥3 (sensitivity 85.4%, specificity 46.9%), ≥4 (sensitivity 66.7%, specificity 66.5%), and ≥5 (sensitivity 51.5%, specificity 81.6%); the PNV at each cut-point was 93.3%, 89.9%, and 88.0%, respectively. The NNT was 5 for scores ≥3 and ≥4, and 4 for ≥5. The mean accuracy using the LLN for Hospital Maciel and PLATINO was 0.67 and 0.70, respectively., Conclusion: External validation of the PUMA prescreening questionnaire in two Latin American populations (general and primary care) suggests moderate accuracy, similar to the original study in which the questionnaire was developed., Competing Interests: Larissa Ramirez is a full-time employee of AstraZeneca Latin America. Ana Menezes has been paid for her work as a statistician for the study. The Hospital Maciel, Montevideo, data of this paper were presented at the European Respiratory Society 2017 Congress as a poster presentation with interim findings. The poster’s abstract was published in the European Respiratory Journal 2017; 50 (Suppl 61): PA1198. DOI: 10.1183/1393003. The authors report no other conflicts of interest in this work., (© 2019 Lopez Varela et al.)

Background: In light of overall increasing healthcare expenditures, it is mandatory to study determinants of future costs in chronic diseases. This study reports the first longitudinal results on healthcare utilization and associated costs from the German chronic obstructive pulmonary disease (COPD) cohort COSYCONET., Material and Methods: Based on self-reported data of 1904 patients with COPD who attended the baseline and 18-month follow-up visits, direct costs were calculated for the 12 months preceding both examinations. Direct costs at follow-up were regressed on baseline disease severity and other co-variables to identify determinants of future costs. Change score models were developed to identify predictors of cost increases over 18 months. As possible predictors, models included GOLD grade, age, sex, education, smoking status, body mass index, comorbidity, years since COPD diagnosis, presence of symptoms, and exacerbation history., Results: Inflation-adjusted mean annual direct costs increased by 5% (n.s., €6,739 to €7,091) between the two visits. Annual future costs were significantly higher in baseline GOLD grades 2, 3, and 4 (factors 1.24, 95%-confidence interval [1.07-1.43], 1.27 [1.09-1.48], 1.57 [1.27-1.93]). A history of moderate or severe exacerbations within 12 months, a comorbidity count >3, and the presence of dyspnea and underweight were significant predictors of cost increase (estimates ranging between + €887 and + €3,679, all p <0.05)., Conclusions: Higher GOLD grade, comorbidity burden, dyspnea and moderate or severe exacerbations were determinants of elevated future costs and cost increases in COPD. In addition we identified underweight as independent risk factor for an increase in direct healthcare costs over time., Competing Interests: Johanna I Lutter reports grants from German Federal Ministry of Education and Research during the conduct of the study. Stefan Karrasch reports grants from German Federal Ministry of Education and Research (BMBF) during the conduct of the study. Holger Schulz report grants from German Federal Ministry of Education and Research (BMBF), during the conduct of the study. Claus Vogelmeier report grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from CSL Behring, personal fees from Chiesi, grants and personal fees from GlaxoSmithKline, grants and personal fees from Grifols, personal fees from Menarini, personal fees from Mundipharma, grants and personal fees from Novartis, personal fees from Teva, personal fees from Cipla, grants from Bayer Schering Pharma AG, grants from MSD, and grants from Pfizer outside the submitted work. Rolf Holle report grants from German Federal Ministry of Education and Research, during the conduct of the study. The authors report no other conflicts of interest in this work.

Purpose: The aim of this study was to examine the changing influence over time of comorbid heart disease on symptoms and health status in patients with COPD., Patients and Methods: This is a prospective cohort study of 495 COPD patients with a baseline in 2005 and follow-up in 2012. The study population was divided into three groups: patients without heart disease (no-HD), those diagnosed with heart disease during the study period (new-HD) and those with heart disease at baseline (HD). Symptoms were measured using the mMRC. Health status was measured using the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT; only available in 2012). Logistic regression with mMRC ≥2 and linear regression with CCQ and CAT scores in 2012 as dependent variables were performed unadjusted, adjusted for potential confounders, and additionally adjusted for baseline mMRC, respectively, CCQ scores., Results: Mean mMRC worsened from 2005 to 2012 as follows: for the no-HD group from 1.8 (±1.3) to 2.0 (±1.4), ( P =0.003), for new-HD from 2.2 (±1.3) to 2.4 (±1.4), ( P =0.16), and for HD from 2.2 (±1.3) to 2.5 (±1.4), ( P =0.03). In logistic regression adjusted for potential confounding factors, HD (OR 1.71; 95% CI: 1.03-2.86) was associated with mMRC ≥2. Health status worsened from mean CCQ as follows: for no-HD from 1.9 (±1.2) to 2.1 (±1.3) with ( P =0.01), for new-HD from 2.3 (±1.5) to 2.6 (±1.6) with ( P =0.07), and for HD from 2.4 (±1.1) to 2.5 (±1.2) with ( P =0.57). In linear regression adjusted for potential confounders, HD (regression coefficient 0.12; 95% CI: 0.04-5.91) and new-HD (0.15; 0.89-5.92) were associated with higher CAT scores. In CCQ functional state domain, new-HD (0.14; 0.18-1.16) and HD (0.12; 0.04-0.92) were associated with higher scores. After additional correction for baseline mMRC and CCQ, no statistically significant associations were found., Conclusion: Heart disease contributes to lower health status and higher symptom burden in COPD but does not accelerate the worsening over time., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Previous studies suggest that gender differences exist in COPD diagnosis and symptoms; these differences may be more pronounced in younger adults. Our objective was to explore age-associated gender differences across a range of COPD severities., Materials and Methods: A total of 4,484 current and former smokers with COPD from the Genetic Epidemiology of COPD cohort were investigated using regression modeling to explore the association between gender, age, disease severity, and the contributing elements of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (symptoms, exacerbation risk, airflow limitation)., Results: The age-gender interaction was observed across multiple age categories. Compared to men with COPD, younger women with COPD had a greater likelihood of more severe dyspnea, airflow limitation, greater risk for exacerbations, and categorization in GOLD groups B and D. These differences were less pronounced in older women with COPD. However, older women remained more likely to experience severe dyspnea and to manifest more severe COPD (B vs A) than older men, despite lower pack-years of smoking., Conclusion: These data demonstrate the significant symptom burden of COPD in women, especially younger women. More research is needed to understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted clinical assessment and management approaches to improve outcomes for women and men with COPD at all ages., Competing Interests: Disclosure DL DeMeo, MD, reports receiving grants from the National Institutes of Health and consultation fees from Novartis. S Ramagopalan, PhD, was an employee of Evidera Inc. (scientific consulting) at the time of the study. A Kavati, PhD, is an employee of Novartis Pharmaceuticals. A Vegesna, PharmD, is an employee of Novartis Pharmaceuticals. MK Han, MD, reports consulting income from GSK, Boehringer Ingelheim, AstraZeneca, Sunovion she also reports research support from GSK and Novartis. A Yadao, MD, is an employee of Novartis Pharmaceuticals. TK Wilcox, PhD, is an employee of Evidera Inc. (scientific consulting). BJ Make, MD, related to the topic of COPD, reports funding from the National Heart, Lung, and Blood Institute for the COPDGene study, grants, and personal fees from Boehringer Ingelheim, AstraZeneca; personal fees and other from Spiration, Consensus Medical Education, Integrity Medical Education, Mt Sinai Medical Center, WebMD, Up-To-Date, National Jewish Health; grants, personal fees, and other from GlaxoSmithKline, Sunovian; personal fees from Novartis, CSL Bering, Verona; other from SPIRE Learning, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, Peer Review Institute, National Jewish Health, Cleveland Clinic; grants from Pearl; grants and other from Medscape, outside the submitted work. The authors report no other conflicts of interest in this work.

Background: Pulmonary tuberculosis (PTB) is a risk factor for COPD, but the clinical characteristics and the chest imaging features (emphysema and bronchiectasis) of COPD with previous PTB have not been studied well., Methods: The presence, distribution, and severity of emphysema and bronchiectasis in COPD patients with and without previous PTB were evaluated by high-resolution computed tomography (HRCT) and compared. Demographic data, respiratory symptoms, lung function, and sputum culture of Pseudomonas aeruginosa were also compared between patients with and without previous PTB., Results: A total of 231 COPD patients (82.2% ex- or current smokers, 67.5% male) were consecutively enrolled. Patients with previous PTB (45.0%) had more severe ( p =0.045) and longer history ( p =0.008) of dyspnea, more exacerbations in the previous year ( p =0.011), and more positive culture of P. aeruginosa ( p =0.001), compared with those without PTB. Patients with previous PTB showed a higher prevalence of bronchiectasis ( p <0.001), which was more significant in lungs with tuberculosis (TB) lesions, and a higher percentage of more severe bronchiectasis (Bhalla score ≥2, p =0.031), compared with those without previous PTB. The overall prevalence of emphysema was not different between patients with and without previous PTB, but in those with previous PTB, a higher number of subjects with middle ( p =0.001) and lower ( p =0.019) lobe emphysema, higher severity score ( p =0.028), higher prevalence of panlobular emphysema ( p =0.013), and more extensive centrilobular emphysema ( p =0.039) were observed. Notably, in patients with TB lesions localized in a single lung, no difference was found in the occurrence and severity of emphysema between the 2 lungs., Conclusion: COPD patients with previous PTB had unique features of bronchiectasis and emphysema on HRCT, which were associated with significant dyspnea and higher frequency of severe exacerbations. While PTB may have a local effect on bronchiectasis, its involvement in airspace damage in COPD may be extensive, probably through interactions with cigarette smoke., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Chronic obstructive pulmonary disease (COPD) and farming are two conditions that have been associated with an increased risk of anxiety and depression. Dairy farming is an independent risk factor for COPD., Objective: To test the hypotheses that the prevalence of anxiety and/or depression is higher in dairy farmers with COPD than in farmers without COPD, and higher in dairy farmers with COPD than in non-farmers with COPD., Methods: Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale in 100 dairy farmers with COPD (DF-COPD), 98 dairy farmers without COPD (DF-controls), 85 non-farming patients with COPD (NF-COPD) and 89 non-farming subjects without COPD (NF-controls), all identified by screening in the Franche-Comté region of France. Anxiety and depression were considered present when the Hospital Anxiety and Depression Scale score was ≥8. COPD was defined by a post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio <0.7., Results: The crude prevalence of anxiety did not differ between the four groups, ranging from 36% in NF-controls to 47% in NF-COPD ( p =0.15 between groups). Similarly, the prevalence of depression did not differ significantly between the four groups ( p =0.16 between groups). In dairy farmers (n=198), the only factors associated with anxiety were quality of life and current smoking. Depression in dairy farmers was associated with airflow limitation (lower forced expiratory volume in 1 second and COPD grade 2 or more) as well as with some COPD-related features (dyspnea severity, current smoking, and poorer quality of life). In non-farmers, both anxiety and depression were associated with airflow limitation and COPD-related features., Conclusion: In our population, the prevalence of anxiety and/or depression was similar in dairy farmers with and without COPD and in non-farmers with COPD. Nevertheless, the degree of airway obstruction and some COPD-related features were associated with depression among dairy farmers, whereas these factors were not associated with anxiety., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Although patients with COPD often have various comorbidities and symptoms, limited data are available on the contribution of these aspects to health care costs. This study analyzes the association of frequent comorbidities and common symptoms with the annual direct and indirect costs of patients with COPD., Methods: Self-reported information on 33 potential comorbidities and symptoms (dyspnea, cough, and sputum) of 2,139 participants from the baseline examination of the German COPD cohort COSYCONET was used. Direct and indirect costs were calculated based on self-reported health care utilization, work absence, and retirement. The association of comorbidities, symptoms, and COPD stage with annual direct/indirect costs was assessed by generalized linear regression models. Additional models analyzed possible interactions between COPD stage, the number of comorbidities, and dyspnea., Results: Unadjusted mean annual direct costs were €7,263 per patient. Other than COPD stage, a high level of dyspnea showed the strongest driving effect on direct costs (+33%). Among the comorbidities, osteoporosis (+38%), psychiatric disorders (+36%), heart disease (+25%), cancer (+24%), and sleep apnea (+21%) were associated with the largest increase in direct costs ( p <0.01). A sub-additive interaction between advanced COPD stage and a high number of comorbidities reduced the independent cost-driving effects of these factors. For indirect costs, besides dyspnea (+34%), only psychiatric disorders (+32%) and age (+62% per 10 years) were identified as significant drivers of costs ( p <0.04). In the subsequent interaction analysis, a high number of comorbidities was found to be a more crucial factor for increased indirect costs than single comorbidities., Conclusion: Detailed knowledge about comorbidities in COPD is useful not only for clinical purposes but also to identify relevant cost factors and their interactions and to establish a ranking of major cost drivers. This could help in focusing therapeutic efforts on both clinically and economically important comorbidities in COPD., Competing Interests: Disclosure CV reports personal fees from the pharmaceutical companies Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Janssen, Mundipharma, Novartis, Takeda, and Cipla, and grants and personal fees from Grifols outside the submitted work. The other authors report no conflicts of interest in this work.

Purpose: Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow obstruction, is a major cause of morbidity and mortality worldwide. However, geographic differences in the clinical characteristics of severe COPD patients have not been widely studied., Methods: We recruited a total of 828 severe COPD cases from three continents. Subjects in Poland were enrolled by the Institute of Tuberculosis and Lung Diseases in Warsaw; subjects in Korea participated at several university hospitals in Korea; and subjects in USA were enrolled at two clinics affiliated with academic medical centers. All subjects were over the age of 30 with at least 10 pack-years of cigarette smoking history. Cases manifested severe to very severe airflow obstruction with post-bronchodilator forced expiratory volume in 1 second (FEV 1 ) <50% predicted and FEV 1 /forced vital capacity <0.7. All subjects completed a detailed questionnaire and underwent standardized pre-bronchodilator and post-bronchodilator spirometry. Subjects with known tuberculosis (TB)-associated lung parenchymal destruction were excluded. Univariate and multivariate assessments of the impact of the country of origin on respiratory symptoms and respiratory illness were performed., Results: In both univariate and multivariate analyses, a history of TB (38.7%) and physician-diagnosed asthma (43.9%) were significantly more common in subjects with severe COPD from Korea than USA or Poland, while attacks of bronchitis (64.2%) were more common in subjects with severe COPD from Poland. COPD subjects from Poland had more severe dyspnea (modified Medical Research Council 3.3±1.0) and more frequently reported symptoms of chronic bronchitis (52.2%). A history of TB was also more common in Poland (10.8%) than in USA (0.3%) severe COPD patients., Conclusion: Respiratory symptoms and other respiratory illnesses associated with severe COPD differed widely among three continents., Competing Interests: Disclosure In the past 3 years, Edwin K Silverman received honoraria and consulting fees from Merck, grant support and consulting fees from GlaxoSmithKline, and honoraria and travel support from Novartis. The other authors report no conflicts of interest in this work.

Background: Patients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQoL) that is disproportionate to their degree of airflow limitation. This study evaluated the association between St George's Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory volume in one second and investigated the factors responsible for high SGRQ-C score according to severity of airflow limitation., Methods: Data from 1,264 COPD patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort. Patients were categorized into two groups according to severity of airflow limitation: mild-to-moderate and severe-to-very severe COPD groups. We evaluated the clinical factors associated with high SGRQ-C score (≥25) in each COPD patient group., Results: Of the 1,264 COPD patients, 902 (71.4%) had mild-to-moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow limitation. Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ-C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had high SGRQ-C score. The association between SGRQ-C score and post-bronchodilator forced expiratory volume in one second (% predicted) was very weak in the mild-to-moderate COPD patients ( r =-0.103, p =0.002) and weak in the severe-to-very severe COPD patients ( r =-0.219, p <0.001). Multiple logistic regression analysis revealed that age, being an ex- or current smoker, lower level of education, cough, dyspnea, and number of comorbidities with congestive heart failure, hyperlipidemia, and depression were significantly associated with high SGRQ-C score in mild-to-moderate COPD patients. In comparison, being an ex-smoker and having respiratory symptoms including sputum and dyspnea were significant factors associated with high SGRQ-C score in severe-to-very severe COPD patients., Conclusions: In addition to the respiratory symptoms of dyspnea and cough, high SGRQ-C score was associated with extra-pulmonary comorbidities in mild-to-moderate COPD patients. However, only respiratory symptoms such as sputum and dyspnea were significantly associated with high SGRQ-C score in severe-to-very severe COPD patients. This indicates the need for an improved management strategy for relieving respiratory symptoms in COPD patients with poor HRQoL. In addition, attention should be paid to extra-pulmonary comorbidities, especially in mild-to-moderate COPD patients with poor HRQoL., Competing Interests: Disclosure Hye Yun Park received lecture fees from AstraZeneca, Novartis, and Boehringer-Ingelheim. The authors report no other conflicts of interest in this work.

Purpose: Smoking can affect both the phenotypic expression of COPD and factors such as disease severity, quality of life, and comorbidities. Our objective was to evaluate if the impact of active smoking on these factors varies according to the disease phenotype., Patients and Methods: This was a Spanish, observational, cross-sectional, multicenter study of patients with a diagnosis of COPD. Smoking rates were described among four different phenotypes (non-exacerbators, asthma-COPD overlap syndrome [ACOS], exacerbators with emphysema, and exacerbators with chronic bronchitis), and correlated with disease severity (body mass index, obstruction, dyspnea and exacerbations [BODEx] index and dyspnea grade), quality of life according to the COPD assessment test (CAT), and presence of comorbidities, according to phenotypic expression., Results: In total, 1,610 patients were recruited, of whom 46.70% were classified as non-exacerbators, 14.53% as ACOS, 16.37% as exacerbators with emphysema, and 22.40% as exacerbators with chronic bronchitis. Smokers were predominant in the latter 2 groups (58.91% and 57.67%, respectively, P =0.03). Active smoking was significantly associated with better quality of life and a higher dyspnea grade, although differences were observed depending on clinical phenotype., Conclusion: Active smoking is more common among exacerbator phenotypes and appears to affect quality of life and dyspnea grade differently, depending on the clinical expression of the disease., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Asthma, dyspnea, and chronic cough are well-established risk factors of COPD and often associated with exacerbation of the disease, which is a leading cause of morbidity and mortality in South Asian countries., Objective: The aims of this study were to, 1) measure the prevalence of asthma, dyspnea, and chronic cough, and 2) assess the relationship between these respiratory problems and self-reported health status among South Asians., Methods: Data for this research came from the World Health Survey (2002-2003) conducted by the World Health Organization. Subjects were 35,929 men and women, aged 18 years and older, selected from Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Crude prevalence rates of asthma, dyspnea, and chronic cough were presented as percentages, and the results of their association with subjective health status were presented as odds ratios and corresponding 95% CIs., Results: Prevalence of daily smoking was highest in Bangladesh (39.9%) and lowest in Sri Lanka (14.1%). Prevalence of asthma was highest in India (6.3%), while Nepal had the highest prevalence of dyspnea (11.3%) and chronic cough (15.3%). Overall prevalence of asthma and dyspnea was higher among women, while that of chronic cough was higher among men. Significant differences were observed in the prevalence rates of all the conditions among regular, occasional, and nonsmokers. A majority of the men and women who had asthma, dyspnea, and chronic cough had higher likelihood of reporting poor health status compared to those who did not have these diseases., Conclusion: Findings suggest that prevalence rates of asthma, dyspnea, and chronic cough were considerably high in all the countries and were significantly associated with poor subjective health. Being a high COPD-prone region, programs targeted to address these diseases could help reduce the burden of COPD and respiratory disease-related mortalities in South Asia., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD). However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear. This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports., Methods: Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000). Respondents aged ≥40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions., Results: Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score ≥2). Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively. Adjusted mean activity impairment (55% vs 37%, P <0.001) and number of emergency room visits (0.61 vs 0.40, P =0.030) were higher in patients with greater dyspnea., Conclusion: Many European patients with COPD continue to experience dyspnea despite treatment and at levels associated with notable impairments in the patients' ability to function across a multitude of domains. These patients may benefit from more intense treatment of their symptoms., Competing Interests: Disclosure Novartis paid fees to Kantar Health for access to survey data, analysis, and reporting. Jean-Bernard Gruenberger and Dorothy Keininger are employees of Novartis. Jeffrey Vietri is an employee of Kantar Health. Donald A Mahler has received consulting fees for advisory boards from Boehringer Ingelheim, GlaxoSmithKline (GSK), Novartis, Sunovion, and Theravance and is on Speaker’s Bureaus of Boehringer Ingelheim, GSK, and Sunovion. The authors report no other conflicts of interest in this work.

Introduction: Past research has suggested significant relationships between symptoms and health outcomes among patients with COPD. However, these studies have generally focused on a broad COPD sample and may have included those not receiving proper treatment. As a result, the aim of this study was to document the burden of COPD symptoms among those who are currently treated with the standard-of-care (SOC) medications in both the US and Western Europe., Methods: Data from the 2013 US (N=75,000) and 2011 (N=57,512)/2013 (N=62,000) European (France, Germany, Italy, Spain, and UK; 5EU) National Health and Wellness Survey (NHWS) were used. The NHWS is a health survey administered to a demographically representative sample of the adult population in each country. A total of 1,666 and 2,006 patients with self-reported physician diagnosis of COPD in the 5EU and US, respectively, were being treated with the appropriate SOC (based on self-reported medication use) and were included in the analyses. Symptoms (eg, dyspnea, coughing, wheezing) were reported descriptively and summed to create a symptom score (with higher score indicating more frequent symptoms). The relationships between the symptom score and patient outcomes (eg, health status using the Short Form-36 version 2 [SF-36v2], work productivity and activity impairment [WPAI], and self-reported health care resource use) were explored using regression modeling., Results: Nearly all patients (99.7% and 99.8% in the 5EU and US, respectively) reported experiencing symptoms and >80% reported experiencing at least one symptom "often". Increasing symptom scores were associated with poorer health status (unstandardized beta [ b ] =-0.87 and -0.78 for mental component summary and physical component summary, respectively, in the US and b =-0.67 and -0.79 in the 5EU, respectively; all P <0.05). Increasing symptom scores were also associated with greater work impairment ( b =0.09 and 0.06 for the US and 5EU, respectively), activity impairment ( b =0.05 and 0.06, respectively), and health care resource utilization (eg, hospitalizations: b =0.05 and 0.06, respectively) (all P <0.05). Approximately 70% of patients reported some level of non-adherence. Greater non-adherence was significantly associated with more frequent symptoms, poorer health status, and greater work impairment and health care resource use (all P <0.05)., Conclusion: Patients with COPD who are using the appropriate SOC still experience symptoms, which have a significant effect on both humanistic and economic outcomes., Competing Interests: Disclosure BD, NK, GB, and UH are full-time employees of AstraZeneca. During the conduct of the study, MD was a full-time employee of Kantar Health, the organization that received funding from AstraZeneca. The authors report no other conflicts of interest in this work.

Objective: To determine the prevalence, change in breathlessness status over time, and risk factors for disabling and persistent disabling breathlessness in relation to treatments in chronic obstructive pulmonary disease (COPD)., Materials and Methods: Longitudinal analysis of data from the Swedish National Register of COPD with breathlessness measured using modified Medical Research Council (mMRC) scores at two subsequent visits. Prevalence of disabling breathlessness (mMRC ≥2 at baseline) and persistent disabling breathlessness (disabling breathlessness at baseline and follow-up) was investigated in relation to COPD treatment. Risk factors for disabling breathlessness, change from non-disabling to disabling breathlessness, and persistent disabling breathlessness were analyzed using multiple logistic regression., Results: A total of 1,689 patients were included in the study with a median follow-up of 12 months (interquartile range: 4 months). Prevalence of disabling breathlessness was 54% at baseline. Persistent disabling breathlessness was present in 43% of patients despite treatment and in 74% of patients despite combined inhaled triple therapy and physiotherapy. Risk factors for disabling breathlessness or change to disabling breathlessness were higher age, lower lung function, frequent exacerbations, obesity, heart failure, depression, and hypoxic respiratory failure (all P <0.05). Persistent disabling breathlessness was associated with lower lung function and ischemic heart disease (all P <0.05)., Conclusion: Disabling breathlessness is common in COPD despite treatment, which calls for improved symptomatic treatments and consideration of factors influencing disabling breathlessness. Factors influencing disabling breathlessness should be considered for COPD management., Competing Interests: The authors report no conflicts of interest in this work.

Background: Low-dose opioids can relieve breathlessness but may be underused in late-stage COPD due to fear of complications, contributing to poor symptom control., Objectives: We aimed to study the period prevalence and indications of opioids actually prescribed in people with end-stage COPD., Methods: The study was a longitudinal, population-based study of patients starting long-term oxygen therapy (LTOT) for COPD between October 1, 2005 and June 30, 2009 in Sweden. A random sample (n=2,000) of their dispensed opioid prescriptions was obtained from the national Prescribed Drugs Register from 91 days before starting LTOT until the first of LTOT withdrawal, death, or study end (December 31, 2009). We analyzed medication type, dispensed quantity, date of dispensing, and indications categorized as pain, breathlessness, other, or unknown., Results: In total, 2,249 COPD patients (59% women) were included. During a median follow-up of 1.1 (interquartile range 0.6-2.0) years, 1,034 patients (46%) were dispensed ≥1 opioid prescription (N=13,722 prescriptions). The most frequently prescribed opioids were tramadol (23%), oxycodone (23%), morphine (16%), and codeine (16%). Average dispensed quantity was 9.3 (interquartile range 3.7-16.7) defined daily doses per prescription. In the random sample, the most commonly stated indication was pain (97%), with only 2% for breathlessness and 1% for other reasons., Conclusion: Despite evidence that supported the use of opioids for the relief of breathlessness predating this study, opioids are rarely prescribed to relieve breathlessness in oxygen-dependent COPD, potentially contributing to less-than-optimal symptom control. This study creates a baseline against which to compare future changes in morphine prescribing in this setting., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: The purpose of this study was to define the prevalence of undiagnosed airflow obstruction (AO) among subjects with a history of smoking but no previous diagnosis of chronic lung disease. The finding of AO likely represents diagnosis of chronic obstructive pulmonary disease., Patients: People aged ≥30 years with a history of smoking who attended public outpatient clinics for primary care services were included in this study., Methods: A cross-sectional survey in five clinics in Hong Kong using the Breathlessness, Cough, and Sputum Scale, the Lung Function Questionnaire, and office spirometry was conducted., Results: In total, 731 subjects (response rate =97.9%) completed the questionnaires and spirometry tests. Most of the subjects were men (92.5%) in the older age group (mean age =62.2 years; standard deviation =11.7). Of the 731 subjects, 107 had AO, giving a prevalence of 14.6% (95% confidence interval =12.1-17.2); 45 subjects with AO underwent a postbronchodilator test. By classifying the severity of chronic obstructive pulmonary disease using the Global Initiative for Chronic Obstructive Lung Disease, 27 (60%) were considered to be in mild category and 18 (40%) in moderate category. None of them belonged to the severe or very severe category. The total score of Lung Function Questionnaire showed that majority of the subjects with AO also had chronic cough, wheezing attack, or breathlessness, although most did not show any acute respiratory symptoms in accordance with the Breathlessness, Cough, and Sputum Scale. Diagnosis of AO was positively associated with the number of years of smoking (odds ratio =1.044, P =0.035) and being normal or underweight (odds ratio =1.605, P =0.046). It was negatively associated with a history of hypertension (odds ratio =0.491, P =0.003)., Conclusion: One-seventh of smokers have undiagnosed AO. Spirometry screening of smokers should be considered in order to diagnose AO at an early stage, with an emphasis on smoking cessation.

Purpose: This study aimed to investigate whether the prevalence of postoperative pulmonary complications (PPCs) in patients with non-small-cell lung cancer (NSCLC) is even higher in the early stages of COPD than in such patients with normal lung function and to verify the usefulness of symptom- or quality of life (QoL)-based scores in predicting risk for PPCs., Patients and Methods: Patients undergoing pulmonary resection for NSCLC between July 2012 and October 2014 were prospectively enrolled. Preoperative measurements of lung function, dyspnea, and QoL, operative characteristics, PPCs, duration of postoperative hospitalization, and in-hospital mortality were assessed., Results: Among 351 consecutive patients with NSCLC, 343 patients with forced expiratory volume in 1 second (FEV1) ≥70% of predicted value were enrolled. At least one PPC occurred in 57 (16.6%) patients. Prevalence of PPC was higher in patients with COPD (30.1%) than in those with normal spirometry (10.0%; P<0.001). However, in patients with COPD, the prevalence of PPC was not different in patients with FEV1 ≥70% compared to those with FEV1 <70% and between group A (low risk and less symptoms) and group B (low risk and more symptoms) patients with COPD, based on the new Global initiative for chronic Obstructive Lung Disease 2011 guidelines. In patients with COPD, body mass index (odds ratio [OR]: 0.80, P=0.007), carbon monoxide diffusing capacity of the lung (DLCO), % predicted value (OR: 0.97, P=0.024), and operation time (OR: 1.01, P=0.003), but not COPD assessment test or St George Respiratory Questionnaire scores, were significantly associated with PPCs., Conclusion: Even in patients with early-stage COPD, the prevalence of PPCs is higher than in patients with NSCLC with normal spirometry. However, this rate is not different between group A and group B patients with COPD. In accordance with this, scores based on symptoms or QoL are not predictors of risk of PPCs in patients with early-stage COPD.

Background: COPD is a civilization disease. It affects up to 8%-10% of population >30 years of age. Coexistence of depression occurs in 20%-40% of patients with COPD. Depression and anxiety reduce compliance and worsen prognosis., Objective: The aims of this study were to determine the degree of illness acceptance among patients with COPD, to examine the relation between disease acceptance and perceived anxiety and depression, and to verify which of the sociodemographic and clinical factors are associated with illness acceptance, anxiety, and depression., Materials and Methods: The study included 102 patients with COPD (mean age 65.8 years), hospitalized due to exacerbations. Acceptance of Illness Scale and Hospital Anxiety and Depression Scale were used. For statistical analysis, Student's t-test and Pearson's r correlation coefficient were carried out., Results: The overall illness acceptance level was moderate with a tendency toward lack of acceptance (mean 20.6, standard deviation [SD] 7.62). The overall scores were 10.2 (SD 3.32) for anxiety and 10.8 (SD 4.14) for depression, which indicate borderline or high intensity of these symptoms. Acceptance of illness was negatively correlated with the intensity of depression symptoms (r=-0.46, P<0.05). Intensity of depression was significantly associated with intensity of smoking, duration of the disease, severity of dyspnea, and living in a rural area., Conclusion: Early identification and assessment of depression and anxiety symptoms allow health care providers to offer patients at risk of depression a special medical supervision. Rapid start of antidepressant therapy may increase illness acceptance and improve prognosis among patients with COPD.

Objective: The aim of this study is to describe the frequency of reasons for elderly patients visits to a general practice (GP) setting., Subjects and Methods: Cross-sectional data from 8,877 randomly selected patients were assessed during a 1-year period by 209 GPs in the German federal state of Saxony. The reasons for visits, performed procedures, and results of visits were documented. In this study, the data of patients aged 65 years and older are analyzed and the procedural and nonprocedural reasons for visits are described., Results: In all, 2,866 patients aged 65 years and older were included. The majority of patients (1,807) were female. A total of 4,426 reasons for visits were found, distributed on 363 International Classification of Primary Care-2 codes. In the mean, there were 1.5 reasons for a GP visit from each patient. The top five nonprocedural reasons for visiting the GP were: cough (1.8%), back complaints (1.6%), shoulder complaints (1.3%), knee complaints (1.1%), and dyspnea (1.0% of all reasons for visit). The top five procedural reasons for visiting the GP included follow-up investigations of cardiovascular or endocrine disorders and immunizations. The top 30 nonprocedural reasons for visits covered 21.9% of all reasons for visiting. The top 30 procedural reasons covered 54.3% of all reasons for visits., Conclusion: The current work indicates that people aged 65 years and older consult the GP more frequently for procedural than for nonprocedural reasons. The top 30 procedural and nonprocedural reasons for visits cover ~75% of all reasons for visits in these patients.

Background: The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR(®), the largest randomized clinical trial in COPD performed to date., Methods: A total of 17,135 patients from TIOSPIR(®) were pooled and grouped by GOLD grading (A-D) according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular (CV) and respiratory mortality were assessed., Results: Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV mortality - hazard ratio [HR] =1.74, P=0.004; all-cause mortality - HR =1.18, P=0.11). Group D patients had a higher incidence of all-cause mortality than Group B patients (10.9% vs 6.6%). Similar trends were observed regardless of respiratory or CV medication at baseline. In contrast, respiratory deaths increased consistently from Groups A-D (0.3%, 0.8%, 1.6%, and 4.2% of patients, respectively)., Conclusion: The data obtained from the TIOSPIR(®) trial, supporting earlier studies, suggest that proportionally more CV medication and CV deaths occur in GOLD Group B COPD patients, although deaths attributed to respiratory causes are more prevalent in Groups C and D.

Background: Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials. Little is known on the correspondence between the two methods., Methods: Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO. Dyspnea was assessed by the mMRC scale and the BDI. Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George's Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained. Correlations between mMRC and BDI scores were assessed using Spearman's correlation coefficient. An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores., Results: Data are given as median (interquartile ranges, [IQR]). Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]). The mMRC grade and BDI score were, respectively, 1 [1-3] and 6 [4-8]. Both BDI and mMRC scores were significantly correlated at the group level (rho =-0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade. In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio. The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index., Conclusion: Dyspnea is a complex symptom with multiple determinants in COPD patients. Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable.

Background and Objective: According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, either a modified Medical Research Council (mMRC) dyspnea score of ≥2 or a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score of ≥10 is considered to represent COPD patients who are more symptomatic. We aimed to identify the ideal CAT score that exhibits minimal discrepancy with the mMRC score., Methods: A receiver operating characteristic curve of the CAT score was generated for an mMRC scores of 1 and 2. A concordance analysis was applied to quantify the association between the frequencies of patients categorized into GOLD groups A-D using symptom cutoff points. A κ-coefficient was calculated., Results: For an mMRC score of 2, a CAT score of 15 showed the maximum value of Youden's index with a sensitivity and specificity of 0.70 and 0.66, respectively (area under the receiver operating characteristic curve [AUC] 0.74; 95% confidence interval [CI], 0.70-0.77). For an mMRC score of 1, a CAT score of 10 showed the maximum value of Youden's index with a sensitivity and specificity of 0.77 and 0.65, respectively (AUC 0.77; 95% CI, 0.72-0.83). The κ value for concordance was highest between an mMRC score of 1 and a CAT score of 10 (0.66), followed by an mMRC score of 2 and a CAT score of 15 (0.56), an mMRC score of 2 and a CAT score of 10 (0.47), and an mMRC score of 1 and a CAT score of 15 (0.43)., Conclusion: A CAT score of 10 was most concordant with an mMRC score of 1 when classifying patients with COPD into GOLD groups A-D. However, a discrepancy remains between the CAT and mMRC scoring systems.

Background: The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012., Methods: Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design., Results: The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years). Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD. Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers. Smoking duration had a linear relationship with COPD (P<0.001) and all three respiratory symptoms (P<0.001) after adjusting for smoking status and other covariates. While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1-9 years, 20-29 years, and ≥30 years duration periods., Conclusion: These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior.

Background: The COPD Assessment Test (CAT) has been recently developed to quantify COPD impact in routine practice. However, no relationship with other measures in the Global Initiative for Obstructive Lung Disease (GOLD) strategy has been evaluated. The present study aimed to evaluate the relationship of the CAT with other GOLD multidimensional axes, patient types, and the number of comorbidities., Methods: This was a cross-sectional analysis of the Clinical presentation, diagnosis, and course of chronic obstructive pulmonary disease (On-Sint) study. The CAT score was administered to all participants at the inclusion visit. A GOLD 2011 strategy consisting of modified Medical Research Council scale (MRC) scores was devised to study the relationship between the CAT, and GOLD 2011 axes and patient types. The relationship with comorbidities was assessed using the Charlson comorbidity index, grouped as zero, one to two, and three or more., Results: The CAT questionnaire was completed by 1,212 patients with COPD. The CAT maintained a relationship with all the three axes, with a ceiling effect for dyspnea and no distinction between mild and moderate functional impairment. The CAT score increased across GOLD 2011 patient types A-D, with similar scores for types B and C. Within each GOLD 2011 patient type, there was a considerably wide distribution of CAT values., Conclusion: Our study indicates a correlation between CAT and the GOLD 2011 classification axes as well as the number of comorbidities. The CAT score can help clinicians, as a complementary tool to evaluate patients with COPD within the different GOLD patient types.

Objectives: In 2013, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) updated the management strategy on COPD based on severity using a combined assessment of symptoms, degree of airflow limitation, and number of exacerbations. This study quantified prevalence and incidence of COPD in the United Kingdom and estimated disease severity by GOLD 2013 categories A/B (low risk) and C/D (high risk)., Methods: The Clinical Practice Research Datalink was used to identify COPD patients ≥40 years. Patient characteristics were described, and prevalence was calculated on December 31, 2013. Five-year incidence (2009-2013) was estimated, with rates standardized using 2011 UK population age and sex. To classify patients by GOLD categories, spirometry results, the modified British Medical Research Council grade, and history of exacerbations were used., Results: The prevalent cohort comprised 49,286 patients with COPD with mean age 70 years; 51.0% were male. Overall prevalence was 33.3 per 1,000 persons (95% confidence interval [CI]: 33.1-33.6); 66.4% were classified as GOLD A/B and 33.6% as C/D. The standardized prevalence of GOLD A/B was 21.9 per 1,000 persons (95% CI: 21.7-22.1) and of C/D was 11.1 (95% CI: 10.9-11.2). A total of 27,224 newly diagnosed COPD patients were identified with mean age 67 years at diagnosis; 53.0% were male. Incidence was 2.2 per 1,000 person-years (95% CI: 2.2-2.3); 68.7% were classified in categories A/B and 31.3% in C/D, of which 17.2% did not receive COPD maintenance medication., Conclusion: A third of COPD patients in the UK are considered high risk (GOLD 2013 categories C/D), and a third of patients are diagnosed for the first time at these severe stages. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD in the UK is warranted.

Background: Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase. The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations., Methods: Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months. The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction., Results: Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase. These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients. In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results. Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients. The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations., Conclusion: Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients.

Background and Objective: Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients., Patients and Methods: In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated., Results: Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage., Conclusion: COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity.

Background: 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., Aim: Comparisons of symptoms, impact of symptoms on function and health between patients with COPD and CHF in primary health care (PHC)., Method: 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., Results: 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., Conclusion: 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.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients., Methods: This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia. The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life., Results: Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea. These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons). Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV(1)], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George's Respiratory Questionnaire [SGRQ] total score, P = 0.001). Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV(1), P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006)., Conclusion: In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life.

Background: Improvement in quality of life (QOL) has become a focus for the management of incurable chronic diseases, including chronic obstructive pulmonary disease (COPD). This study investigates factors influencing the QOL of patients with COPD in India., Methods: Seventy-three consecutive COPD patients visiting an outpatient pulmonary clinic underwent health-related QOL (HRQOL) assessment using the World Health Organization's QOL abbreviated questionnaire and St George's Respiratory Questionnaire (SGRQ). Symptom severity and grade of dyspnea were estimated by the Chronic Lung Disease Severity Index (CLD) and Medical Research Council assessments, and patient demographic data were collected. Spirometry and 6-minute walk tests were performed to assess lung function and functional status., Results: Patients with COPD showed significantly reduced HRQOL when measured by the World Health Organization's QOL abbreviated questionnaire and the SGRQ. CLD estimate for severity of lung disease (P < 0.001), Medical Research Council assessment for dyspnea (P < 0.01), and duration of illness (P < 0.05) showed close correlation with HRQOL. Worsening forced expiratory volume in 1 second and 6-minute walk test results closely correlated with poorer HRQOL (P < 0.01). No association between QOL and age, quantum of smoking, education, comorbid illnesses, or occupational exposure was found., Conclusion: This study showed that Indian patients with COPD had reduced HRQOL. Longer disease duration, patient perception of disease severity, and worsening dyspnea impacted negatively on HRQOL.