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Background: Risk of exacerbations in individuals with mild chronic obstructive pulmonary disease (COPD) in the general population is less well described than in more advanced disease. We hypothesized that in addition to history of previous exacerbation also other clinical characteristics predict future moderate exacerbations., Methods: In 96,462 individuals in the Copenhagen General Population Study, we identified 3175 with clinical COPD defined as forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) < 0.70 and FEV 1 <80% predicted in symptomatic individuals without asthma. We estimated the importance of age, sex, FEV 1 , modified Medical Research Council (mMRC) dyspnea scale, chronic bronchitis, exacerbation history, comorbidities, cohabitation, body mass index, smoking, and blood eosinophils for the 1-year and 3-year future risk of moderate COPD exacerbations and developed a prediction tool for future exacerbations in COPD in the general population based on easily available clinical information., Results: We observed 265 exacerbations in 2543 maintenance treatment naïve individuals with COPD and 197 exacerbations in 632 individuals with COPD on maintenance treatment. In the maintenance treatment naïve group, exacerbation history (hazard ratio (HR): 8.53), low FEV 1 (HR: 4.82 for <30% predicted versus 50-79% predicted), and higher age (HR: 1.46 for ≥75 years versus <65 years) were significant predictors of future exacerbations. In the group on maintenance treatment, male sex and mMRC ≥2 also predicted higher risk with borderline significance., Conclusions: In addition to exacerbation history also higher age and lower FEV 1 predict future exacerbation risk in COPD in the general population., Competing Interests: Declaration of competing interest TS Ingebrigtsen reports a personal fee from AstraZeneca. Y Çolak reports personal fees from AstraZeneca, Boehringer-Ingelheim, GSK, and Sanofi and grant support from Sanofi. J Vestbo reports personal fees from ALK-Abello, AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, Novartis, and Teva. P Lange reports personal fees from AstraZeneca, GSK, and Sanofi and grant support from Sanofi and another in relation to the present work from AstraZeneca. JL Marott and BG Nordestgaard have no disclosures to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: It is unclear if type-2 inflammation is associated with accelerated lung function decline in individuals with asthma and chronic obstructive pulmonary disease (COPD). We tested the hypothesis that type-2 inflammation indicated by elevated blood eosinophils (BE) and fraction of exhaled nitric oxide (FeNO) is associated with accelerated lung function decline in the general population., Methods: We included adults from the Copenhagen General Population Study with measurements of BE (N=15 605) and FeNO (N=2583) from a follow-up examination and assessed forced expiratory volume in 1 s (FEV 1 ) decline in the preceding 10 years. Based on pre- and post-bronchodilator lung function, smoking history and asthma at follow-up examination, participants were assigned as not having airway disease, asthma with full reversibility (AR), asthma with persistent obstruction (APO), COPD, and not classifiable airflow limitation (NAL)., Results: FEV 1 decline in mL/year increased with 1.0 (95% CI 0.6 to 1.4, p<0.0001) per 100 cells/µL higher BE and with 3.2 (95% CI 2.0 to 4.5, p<0.0001) per 10 ppb higher FeNO. Adjusted FEV 1 decline in mL/year was 18 (95% CI 17 to 20) in those with BE<300 cells/µL and FeNO<20 ppb, 22 (19-25) in BE≥300 cells/µL or FeNO≥20 ppb, and 27 (21-33) in those with BE≥300 cells/µL and FeNO≥20 ppb (p for trend<0.0001). Corresponding FEV 1 declines were 24 (19-29), 33 (25-40) and 44 (31-56) in AR (0.002), 26 (14-37), 36 (12-60) and 56 (24-89) in APO (0.07), 32 (27-36), 31 (24-38) and 44 (24-65) in COPD (0.46), and 27 (21-33), 35 (26-45), and 37 (25-49) in NAL (0.10), respectively., Conclusions: Type-2 inflammation indicated by elevated BE and FeNO is associated with accelerated FEV 1 decline in individuals with chronic airway disease in the general population, and this association was most pronounced in an asthma-like phenotype., Competing Interests: Competing interests: YÇ reports grants from Sanofi and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Sanofi outside the submitted work. JV reports personal fees from ALK, AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline and Teva outside the submitted work. PL reports grants and personal fees from AstraZeneca and Sanofi and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi outside the submitted work. SA, JLM and BGN have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The relationships between spirometric assessment of lung function and symptoms (including exacerbations) in patients with asthma and/or chronic obstructive pulmonary disease (COPD) in a real-life setting are uncertain., Objectives: To assess the relationships between baseline post-bronchodilator (post-BD) spirometry measures of lung function and symptoms and exacerbations in patients with a physician-assigned diagnosis of asthma and/or COPD., Design: The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, 3-year observational study., Methods: Logistic regression analysis was used to evaluate relationships. Spirometry measures were assessed as percent predicted (%pred). Symptoms were assessed at baseline, and exacerbations were assessed at baseline and Year 1., Results: A total of 11,181 patients in NOVELTY had spirometry data (asthma, n  = 5903; COPD, n  = 3881; asthma + COPD, n  = 1397). A 10% lower post-BD %pred forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) - adjusted for age and sex - were significantly associated with dyspnea (modified Medical Research Council ⩾ grade 2), frequent breathlessness [St George's Respiratory Questionnaire (SGRQ)], frequent wheeze attacks (SGRQ), nocturnal awakening (Respiratory Symptoms Questionnaire; ⩾1 night/week), and frequent productive cough (SGRQ). Lower post-BD %pred FEV 1 and, to a lesser extent, lower post-BD %pred FVC were significantly associated with ⩾1 physician-reported exacerbation at baseline or Year 1. This association was stronger in patients with COPD than in those with asthma., Conclusion: In a real-life setting, reduced lung function is consistently associated with symptoms in patients with asthma, COPD, or asthma + COPD. The relationship with exacerbations is stronger in COPD only than in asthma., Trail Registration: clinicaltrials.gov identifier: NCT02760329 (www.clinicaltrials.gov).

Introduction: Viruses are detected in over 50% of acute asthma attacks and in a notable proportion of patients with asthma during stable disease state They are associated with worse outcomes. We will conduct a series of systematic reviews and meta-analyses to quantify the prevalence and clinical burden of various respiratory viruses in stable asthma and acute asthma attacks. In addition, we will assess the viral loads of respiratory viruses during stable and acute asthma, to explore whether viral load could differentiate attacks triggered by viruses versus those where viruses are present as "innocent bystanders"., Materials and Methods: Based on a prospectively registered protocol (PROSPERO, ID: CRD42023375108) and following standard methodology recommended by Cochrane, we will systematically search Medline/PubMed, EMBASE, the Cochrane Library and relevant conference proceedings for studies assessing the prevalence or clinical burden of respiratory viruses in asthma. Methodological rigour of the included studies will be appraised using a tool specific for prevalence studies and the Newcastle-Ottawa Scale respectively. In anticipation of significant clinical and methodological heterogeneity, we will conduct random effect meta-analyses. For evaluating the prevalence of viruses, we will perform meta-analyses of proportions using the inverse variance method, and the Freeman-Tukey transformation. We will conduct meta-regression analyses for exploring heterogeneity., Conclusion: We envisage that these systematic reviews and meta-analyses will quantify the prevalence and burden of respiratory viruses in stable and acute asthma and will drive future research and clinical practice., Competing Interests: All authors have completed the ICMJE uniform disclosure form. None of the authors had any conflicts of interest directly related to this work. GSA, SA, CB, JV, EK, EP, AGM report no conflicts of interest NGP reports grants from Capricare, Nestle, Numil, and Vianex, and consulting fees from Abbott, Abbvie, Astra Zeneca, GSK, HAL, Medscape, Menarini/Faes Farma, Mylan, Novartis, Nutricia, OM Pharma, Regeneron/Sanofi not related to this work. CK reports grants from the NIHR Research for Patient Benefit Programme and from the MRC Newton Fund, honoraria from Pfizer Inc, and support for attending meetings and/or travel by Pfizer Inc, not related to this work. GR reports grants from the NIHR Research for Patients’ Benefit Programme and NIHR Efficacy and Mechanism Evaluation Programme, not related to this work. AB reports grants from Gilead and GlaxoSmithKline, not related to this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2023 Alimani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Asthma and chronic obstructive pulmonary disease (COPD) are complex diseases, the definitions of which overlap., Objective: To investigate clustering of clinical/physiological features and readily available biomarkers in patients with physician-assigned diagnoses of asthma and/or COPD in the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329)., Methods: Two approaches were taken to variable selection using baseline data: approach A was data-driven, hypothesis-free and used the Pearson dissimilarity matrix; approach B used an unsupervised Random Forest guided by clinical input. Cluster analyses were conducted across 100 random resamples using partitioning around medoids, followed by consensus clustering., Results: Approach A included 3796 individuals (mean age, 59.5 years; 54% female); approach B included 2934 patients (mean age, 60.7 years; 53% female). Each identified 6 mathematically stable clusters, which had overlapping characteristics. Overall, 67% to 75% of patients with asthma were in 3 clusters, and approximately 90% of patients with COPD were in 3 clusters. Although traditional features such as allergies and current/ex-smoking (respectively) were higher in these clusters, there were differences between clusters and approaches in features such as sex, ethnicity, breathlessness, frequent productive cough, and blood cell counts. The strongest predictors of the approach A cluster membership were age, weight, childhood onset, prebronchodilator FEV 1 , duration of dust/fume exposure, and number of daily medications., Conclusions: Cluster analyses in patients from NOVELTY with asthma and/or COPD yielded identifiable clusters, with several discriminatory features that differed from conventional diagnostic characteristics. The overlap between clusters suggests that they do not reflect discrete underlying mechanisms and points to the need for identification of molecular endotypes and potential treatment targets across asthma and/or COPD., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The increasing prevalence of reported annoyances in the indoor environment threatens public health. This study aimed to investigate the association between perceived annoyances from the home environment and respiratory infections among individuals with and without asthma or chronic obstructive pulmonary disease (COPD). A total of 16,688 individuals from the Danish Health and Morbidity Survey initiated in 2000 were grouped according to their patterns of perceived annoyances. Information on respiratory infections (all causes, bacterial, viral, and those leading to hospital admissions) was obtained from Danish registers up to 19 years after the survey. Poisson regression of incidence rates (IRs) was applied to estimate incidence rate ratios (IRRs). Annoyances significantly increased the IR for respiratory infections of all causes and bacterial respiratory infections in individuals without asthma or COPD, adjusted IRR 1.16 (95% CI: 1.01, 1.34) and 1.15 (95% CI: 1.02, 1.31), respectively. However, no difference was observed for viral respiratory infections nor hospital admissions. Individuals with asthma or COPD and a high level of annoyances had a non-significantly increased IR in all four analyses of respiratory infections. These findings provide support for perceived annoyances as an important risk factor for respiratory infections.

Background: Novel biomarkers and targeted treatments are needed for patients with chronic obstructive pulmonary disease (COPD)., Objective: To test the hypothesis that high plasma immunoglobulin (Ig)E concentrations associate with increased risk of exacerbation and mortality in individuals with COPD in the general population., Methods: Among 46,598 adults in the Copenhagen General Population Study, we included 1559 with COPD, defined as forced expiratory volume in 1 second/forced vital capacity &lt; 0.70 and forced expiratory volume in 1 second &lt; 80% predicted in individuals aged ≥ 40 years with chronic respiratory symptoms and smoking exposure ≥ 10 pack-years, and without asthma. We assessed risk of future severe exacerbation and all-cause mortality according to baseline plasma IgE ≥ 76 IU/mL, a clinical cutoff for omalizumab treatment in severe asthma., Results: During 14 years of follow-up (median, 6.9; interquartile range, 3.4), we recorded 224 severe exacerbations and 434 deaths in 1559 individuals with COPD. Individuals with COPD with IgE ≥ 76 IU/mL vs those with &lt; 76 IU/mL had a multivariable adjusted hazard ratio (HR) of 1.43 (95% confidence interval, 1.07-1.89) for severe exacerbation and 1.30 (1.05-1.62) for all-cause mortality. Compared with individuals with IgE &lt; 76 IU/mL and blood eosinophils &lt; 300 cells/µL, the multivariable adjusted HR for severe exacerbation was 1.12 (0.76-1.67) for those with IgE &lt; 76 IU/mL and blood eosinophils ≥ 300 cells/µL, 1.62 (1.17-2.24) for IgE ≥ 76 IU/mL and blood eosinophils &lt; 300 cells/µL, and 1.06 (0.63-1.77) for those with IgE ≥ 76 IU/mL and blood eosinophils ≥ 300 cells/µL. Corresponding HRs for all-cause mortality were 1.27 (0.99-1.63), 1.47 (1.14-1.88), and 1.17 (0.83-1.64), respectively., Conclusion: High plasma IgE was associated with an increased risk of severe exacerbation and all-cause mortality in individuals with COPD in the general population, independent of blood eosinophils., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Randomized controlled trials only include a subset of patients with chronic obstructive pulmonary disease (COPD) fulfilling strict inclusion criteria. Thus, most patients with COPD in a real-world setting do not have the necessary evidence to support treatment effectiveness. Objectives: To test the hypotheses that most individuals with COPD in the general population are not represented in major clinical trials despite clinically significant disease with exacerbations and early death. Methods: In 105,630 adults from a Danish contemporary population-based cohort, we defined COPD as age 40 or more years, chronic respiratory symptoms, history of smoking exposure, and airflow limitation with FEV 1 /FVC < 0.70. Outcomes included acute exacerbations and all-cause mortality. Symptomatic smokers without COPD were used as a reference group. Measurements and Main Results: Of all, 7,516 (7%) and 16,079 (15%) were symptomatic smokers with and without COPD. Only 44% of those with COPD were eligible for major clinical trials when applying FEV 1  < 80% predicted, smoking history of 10 or more pack-years, and no comorbid asthma as common inclusion criteria. During the median 8.9 years of follow-up, we observed 2,130 acute exacerbations and 3,973 deaths in symptomatic smokers. Compared with symptomatic smokers without COPD, multivariable-adjusted hazard ratios for exacerbations were 7.45 (95% confidence interval, 5.41-10.3) and 29.0 (21.1-39.8) in those with COPD, respectively, excluded and eligible for clinical trials. Corresponding hazard ratios for all-cause mortality were 1.21 (1.11-1.31) and 1.67 (1.54-1.81), respectively. Conclusions: More than half of individuals with COPD in the general population are excluded from major clinical trials; however, these individuals have a clinically significant disease with exacerbations and early death compared with symptomatic smokers without COPD.

Background: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort., Methods: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis., Results: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses., Conclusion: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications., Competing Interests: Conflict of interest: H.K. Reddel reports grants, personal fees and non-financial support from AstraZeneca, during the conduct of the study; grants and personal fees for data monitoring committee work, advisory board work and providing independent medical education from AstraZeneca and GlaxoSmithKline, personal fees for data monitoring committee work from Merck, personal fees for data monitoring committee work, advisory board work and grant for registry from Novartis, personal fees for providing independent medical education from Teva, personal fees for advisory board work and providing independent medical education from Boehringer Ingelheim, and personal fees for advisory board work from Sanofi Genzyme and Chiesi, outside the submitted work; and is Chair of the GINA Scientific Committee and a member of the GINA Board. Conflict of interest: J. Vestbo reports personal fees for steering committee work from AstraZeneca, during the conduct of the study; and personal fees for consultancy and lectures from GlaxoSmithKline, Chiesi Pharmaceuticals, Novartis and AstraZeneca, and grants and personal fees for consultancy and lectures from Boehringer Ingelheim, outside the submitted work. Conflict of interest: A. Agusti reports personal fees for scientific committee work from AstraZeneca, during the conduct of the study; and grants and personal fees for lectures and advisory board work from GlaxoSmithKline and Menarini, and personal fees for lectures and advisory board work from Chiesi, outside the submitted work. Conflict of interest: G.P. Anderson reports personal fees for consultancy and share options from Pieris Pharmaceuticals, ENA Therapeutics and ENA Respiratory, personal fees for scientific committee work from AstraZeneca, and personal fees for lectures from GlaxoSmithKline, AstraZeneca, Menarini and Novartis, outside the submitted work; and has US Patent 7,455,836 licensed to MorphoSys, sublicensed to GlaxoSmithKline. Conflict of interest: A.T. Bansal has nothing to disclose. Conflict of interest: R. Beasley reports personal fees for steering committee work from AstraZeneca, during the conduct of the study; and grants and personal fees from AstraZeneca and GlaxoSmithKline, personal fees from Avillion and Theravance, and grants from Genentech, outside the submitted work. Conflict of interest: E.H. Bel reports grants and personal fees from AstraZeneca, GlaxoSmithKline, Novartis and Teva, and personal fees from Sanofi/Regeneron, Sterna and Chiesi, outside the submitted work. Conflict of interest: C. Janson reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, outside the submitted work. Conflict of interest: B. Make reports grants, non-financial support and other (advisory board and presentations) from AstraZeneca, grants, non-financial support and other from GlaxoSmithKline, non-financial support for data monitoring committee work from Spiration, grants, non-financial support and other (advisory board) from Sunovion, other (CME activity) from Mt. Sinai, Web MD, National Jewish Health, Novartis, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, Medscape, Ultimate Medical Academy, Eastern Pulmonary Society, Catamount Medical, Eastern VA Medical Center, Academy Continued Health Care Learning and Wolters Kluwer Health, grants from Pearl Research and NHLBI, other (advisory board) from Verona, Boehringer Ingelheim, Theravance and Science 24/7, non-financial support and other (advisory board) from Circassia and Phillips, personal fees and non-financial support for consultancy from Third Pole, non-financial support and other (data monitoring committee) from Shire, and personal fees for data monitoring committee work from Takeda, outside the submitted work. Conflict of interest: I.D. Pavord reports personal fees for lectures, advisory board work, meeting attendance and organising educational events from AstraZeneca, personal fees for lectures, advisory board work and meeting attendance from Boehringer Ingelheim and GlaxoSmithKline, personal fees for lectures from Aerocrine and Chiesi, personal fees for lectures and advisory board work from Almirall and Novartis, personal fees for advisory board work from Genentech, Regeneron, Sanofi, Circassia and Knopp, personal fees for lectures, meeting attendance and organising educational events from Teva, and grants from NIHR, outside the submitted work. Conflict of interest: D. Price reports study funding from AstraZeneca, during the conduct of the study; personal fees for advisory board work and consultancy from Amgen, grants and personal fees for advisory board work, lectures, consultancy and travel/accommodation/meeting expenses from AstraZeneca and Boehringer Ingelheim, grants and personal fees for advisory board work, lectures and consultancy from Chiesi, Mylan and Teva, grants and personal fees for advisory board work from Circassia, personal fees for lectures from Cipla and Kyorin, personal fees for consultancy and lectures from GlaxoSmithKline, grants and personal fees for advisory board work, lectures, consultancy, travel/accommodation/meeting expenses and educational activities from Mundipharma and Novartis, grants and personal fees for consultancy from Pfizer and Theravance, grants and personal fees for advisory board work and lectures from Regeneron Pharmaceuticals and Sanofi Genzyme, grants from Respiratory Effectiveness Group and UK National Health Service, personal fees for advisory board work and travel/accommodation/meeting expenses from ThermoFisher, non-financial support for grant committee reviewing from Efficacy and Evaluation Mechanism Programme and Health Technology Assessment, outside the submitted work; has stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; and is part owner of the social enterprise Optimum Patient Care Ltd (Australia and UK) and of the Observational and Pragmatic Research Institute Pte Ltd (Singapore). Conflict of interest: E. Rapsomaniki is an employee of AstraZeneca (UK). Conflict of interest: N. Karlsson is an employee of AstraZeneca. Conflict of interest: D.K. Finch was an employee of AstraZeneca at the time of authorship. Conflict of interest: J. Nuevo is an employee of AstraZeneca. Conflict of interest: A. de Giorgio-Miller has nothing to disclose. Conflict of interest: M. Alacqua has nothing to disclose. Conflict of interest: R. Hughes reports personal fees from GlaxoSmithKline, Novartis, Boehringer Ingelheim and AstraZeneca, outside the submitted work; and is an employee of AstraZeneca. Conflict of interest: H. Müllerová is an employee of AstraZeneca. Conflict of interest: M. Gerhardsson de Verdier is an employee of AstraZeneca., (Copyright ©The authors 2021.)

Background: Asthma and COPD diagnoses are used to classify chronic airway diseases; however, both diseases are related to phenotypic traits like allergy, obesity, cough, sputum production, low-grade inflammation, smoking, elevated blood eosinophil count, comorbidities, and occupational exposures. Whether such traits can replace asthma and COPD diagnoses when assessing risk of exacerbation is unclear. We tested the hypothesis that individuals with either asthma or COPD diagnoses have similar risk of moderate and severe exacerbations when adjusted for differences in phenotypic traits., Methods: From the Copenhagen General Population Study, a cohort study of the general population, we included 7190 individuals with chronic airway disease. Phenotypic traits were recorded at baseline and risk of exacerbations was assessed during follow-up from 2003 to 2013., Results: The incidence rate ratio (IRR) of moderate exacerbations in individuals with clinical COPD was 1.61 (95% Confidence Interval, 1.27-2.02) compared to individuals with asthma in a model only adjusted for age, sex, and education, but after the inclusion of phenotypic traits IRR was 1.05 (0.82-1.35). Corresponding IRRs of severe exacerbations in individuals with clinical COPD versus asthma were 3.82 (2.73-5.35) and 2.28 (1.63-3.20), respectively., Conclusions: When taking phenotypic traits into account, individuals with asthma and COPD had comparable risk of moderate exacerbations; however, corresponding risk of severe exacerbations was higher in individuals with COPD than in those with asthma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant- and fungal-derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Introduction: We investigated risk of coronary heart disease and heart failure in phenotypes of obstructive airway disease., Methods: Among 91 692 participants in the Copenhagen General Population Study, 42 058 individuals were classified with no respiratory disease, and 11 988 individuals had different phenotypes of obstructive airways disease: asthma with early onset or late-onset, chronic obstructive pulmonary disease (COPD) with forced expiratory volume in one second (FEV 1 ) above or below 50% of predicted value (%p) or asthma-COPD overlap (ACO)., Results: During a mean follow-up of 5.7 years we registered 3584 admissions for coronary heart disease and 1590 admissions for heart failure. Multivariable Cox regression analyses of time to first admission were used with a two-sided p value of 0.05 as significance level. Compared with no respiratory disease the highest risks of coronary heart disease and heart failure were observed in ACO with late-onset asthma and FEV 1 <50% p, HR=2.2 (95% CI 1.6 to 3.0), and HR=2.9 (95% CI 2.0 to 4.3), respectively. In COPD with FEV 1 above 50% p the HRs were 1.3 (95% CI 1.2 to 1.5) for coronary heart disease and 1.9 (95% CI 1.6 to 2.3) for heart failure. Asthma associated with increased risks of coronary heart disease and heart failure, however, in asthma without allergy the HR was 1.1 (95% CI 0.7 to 1.6) for coronary heart disease while individuals with allergy had an HR of 1.4 (95% CI 1.1 to 1.6)., Conclusions: Risks of coronary heart disease and heart failure were increased in asthma, COPD and ACO. In asthma, the risk of coronary heart disease depended on presence of allergy. We suggest that cardiovascular risk factors should be assessed systematically in individuals with obstructive airway disease with the potential to facilitate targeted treatments., Competing Interests: Competing interests: TSI has received fee for speaking from AstraZeneca. JV has received fee for speaking from AstraZeneca, Boehringer Ingelheim, Chiesi and Novartis; received fee for consulting from AstraZeneca, Boehringer Ingelheim, Chiesi and Novartis. PL has received research grants from Astra Zeneca, Boehringer Ingelheim and GlaxoSmithKline; received fee for speaking from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithCline; received fee for consulting from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Asthma Salford Lung Study demonstrated the effectiveness and safety of initiating once-daily inhaled fluticasone furoate/vilanterol (FF/VI) versus continuing usual care (UC) in asthma patients in UK primary care [1]. Here, we report a detailed analysis of patient-reported outcome (PRO) endpoints., Methods: Adults with symptomatic asthma maintained on inhaled corticosteroids (ICS) ± long-acting beta 2 -agonists (LABA) were randomized 1:1 to initiate FF/VI (100 [200]/25 μg) or continue UC. PROs were measured using the Asthma Control Test (ACT), Standardized Asthma Quality of Life Questionnaire (AQLQ [S]), Work Productivity and Activity Impairment: asthma questionnaire, and EQ-5D-3L (EuroQol 5-Dimensions 3-Levels) questionnaire, at timepoints across the 12-month study period., Results: The individual components of ACT response (total score ≥20 or improvement from baseline ≥3) both contributed to the composite primary effectiveness endpoint at Week 24, with odds ratios favoring FF/VI over UC in both cases. Patients initiating FF/VI versus continuing UC were more likely to maintain/improve asthma control, regardless of baseline control status. The odds of patients being responders on AQLQ (S) total score and on individual AQLQ domains at Week 52 were significantly higher for FF/VI versus UC (all p < .001). FF/VI was associated with significantly greater reductions in overall work and activity impairment due to asthma (both p < .001), and a significantly greater change from baseline in EQ visual analogue scale score (p = .007), versus UC at Week 52. PRO findings were consistent across baseline ICS and ICS/LABA subsets., Conclusions: Initiation of FF/VI versus continuing UC was associated with consistent improvements in PROs., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice., Methods: We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK. Patients aged 18 years or older with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy were randomly assigned to initiate treatment with a once-daily inhaled combination of either 100 μg or 200 μg fluticasone furoate with 25 μg vilanterol or optimised usual care and followed up for 12 months. The primary endpoint was the percentage of patients who achieved an asthma control test (ACT) score of 20 or greater or an increase in ACT score from baseline of 3 or greater at 24 weeks (termed responders), in patients with a baseline ACT score less than 20 (the primary effectiveness analysis population). All effectiveness analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01706198., Findings: Between Nov 12, 2012, and Dec 16, 2016, 4725 patients were enrolled and 4233 randomly assigned to initiate treatment with fluticasone furoate and vilanterol (n=2114) or usual care (n=2119). 1207 patients (605 assigned to usual care, 602 to fluticasone furoate and vilanterol) had a baseline ACT score greater than or equal to 20 and were thus excluded from the primary effectiveness analysis population. At week 24, the odds of being a responder were higher for patients who initiated treatment with fluticasone furoate and vilanterol than for those on usual care (977 [71%] of 1373 in the fluticasone furoate and vilanterol group vs 784 [56%] of 1399 in the usual care group; odds ratio [OR] 2·00 [95% CI 1·70-2·34], p<0·0001). At week 24, the adjusted mean ACT score increased by 4·4 points from baseline in patients initiated with fluticasone furoate and vilanterol, compared with 2·8 points in the usual care group (difference 1·6 [95% CI 1·3-2·0], p<0·0001). This result was consistent for the duration of the study. Pneumonia was uncommon, with no differences between groups; there was no difference in other serious adverse events between the groups., Interpretation: In patients with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy, initiation of a once-daily treatment regimen of combined fluticasone furoate and vilanterol improved asthma control without increasing the risk of serious adverse events when compared with optimised usual care., Funding: GlaxoSmithKline., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated with the risk of asthma exacerbations among individuals with asthma from the general population., Methods: From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during follow-up in 2003-2011, defined as moderate (short-course treatment of prednisolone) or severe (hospitalization)., Results: The multivariable-adjusted incidence rate ratios (IRRs) were 1.28 (95% CI, 1.06-1.55) for moderate exacerbations and 1.55 (1.20-2.00) for severe exacerbations for individuals with blood eosinophil counts >0.29 × 10 9 /L (highest tertile) vs individuals with blood eosinophil counts <0.18 × 10 9 /L (lowest tertile). For blood neutrophils, the multivariable-adjusted IRRs were 2.14 (1.74-2.63) for moderate exacerbations and 1.18 (0.89-1.55) for severe exacerbations for individuals with blood neutrophil counts >4.85 × 10 9 /L (highest tertile) vs individuals with blood neutrophil counts <3.77 × 10 9 /L (lowest tertile). Blood eosinophil and neutrophil counts interacted on moderate exacerbations ( P = 3 × 10 -4 ), but not on severe exacerbations., Conclusions: High blood eosinophil counts are associated with an increased risk of both moderate and severe asthma exacerbations, while high blood neutrophil counts are associated with an increased risk of moderate, but not severe exacerbations., (© 2016 American Association for Clinical Chemistry.)

Background: Long-term prognosis of patients with characteristics of both chronic obstructive pulmonary disease (COPD) and asthma, named asthma-COPD overlap, is poorly described. We investigated the long-term prognosis of individuals with different types of chronic airway disease, with a special focus on individuals with asthma-COPD overlap., Methods: We assigned participants from the Copenhagen City Heart Study into six subgroups: healthy never-smokers, ever-smokers without asthma and COPD, those with asthma with low cumulated smoking exposure and no airflow limitation, those with COPD, those with asthma-COPD overlap with asthma onset before the age of 40 years, and those with asthma-COPD overlap with asthma onset after the age of 40 years. We defined asthma-COPD overlap as current self-reported asthma and a postbronchodilatatory forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio of less than 0·7, without any restrictions regarding smoking. We investigated the course of FEV1 decline for 18 years and risk of admission to hospital due to exacerbations or pneumonias and respiratory and all-cause mortality for 22 years. We analysed FEV1 decline in the six groups using a linear mixed-effects model., Findings: We included 8382 participants from the Copenhagen City Heart Study in our study: 2199 never-smokers, 5435 ever-smokers, 158 with asthma, 320 with COPD, 68 with asthma-COPD overlap with early-onset asthma, and 202 with asthma-COPD overlap with late-onset asthma. The multivariable-adjusted decline in FEV1 in asthma-COPD overlap with early-onset asthma was 27·3 mL (standard error 5·0) per year, which did not differ significantly from the decline of 20·9 mL (1·2) per year in healthy never-smokers (p=0·19). FEV1 decline in individuals with asthma-COPD overlap with late-onset asthma was 49·6 mL (3·0) per year, higher than the decline in asthma-COPD overlap with early-onset asthma (p=0·0001), the decline of 39·5 mL (2·5) per year in COPD (p=0·003), and the decline in healthy never-smokers (p<0·0001). Hazard ratios for hospital admissions due to exacerbations of asthma or COPD were 39·48 (95% CI 25·93-60·11) in asthma-COPD overlap with early-onset asthma, 83·47 (61·67-112·98) in asthma-COPD overlap with late-onset asthma, 23·80 (17·43-33·50) in COPD, and 14·74 (10·06-21·59) in asthma compared with never-smokers without lung disease (all p<0·0001). Life expectancy was 9·3 years (5·4-13·1) shorter in participants with asthma-COPD overlap with early-onset asthma, 12·8 years (11·1-14·6) shorter in those with asthma-COPD overlap with late-onset asthma, 10·1 years (8·6-11·5) shorter in those with COPD (all p<0·0001), and 3·3 years (1·0-5·5) shorter in those with asthma (p=0·004) than in healthy never-smokers., Interpretation: Prognosis of individuals with asthma-COPD overlap is poor and seems to be affected by the age of recognition of asthma, being worst in those with late asthma onset (after 40 years of age). Such patients should be followed up closely to prevent fast lung function decline and exacerbations., Funding: Capital Region of Copenhagen, Danish Heart Foundation, Danish Lung Foundation, Velux Foundation, AstraZeneca., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway diseases that have a high personal and social impact. They likely represent a continuum of different diseases that may share biological mechanisms (i.e. endotypes), and present similar clinical, functional, imaging and/or biological features that can be observed (i.e. phenotypes) which require individualised treatment. Precision medicine is defined as "treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations". In this Perspective, we propose a precision medicine strategy for chronic airway diseases in general, and asthma and COPD in particular., (Copyright ©ERS 2016.)

Background: Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings., Methods/design: The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 μg or 200 μg)/vilanterol 25 μg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors., Primary Endpoint: Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data., Discussion: The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings., Trial Registration: Clinicaltrials.gov, NCT01706198; 04 October 2012.

Background: Several studies have documented a substantial genetic component in the aetiology of allergic diseases and a number of atopy susceptibility loci have been suggested. One of these loci is 3q21, at which linkage to multiple atopy phenotypes has been reported. This region harbours the CD86 gene encoding the costimulatory B7.2 protein. The costimulatory system, consisting of receptor proteins, cytokines and associated factors, activates T cells and regulates the immune response upon allergen challenge., Methods: We sequenced the CD86 gene in patients with atopy from 10 families that showed evidence of linkage to 3q21. Identified polymorphisms were analysed in a subsequent family-based association study of two independent Danish samples, respectively comprising 135 and 100 trios of children with atopy and their parents. Functional analysis of the costimulatory effect on cytokine production was performed in an autologous cell-based system based on cells expressing CD86 variants., Results: Two polymorphisms were identified, encoding the amino acid changes Ile179Val and Ala304Thr, respectively. Significant associations were observed between the Ile179Val polymorphism and allergy phenotypes in both samples (eg, asthma, p = 4 x 10(-3) in the two samples combined). The undertransmitted (protective) Val179 allele was found to induce higher production of both Th1 and Th2 cytokines than the overtransmitted (risk) Ile179 allele, suggesting a functional impact of the polymorphism., Conclusion: The CD86 gene, and specifically the Ile179Val polymorphism, may be a novel aetiological factor in the development of asthma and related allergic disorders.

Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. As oxidative stress is a key component of inflammation, variations in genes involved in antioxidant defense could therefore be likely candidates for asthma. Three enzymes from the superfamily glutathione-S-transferase (GST) involved in the antioxidant defense were tested for association to asthma using 246 Danish atopic families in a family-based transmission disequilibrium test (TDT) design. A real-time PCR assay for relative quantification of gene copy number of GSTM1 and GSTT1 was developed. The assay made it possible to distinguish individuals with zero, one, and two copies and thereby to investigate whether the GST genes influenced susceptibility to asthma in a dose-dependent manner. We found that asthmatic patients with two copies of GSTM1 were significantly underrepresented (p<0.0005) and the significance increased by 10-fold when only atopic asthmatics were analyzed (p<0.00005). GSTT1 was significantly associated in an additive model to asthma, in which the alleles carrying the deletion of the gene were transmitted to affected offspring more often than expected by chance (p=0.019). The same transmission disequilibrium of the null GSTT1 allele was seen in patients with atopic asthma (p=0.021). The polymorphism c.342A>G (p.I105V) in GSTP1 has previously been suggested as a risk factor for asthma. However, significant association with asthma or related atopic phenotypes could not be established in our study. We conclude that deletions of GSTM1 and GSTT1 could be risk factors for asthma and that the genes might have a protective role in the development of atopic asthma., (Copyright 2004 Wiley-Liss, Inc.)

Introduction: We wanted to examine the factors that were of importance for the hospital outpatient treatment of teenagers with asthma., Material and Methods: A total of 89 teenagers received a postal questionnaire and an invitation to participate in a focus group interview on outpatient asthma follow-up., Results: Only 16 answered the questionnaire and 7 participated in the interview. The importance of personal contact was stressed and the teenagers expected much from the personnel aiming to help them. In a questionnaire follow-up of initial non-responders, 82% still had asthma and 75% of these received asthma medication., Discussion: The low participation rate and the high expectations explain why teenagers with asthma constitute a group of patients with less than optimal results of treatment.

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n = 1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n = 1,895). A subset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300 cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300 cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300 cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Summary: Background: A substantial proportion of patients with chronic obstructive pulmonary disease (COPD) have never smoked. We tested the hypothesis that, in individuals with COPD, never smokers have different characteristics and less severe outcomes of the disease than smokers do. Methods: We included individuals from the Copenhagen General Population Study, a prospective population study. We identified individuals with COPD spirometrically; that is, as the ratio between forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) under the lower limit of normal (LLN), excluding individuals with self-reported asthma. We examined general characteristics, symptoms, disease severity, and levels of inflammatory biomarkers and α1-antitrypsin at baseline. We assessed risk of lung-related hospital admissions, cardiovascular comorbidities, and all-cause mortality during a median follow-up of 4 years (IQR 2·5–5·6). Findings: Between Nov 26, 2003, and July 29, 2010, 68 501 participants from the Copenhagen General Population Study had lung function measurements and complete information on smoking habits available. Of those, we identified 6623 with COPD and no asthma. Of these, 1476 (22%) were never smokers, 2696 (41%) former smokers, and 2451 (37%) current smokers. For comparison we included 24 529 never smokers without COPD. Never smokers with COPD had different clinical characteristics, fewer symptoms, milder disease, and lower levels of inflammatory biomarkers than did current and former smokers with COPD. During follow-up, HRs for hospital admission due to COPD were 8·6 (95% CI 5·3–14) in never smokers, 30 (22–41) in former smokers, and 43 (32–59) in current smokers compared with never smokers without COPD. HRs for hospital admission due to pneumonia were 1·9 (1·4–2·6) in never smokers, 2·8 (2·3–3·4) in former smokers, and 3·4 (2·9–4·2) in current smokers. For hospital admission due to lung cancer, HRs were 11 (5·7–23) in former smokers and 18 (9·2–35) in current smokers, whereas no cases were noted in never smokers. Furthermore, risk of cardiovascular comorbidities and all-cause mortality was increased in former and current smokers but not in never smokers with COPD. Interpretation: Compared with current and former smokers, never smokers with COPD had different characteristics and milder disease, limited to the lungs. However, morbidity due to lung-related hospital admissions was nonetheless substantial in never smokers with COPD. Funding: Herlev Hospital, Copenhagen University Hospital, Copenhagen County Foundation, and University of Copenhagen. [ABSTRACT FROM AUTHOR]

Allergic diseases affect an increasing number of individuals and are a major global health problem. A substantial genetic contribution in the aetiology of allergic diseases is well documented. We have previously reported linkage of allergic diseases and atopy to the region harbouring the IL2 gene (4q27). IL15 is located approximately 20 Mb distal to IL2. The two genes encode cytokines that are structurally and functionally related, both inducing T-cell activation and proliferation. We screened the two genes for sequence variation and applied the seven single-nucleotide polymorphisms (SNPs) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and IgE-mediated allergy, asthma and atopic eczema. The SNP (rs2069762) that showed the most consistent results is located in the promoter and has previously been shown to influence the level of IL2 expression. We suggest that the observed overtransmission of the T allele of this SNP may convey increased susceptibility to allergic disease by skewing the Th1/Th2 balance towards Th2.European Journal of Human Genetics (2006) 14, 227–235. doi:10.1038/sj.ejhg.5201541; published online 7 December 2005 [ABSTRACT FROM AUTHOR]

Background: The relationship between respiratory diseases and individual cardiovascular diseases, and the impact of cardiovascular diseases on mortality in patients with respiratory disease, are unclear.Objectives: This study sought to determine the relationship between chronic obstructive pulmonary disease (COPD), asthma and interstitial lung disease (ILD), and individual cardiovascular diseases, and evaluate the impact of individual cardiovascular diseases on all-cause mortality in respiratory conditions.Methods: The authors conducted a cohort study of all patients admitted to 7 National Health Service hospitals across the North West of England, between January 1, 2000, and March 31, 2013, with relevant respiratory diagnoses, with age-matched and sex-matched control groups.Results: A total of 31,646 COPD, 60,424 asthma, and 1,662 ILD patients were included. Control groups comprised 158,230, 302,120, and 8,310 patients, respectively (total follow-up 2,968,182 patient-years). COPD was independently associated with ischemic heart disease (IHD), heart failure (HF), atrial fibrillation, and peripheral vascular disease, all of which were associated with all-cause mortality (e.g., odds ratio for the association of COPD with HF: 2.18 [95% confidence interval (CI): 2.08 to 2.26]; hazard ratio for the contribution of HF to mortality in COPD: 1.65 [95% CI: 1.61 to 1.68]). Asthma was independently associated with IHD, and multiple cardiovascular diseases contributed to mortality (e.g., HF hazard ratio: 1.81 [95% CI: 1.75 to 1.87]). ILD was independently associated with IHD and HF, both of which were associated with mortality. Patients with lung disease were less likely to receive coronary revascularization.Conclusions: Lung disease is independently associated with cardiovascular diseases, particularly IHD and HF, which contribute significantly to all-cause mortality. However, patients with lung disease are less likely to receive coronary revascularization. [ABSTRACT FROM AUTHOR]