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Competing Interests: Declaration of competing interest RCW, JGW, RM, BL, NA, VL, NM, KR, CH, LGQ and DS have no disclosures. SB reports participating on the advisory board of Sanofi.

Background & Aims: Limited research exists on the association between dietary patterns (DP) and COPD risk or health-related outcomes. We reviewed existing literature to identify DP as a potential factor influencing COPD development and associated health outcomes in diagnosed individuals., Methods: We followed the Joanna Briggs Institute methodology for this scoping review, conducting searches on PubMed, Scopus, Embase, and Web of Science to identify studies meeting our inclusion criteria (P, population - adults from the general population with or without COPD diagnosis; C, concept - DP; C, context - any setting). Two reviewers screened titles and abstracts, confirmed eligibility through full-text examination, extracted data using Redcap®, and assessed bias risk with the Newcastle Ottawa Scale., Results: We analyzed 24 studies with sample sizes ranging from 121 to 421,426 individuals aged 20 to 75. Eighty-three percent investigated the role of DP in the COPD etiology, while 16.7 % examined health-related COPD outcomes. Food frequency questionnaires predominated (75 %) in exploring 23 distinct DP. Sixty-seven percent employed a priori-defined DP, focusing on the Mediterranean Diet (MedDiet) and Healthy Eating Index (HEI), while 33.3 % utilized a posteriori-defined DP, mainly represented by the Prudent and Traditional DP. Sixty percent of the studies reported significant associations between DP and COPD risk/odds. However, studies examining DP and COPD patient outcomes produced varied results., Conclusions: Most studies focused on assessing COPD risk using a priori-defined DP, particularly emphasizing the Med Diet and HEI. Overall, the studies found that healthy DPs are associated with reduced risk of COPD and improved outcomes in diagnosed patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite the increasing popularity and use of Global Lung Function Initiative (GLI) spirometric reference equations, the appropriateness of the race-specific and race-neutral GLI spirometric reference models among the Indian population has not been systematically investigated., Methods: In this cross-sectional analysis, we used spirometric measurements of 1123 healthy Indian adults (≥18 years of age). We computed reference values and z-scores for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), and FEV 1 /FVC from race-specific and race-neutral GLI reference equations as well as from a widely used Indian reference equation. We studied heterogeneity between GLI equations and the Indian equations using Bland-Altman analysis, and the differences between the reference and observed values were compared using the Friedman test., Results: In Bland-Altman analysis, significant heterogeneity in FVC and FEV 1 between race-specific and Indian equations was observed (bias: 10.4 % and 14.1 %, respectively), with less bias for FEV 1 /FVC (3.76 %). The race-neutral equations showed almost similar bias (9.8 %, 13.8 %, and 3.8 % for FVC, FEV 1 , and FEV 1 /FVC, respectively). Median differences in race-specific reference values from observed values for FVC and FEV 1 were 0.49L and 0.44L, respectively, decreasing slightly with race-neutral equations (0.46L and 0.43L) whereas Indian models showed minimal differences (FVC: 0.10L, FEV 1 : 0.05L). Z-scores for FVC and FEV 1 were significantly different between race-specific and race-neutral GLI equations, and both differed from Indian equations., Conclusion: Both race-specific and race-neutral GLI reference equations are significantly different from the Indian equations, which underscores the importance of determining the suitability of global reference models before being used indiscriminately., Competing Interests: Declaration of competing interest The authors do not have any conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: TRAVERSE (NCT02134028), a phase 3 open-label extension study, assessed dupilumab safety and efficacy in patients with asthma aged ≥12 years who completed a previous dupilumab asthma study. This analysis evaluated changes in multiple lung function parameters in patients with moderate-to-severe asthma with elevated type 2 biomarkers (baseline eosinophils ≥150 cells·μL -1 or fractional exhaled nitric oxide ≥25 ppb) who completed QUEST (parent study) and 2 years of dupilumab treatment in TRAVERSE., Methods: Endpoints analyzed included: pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), forced expiratory flow (FEF 25 - 75 % ), and pre- and post-bronchodilator FEV 1 /FVC at parent study baseline (PSBL) at Weeks 0, 2, 48, and 96 in TRAVERSE, as well as pre- and post-bronchodilator FEV 1 slopes in QUEST and TRAVERSE. Statistical analyses were descriptive., Results: Dupilumab improved pre-bronchodilator FEV 1 , FVC, and FEF 25-75 % in QUEST; these improvements were sustained in TRAVERSE. In QUEST patients who received placebo, dupilumab initiation in TRAVERSE resulted in rapid lung function improvements. Mean (standard deviation) changes from PSBL at TRAVERSE Weeks 48 and 96 in pre-bronchodilator FEV 1 were 0.52 (0.59) and 0.45 (0.49) L in the dupilumab/dupilumab group and 0.47 (0.42) and 0.44 L (0.45) in the placebo/dupilumab group, respectively. Similar trends were observed for FVC and FEF 25-75 % . Dupilumab also improved FEV 1 slopes in QUEST and TRAVERSE., Conclusion: Dupilumab demonstrated sustained improvements across multiple spirometric lung function measurements for up to 3 years; patients who received placebo in QUEST experienced rapid lung function improvement upon initiation of dupilumab in TRAVERSE., Competing Interests: Declaration of competing interest A. Papi reports grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, and Teva; personal fees and non-financial support from Menarini, Novartis, and Zambon; and grants from Sanofi. M. Castro reports research support from the American Lung Association, AstraZeneca, GSK, NIH, Novartis, PCORI, Pulmatrix, sanofi-aventis, and Shionogi; consultancy fees from Genentech, Novartis, sanofi-aventis, and Teva; speaker fees from AstraZeneca, Genentech, GSK, Regeneron Pharmaceuticals, Inc., Sanofi and Teva; and royalties from Elsevier. J. Corren reports research grants from AstraZeneca, Genentech, Novartis and Regeneron Pharmaceuticals Inc.; research grants and consultancy fees from Sanofi; and speaker fees from AstraZeneca, Genentech, and Novartis. I.D. Pavord reports speaker fees from Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Teva; payments for organizing educational events from AstraZeneca and Teva; consultancy fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals Inc., RespiVert, Sanofi, Schering-Plough, and Teva; international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, and Teva; and research grants from Chiesi. Y. Tohda reports consultancy fees from AstraZeneca, Kyorin Pharmaceutical, Novartis, Sanofi, and Teijin Pharma. A. Altincatal, N. Pandit-Abid, E. Laws, L.P. Mannent, J.A. Jacob-Nara, P.J. Rowe, and M. Hardin are employees of Sanofi and may hold stock and/or stock options in the company. B. Akinlade, R. Gall, Y. Deniz, and D.J. Lederer are employees and shareholders of Regeneron Pharmaceuticals Inc., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

BackgroundForced vital capacity (FVC) is a key measure of disease severity in patients with idiopathic pulmonary fibrosis (IPF) and is an important clinical trial endpoint. We hypothesize that reversible airflow limitation co-exists in a subgroup of patients with IPF, and that bronchodilator use will improve the performance characteristics of FVC.MethodsIPF patients with pre and post-bronchodilator spirometry testing performed were identified from two tertiary referral cohorts. The difference between pre and post-bronchodilator FVC (intra-test difference) was calculated. The test characteristics of pre and post-bronchodilator FVC change over time (inter-test difference) were assessed in patients with sequential spirometry, and were used to generate sample size estimates for hypothetical clinical trials using change in FVC as the primary endpoint.ResultsThere were 551 patients, contributing 967 unique spirometry tests. The mean intra-test increase in FVC with bronchodilator use was 0.04 L (2.71 vs. 2.75 L, p

Background and Objective: Patients with preserved ratio impaired spirometry (PRIsm) have higher incidence rate of cardiovascular disease (CVD). However, few studies focused on PRIsm in China. We determined the prevalence and characteristics of patients with PRIsm in Chinese population. We also aimed to investigate the significant predictive factors of CVD in PRIsm patients., Methods: In total, 6994 subjects aged from 35 to 70 years old and free of CVD at baseline were categorized into normal (n = 3895), PRIsm (the ratio of forced expired volume in the first second (FEV1) to forced vital capacity (FVC) ≥0.7 and FEV1 <80 % predicted; n = 1997) and obstructive spirometry (FEV1:FVC<0.7; n = 1102). Cox proportional hazards multivariable regression was performed to investigate how baseline characteristics impact CVD incidence., Results: In participants with PRIsm, men had a 0.68-fold higher risk of CVD incidence than women (HR, 1.68; 95%CI, 1.09-2.59; p = 0.020). Our study showed that the rate of CVD incidence increased by 6.0 % with every year's increase in age (HR, 1.06; 95%CI, 1.04-1.09; p < 0.001). A 0.1 increase in FEV1/FVC was significantly associated with a 23.0 % decrease in CVD incidence (HR, 0.77; 95%CI, 0.61-0.97; p = 0.028). Family history of CVD greatly increased the risk of cardiovascular disease incidence (HR, 1.83; 95%CI, 1.18-2.83; p = 0.007). Higher BMI was also a significant risk factor of CVD incidence (HR, 1.06; 95%CI, 1.01-1.10; p = 0.013)., Conclusion: The prevalence of PRIsm in China was high. PRIsm subjects should be monitored carefully, especially for the older, male, those with higher BMI, lower FEV1/FVC and family history of CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Impaired lung function is associated with cardiovascular mortality, but the origins of this association are poorly understood. We investigated associations between lung function and cardiovascular risk scores in a general population cohort of men and women aged 45 years., Methods: Participants are members of an unselected birth cohort followed to adulthood. Lung function determined at ages 32 and 45 by spirometry, body plethysmography, gas diffusion, and airway conductance were the main predictors. Future cardiovascular risk was estimated at age 45 using a multivariable cardiovascular risk algorithm - PREDICT. Risk scores were log-transformed and used as the dependent variable in linear regression analyses. We investigated cross-sectional associations with lung function at age 45 and longitudinal associations using changes in lung function between ages 32-45 as the predictors., Results: 863 of 1037 original cohort participants had data for analysis. Low lung volumes (FEV 1 , FVC, VA, TLC, and FRC) were associated with greater cardiovascular risk scores in the cross-sectional analyses at age 45 and the longitudinal analyses. These associations were stronger in women than in men, were independent of smoking history, and present in never smokers, even after adjusting for body mass index. Associations were not found for measures of airway function (FEV 1 /FVC ratio and sGaw) or gas transfer (TLco/VA)., Conclusions: Low lung volumes at age 45 and accelerated pulmonary function decline are associated with a higher estimated cardiovascular risk scores in mid-adulthood. This association is stronger in women and is not explained by smoking or obesity., Competing Interests: Declaration of competing interest No conflict of interest, (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Understanding early life risk factors for decreased lung function could guide prevention efforts and improve lung health throughout the lifespan. Our objective was to investigate the association between history of severe (hospitalized) bronchiolitis in infancy and age 6-year lung function., Methods: We analyzed data from two prospective cohort studies: infants hospitalized with bronchiolitis and a parallel cohort of healthy infants. Children were followed longitudinally, and spirometry was performed at age 6 years. To examine the relationship between history of severe bronchiolitis and primary outcomes - FEV1% predicted (pp) and FEV1/FVCpp - we used multivariable linear regression models adjusted for insurance status, perterm birth, secondhand smoke exposure, breastfeeding status, traffic-related air pollution and polygenic risk score. Secondary outcomes included FVCpp and bronchodilator responsiveness (BDR)., Results: Age 6-year spirometry was available for 425 children with history of severe bronchiolitis in infancy and 48 controls. Unadjusted analysis revealed that while most children had normal range lung function, children with a history of severe bronchiolitis had lower FEV1pp and FEV1/FVCpp. In adjusted analyses, the same findings were observed: FEV1pp was 8% lower (p = 0.004) and FEV1/FVCpp was 4% lower (p = 0.007) in children with history of severe bronchiolitis versus controls. FVC and BDR did not differ between groups., Conclusions: Children with severe bronchiolitis in infancy have decreased FEV1 and FEV1/FVC at age 6 years, compared to controls. These children may be at increased risk for chronic respiratory illness later in life., Competing Interests: Declaration of competing interest The other authors have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Baseline characteristics could potentially guide asthma treatments. We evaluated whether baseline eosinophil levels affect the efficacy of mometasone/indacaterol/glycopyrronium (MF/IND/GLY) in patients with inadequately controlled asthma., Method: In this post hoc analysis of IRIDIUM study, efficacy of high-dose MF/IND/GLY (160/150/50 μg, once-daily [o.d.]) versus high-dose MF/IND (320/150 μg o.d.) and high-dose fluticasone/salmeterol (FLU/SAL [500/50 μg, twice-daily [b.i.d.]); and efficacy of pooled MF/IND/GLY (160/150/50 μg and 80/150/50 μg) versus pooled MF/IND (320/150 μg and 160/150 μg) was evaluated in patient subgroups with baseline blood eosinophil count of <300 cells/μL or ≥300 cells/μL., Results: Overall, 3065 patients were included. At Week 26, high-dose MF/IND/GLY showed improved trough FEV 1 versus high-dose MF/IND (Δ78mL [<300 cells/μL]; Δ54mL [≥300 cells/μL]) and FLU/SAL (Δ112mL [<300 cells/μL]; Δ98mL [≥300 cells/μL]). Similarly, pooled MF/IND/GLY also showed improved trough FEV 1 versus pooled MF/IND (Δ75mL [<300 cells/μL]; Δ68mL [≥300 cells/μL]). Over 52 weeks, high-dose MF/IND/GLY reduced the annualized rate of moderate or severe asthma exacerbations by 23% and 10%, severe exacerbations by 31% and 15%, and all exacerbation by 33% and 10% versus high-dose MF/IND for subgroups with <300 cells/μL and ≥300 cells/μL, respectively; and by 33% and 41%, 45% and 42%, 42% and 39% versus FLU/SAL, respectively. Similarly, pooled MF/IND/GLY reduced exacerbations by 22% and 8%, 21% and 7%, 27% and 8%, versus pooled MF/IND, for the respective subgroups., Conclusion: MF/IND/GLY showed improvement in lung function and reduction in asthma exacerbations over MF/IND and FLU/SAL independent of baseline eosinophil levels, indicating that eosinophil levels did not affect the efficacy of MF/IND/GLY in patients with inadequately controlled asthma., Trial Registration: ClinicalTrials.gov, NCT02571777 (IRIDIUM)., Competing Interests: Declaration of competing interest Konstantinos Kostikas reports honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, ELPEN, GILEAD, GSK, Menarini, Novartis, Sanofi, Specialty Therapeutics, WebMD (paid to the University of Ioannina), is a member of the GOLD Assembly and was an employee of Novartis Pharma AG until October 31, 2018; his department received funding and grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir (paid to the University of Ioannina). Jorge F. Maspero reports grants and personal fees from Novartis during the conduct of the study, grants and personal fees from Sanofi, and personal fees from AstraZeneca and ImmunoTek. Kenneth R. Chapman reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Novartis, Regeneron, Sanofi, and Takeda, grants from Vertex, and personal fees from CSL Behring, Inhibrx, and Kamada, all outside of the submitted work. Richard van Zyl-Smit reports personal fees from Aspen–GSK, AstraZeneca, Cipla, Merck Sharp & Dohme, Novartis, Pfizer, and Roche, Glenmark and Boehringer Ingelheim outside of the submitted work. Karen Mezzi, Xavier Jaumont are employees of Novartis. David Lawrence is an employee as well as share owner of Novartis., (Copyright © 2023 Novartis Pharma AG. Published by Elsevier Ltd.. All rights reserved.)

Background: Lung function decline is associated with sarcopenia, known as loss of skeletal muscle mass. The serum creatinine to cystatin C ratio (CCR) has been proposed as a biomarker of muscle mass. The associations between CCR and lung function decline are unknown., Methods: The study used two waves of data from China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2015. Serum creatinine and cystatin C were collected at baseline survey (2011). Lung function was assessed by peak expiratory flow (PEF) at 2011 and 2015. Linear regression models adjusted for potential confounders were conducted to analyze the cross-sectional association between CCR and PEF, and the longitudinal association between CCR and annual decline in PEF., Results: Totally, 5812 participants aged over 50 years (50.8% women; mean age 63.3 ± 6.5 years) were enrolled in a cross-sectional analysis in 2011, and further 4164 individuals were followed up in 2015. Serum CCR was positively associated with PEF and the PEF% pred. Per 1 SD higher of CCR was associated with 41.55 L/min increases in PEF (p < 0.001) and 10.77 (%) increase in PEF% pred (p < 0.001). Longitudinal analyses indicated that higher CCR level at baseline was related to slower annual decline in PEF and PEF% pred. And this relationship was significant only in women and in never smokers., Conclusions: Higher CCR was associated with slower longitudinal PEF decline in women and never smokers. CCR may be a valuable marker to monitor and predict lung function decline in middle-aged and older adults., Competing Interests: Declaration of competing interest The authors confirm that no conflicts of interest exist., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A novel, once-daily, fixed-dose combination of mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY) delivered via Breezhaler® is the first inhaled corticosteroid/long-acting ꞵ 2 -agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) therapy approved for the maintenance treatment of asthma in adults inadequately controlled on ICS/LABA combination. In patients with asthma and persistent airflow limitation (PAL), maximal treatment, especially with combination is suggested. This post hoc analysis of data from the IRIDIUM study assessed the efficacy of MF/IND/GLY in asthma patients with and without PAL., Methods: Patients with post-bronchodilator FEV 1 ≤80% of predicted and FEV 1 /FVC ratio of ≤0.7 were categorised as PAL subgroup and the remaining as the non-PAL subgroup. Lung function parameters (FEV 1 , PEF, and FEF 25%-75% ) and annualised asthma exacerbations rates were evaluated in both subgroups across the treatment arms: once-daily high-dose MF/IND/GLY (160/150/50 μg), high-dose MF/IND (320/150 μg) and twice-daily high-dose fluticasone/salmeterol (FLU/SAL; 500/50 μg)., Results: Of the 3092 randomised patients, 64% (n = 1981) met the criteria for PAL. Overall, there was no evidence of treatment difference between PAL and non-PAL subgroups (interaction P-value for FEV 1 , FEF 25%-75% , PEF, moderate or severe exacerbations, severe exacerbations and all exacerbations were 0.42, 0.08, 0.43 0.29, 0.35 and 0.12, respectively). In the PAL subgroup, high-dose MF/IND/GLY versus high-dose MF/IND and high-dose FLU/SAL improved trough FEV 1 (mean difference: 102 mL [P < 0.0001] and 137 mL [P < 0.0001]) and reduced moderate or severe (16% and 32%), severe (25% and 39%) and all exacerbations (19% and 38%), respectively., Conclusions: Once-daily fixed-dose MF/IND/GLY was efficacious in asthma patients with and without persistent airflow limitation., Competing Interests: Declaration of competing interest RVZS reports personal fees from Aspen/GSK, Pfizer, Roche, MSD, AstraZeneca, Novartis, Glenmark, Boehringer Ingelheim and Cipla, outside the submitted work. HAK reports grants and consultancy/advisory board participation from/for Novartis during the conduct of the study, grants and consultancy/advisory board participation from/for GlaxoSmithKline and Boehringer Ingelheim, and a grant from Chiesi, outside the submitted work. All were paid to his institution. JFM reports personal fees and grants from Novartis during the conduct of the study, personal fees from AstraZeneca, grants and personal fees from Sanofi and personal fees from ImmunoTek. KK reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK, Novartis and Menarini; personal fees from Sanofi; and grants from NuvoAir, outside the submitted work, and was an employee of Novartis Pharma AG until October 31, 2018. KRC reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Sanofi, Regeneron, Novartis and Takeda; personal fees from CSL Behring, Inhibrx and Kamada; and grants from Vertex, outside the submitted work. MH, AMT, KM, DB and DL are employees of Novartis Pharma AG. PD is an employee of Novartis Pharmaceutical Corporation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Children hospitalized for bronchiolitis have increased risk of asthma and low lung function persisting into adulthood, but the underlying mechanisms are poorly understood. Body mass index (BMI) and adipokines are associated with respiratory morbidity. We aimed to investigate if associations between BMI and adipokines and the outcomes asthma, atopy, and lung function differed between young adults previously hospitalized for bronchiolitis and control subjects., Methods: This sub study of a historical cohort enrolled 185 young adults previously hospitalized for bronchiolitis and 146 matched control subjects. Exposures (BMI and the adipokines: adiponectin, leptin, resistin, and ghrelin) and outcomes (asthma, atopy, and lung function) were measured cross-sectionally at 17-20 years of age. Associations were tested in regression models, and differences between the post-bronchiolitis- and control group were tested by including interaction terms., Results: BMI was associated with asthma and lung function, but we did not find that the associations differed between the post-bronchiolitis- and control group. We also found some associations between adipokines and outcomes, but only associations between adiponectin and forced vital capacity (FVC) and between resistin and current asthma differed between the groups (p-value interaction term 0.027 and 0.040 respectively). Adiponectin tended to be positively associated with FVC in the post-bronchiolitis group, with an opposite tendency in the control group. Resistin was positively associated with current asthma only in the control group., Conclusion: The increased prevalence of asthma and impaired lung function observed in young adults previously hospitalized for bronchiolitis do not seem to be related to growth and fat metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The present study examined the association between Five Factor Model personality traits and lung function and dyspnea., Methods: Participants were middle aged and older adults aged 34-103 years old (N > 25,000) from the Midlife in the United States Study (MIDUS), the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the National Health and Aging Trends Survey (NHATS), and the Wisconsin Longitudinal Study graduate (WLSG) and sibling (WLSS) samples. Data on peak expiratory flow (PEF), dyspnea, personality traits, smoking, physical activity, body mass index (BMI), emotional/psychiatric problems, and demographic factors were obtained in each sample., Results: A meta-analysis indicated that higher neuroticism was related to lower PEF, higher risk of PEF less than 80% of predicted value, and higher risk of dyspnea. In contrast, higher extraversion and conscientiousness were associated with higher PEF, lower likelihood of PEF lower than 80% of the predicted value, and lower risk of dyspnea. Higher openness was related to higher PEF and lower risk of PEF less than 80%, whereas agreeableness was related to higher PEF and lower risk of dyspnea. Smoking, physical activity, BMI and emotional/psychiatric problems partially accounted for these associations. There was little evidence that lung disease moderated the association between personality and PEF and dyspnea., Conclusions: Across cohorts, this study found replicable evidence that personality is associated with lung function and associated symptomatology., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). In IMPACT, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy significantly reduced moderate/severe exacerbation rates and improved lung function and health status versus FF/VI or UMEC/VI in COPD patients. This post hoc analysis investigated trial outcomes by smoking status., Methods: IMPACT was a double-blind, 52-week trial. Patients aged ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. Endpoints assessed by smoking status at screening included rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score at Week 52. Safety was also assessed., Results: Of the 10,355 patients in the intent-to-treat population, 3,587 (35%) were current smokers. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in current (rate ratio 0.85 [95% confidence interval: 0.77-0.95]; P = 0.003 and 0.86 [0.76-0.98]; P = 0.021) and former smokers (0.85 [0.78-0.91]; P < 0.001 and 0.70 [0.64-0.77]; P < 0.001). FF/UMEC/VI significantly reduced time-to-first on-treatment moderate/severe exacerbation versus FF/VI and UMEC/VI in former smokers, and versus FF/VI in current smokers. Similar trends were seen for lung function and health status. Former smokers receiving inhaled corticosteroid-containing therapy had higher pneumonia incidence than current smokers., Conclusions: FF/UMEC/VI improved clinical outcomes versus dual therapy regardless of smoking status. Benefits of FF/UMEC/VI versus UMEC/VI were greatest in former smokers, potentially due to relative corticosteroid resistance in current smokers., Clinical Trial Registration: GSK (CTT116855/NCT02164513)., Competing Interests: Declaration of competing interest DM and DAL are GSK employees and hold GSK stocks/shares. SB is a former GSK employee and holds GSK stocks/shares. GJC has received personal fees from Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Broncus Medical, Chiesi, CSA Medical, Eolo, Gala Therapeutics, GSK, Helios Medical, HGE Technologies, Merck, Medtronic, Mereo BioPharma, NGM Biopharmaceuticals, Novartis, Nuvaira, Olympus, Philips, Pulmonx, Respironics, Respivant Sciences, The Implementation Group and Verona. DMGH has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Pfizer and Sanofi, and non-financial support from Boehringer Ingelheim and GSK. MKH reports personal fees from Medscape and Integrity, as well as consulting fees from GSK, AstraZeneca, Boehringer Ingelheim, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, Altesa Biopharma and United Therapeutics. She has received royalties from UpToDate, WW Norton and Penguin Random House. She has received payment or honoraria for consultancy from Cipla, Chiesi, AstraZeneca, Boehringer Ingelheim, GSK, Medscape and Integrity. She has served roles on boards or scientific committees for COPD foundation, ALA, Emerson School and GOLD, and has been a volunteer spokesperson for ALA and deputy editor of the ATS journal. She has received either in-kind research support or funds paid to the institution from the NIH, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation and the American Lung Association. She has participated in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution. She holds stock options from Meissa Vaccines and Altesa Biopharma. NAH is the Editor-in-Chief for Respiratory Medicine and was an investigator on the IMPACT study. He reports receiving personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Sanofi Genzyme, Novartis, Regeneron, Genentech, Sunovion, and Mylan for serving as an advisor or consultant. He also received research support from GSK, Boehringer Ingelheim and AstraZeneca. DH has received personal fees from GSK, Boehringer Ingelheim, AstraZeneca, Mylan, Novartis, and Sunovion. Research support from GSK, Boehringer Ingelheim and Mylan. He is a National Board of Directors member for the American Lung Association. PL has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi and GSK. FJM has received consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Gala, GSK, Novartis, Polarean, Pulmonx, Sanofi/Regeneron, Sunovion, Teva, Theravance/Viatris and Verona; grant support from AstraZeneca, Chiesi, GSK and Sanofi/Regeneron; payment or honoraria from UpToDate for participation in COPD CME activities; and participated in an event adjudication committee for MedTronic. FJM states that AstraZeneca, Boehringer Ingelheim and GSK are partners of the SPIROMICS program and partners in the NHLBI CAPTURE validation study; Novartis, Sanofi/Regeneron, Sunovion and Teva are partners of the SPIROMICS program; Theravance/Viatris are partners in the NHLBI CAPTURE validation study. TMS has received research grants from Amphastar, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla, Compleware, Evidera (PPD), Forest Research Institute (now AstraZeneca), GSK, Novartis, Pearl Therapeutics, Proterix BioPharma, Oncocyte, Sanofi, Seer, Sunovion, Teva, Theravance BioPharma, Vapotherm, Verona Pharma, Restorbio and Westward, and personal fees from GSK, Sunovion, Theravance Biopharma and Vapotherm. DS has received consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GSK, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance, and Verona. RAW has received personal fees from AstraZeneca, Boehringer Ingelheim, Contrafect, Roche-Genentech, Bristol Myers Squibb, Merck, Verona, Theravance, AbbVie, GSK, Chemerx, Kiniksa, Savara, Galderma, Kamada, Pulmonx, Kinevant, Vaxart, Polarean, Chiesi, 4D Pharma, Puretech, and grant support from AstraZeneca, Sanofi, Verona, Genentech, Boehringer Ingelheim and 4DX imaging. He has received payment for expert testimony from the United States Government and Genentech; and support for attending meetings and/or travel from AstraZeneca. Additionally, he has received editorial support from GSK, AstraZeneca, Boehringer Ingelheim and Merck Foundation; and has served on the Board of Directors/Medical and Scientific Advisory Committee for the COPD Foundation, and on a Scientific Advisory Board for the American Lung Association. RNvZS was an investigator on the IMPACT study and reports receiving personal fees from Aspen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GSK, MSD, Pfizer, Sanofi, Novartis and Roche. NB was an investigator on the IMPACT study and reports receiving consulting fees and serving as a participant in advisory boards for Kamada, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi Genzyme and Novartis, as well as serving as a participant in advisory boards for Teva. He has also received lecture fees for Kamada, AstraZeneca, Boehringer Ingelheim, GSK and Sanofi Genzyme., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Volatile organic compounds (VOCs) are associated with adverse respiratory outcomes at high occupational exposures. However, whether exposure levels found in the general population have similar effects is unknown., Methods: We analyzed data on 1342 adult participants in the 2011-2012 National Health and Nutrition Examination Survey aged ≥18 years old who had urinary VOC metabolites and spirometry measurements available. Linear regression models adjusting for covariates were fitted to estimate the associations of VOC exposures levels and spirometry outcomes, while accounting for survey design and sampling weights to generate nationally representative estimates., Results: The urinary metabolites for xylene, acrylamide, acrolein, 1,3-butadiene, cyanide, toluene, 1-bromopropane, acrylonitrile, propylene oxide, styrene, ethylbenzene, and crotonaldehyde in our analysis were all detected in >75% of participants. Forced expiratory volume in 1 s (FEV 1 ) to forced vital capacity (FVC) ratio % was lower with urinary metabolites of acrylamide (β: -2.65, 95% CI: -4.32, -0.98), acrylonitrile (β: -1.02, 95% CI: -2.01, -0.03), and styrene (β: -3.13, 95% CI: -5.35, -0.90). FEV 1 % predicted was lower with the urinary metabolites of acrolein (β: -7.77, 95% CI: -13.29, -2.25), acrylonitrile (β: -2.05, 95% CI: -3.77, -0.34), propylene oxide (β: -2.90, 95% CI: -5.50, -0.32), and styrene (β: -4.41, 95% CI: -6.97, -1.85)., Conclusions: This is the first study of a representative sample of the U.S. adult population to reveal associations of acrylonitrile, propylene oxide, and styrene urinary metabolites with reduced lung function at non-occupational exposures. Results also support previous evidence of acrylamide and acrolein's association with adverse respiratory outcomes., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Several studies have reported a positive relationship between lung function impairment and the metabolic syndrome. This is most usually explained by abdominal adiposity. We hypothesized that the main determinant of the association between lung function impairment and abdominal obesity is the presence of visceral fat. Methods: The present study is a cross-sectional analysis of 98 non-diabetic men aged between 50 and 70 years with the metabolic syndrome. The amount of visceral and subcutaneous adipose tissue was determined by an MRI scan. The association between visceral fat and measures of lung function (FEV1, FVC, exhaled and NO) was assessed using linear regression. Results: 98 participants were included in this analysis. There was a linear inverse association between visceral fat and both FEV1 and FVC. None of the other different fat-related measurements (subcutaneous fat, waist circumference and BMI) or features of the metabolic syndrome were found to be associated with these lung function measurements. Conclusion: In non-diabetic subjects with the metabolic syndrome and a lung function that is within the normal range, visceral fat is negatively correlated with FEV1 and FVC. [ABSTRACT FROM AUTHOR]

Background: This post-hoc analysis examined the impact of roflumilast on chronic obstructive pulmonary disease (COPD) exacerbations and lung function in patients with COPD who received concomitant long-acting ß2-agonists (LABA) with or without prior inhaled corticosteroid (ICS) and the influence of various demographic and clinical characteristics on these outcomes. Methods: Data were pooled from 2 double-blind, placebo-controlled, 52-week studies of once-daily roflumilast 500 mg in patients with COPD. Endpoints were mean rate of exacerbations and change from baseline in pre- and postbronchodilator FEV1. Results: In this pooled analysis (N = 3091), addition of roflumilast to LABAs for 1 year in patients who discontinued ICS prior to study entry (n = 945) significantly reduced the risk of COPD exacerbations vs. placebo by 19.2% (p < 0.05) and significantly improved pre- and postbronchodilator FEV1 by 40 mL and 34 mL, respectively (both, p < 0.01). Similar improvements were observed in patients who received concomitant LABAs but were not taking ICS prior to study entry (n = 597). A significant reduction in COPD exacerbation risk with roflumilast vs. placebo was observed regardless of age or smoking status, and in patients who had severe or very severe COPD. Significantly improved lung function was observed with roflumilast in all the subgroups (p < 0.05), with the exception of patients with moderate COPD. Conclusions: Roflumilast reduced exacerbation rates and improved lung function in patients with COPD who received concomitant LABA, regardless of prior ICS use, and across various patient subgroups regardless of age and smoking status. [ABSTRACT FROM AUTHOR]

Background: Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods: We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT. Results: For the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38-79)} compared to healthy subjects matched for age {Median (IQR): 49% (17e67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA. Conclusions: There was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year. [ABSTRACT FROM AUTHOR]

Background: YKL-40 is a chitinase-like protein that, in cross-sectional clinical studies, has been associated with severe asthma and COPD in smokers. Aim: To determine the longitudinal relation of circulating YKL-40 to levels and decline of lung function in the general population. Methods: We used longitudinal data from up to 13 surveys from the population-based TESAOD study which was conducted in Tucson, Arizona between 1972 and 1996. In cross-sectional analyses, we also used data from 3 Spanish centers of the multicenter ECRHS study (ECRHS-Sp). Serum YKL-40 was measured at baseline in TESAOD and in survey 2 in ECRHS-Sp using ELISAs. Multivariate linear regression was used to test associations of serum YKL-40 to concomitant lung function. In TESAOD, random coefficients models were used to test associations of serum YKL-40 to subsequent decline of lung function. Results: Data on YKL-40 and lung function were available from 1088 TESAOD and 854 ECRHS-Sp adult participants (59% and 51% females; respectively). In adjusted multivariate meta-analyses, being in the highest YKL-40 quartile was associated cross-sectionally with significant deficits in FEV1 and FVC %predicted. In adjusted longitudinal analyses, TESAOD participants in the top YKL-40 quartile had an FEV1 decline that was 5 ml/yr (p = 0.05) faster than subjects in the third quartile, 5 ml/yr (p = 0.02) faster than subjects in the second quartile, and 10 ml/yr (p < 0.001) faster than subjects in the lowest YKL-40 quartile. These longitudinal effects were particularly strong in smokers and absent in never smokers. After adjusting for covariates, as compared with the other three quartiles combined, the top YKL-40 quartile was associated with a 9 ml/yr (p = 0.001) faster FEV1 decline among smokers, while no significant effects were found among never smokers (2 ml/yr, p = 0.35). Conclusions: Circulating YKL-40 is associated with levels and decline of lung function in the general population and may be a biomarker of susceptibility to the long-term effects of cigarette smoking. [ABSTRACT FROM AUTHOR]

Background: QVA149 is an inhaled, once-daily fixed-dose dual bronchodilator combination of the long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrronium (NVA237) for the treatment of chronic obstructive pulmonary disease (COPD). We investigated the safety and efficacy of QVA149 over 52 weeks. Methods: This 52-week, multicenter, double-blind, parallel-group, placebo-controlled study randomized (2:1) patients with moderate-to-severe COPD to once-daily QVA149 (110 µg indacaterol/50 µg glycopyrronium) or placebo delivered via the Breezhaler® device. Primary endpoint was safety and tolerability for treatment-emergent adverse events (AEs). Secondary endpoints included safety based on vital signs, electrocardiograms (ECGs), laboratory evaluations, and pre-dose forced expiratory volume in 1 s (FEV1). Results: Of 339 patients randomized, QVA149 [n = 226], placebo [n = 113]; 76.9% male, mean age: 62.6 years, post-bronchodilator FEV1: 57.4% predicted, 83.5% completed study. A smaller percentage of patients discontinued in the QVA149 group (14.2%) compared with placebo (21.2%). Overall incidence of AEs was similar in the QVA149 (57.8%) and placebo (56.6%) groups, with most AEs being mild to moderate in severity. The numerical differences in some AEs observed could be at least in part explained by differences in baseline patient characteristics. No clinically relevant differences were observed between treatment groups for vital signs or ECG parameters. The five deaths reported were unrelated to study medication (QVA149, n = 4 [1.8%]; placebo, n = 1 [0.9%]). QVA149 demonstrated rapid and clinically meaningful bronchodilation sustained over 52 weeks versus placebo. Conclusion: QVA149 demonstrated a good safety and tolerability profile, providing rapid and sustained bronchodilation over 52 weeks in patients with moderate-to-severe COPD. ClinicalTrials.gov identifier: NCT01120717. [ABSTRACT FROM AUTHOR]

Background: The Epigenetic Smoking Status Estimator (EpiSmokEr) predicts smoking phenotypes based on DNA methylation at 121 CpG sites., Objective: Evaluate associations of EpiSmokEr-predicted versus self-reported smoking phenotypes with lung function and all-cause mortality in a cohort of older adults., Methods: The prospective Normative Aging Study collected DNA methylation measurements from 1999 to 2012 with follow-up through 2016. The R package EpiSmokEr derived predicted smoking phenotypes based on DNA methylation levels assayed by the Illumina HumanMethylation450 Beadchip. Spirometry was collected every 3-5 years. Airflow limitation was defined as forced expiratory volume in 1 s/forced vital capacity <0.7. Vital status was monitored through periodic mailings., Results: Among 784 participants contributing 5414 person-years of follow-up, the EpiSmokEr-predicted smoking phenotypes matched the self-reported phenotypes for 228 (97%) never smokers and 22 (71%) current smokers. In contrast, EpiSmokEr classified 407 (79%) self-reported former smokers as never smokers. Nonetheless, the EpiSmokEr-predicted former smoking phenotype was more strongly associated with incident airflow limitation (hazard ratio [HR] = 3.15, 95% confidence interval [CI] = 1.50-6.59) and mortality (HR = 2.11, 95% CI = 1.56-2.85) compared to the self-reported former smoking phenotype (airflow limitation: HR = 2.21, 95% CI = 1.13-4.33; mortality: HR = 1.08, 95% CI = 0.86-1.36). Risk of airflow limitation and death did not differ among self-reported never smokers and former smokers who were classified as never smokers. The discriminative accuracy of EpiSmokEr-predicted phenotypes for incident airflow limitation and mortality was improved compared to self-reported phenotypes., Conclusions: The DNA methylation-based EpiSmokEr classifier may be a useful surrogate of smoking-induced lung damage and may identify former smokers most at risk of adverse smoking-related health effects., (Copyright © 2022 Elsevier Ltd. All rights reserved.)