Search

Background: Whether simple lifestyle-integrated exercise training can improve insomnia remains unclear. In this study, we examined whether zero-time exercise, a simple exercise incorporated into daily routines without extra time, can improve sleep in physically inactive adults with insomnia., Methods: This was a single-blinded, parallel-group, randomized controlled trial. A total of 140 physically inactive adults (mean [SD] age, 46.7 [14.0] years; 115 [82.1 %] women; mean [SD] insomnia duration, 4.9 [6.7] years) with insomnia disorders were randomly allocated (1:1) to the zero-time exercise intervention group or the sleep hygiene education control group. They received two 2-h zero-time exercise training sessions or sleep hygiene education lessons within 2 weeks and two phone call reminders per week for 8 weeks to follow their respective programs. The outcomes were assessed at 8, 16, and 24 weeks. The primary outcome was the Insomnia Severity Index score at week 24., Results: The intervention group showed a significantly greater decrease in the Insomnia Severity Index scores than those in the control group at weeks 16 (-1.59 points, 95 % CI -3.09 to -0.08; P = 0.039) and 24 (-2.59 points, 95 % CI -4.17 to -1.01; P = 0.001); however, the difference at week 8 was not significant (-1.23 points, 95 % CI -2.54 to 0.07; P = 0.065). No serious adverse events were observed., Conclusions: Zero-time exercise effectively reduces insomnia severity in physically inactive adults and can be easily incorporated into daily routines to improve insomnia symptoms and daytime impairment., Trial Registration: ClinicalTrials.gov, NCT04227587 (Registration date: January 13, 2020; The first participant was recruited on September 1, 2020). Word count: 240., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wing-Fai Yeung reports financial support was provided by Research Grants Council, Hong Kong SAR. If there are other authors, they 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 © 2025 Elsevier Ltd. All rights reserved.)

Introduction: Neutrophilic asthma has been suggested to be a clinically distinct phenotype characterised by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results. We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls. The aim of the present study was to examine whether neutrophilic inflammation, either in sputum or blood, is more prevalent in asthma and whether it correlates with disease severity., Methods: ATLANTIS included 773 asthma patients, with blood collected from 767 (99%) and sputum from 228 patients (30%). Data were available from 244 healthy controls, all providing blood and 126 (52%) providing sputum. Asthma patients were characterised, including parameters of large and small airways disease at baseline and after 6 and 12 months of follow-up. Sputum and blood neutrophilia were defined as values exceeding the upper quartile in asthma patients., Results: The prevalence of sputum neutrophilia did not differ between asthma patients and healthy controls. Asthma patients with sputum neutrophilia did not display more severe symptoms, large or small airways disease or more frequent exacerbations. Blood neutrophilia was more common in asthma and was associated with higher body mass index, female sex, current smoking and systemic corticosteroid use. Patients with blood neutrophilia had a statistically significant, but small, increase in residual volume/total lung capacity. Blood neutrophilia was not associated with large or small airways disease or exacerbation risk., Conclusion: Sputum and blood neutrophilia do not define a distinct clinical phenotype in asthma., Competing Interests: Conflict of interest: P.J.M. Kuks reports support for the present study from the Dutch Ministry of Economic Affairs and Climate Policy by means of the public–private partnership programme. Conflict of interest: T.M. Kole reports support for the present study from the Dutch Ministry of Economic Affairs and Climate Policy by means of the public–private partnership programme. Conflict of interest: M. Kraft reports grants or contacts from the National Institutes of Health, American Lung Association, Synairgen, Janssen, AstraZeneca (AZ) and Sanofi (funds paid to the University of Arizona until June 2022 and currently to the Icahn School of Medicine at Mount Sinai, all pharmaceutical industry studies now completed); consulting fees from AZ, Sanofi, Chiesi, GSK, Kinaset and Genentech (funds paid to M. Kraft); payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chiesis (funds paid to M. Kraft); support from the European Respiratory Society (ERS) to attend the ERS Congress in 2023 (partial support paid to M. Kraft); that they are a cofounder and chief medical officer of RaeSedo Inc. (one patent issued and two files for the development of therapeutics for inflammatory lung disease); participation on the ALung data safety monitoring board (DSMB) (funds paid to M. Kraft); leadership or fiduciary roles on the National Heart, Lung and Blood Advisory Council (completed in 2022, funds paid to M. Kraft) and the Association of Professors of Medicine (no compensation); equity ownership in RaeSedo Inc. (company is developing therapeutics for asthma in the preclinical phase, no human trials or IND); and that they are a Section Editor of UpToDate (funds paid to M. Kraft), all in the past 36 months. Conflict of interest: S. Siddiqui reports consulting fees from CSL Behring, AZ, GSK, Areteia Therapeutics and Novartis; speaker fees from Chiesi for presenting ATLANTIS data; support from the ERS to attend ERS Science Council meetings; and being a member of the ATLANTIS scientific steering group, all in the past 36 months. Conflict of interest: L.M. Fabbri reports consulting fees from Chiesi, GSK, AZ, Novartis, Verona Pharma and ICON; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chiesi and GSK; and participation on a DSMB or advisory board for Novartis and Chiesi, all in the past 36 months. Conflict of interest: K.F. Rabe reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AZ, Boehringer Ingelheim, Chiesi, Novartis, Sanofi Regeneron, GSK, Berlin Chemie and Roche Pharma (payments made to K.F. Rabe); participation on a DSMB or advisory board for AZ, Boehringer Ingelheim and Sanofi Regeneron; and leadership or fiduciary roles in the German Center for Lung Research, German Chest Society and American Thoracic Society, all in the past 36 months. Conflict of interest: A. Papi reports that the ATLANTIS study was supported by Chiesi. They also report grants to their institution from Chiesi, AZ, GSK and Sanofi; consulting fees from Chiesi, AZ, GSK, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, Moderna and Roche (to A. Papi); payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chiesi, AZ, GSK, Menarini, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion, Sanofi and Regeneron (to A. Papi); participation on advisory boards for Chiesi, AZ, GSK, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals and Moderna (to A. Papi); and receipt of equipment, materials, drugs, medical writing, gifts or other services from Consorzio Futuro in Ricerca, all in the past 36 months. Conflict of interest: C. Brightling reports support for the ATLANTIS study from a grant from Chiesi and for the Leicester National Institute for Health and Care Research (NIHR) Biomedical Research Centre from the NIHR; and grants and consultancy fees from 4D Pharma, Areteia, AZ, Chiesi, Genentech, GSL, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi (paid to their institution), in the past 36 months. Conflict of interest: D. Singh reports consulting fees from Aerogen, AZ, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, EpiEndo, Genentech, GSK, Glenmark, Gossamer Bio, Kinaset Therapeutics, Menarini, Novartis, Orion, Pulmatrix, Sanofi, Synairgen, Teva, Theravance Biopharma and Verona Pharma, in the past 36 months. Conflict of interest: T. van der Molen reports that Chiesi funded the present study through their department; and Chiesi funded presentations, and GSK funded presentations and travel (to their company), in the past 36 months. Conflict of interest: J.W.W.H. Kocks reports grants or contracts from AZ, Boehringer Ingelheim, Chiesis, GSK and Valneva; consulting fees from AZ, Boehringer Ingelheim, Chiesi, GSK, Teva, MSD, COVIS Pharma and Janssen (payments made to their institution); and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Mundi Pharma and ALK-Bello (payments made to their institution); that they are an ERS group chair, President and a board member of the International Primary Care Respiratory Group, a member of the CAHAG scientific committee, and a board member of the Inhalation Institute Netherlands; and that they are Director of and hold stocks in the General Practitioners Research Institute, and hold <5% stocks in Lothar Medtec, all in the past 36 months. Conflict of interest: K.F. Chung reports a Medical Research Council (MRC) grant on precision medicine for severe asthma, an Engineering and Physical Sciences Research Council (EPSRC) on air pollution and asthma, a GSK grant on mepolizumab and eosinophils in asthma, a Merck grant on the effects of ATP on cough hypersensitivity, and a National Institute of Environmental Health Sciences grant on air pollution and lipid metabolites in asthma (all to their institution); speaking engagements for GSK, Novartis and AZ (payments to K.F. Chung); and advisory board meetings for GSK, AZ, Novartis, Roche, Merck, Trevi, Rickett-Beckinson, Nocion and Shionogi on asthma, COPD and chronic cough, and the Scientific Advisory Board of the Clean Breathing Institute supported by Haleon (all payments to K.F. Chung), all in the past 36 months. Conflict of interest: I.M. Adcock reports European Union Innovative Medicines Initiative funding for the U-BIOPRED project. They also report grants to their institution from GSK, MRC, EPSRC and Sanofi; consulting fees from GSK, Sanofi and Kinaset (all for advisory boards); and lecture fees from AZ and Sanofi, all in the past 36 months. Conflict of interest: P.K. Bhavsar is an associate editor of this journal. Conflict of interest: N.Z. Kermani has nothing to disclose. Conflict of interest: I.H. Heijink reports research grants from NWO, Longfonds and Health∼Holland outside the scope of the present study, in the past 36 months. Conflict of interest: S.D. Pouwels has nothing to disclose. Conflict of interest: H.A.M. Kerstjens reports support for the present study from Chiesi. They also report unrestricted research grants from Boehringer Ingelheim, GSK and Novartis; and participation on a DSMB or advisory board for GSK, AZ, Novartis and Teva (all payments to their institution), in the past 36 months. Conflict of interest: D-J. Slebos reports support for the ATLANTIS consortium from Chiesi. Conflict of interest: M. van den Berge reports research grants paid to their institution from GSK, Chiesi, AZ, Novartis, Genentech and Roche, in the past 36 months., (Copyright ©The authors 2025.)

Allergic asthma is a significant international concern in respiratory health, which can be exacerbated by the increasing levels of non-allergenic pollutants. This rise in airborne pollutants is a primary driver behind the growing prevalence of asthma, posing a health emergency. Additionally, climatic risk factors can contribute to the onset and progression of asthma. Understanding the complex interplay between pollution, climate, and asthma induction is crucial to elucidate how environmental changes intensify asthma. In this study, we investigated the proteomic and metabolomic changes in the lungs of a mouse asthma model following co-exposure to carbon black nanoparticles and high humidity, which represent airborne and climatic factors, respectively. An asthma model was established using ovalbumin, and mice were intratracheally instilled with 15 or 30 μg/kg of carbon black and simultaneously exposed to either 70% or 90% relative humidity. Protein and metabolite profiles from the lung were used to analyze the most significantly changed clusters, and potential biomarkers and enriched pathways were identified to dissect the adverse effects of the two risk factors. The lung proteome and metabolome are significantly altered by the co-exposure, with the effects modulated by carbon black concentration and humidity level. This study proposes 10 proteins and 18 metabolites as candidate biomarkers. The significantly enriched KEGG pathways include one protein pathway (primary immunodeficiency) and six metabolic pathways (ABC transporters, nucleotide metabolism, Parkinson's disease, purine metabolism, choline metabolism in cancer, and biosynthesis of cofactors). A joint proteomic and metabolomic analysis identifies five common pathways across both omics, namely, ABC transporters, central carbon metabolism in cancer, EGFR tyrosine kinase inhibitor resistance, glioma, and NF-kappa B signaling pathway, disturbed by the co-exposure. We provide a multi-omic basis for the health risk assessment and management of co-exposures to environmental risk factors., 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 © 2025 Elsevier Ltd. All rights reserved.)

COPD has many hallmarks of autoimmune dysfunction. Driving this autoimmune response are self-antigens, such as highly abundant structural proteins and cellular proteins, which can lead to the production of auto-antibodies. However, controversy surrounds the detection of some of these auto-antibodies as they have often been screened against native, unmodified proteins. Autoantigens arise as a result of a conformational change in the native protein exposing hidden epitopes or by the creation of neo-epitopes through chemical or enzymatic modifications, often caused by oxidative/carbonyl stress. In this study, we screened for auto-antibodies targeting key structural proteins modified by oxidative/carbonyl stress in peripheral blood from stable COPD patients versus control subjects using ELISA. We found an auto-antibody response against unmodified, carbonyl-modified and citrinylated vimentin, with the highest response observed against carbonyl-modified vimentin. Both the IgG and IgM antibody titres against carbonyl-modified were significantly increased in COPD patients compared to healthy non-smokers. Smokers also displayed increased antibody levels against carbonyl-modified vimentin, but only for the IgG isotype. Selectivity analysis indicated that 70% and 63% of COPD patients had higher IgM and IgG titres, respectively, compared to non-smokers. In contrast only 26% and 48% of smokers had higher IgM and IgG titres, respectively, than non-smokers. ROC analysis gave AUC values of 0.78 (p < 0.01) and 0.84 (p < 0.001) for IgM and IgG, respectively, for COPD versus non-smokers, which fell to 0.70 (p < 0.01) and 0.64 (NS), respectively, when asymptomatic smokers were included. No significant increase in antibody titre against carbonyl-modified elastin or collagen was observed in COPD patients or asymptomatic smokers. We conclude that IgM autoantibody responses against carbonyl modified vimentin could serve as a simple blood-based biomarker for COPD, reflecting the disease's pathophysiology, and could help in patient stratification and diagnosis., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent was provided by all subjects and the study approved by the institutional local ethics committee at Ferrara University and Imperial College London. Consent for publication: All authors consent to the publication of this manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Particulate matter less than 2.5 microns in aerodynamic diameter (PM 2.5 ) is a significant air pollutant known to adversely affect respiratory health and increase the incidence of chronic obstructive pulmonary disease (COPD). Furthermore, climate change exacerbates these impacts, as extreme temperatures and relative humidity (RH) levels can intensify the effects of PM 2.5 . This study aims to examine the joint effects of PM 2.5 , temperature, and RH on the risk of COPD., Methods: A case-control study was conducted among 1,828 participants from 2017 to 2022 (995 COPD patients and 833 controls). The radial basis function interpolation was utilized to estimate participants' individual mean and differences in PM 2.5 , temperature, and RH in 1-day, 7-day, and 1-month periods. Logistic regression models examined the associations of environmental exposures with the risk of COPD adjusting for confounders. Joint effects of PM 2.5 by quartiles of temperature and RH were also examined., Results: We observed that a 1 µg/m 3 increase in PM 2.5 7-day and 1-month mean was associated with a 1.05-fold and 1.06-fold increase in OR of COPD (p < 0.05). For temperature and RH, we observed U-shaped effects on OR for COPD with optimal temperatures identified as 21.2 °C, 23.8 °C, and 23.8 °C for 1-day, 7-day, and 1-month mean temperature, respectively, and optimal RH levels identified as 73.8%, 76.7%, and 75.4% for 1-day, 7-day, and 1-month mean RH, respectively (p < 0.05). The joint effect models show that high temperatures (> 23.5 °C) and both extremely low (69.3%) and high (80.9%) RH levels generally exacerbate the effects of PM 2.5 on OR for COPD, especially over longer exposure durations., Conclusion: The joint effects of PM 2.5 , temperature, and RH on the risk of COPD underscore the importance of air pollution control and comprehensive research to mitigate COPD risk in the context of climate change., Competing Interests: Declarations. Ethics approval and consent to participate: The study was undertaken in accordance with the Declaration of Helsinki. Informed consent was obtained from all study participants before the research. This study adheres to the ethical standards, with all necessary approvals obtained from the Taipei Medical University-Joint Institution Review Board (TMU-JIRB no. N202302060). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Cigarette smoking has been reported to be associated with SARS-CoV-2 negative conversion, while little is known about the effect of its dual use with e-cigarettes. This study aimed to investigate whether tobacco product use patterns including e-cigarette use were linked with delayed negative conversion of SARS-CoV-2., Methods: An online national survey was conducted from January 28 through February 21, 2023, targeting a community-based population in mainland of China after peak waves of the coronavirus disease 2019 (COVID-19). Participants were followed from the onset of COVID-19 symptoms until the negative conversion day or the day of answering the questionnaire as the endpoint of the study. Multi-variable adjusted Cox proportional hazard models were used to compare the negative conversion time of SARS-CoV-2 across different cigarette and e-cigarette use patterns., Results: A total of 66,537 participants infected with COVID-19 were enrolled and 13,294 were included in the analyses. During the median duration of 7 days (interquartile range 5 to 10 days), a total of 11,587 (87.2%) had a negative conversion. Compared with never users, current exclusive smokers (multi-variable adjusted HR 0.59, 95% CI 0.48-0.71), current dual users (HR 0.31, 95% CI 0.22-0.44), and previous smokers (HR 0.56, 95% CI 0.37-0.83) took longer to turn negative after 10 days of follow-up., Conclusions: Both current exclusive cigarette use and dual use of cigarettes and e-cigarettes were associated with the delayed negative conversion of SARS-CoV-2, which strengthens the importance of smoking and vaping cessation messaging and community-based tobacco control strategies during pandemics like COVID-19 next time., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Clinical Research Ethics Committee of China-Japan Friendship Hospital (2022-KY-183-1) and conducted in accordance with the Declaration of Helsinki. All the participants provided online informed consent before enrolment. Consent for publication: All the authors have agreed to submit the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Competing Interests: W-JS receives consulting fees from MSD, Bellus, and GlaxoSmithKline and receives lecture fees from GlaxoSmithKline. LMcG receives research grants from Bellus Health, Chiesi, Merck, and GlaxoSmithKline; receives lecture fees from Chiesi, GlaxoSmithKline, Merck, Bionorica, and Reckitt Benkiser; and receives consultancy fees from Chiesi, Merck, GlaxoSmithKline, NeRRe Therapeutics, Nocion Therapeutics, Trevi, Reckitt Benkiser and Kenvue. SBM receives grants from Merck and Reckitt Benkiser; receives consultancy fees from Trevi Therapeutics, Reckitt Benkiser, and Chiesi; and has received lecture fees from Reckitt Benkiser. KFC receives research grants, paid to their institution, from the UK Research and Innovation Medical Research Council, the UK Research and Innovation Engineering and Physical Sciences Research Council, the US National Institute of Environmental Health Sciences, Merck, and GlaxoSmithKline; lecture fees from GlaxoSmithKline, Novartis, and AstraZeneca; has been on advisory boards for Roche, Merck, Novartis, GlaxoSmithKline, AstraZeneca, Trevi, Reckitt Benkiser, Nocion, and Shionogi; and is on the scientific advisory board of The Clean Breathing Institute, supported by Haleon.

Asthma continues to cause morbidity and mortality despite advances in treatment that include biologics targeting Type 2 inflammation. The International Collaborative Asthma Network (ICAN) forum was developed with the primary goal of promoting innovative, collaborative research that focuses on mechanisms and treatment for asthma that does not respond or that responds poorly to currently available treatments. The mission of ICAN is innovation, collaboration, translation, and increasing high quality research. At the second ICAN meeting, presenters covered a broad scope and depth of asthma-related topics in the categories of complex data, novel therapeutics and diagnostics, breath analysis and microbiome, disease mechanisms, systemic effects, and circadian rhythm. Key actionable needs and research topics were identified during the group discussions. The presentations and discussions that occurred at the second ICAN had an immediate impact on asthma research in the form of new collaborations and implementation of new research ideas and techniques. The forum also served to connect early-stage investigators with investigators who are well established, thereby fostering innovation, translation, and collaboration well into the future. A third ICAN meeting is planned for 2025 to further the innovations and collaborations that will translate into novel therapies and diagnostics to improve the lives of patients with asthma.

Depression is associated with premature mortality, but evidence is mainly derived from Western countries. Very limited research has evaluated shortened lifespan in depression using life-years-lost (LYLs), a recently developed mortality metric taking into account the illness onset for life expectancy estimation. Temporal trends of differential mortality gap are understudied. This population-based cohort study, which utilized a territory-wide medical-record database of public inpatient and outpatient healthcare services in Hong Kong, evaluated the extent of premature mortality in 126,573 individuals with depression (persons-years=1,139,073) between January 2002 and December 2021 regarding the standardized mortality ratio (SMR) and excess LYLs. Trends in annual SMRs over 20 years were assessed by joinpoint analyses. The results showed that individuals with depression exhibited significantly higher all-cause (SMR=1.84 [95% CI=1.82-1.88]), natural-cause (1.69 [1.66-1.72]), and unnatural-cause (5.24 [4.97-5.51]) mortality rates than the general population. Suicide-specific SMR was markedly elevated (7.92 [7.47-8.38]), particularly in the 15-34 year-olds (12.75 [10.87-14.79]). Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Excess LYLs extended to men (5.67 years, 95% CI = 5.45-5.90) and women (4.06 years, 95% CI = 3.89-4.23). Overall and natural-cause mortality rates improved over time, but unnatural-cause and suicide-related mortality gaps persisted. Taken together, this study indicates that depression is associated with increased premature mortality and reduced lifespan in a predominantly Chinese population, mainly attributed to natural causes. Relative suicide-specific mortality is substantially elevated, especially among young people. The pronounced mortality gap underscores an urgent need for effective interventions targeting improved physical health and suicide risk reduction in individuals with depression., Competing Interests: Declaration of competing interest M.S. received honoraria/has been a consultant for Angelini, AbbVie, Lundbeck, Otsuka. C.U.C. has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Adock Ingram, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Car dio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Tolmar, Vertex, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic. The other authors declare no competing interests. The authors alone are responsible for the content and writing of the paper., (Copyright © 2024 Elsevier B.V. and ECNP. All rights reserved.)