Abstract
Original language | English |
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Pages (from-to) | 55-64 |
Number of pages | 10 |
Journal | The Lancet Respiratory Medicine |
Volume | 11 |
Issue number | 1 |
Early online date | 2022 |
DOIs | |
Publication status | Published - Jan 2023 |
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In: The Lancet Respiratory Medicine, Vol. 11, No. 1, 01.2023, p. 55-64.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Predictors and associations of the persistent airflow limitation phenotype in asthma
T2 - a post-hoc analysis of the ATLANTIS study
AU - Kole, Tessa M.
AU - Vanden Berghe, Elise
AU - Kraft, Monica
AU - Vonk, Judith M.
AU - Nawijn, Martijn C.
AU - Siddiqui, Salman
AU - Sun, Kai
AU - Fabbri, Leonardo M.
AU - Rabe, Klaus F.
AU - Chung, Kian Fan
AU - Nicolini, Gabriele
AU - Papi, Alberto
AU - Brightling, Chris
AU - Singh, Dave
AU - van der Molen, Thys
AU - Dahlén, Sven-Erik
AU - Agusti, Alvar
AU - Faner, Rosa
AU - Wedzicha, Jadwiga A.
AU - Donaldson, Gavin C.
AU - Adcock, Ian M.
AU - Lahousse, Lies
AU - Kerstjens, Huib A. M.
AU - van den Berge, Maarten
AU - ATLANTIS
AU - Badorrek, P.
AU - Broeders, M.
AU - Boersma, W. G.
AU - Chetta, A.
AU - Cukier, A.
AU - D'Amato, M.
AU - Djukanovic, R.
AU - Foschino, M. P.
AU - Gessner, C.
AU - Hanania, N.
AU - Martin, R.
AU - Milleri, S.
AU - Olivenstein, R.
AU - Paggiaro, P.
AU - Pizzichini, E.
AU - Plaza Moral, V.
AU - Postma, D. S.
AU - Scichilone, N.
AU - Schilz, R.
AU - CADSET investigators
AU - U-BIOPRED
AU - Brinkman, P.
AU - Lutter, R.
AU - van Aalderen, W. M.
AU - van Drunen, C. M.
AU - Zwinderman, A. H.
AU - Maitland-van der Zee, A. H.
AU - Sterk, P. J.
N1 - Funding Information: The submitted work was co-financed by the Dutch Ministry of Economic Affairs and Climate Policy by means of the public private partnership programme. Funding Information: MK reports grants paid personally from Chiesi Farmaceutici for support of this study; grants paid to institution from the National Institute of Health, American Lung Association, Astra-Zeneca, Sanofi-Regeneron; personal fees for consultancies from Chiesi Farmaceutici, AstraZeneca, Genetech, Sanofi-Regeneron; speaker fees from Chiesi Farmaceutici; personal fees from participation in a data safety and monitoring board for AstraZeneca and ALung; and previous leadership in the American Thoracic Society (ATS) and Association for Professors of Medicine. MCN reports research grants paid to their institution from the European Commission and Netherlands Lung Foundation. SS reports personal fees for consulting from AstraZeneca, GSK, CSL Behring, Owlstone Medical, Boehringer Ingelheim, and ERT Medical; speaker fees from Chiesi Farmaceutici; and reports board membership of both the Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR) Artificial Intelligence, and leadership in the European Respiratory Society (ERS) Clinical Research Collaboration and UK National Asthma Strategy Group. LMF reports personal grants paid by Chiesi Farmaceutici for consultation for this study; consulting fees from Chiesi Farmaceutici; speaker fees or fees for membership of advisory boards for Chiesi Farmaceutici, AstraZeneca, GlaxoSmithKline, Alfasigma, Novartis, Verona Pharma, Lusofarmaco; travel expenses reimbursements from Chiesi Farmaceutici, Novartis, and Menarini; and participation of a data safety and monitoring board or advisory board of Novartis. KFR reports personal speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, Sanofi-Regeneron, GlaxoSmithKline, Berlin Chemie, and Roche Pharma; participation on data safety and monitoring board or advisory boards for AstraZeneca, Boehringer Ingelheim and Sanofi-Regeneron; and KFR is a current board member of German Center for Lung Research, past president of the German Chest Society, and past member of ATS committees. KFC reports grants paid to institution from GlaxoSmithKline, UK MRC, Engineering and Physical Sciences Research Council (EPSRC); personal speaker fees from Novartis and AstraZeneca; and membership of advisory boards for AstraZeneca, GlaxoSmithKline, Roche, and Novartis. GN is an employee of Chiesi Farmaceutici. AP reports grants paid to institution from Chiesi Farmaceutici, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Teva, and Sanofi; personal consulting fees from Chiesi Farmaceutici, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, IQVIA, Avillion, and Elpen pharmaceuticals; and personal speaker fees from Chiesi Farmaceutici, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Menarini, Novartis, Zambon, Mundipharma, TEVA, Sanofi, Edmond pharma, IQVIA, Merck Sharp & Dohme (MSD), Avillion, Elpen pharmaceuticals. CB reports personal grants paid by Chiesi Farmaceutici for support of this study; grants paid to institution from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, MSD, Teva Pharmaceuticals, Novartis, Sanofi, Genentech, Roche, 4DPharma, Mologic; consulting fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, MSD, Teva Pharmaceuticals, Sanofi, Genentech, Roche, 4DPharma, Mologic; and chair of the ERS Science Council. DS reports consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, TEVA, Theravanca, and Verona. TvdM reports consulting fees from Chiesi Farmaceutici. SED reports a grant paid to institution from Chiesi Farmaceutici for execution of the study; grants paid to institution by the Swedish MRC, Heart-Lung foundation, Country council funds for clinical research; personal consulting fees from AstraZeneca, GlaxoSmithKline, Merck, Novartis, Regeneron, Sanofi, TEVA; and personal speaker fees from AstraZeneca, GlaxoSmithKline, and Sanofi. AA reports grants from AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini; consulting fees from AstraZeneca, GlaxoSmithKline, Chiesi Farmaceutici, and Menarini; speaker fees from AstraZeneca, GlaxoSmithKline, Chiesi Farmaceutici, Menarini; travel reimbursements from AstraZeneca, GlaxoSmithKline, Chiesi Farmaceutici, Menarini; and participation of a data safety and monitoring or advisory board of AstraZeneca, GlaxoSmithKline, Chiesi Farmaceutici, and Menarini. RF reports grants paid to the CADSET collaboration for this study; grants from Instituto de Salud Carlos III, Menarini, GlaxoSmithKline, and AstraZeneca outside of submitted work; and speaker fees from Chiesi Farmaceutici. JAW reports grants paid to institution from Genentech, GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi Farmaceutici; and meeting expenses from Novartis, Boehringer Ingelheim, and Astra Zeneca. GCD reports grants from Novartis, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Boheringer-Ingelheim; royalties or licenses from a book chapter on Respiratory Physiology; honoraria from ATS as statistical editor; and participation of a data safety and monitoring or advisory board for the Mister Study. IMA reports grant paid to institution for the execution of the study from the EU Innovative Medicines Initiative; grants paid to institution from GlaxoSmithKline, MRC, and EPSRC; consulting fees from GlaxoSmithKline, Sanofi, Chiesi Farmaceutici, Kinaset; presenter fees from AstraZeneca, Sanofi, Eurodrug, Sunovion; payment for expert testimony from Chiesi Farmaceutici; and travel grants from AstraZeneca. LL reports speaker fees paid to institution from the Instituut voor Permanente Studie voor Apothekers (non-profit organisation). HAMK reports grants from Chiesi Farmaceutici, GlaxoSmithKline, Novartis; and consulting fees paid to institution by GlaxoSmithKline and Novartis. MvdB report research grants paid to institution by GlaxoSmithKline, Chiesi Farmaceutici, AstraZeneca, Novartis, Genentech, and Roche. All other authors declare no competing interests. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/1
Y1 - 2023/1
N2 - Background: Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study. Methods: In this post-hoc analysis of the ATLANTIS study, we assessed the prevalence, clinical characteristics, and implications of PAL across the full range of asthma severity. The study population included patients aged 18–65 years who had been diagnosed with asthma at least 6 months before inclusion. We defined PAL as a post-bronchodilator FEV1/forced vital capacity (FVC) of less than the lower limit of normal at recruitment. Asthma severity was defined according to the Global Initiative for Asthma. We used Mann-Whitney U test, t test, or χ2 test to analyse differences in baseline characteristics between patients with and without PAL. Logistic regression was used for multivariable analysis of the associations between PAL and baseline data. Cox regression was used to analyse risk of exacerbation in relation to PAL, and a linear mixed-effects model was used to analyse change in FEV1 over time in patients with versus patients without PAL. Results were validated in the U-BIOPRED cohort. Findings: Between June 30, 2014 and March 3, 2017, 773 patients were enrolled in the ATLANTIS study of whom 760 (98%) had post-bronchodilator FEV1/FVC data available. Of the included patients with available data, mean age was 44 years (SD 13), 441 (58%) of 760 were women, 578 (76%) were never-smokers, and 248 (33%) had PAL. PAL was not only present in patients with severe asthma, but also in 21 (16%) of 133 patients with GINA step 1 and 24 (29%) of 83 patients with GINA step 2. PAL was independently associated with older age at baseline (46 years in PAL group vs 43 years in non-PAL group), longer duration of asthma (24 years vs 12 years), male sex (51% vs 38%), higher blood eosinophil counts (median 0·27 × 109 cells per L vs 0·20 × 109 cells per L), more small airway dysfunction, and more exacerbations during 1 year of follow-up. Associations between PAL, age, and eosinophilic inflammation were validated in the U-BIOPRED cohort, whereas associations with sex, duration of asthma, and risk of exacerbations were not validated. Interpretation: PAL is not only present in severe disease, but also in a considerable proportion of patients with milder disease. In patients with mild asthma, PAL is associated with eosinophilic inflammation and a higher risk of exacerbations. Our findings are important because they suggest that increasing treatment intensity should be considered in patients with milder asthma and PAL. Funding: Chiesi Farmaceutici and Dutch Ministry of Economic Affairs and Climate Policy (by means of the public–private partnership programme).
AB - Background: Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study. Methods: In this post-hoc analysis of the ATLANTIS study, we assessed the prevalence, clinical characteristics, and implications of PAL across the full range of asthma severity. The study population included patients aged 18–65 years who had been diagnosed with asthma at least 6 months before inclusion. We defined PAL as a post-bronchodilator FEV1/forced vital capacity (FVC) of less than the lower limit of normal at recruitment. Asthma severity was defined according to the Global Initiative for Asthma. We used Mann-Whitney U test, t test, or χ2 test to analyse differences in baseline characteristics between patients with and without PAL. Logistic regression was used for multivariable analysis of the associations between PAL and baseline data. Cox regression was used to analyse risk of exacerbation in relation to PAL, and a linear mixed-effects model was used to analyse change in FEV1 over time in patients with versus patients without PAL. Results were validated in the U-BIOPRED cohort. Findings: Between June 30, 2014 and March 3, 2017, 773 patients were enrolled in the ATLANTIS study of whom 760 (98%) had post-bronchodilator FEV1/FVC data available. Of the included patients with available data, mean age was 44 years (SD 13), 441 (58%) of 760 were women, 578 (76%) were never-smokers, and 248 (33%) had PAL. PAL was not only present in patients with severe asthma, but also in 21 (16%) of 133 patients with GINA step 1 and 24 (29%) of 83 patients with GINA step 2. PAL was independently associated with older age at baseline (46 years in PAL group vs 43 years in non-PAL group), longer duration of asthma (24 years vs 12 years), male sex (51% vs 38%), higher blood eosinophil counts (median 0·27 × 109 cells per L vs 0·20 × 109 cells per L), more small airway dysfunction, and more exacerbations during 1 year of follow-up. Associations between PAL, age, and eosinophilic inflammation were validated in the U-BIOPRED cohort, whereas associations with sex, duration of asthma, and risk of exacerbations were not validated. Interpretation: PAL is not only present in severe disease, but also in a considerable proportion of patients with milder disease. In patients with mild asthma, PAL is associated with eosinophilic inflammation and a higher risk of exacerbations. Our findings are important because they suggest that increasing treatment intensity should be considered in patients with milder asthma and PAL. Funding: Chiesi Farmaceutici and Dutch Ministry of Economic Affairs and Climate Policy (by means of the public–private partnership programme).
UR - http://www.scopus.com/inward/record.url?scp=85136757355&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S2213-2600(22)00185-0
DO - https://doi.org/10.1016/S2213-2600(22)00185-0
M3 - Article
C2 - 35907424
SN - 2213-2600
VL - 11
SP - 55
EP - 64
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 1
ER -