Portal de Periódicos da CAPES

Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study

2022; Elsevier BV; Volume: 11; Issue: 1 Linguagem: Inglês

10.1016/s2213-2600(22)00185-0

2213-2619

Tessa Kole, Elise Vanden Berghe, Monica Kraft, Judith M. Vonk, Martijn C. Nawijn, Salman Siddiqui, Kai Sun, Leonardo M. Fabbri, Klaus F. Rabe, Kian Fan Chung, Gabriele Nicolini, Alberto Papi, Christopher E. Brightling, Dave Singh, Thys van der Molen, Sven‐Erik Dahlén, Àlvar Agustí, Rosa Faner, Jadwiga A. Wedzicha, Gavin C. Donaldson, Ian M. Adcock, Lies Lahousse, Huib A.M. Kerstjens, Maarten van den Berge, Philipp Badorrek, M.E.A.C. Broeders, Willem Boersma, Alfredo Chetta, Alberto Cukier, Maria D’Amato, Ratko Djukanović, Maria Pia Foschino, Christian Geßner, Nicola A. Hanania, Richard J. Martin, Stefano Milleri, Ronald Olivenstein, Pierluigi Paggiaro, Emílio Pizzichini, Vicente Plaza, Dirkje S. Postma, Nicola Scichilone, Robert Schilz, Antonio Spanevello, Rafaël Stelmach, J. Sebastiaan Vroegop, Omar S. Usmani, Q. Zhang, Hassan Ahmed, David J. Allen, S. Ballereau, Manohara Batuwitage, A. Bedding, Annelie F. Behndig, A. Berglind, Alix Berton, Jeanette Bigler, Michael Boedigheimer, Klaus Bønnelykke, Paul Brinkman, Andrew Bush, Davide Campagna, Carmen Casaulta, Amphun Chaiboonchoe, Timothy S. Davison, Bertrand De Meulder, Ingrid Delin, P. A. Dennison, P M Dodson, L. El Hadjam, Damijan Eržen, Cornelia Faulenbach, K. Fichtner, Neil Fitch, E. Formaggio, Martina Gahlemann, Gabriella Gálffy, D. Garissi, T. Garret, E. Guillmant-Farry, Elisabet Welin Henriksson, Umair Shamsul Hoda, J.M. Hohlfeld, Xinyue Hu, Anna James, Katherine Waltman Johnson, N. Jullian, Gina Kerry, Matthias Klüglich, Richard Knowles, Jon R. Konradsen, Kosmas Kretsos, Linn Krueger, A-S. Lantz, Christopher Larminie, Philipp Latzin, Diane Lefaudeux, Nicolas Lemonnier, Lesley Lowe, R. Lutter, Alexander Manta, Alexander Mazein, L M McEvoy, Andrew Menzies‐Gow, Nadia Mores, Clare Murray, Katja Nething, Ulf Nihlén, Robert Niven, Björn Nordlund, S. Nsubuga, J. Pellet, Christophe Pison, G. Praticò, M. Puig Valls, Kathrin Riemann‐Campe, J.P. Rocha, Christos Rossios, Giuseppe Santini, M. Sagi, Stephen Scott, Neha Sehgal, Anna Selby, P. Söderman, A. Sogbesan, F. Spycher, S. Stephan, Jakob Stokholm, M. Sunther, Márton Szentkereszty, Lilla Tamási, Kamran Tariq, Salvatore Valente, W. M. van Aalderen, Cornelis M. van Drunen, Jonathan van Eyll, Aditya Vyas, Weichang Yu, W. Zetterguist, Zaraquiza Zolkipli, A. H. Zwinderman, Àlvar Agustí, Jadwiga A. Wedzicha, Gavin C. Donaldson, Rosa Faner, Robab Breyer‐Kohansal, Anke H. Maitland‐van der Zee, Erik Melén, James P. Allinson, Lowie E.G.W. Vanfleteren, Jørgen Vestbo, Ian M. Adcock, Lies Lahousse, Maarten van den Berge, Peter Alter, Ferrán Barbé, Christopher E. Brightling, Marie‐Kathrin Breyer, Otto C. Burghuber, Maribel Casas, Kian Fan Chung, Borja G. Cosío, F. Crispi, J. De Batlle, Jean-William Fitting, J.M. Pino García, Jenny Hallberg, Sylvia Hartl, Deborah Jarvis, Alexander G. Mathioudakis, Laurent Nicod, Alberto Papi, Andrew I. Ritchie, Torben Sigsgaard, Peter J. Sterk, A. Ullman, Kilian Vellvé, Claus Vogelmeier, Åsa M. Wheelock, Craig E. Wheelock, Antonio Spanevello,

Inhalation and Respiratory Drug Delivery

Summary 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 FEV 1 /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 χ 2 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 FEV 1 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 FEV 1 /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 × 10 9 cells per L vs 0·20 × 10 9 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).