{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:47:18Z","timestamp":1791942438497,"version":"4.3.4"},"reference-count":24,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["11N3922N"],"award-info":[{"award-number":["11N3922N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S30225N"],"award-info":[{"award-number":["1S30225N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0C9623N"],"award-info":[{"award-number":["G0C9623N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011878","name":"Flemish Government","doi-asserted-by":"crossref","award":["AI in Flanders program 'no award\/grant number\u2019"],"award-info":[{"award-number":["AI in Flanders program 'no award\/grant number\u2019"]}],"id":[{"id":"10.13039\/501100011878","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["KU Leuven Chair in Respiratory Diseases \u2019no award\/"],"award-info":[{"award-number":["KU Leuven Chair in Respiratory Diseases \u2019no award\/"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2025,5,2]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Long-term azithromycin treatment effectively prevents acute exacerbations of chronic obstructive pulmonary disease (COPD). However, patients would benefit from better identification of responders and non-responders to minimise unnecessary exposure. We aimed to assess treatment effect heterogeneity and estimate individual treatment effects (ITEs) to distinguish patients most likely to benefit from prophylactic treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from 1025 patients of the MACRO trial to assess the ITE of azithromycin on annual exacerbation rate. A Causal Forest was used as a causal machine learning model. We independently validated our findings using data from 83 patients of the COLUMBUS trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The tertile of patients with the best predicted ITE within MACRO and within the COLUMBUS independent validation cohort showed significant and substantially greater reductions in annual exacerbation rates (in MACRO \u22120.50, rate ratio 0.70, p=0.01, in COLUMBUS: \u22122.28, rate ratio 0.43, p&lt;0.001) compared with the average treatment effect across the entire cohort (MACRO \u22120.35, rate ratio 0.83, p=0.01\u2009and COLUMBUS \u22121.28, rate ratio 0.58, p=0.001). Conversely, no significant treatment effect was observed in the remaining two-thirds of patients. Primary determinants of ITE included respiratory symptoms, white blood cell count, haemoglobin, C-reactive protein and forced vital capacity. Smoking status did not emerge as a significant predictor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on five easily obtainable parameters to predict ITE, we identified treatment effect heterogeneity in COPD subjects treated with azithromycin maintenance therapy and found a small subgroup of responders driving the average reduction in exacerbations reported in previous trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/thorax-2025-223095","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T13:20:19Z","timestamp":1751548819000},"page":"900-908","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Identifying azithromycin responders with an individual treatment effect model in COPD"],"prefix":"10.1136","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-417X","authenticated-orcid":false,"given":"Kenneth","family":"Verstraete","sequence":"first","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium"},{"name":"STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-7228","authenticated-orcid":false,"given":"Iwein","family":"Gyselinck","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium"},{"name":"Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Huts","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium"},{"name":"STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-5532","authenticated-orcid":false,"given":"Remco Stuart","family":"Djamin","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Amphia Hospital, Breda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u00ebl","family":"Staes","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium"},{"name":"Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"Talman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Amphia Hospital, Breda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno","family":"van der Eerden","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-5145","authenticated-orcid":false,"given":"Maarten","family":"De Vos","sequence":"additional","affiliation":[{"name":"STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium"},{"name":"Department of Development and Regeneration, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Janssens","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium"},{"name":"Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"2025112103101083000_80.12.900.1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0121257","article-title":"Prophylactic use of macrolide antibiotics for the prevention of chronic obstructive pulmonary disease exacerbation: a meta-analysis","volume":"10","author":"Ni","year":"2015","journal-title":"PLoS 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