Acute exacerbations in patients with progressive pulmonary fibrosis

Acute exacerbations in patients with progressive pulmonary fibrosis

Background Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis. Method...

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Main Authors: Michael Kreuter, Elizabeth A. Belloli, Elisabeth Bendstrup, Stefania Cerri, Kevin R. Flaherty, Shane Shapera, Jin Woo Song, Heiko Mueller, Klaus B. Rohr, Yasuhiro Kondoh, on behalf of the INBUILD trial investigators, S. Quadrelli, M. Otaola, M.A. Bergna, P. Elias, G. Arce, A. Cazaux, J. Guiot, B. Bondue, C. Dahlqvist, L. Homik, S. Shapera, A. Cantin, M. Kolb, M. Salinas Fénero, R. Maturana Rozas, A. Silva Orellana, Z. Xu, Q. Luo, J. Kang, H. Cai, S. Marchand-Adam, E. Bergot, A. Gamez-Dubuis, F. Riviere, R. Kessler, H. Nunes, C. Marquette, L. Wemeau, S. Jouneau, F. Lebargy, B. Crestani, V. Cottin, M. Reynaud-Gaubert, S. Blaas, F. Bonella, W. Randerath, J. Hetzel, D. Koschel, M. Kreuter, A. Prasse, D. Skowasch, S. Stieglitz, R. Refini, S. Cerri, A. Pesci, S. Tomassetti, C. Vancheri, F. Varone, N. Sakamoto, S. Abe, H. Hayashi, T. Saito, T. Suda, H. Kitamura, M. Okamoto, Y. Kondoh, S. Makino, T. Takeuchi, Y. Yamada, C. Kono, Y. Inoue, H. Sugiura, K. Kishi, H. Takaya, H. Yamauchi, K. Ichikado, K. Tomii, H. Takahashi, S. Izumi, T. Kawamura, Y. Nishioka, Y. Miyazaki, J.W. Song, J.S. Park, Y. Kim, E. Jassem, J. Kus, W. Piotrowski, A. Barczyk, D. Ziora, E. Bazdyrev, S. Moiseev, S. Avdeev, M. Ilkovich, V. Yakusevich, C. Valenzuela, O. Acosta, M. Martínez, L. Gómez, M. Molina-Molina, D.M. Castillo Villegas, M. Aburto, J.A. Rodríguez Portal, A. Villar, A. León Jiménez, J. Sauleda, M. Arias, P. Beirne, H. Stone, B. Hope-Gill, N. Hirani, N. Chaudhuri, A. Gifford, L. Jones, L. Morrison, D. Antin-Ozerkis, N. Bhatt, T. Kulkarni, T. Moua, N. Ettinger, L. Pitts, S. Veeraraghavan, M. Padilla, E.R. Fernández Pérez, G. Giessel, M. Strek, S. Danoff, J. Burk, M. Rossman, N. Patel, E. Belloli, D. Hotchkin, S. Weigt, M.B. Scholand, R. Kaner, B. Sigal, Z. Safdar, L. Tolle, R. Martinez, M. Glassberg, R. Hallowell, J. Golden, M. Schwartz, E. Britt, L. Morrow, Y. Mageto, K. Buch, S. Chaaban, H. Poonyagariyagorn, D. Dilling, O. Shlobin, K. Thavarajah, A. Nambiar, I. Rosas, R. Bascom, J. Oldham, S. Schmidt, J. Dematte D'Amico, J. Falk, C. Glazer, G. Criner
Format: Article
Language:English
Published: European Respiratory Society 2024-12-01
Series:ERJ Open Research
Online Access:http://openres.ersjournals.com/content/10/6/00403-2024.full
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Summary:Background Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis. Methods Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib or placebo. Associations between baseline characteristics and time to first acute exacerbation were assessed using pooled data from both treatment groups using Cox proportional hazard models, firstly univariable models and then a multivariable model using forward stepwise selection. The risk of death was estimated based on the Kaplan−Meier method. Results Over a median follow-up of approximately 19 months, acute exacerbations were reported in 58 (8.7%) of 663 patients. In the risk factor analysis, the final model included diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, treatment and age. Lower DLCO % predicted was associated with an increased risk of acute exacerbation with a hazard ratio (HR) of 1.56 (95% CI 1.21–2.02) per 10 units lower (p<0.001). Age ≥65 years was associated with a numerically increased risk (HR 1.55, 95% CI 0.87–2.77; p=0.14). Treatment with nintedanib conferred a numerically reduced risk versus placebo (HR 0.60, 95% CI 0.35–1.02; p=0.06). The estimated risks of death ≤30 days and ≤90 days after an acute exacerbation were 19.0% (95% CI 8.9–29.2) and 32.0% (95% CI 19.7–44.2). Conclusions Acute exacerbations of progressive pulmonary fibrosis may have similar risk factors and prognostic impact as acute exacerbations of IPF.
ISSN:2312-0541

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