Exacerbations of bronchiectasis.

Bronchiectasis presents a significant challenge due to its rising prevalence, associated economic burden and clinical heterogeneity. This review synthesises contemporary understanding and literature of bronchiectasis exacerbations, addressing the transition from stable state to exacerbations, underlining the importance of early and precise recognition, rigorous severity assessment, prompt treatment, and prevention measures, as well as emphasising the need for strategies to assess and improve early and long-term patient outcomes. The review highlights the interplay between stable state phases and exacerbations in bronchiectasis, introducing the concept of "exogenous and endogenous changes in airways homeostasis" and the "adapted island model" with a particular focus on "frequent exacerbators", a group of patients associated with specific clinical characteristics and worse outcomes. The pathophysiology of exacerbations is explored through the lens of microbial and nonmicrobial triggers and the presence and the activity of comorbidities, elaborating on the impact of both exogenous insults, such as infections and pollution, and endogenous factors such as inflammatory endotypes. Finally, the review proposes a multidisciplinary approach to care, integrating advancements in precision medicine and biomarker research, paving the way for tailored treatments that challenge the traditional antibiotic paradigm.

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Copyright ©The authors 2024.

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Previous articles in this series: No. 1: Perea L, Faner R, Chalmers JD, et al. Pathophysiology and genomics of bronchiectasis. Eur Respir Rev 2024; 33: 240055. No. 2: Mac Aogáin M, Dicker AJ, Mertsch P, et al. Infection and the microbiome in bronchiectasis. Eur Respir Rev 2024; 33: 240038. No. 3: Van Braeckel E, Bosteels C. Growing from common ground: nontuberculous mycobacteria and bronchiectasis. Eur Respir Rev 2024; 33: 240058.Conflict of interest: A. De Angelis and E.D. Johnson have nothing to disclose. S. Sutharsan reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharamceuticals, Insmed and Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Vertex Pharamceuticals. S. Alberti reports grants from INSMED Incorporated, Chiesi, Fisher & Paykel and GSK, royalties or licences from McGraw Hill, consultancy fees from INSMED Incorporated, INSMED Italy, INSMED Ireland Ltd, INSMED Netherlands BV, ZAMBON Spa, AstraZeneca UK Limited, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna Italy, Moderna TX, Boehringer Ingelheim, Chiesi farmaceutica Spa, MSD Italia S.r.l., Vertex Pharmaceuticals, BRAHMS GMBH, Physioassist SAS, AN2 Therapeutics and GlaxoSmithKline Spa, payment or honoraria for lectures, presentations, manuscript writing or educational events from GlaxoSmithKline Spa, Thermofisher Scientific, INSMED Italy, INSMED Ireland Ltd, Boehringer Ingelheim, Zambon, Vertex Pharmaceuticals and Fondazione Internazionale Menarini, and participation on a data safety monitoring board or advisory board with INSMED Incorporated, INSMED Italy, AstraZeneca UK Limited and MSD Italia S.r.l.