• Lídia Perea, Elisabet Cantó, Guillermo Suarez-Cuartin, Stefano Aliberti, James D Chalmers, Oriol Sibila, and Silvia Vidal.
• Department of Inflammatory Diseases, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
• Chest. 2021 May 1; 159 (5): 1758-1767.

BackgroundClinical heterogeneity in bronchiectasis remains a challenge for improving the appropriate targeting of therapies and patient management. Antimicrobial peptides (AMPs) have been linked to disease severity and phenotype.Research QuestionCan we identify clusters of patients based on the levels of AMPs, airway inflammation, tissue remodeling, and tissue damage to establish their relationship with disease severity and clinical outcomes?Study Design And MethodsA prospective cohort of 128 stable patients with bronchiectasis were recruited across three centers in three different countries (Spain, Scotland, and Italy). A two-step cluster strategy was used to stratify patients according to levels of lactoferrin, lysozyme, LL-37, and secretory leukocyte protease inhibitor in sputum. Measurements of inflammation (IL-8, tumor growth factor β, and IL-6), tissue remodeling and damage (glycosaminoglycan, matrix metallopeptidase 9, neutrophil elastase, and total and bacterial DNA), and neutrophil chemotaxis were assessed.ResultsThree clusters of patients were defined according to distinct airway profiles of AMPs. They represented groups of patients with gradually distinct airway infection and disease severity. Each cluster was associated with an airway profile of inflammation, tissue remodeling, and tissue damage. The relationships between soluble mediators also were distinct between clusters. This analysis allowed the identification of the cluster with the most deregulated local innate immune response. During follow-up, each cluster showed different risk of three or more exacerbations occurring (P = .03) and different times to first exacerbations (P = .03).InterpretationBronchiectasis patients can be stratified in different clusters according to profiles of airway AMPs, inflammation, tissue remodeling, and tissue damage. The combination of these immunologic variables shows a relationship with disease severity and future risk of exacerbations.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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