TY - JOUR
T1 - A Cluster Analysis of Bronchiectasis Patients Based on the Airway Immune Profile
AU - Perea, Lídia
AU - Cantó, Elisabet
AU - Suarez-Cuartin, Guillermo
AU - Aliberti, Stefano
AU - Chalmers, James D.
AU - Sibila, Oriol
AU - Vidal, Silvia
N1 - Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: J. D. C. has received research grants from GlaxoSmithKline , Boehringer-Ingelheim, AstraZeneca , Gilead Sciences, Zambon, and Insmed and has received personal fees from Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Chiesi , Novartis , Insmed, and Zambon. S. A. has received research grants from Chiesi, Insmed, and Fisher & Paykel and has received personal fees from Bayer HealthCare , Grifols , AstraZeneca, Zambon, Chiesi, Insmed, GlaxoSmithKline, Menarini, and ZetaCube Srl. None declared (L. P., E. C., G. S.-C., O. S., S. V.).
Funding Information:
FUNDING/SUPPORT: This study is supported by Instituto de Salud Carlos III and Fondos FEDER [Grant PI18/00311 ] and Sociedad Española de Neumología y Cirugía Torácica (SEPAR). This work was performed within the Ph.D. Immunology Program of Universitat Autònoma de Barcelona.
Publisher Copyright:
© 2020 American College of Chest Physicians
PY - 2021/5
Y1 - 2021/5
N2 - Background: Clinical 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 Question: Can 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 Methods: A 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. Results: Three 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). Interpretation: Bronchiectasis 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.
AB - Background: Clinical 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 Question: Can 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 Methods: A 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. Results: Three 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). Interpretation: Bronchiectasis 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.
KW - airway immunity
KW - bronchiectasis
KW - cluster analysis
KW - exacerbations
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U2 - 10.1016/j.chest.2020.11.011
DO - 10.1016/j.chest.2020.11.011
M3 - Article
C2 - 33217421
AN - SCOPUS:85102785568
VL - 159
SP - 1758
EP - 1767
JO - Chest
JF - Chest
SN - 0012-3692
IS - 5
ER -