Lídia Perea1, Elisabet Cantó1, Guillermo Suarez-Cuartin2, Stefano Aliberti3, James D Chalmers4, Oriol Sibila5, Silvia Vidal6. 1. 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. 2. Respiratory Department, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, Spain. 3. Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy. 4. Tayside Respiratory Research Group, University of Dundee, Dundee, Scotland. 5. Respiratory Department, Hospital Clinic, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain. 6. 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. Electronic address: svidal@santpau.cat.
Abstract
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.
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.
Authors: Xuejie Wang; Carmen Villa; Yadira Dobarganes; Casilda Olveira; Rosa Girón; Marta García-Clemente; Luis Máiz; Oriol Sibila; Rafael Golpe; Rosario Menéndez; Juan Rodríguez-López; Concepción Prados; Miguel Angel Martinez-García; Juan Luis Rodriguez; David de la Rosa; Xavier Duran; Jordi Garcia-Ojalvo; Esther Barreiro Journal: Biomedicines Date: 2022-01-21
Authors: Martina Oriano; Francesco Amati; Andrea Gramegna; Anthony De Soyza; Marco Mantero; Oriol Sibila; Sanjay H Chotirmall; Antonio Voza; Paola Marchisio; Francesco Blasi; Stefano Aliberti Journal: Int J Mol Sci Date: 2021-06-01 Impact factor: 5.923