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Volume 13
Issue 9
10.3390/biomedicines13092124
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Phenotyping Bronchiectasis Frequent Exacerbator: A Single Centre Retrospective Cluster Analysis

by
Francesco Rocco Bertuccio
1,2,
Nicola Baio
3,
Simone Montini
1,2,
Valentina Ferroni
1,2,
Vittorio Chino
4,
Lucrezia Pisanu
1,2,
Marianna Russo
1,2,
Ilaria Giana
1,2,
Elisabetta Gallo
1,2,
Lorenzo Arlando
1,2,
Klodjana Mucaj
1,2,
Mitela Tafa
1,2,
Maria Arminio
1,2,
Emanuela De Stefano
1,2,
Alessandro Cascina
1,2,
Amelia Grosso
2,
Erica Gini
2,
Federica Albicini
2,
Virginia Valeria Ferretti
5,
Eleonora Fresi
5,
Angelo Guido Corsico
1,2,
Giulia Maria Stella
1,2,* and
Valentina Conio
1,2,*add Show full author list remove Hide full author list
1
Unit of Respiratory Disease, Cardiothoracic and Vascular Department, IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy
2
Department of Internal Medicine and Pharmacology, University of Pavia, 27100 Pavia, Italy
3
Ospedale Maggiore, ASST Crema, 26013 Crema, Italy
4
Ospedale Pederzoli, Peschiera del Garda, 37121 Verona, Italy
5
Biostatistica e Clinical Trial Center, Direzione Scientifica, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy
*
Authors to whom correspondence should be addressed.
Biomedicines 2025, 13(9), 2124; https://doi.org/10.3390/biomedicines13092124 (registering DOI)
Submission received: 16 July 2025 / Revised: 24 August 2025 / Accepted: 29 August 2025 / Published: 30 August 2025
(This article belongs to the Special Issue Advanced Research in Chronic Respiratory Diseases (CRDs))
Versions Notes

Abstract

Background: Bronchiectasis is a chronic respiratory condition characterized by permanent bronchial dilation, recurrent infections, and progressive lung damage. A subset of patients, known as frequent exacerbators, experience multiple exacerbations annually, leading to accelerated lung function decline, hospitalizations, and reduced quality of life. The aim of this study is to identify distinct phenotypes and treatable traits in bronchiectasis frequent exacerbators, since it could be crucial for optimizing patient management. Research question: Could clinically distinct phenotypes and treatable traits be identified among frequent exacerbators with bronchiectasis to guide personalized management strategies? Methods: We analysed a cohort of 56 bronchiectasis frequent exacerbator patients using 21 clinically relevant variables, including pulmonary function tests, radiological patterns, and microbiological data. Hierarchical clustering and k-means algorithms were applied to identify subgroups. Key outcomes included cluster-specific characteristics, treatable traits, and their implications for management. Results: Four distinct clusters were identified: 1. Mild, idiopathic bronchiectasis (Cluster 1): Predominantly mild disease (FACED), idiopathic etiology (93.3%), and cylindrical bronchiectasis with moderate obstruction (60%). 2. Rheumatological and NTM-associated bronchiectasis (Cluster 2): Patients with systemic inflammatory diseases (50%) and NTMever (50%) but minimal infections by Pseudomonas aeruginosa. 3. Mild, post-infective bronchiectasis (Cluster 3): Exclusively mild disease, mixed idiopathic and post-infective etiologies, and preserved lung function. 4. Severe, chronic infection phenotype (Cluster 4): Severe disease with high colonization rates of Pseudomonas aeruginosa (71.4%), advanced structural damage (57.1% varicose, 50% cystic bronchiectasis), and frequent exacerbations. Interpretation: This analysis highlights the heterogeneity of bronchiectasis and its frequent exacerbator phenotype. The treatable traits framework underscores the importance of aggressive infection control and management of airway inflammation in severe cases, while milder clusters may benefit from preventive strategies. These findings support the integration of precision medicine in bronchiectasis care, focusing on phenotype-specific interventions to improve outcomes.
Keywords: non-cystic fibrosis bronchiectasis; phenotypic clusters; multivariate analyses; clinical outcomes non-cystic fibrosis bronchiectasis; phenotypic clusters; multivariate analyses; clinical outcomes

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MDPI and ACS Style

Bertuccio, F.R.; Baio, N.; Montini, S.; Ferroni, V.; Chino, V.; Pisanu, L.; Russo, M.; Giana, I.; Gallo, E.; Arlando, L.; et al. Phenotyping Bronchiectasis Frequent Exacerbator: A Single Centre Retrospective Cluster Analysis. Biomedicines 2025, 13, 2124. https://doi.org/10.3390/biomedicines13092124

AMA Style

Bertuccio FR, Baio N, Montini S, Ferroni V, Chino V, Pisanu L, Russo M, Giana I, Gallo E, Arlando L, et al. Phenotyping Bronchiectasis Frequent Exacerbator: A Single Centre Retrospective Cluster Analysis. Biomedicines. 2025; 13(9):2124. https://doi.org/10.3390/biomedicines13092124

Chicago/Turabian Style

Bertuccio, Francesco Rocco, Nicola Baio, Simone Montini, Valentina Ferroni, Vittorio Chino, Lucrezia Pisanu, Marianna Russo, Ilaria Giana, Elisabetta Gallo, Lorenzo Arlando, and et al. 2025. "Phenotyping Bronchiectasis Frequent Exacerbator: A Single Centre Retrospective Cluster Analysis" Biomedicines 13, no. 9: 2124. https://doi.org/10.3390/biomedicines13092124

APA Style

Bertuccio, F. R., Baio, N., Montini, S., Ferroni, V., Chino, V., Pisanu, L., Russo, M., Giana, I., Gallo, E., Arlando, L., Mucaj, K., Tafa, M., Arminio, M., Stefano, E. D., Cascina, A., Grosso, A., Gini, E., Albicini, F., Ferretti, V. V., ... Conio, V. (2025). Phenotyping Bronchiectasis Frequent Exacerbator: A Single Centre Retrospective Cluster Analysis. Biomedicines, 13(9), 2124. https://doi.org/10.3390/biomedicines13092124

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