Phenotyping Bronchiectasis Frequent Exacerbator: A Single Centre Retrospective Cluster Analysis

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.