Phenotype Analysis of Chronic Bronchial Infection Patients on Nebulized Antibiotic Therapy: A Multicenter Retrospective Cohort Study in Spain (INBREATHING Study)

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Abstract Rationale The clinical phenotype of chronic bronchial infection (CBI) patients may predict response to nebulized antibiotic (NA) treatment. Methods We conducted a retrospective, multicentre Spanish study on CBI patients receiving NA-treatment from January 2018 to June 2024. Baseline sociodemographic, clinical, and radiographic data were collected, with changes in exacerbations, symptoms, and tolerance assessed one-year post-NA initiation Phenotype identification and validation were conducted, and their prognostic implications for response to nebulized antibiotics (NA) were evaluated. A predictive model for exacerbations post-NA-treatment was developed. Results Patients were predominantly older males (55.2%; mean age 71.6 [SD 13.3]) with bronchiectasis (77.8%) and chronic obstructive lung disease (COPD) (39.6%). Colistin (72.9%) was the most prescribed NA. Three phenotypes were identified and validated (Figure1): (1) preserved lung function (FEV₁ 93.9% [13.8]), mostly females with bronchiectasis; (2) moderately impaired lung function (FEV₁ 62.6% [25.1]), in patients with both COPD and bronchiectasis; and (3) severely impaired lung function (FEV₁ 35.9% [8.26]), older COPD patients with comorbidities. After one-year follow-up, phenotype 3 showed higher risk of exacerbation (63.8% with ≥1 exacerbation), more side effects and NA discontinuation (33%). The multivariate model for post-NA exacerbations identified prior exacerbations (OR 1.37 [1.19-1.59]), varicose/cystic bronchiectasis (OR 1.84 [1.08-3.16]), comorbidities (OR 1.48 [1.11-2.01]), age (OR 1.01 [0.99-1.03]), and phenotype 3 (OR 2.36 [1.27-4.42]). A web application (https://trrm.shinyapps.io/NAscore) and a nomogram were developed. Conclusion Three clinical phenotypes of CBI were identified, with prognostic implications for NA response, and a new model was developed to predict post-NA exacerbations.

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