Enhancing lung health in children with structural damage and malformations: trial protocol for a randomised controlled trial of azithromycin for airway infection prevention.

Background: Children with early-onset structural lung damage or lung and airway malformations - congenital or acquired - are highly susceptible to recurrent respiratory tract infections, leading to frequent hospitalisations, impaired lung function and reduced quality of life. Although azithromycin maintenance therapy is commonly used in this population, robust clinical evidence supporting its efficacy is lacking. Objectives: The primary aim of this trial is to evaluate the efficacy of azithromycin maintenance therapy in reducing respiratory infections among young children with structural lung damage or lung and airway malformations. Secondary objectives are to assess the efficacy of azithromycin on lung function, daily respiratory symptoms and quality of life, as well as the safety of long-term azithromycin use in this age group. Methods: This is a national, multicentre, double-blind, placebo-controlled randomised clinical trial conducted across three specialised paediatric pulmonology centres in Denmark. A total of 150 children aged 0-72 months with structural lung damage or lung or airway malformations confirmed by bronchoscopy or radiology will be enrolled. Participants will be randomised 1:1 to receive either oral azithromycin (10 mg·kg Ethics and dissemination: The trial has been approved by the European Medical Agency (EMA). It is expected to provide high-quality evidence on efficacy and safety of azithromycin maintenance therapy in a vulnerable paediatric population with rare respiratory conditions. Positive findings will inform clinical guidelines and help enhance lung health; conversely, if treatment proves ineffective, results may support efforts to reduce unnecessary antibiotic use.