Sequencing Therapies for Bronchiectasis: A Practical Approach

This episode, "Sequencing Therapies for Bronchiectasis: A Practical Approach," features the panel weighing how to choose among macrolides, DPP1 inhibitors, and emerging antibody therapies.

Dr. Basavaraj asks Dr. Metersky how he sequences macrolides, brensocatib, and monoclonal antibodies for individual patients. Dr. Metersky notes that a large unmet need remains even in patients who respond somewhat to macrolide therapy. For those patients, he adds brensocatib on top of the macrolide; for patients who are not macrolide candidates, he starts with brensocatib instead. He says he almost exclusively uses the 25-milligram dose, since only that dose demonstrated benefit across all three measured outcomes in trial data: exacerbation reduction, symptom improvement, and slowed FEV1 decline. The 10-milligram dose, by contrast, showed benefit only for exacerbations, and the higher dose was not associated with increased toxicity.

Turning to monoclonal antibodies, Dr. Metersky notes that currently approved options target Th2 or eosinophilic inflammation and were originally developed for asthma. These agents may help bronchiectasis patients with overlapping eosinophilic or asthmatic features, supported by case series though not yet randomized trials. Antibodies targeting IL-17, IL-13, and IL-33 remain in phase 2 development and are not yet available.

Dr. ElMaraachli describes his approach as built around identifying underlying etiology and comorbidities alongside a consistently tailored airway clearance plan. When an immunoglobulin deficiency is found, replacement therapy is started; chronic aspiration prompts a speech pathology referral; and alpha-1 antitrypsin deficiency or CFTR defects may warrant targeted replacement or modulator therapy. Frequent exacerbators and patients colonized with drug-resistant organisms need closer respiratory therapist follow-up and more vigilant microbiology surveillance. Dr. ElMaraachli highlights routine surveillance sputum cultures as a practical way to have recent microbiologic data available before a patient becomes acutely ill.

Our next episode, "Emerging DPP1 Inhibitors and Closing the Education Gap in Bronchiectasis," turns to the next generation of DPP1 inhibitors and the education gaps still facing the field.