He also covered care that falls outside the formal recommendations. Clinicians should manage reflux, aspiration, and sinus disease to limit further airway inflammation. They should encourage exercise, which he said “is also a form of airway clearance in and of itself.” Nutrition matters too, because chronically colonized patients can have higher metabolic demands and can lose weight without trying. Clinicians should also refer patients with anxiety or depression to mental health services.

“This could be a chronic illness that they’re faced with that may not have a cure or end,” Basavaraj said.

For the female patient, the acute-exacerbation and eradication recommendations did not apply. Her exacerbation history made her a candidate for nebulized antibiotics or brensocatib, and her MAC culture argued against starting with a macrolide.

Airway Clearance in Practice

Malvika Kaul, MD, of the Division of Pulmonary, Critical Care, Sleep, and Allergy at UI Health, explained why airway clearance matters. Healthy mucus is mostly water. In bronchiectasis, chronic neutrophilic inflammation makes mucus thicker and drives the “vicious vortex” of infection, inflammation, and airway damage. Patients then describe coughing constantly without bringing anything up.

Kaul reviewed pharmacologic options such as hypertonic saline, often given after albuterol, alongside nonpharmacologic techniques. She noted that the guideline’s recommendations are conditional because the disease is so heterogeneous, and that patient-centered outcomes should guide choices. Many practices do not have a respiratory therapist, so clinicians need to know techniques such as active cycle of breathing well enough to teach them. She also pointed to practical barriers: patients may already be managing several devices, and insurance coverage and access vary. The guideline notes that HFCWO equipment can cost more than $10,000.3

Choosing a Preventive Therapy

Sunjay Devarajan, MD, a pulmonologist with Baylor Medicine, addressed the question the guideline leaves to clinicians: once all 3 preventive therapies are endorsed, which should come first?

To begin, he pointed to what does not change. “Airway clearance is the non-negotiable for me,” he said. He described the guideline as setting an overall direction, with the clinician’s job being to apply it to the individual patient, because who the patient is matters. Exacerbation risk, symptom burden, genetic disorders, and overlap with asthma or COPD should all shape the choice.

Devarajan then reviewed each option:

Macrolides are strongly associated with large reductions in exacerbations. Ototoxicity—or inner ear damage—is a known risk, and he cited estimates that 50% to 60% of US patients have NTM, which limits macrolide use. The guideline recommends a baseline electrocardiogram for high-risk patients and audiometry for patients with existing hearing impairment.3Inhaled antibiotics are not a single class, he said. The molecules differ from one another, and data on reducing severe exacerbations are mixed. Some patients do not have a nebulizer, and many find the regimen burdensome.DPP1 inhibition is “the new kid on the block.” In the phase 3 ASPEN trial (NCT04594369), which enrolled 1721 patients, brensocatib 10 mg and 25 mg lowered the annualized exacerbation rate to 1.02 and 1.04, compared with 1.29 for placebo, a reduction of about 20%. At 52 weeks, FEV1 had declined by 24 mL with the 25-mg dose vs 62 mL with placebo.4 Devarajan said he had seen no real safety signals but that long-term data are still needed. Hyperkeratosis was more common with brensocatib, and a recent review recommends dermatologic and periodontal monitoring.4,5Inhaled corticosteroids should not be used routinely.

Devarajan cited a network meta-analysis by Yamamoto and colleagues. It found that macrolides had the largest effect size, that DPP1 inhibition also had a positive effect, and that these were the only classes to show an effect on the end point.6 ASPEN patients already taking macrolides did no better on the combination, he noted, which means a DPP1 inhibitor can work without a macrolide on board. The guideline reports similar rate ratios with and without background macrolide use, 0.79 and 0.80, in an exploratory subgroup analysis.3

His sequencing priorities came down to cost, access, and NTM status. Azithromycin comes first for most patients because of its effect size, cost-effectiveness, and tolerability. Brensocatib comes first for patients colonized with NTM, although it is more expensive and harder to get, and its long-term effects are unknown. Inhaled antibiotics remain an option for patients who can manage the treatment burden. Inhaled corticosteroids should be avoided where possible.

What’s in the Pipeline?

Ashley Losier, MD, assistant professor at Yale School of Medicine, closed with refractory disease. She said the goals are fewer exacerbations and better patient-reported quality of life through a multimodal approach and, eventually, biomarker-guided treatment.

More DPP1 inhibitors are coming. Boehringer Ingelheim’s verducatib has completed the phase 2 AIRLEAF trial (NCT05238675) and is in phase 3,7 and Chiesi’s florensocatib is in a phase 3 trial (NCT07577804) that includes adolescents.8 Results with biologics have been mixed. A trial of an anti–IL-5 receptor α antibody closed early, and attention has moved upstream to targets such as IL-33, with a phase 2 anti–IL-33 study under way. Other candidates include multispecific antibodies, a bispecific monoclonal antibody aimed at the bacteria themselves, and novel agents such as ARINA-1.

Losier ended with a note of caution. “Promising biology does not always lead to clinical benefit,” she said.

References

McCormick B. Brensocatib becomes first FDA-approved therapy for bronchiectasis. AJMC. August 12, 2025. Accessed October 18, 2026. https://www.ajmc.com/view/brensocatib-becomes-first-fda-approved-therapy-for-bronchiectasisChalmers JD, Haworth CS, Flume P, et al. European Respiratory Society clinical practice guideline for the management of adult bronchiectasis. Eur Respir J 2025;66(6):2501126. doi: 10.1183/13993003.01126-2025.Thomson R, Thornton C, Aksamit T, et al. Management of adult bronchiectasis: an American College of Chest Physicians clinical practice guideline. Chest. 2026;170(4):1060-1073. doi:10.1016/j.chest.2026.06.057Chalmers JD, Burgel PR, Daley CL, et al; ASPEN Investigators. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. 2025;392(16):1569-1581. doi:10.1056/NEJMoa2411664Akhtar MS. Brensocatib in non-cystic fibrosis bronchiectasis: neutrophil serine protease modulation, clinical evidence, and therapeutic positioning. Expert Rev Clin Pharmacol. Published online October 1, 2026:891-901. doi:10.1080/17512433.2026.2739561Yamamoto S, Niitsu T, Fukushima K, et al. Efficacy of antiinflammatory therapies for adults with non-cystic fibrosis bronchiectasis: a systematic review and network meta-analysis. Chest. 2026;169(6):1476-1487. doi:10.1016/j.chest.2025.12.035.#ATS2026: DPP1 inhibitors reinforced with phase II final pooled data from verducatib. Clinical Trials Arena. Accessed October 19, 2026. https://www.clinicaltrialsarena.com/analyst-comment/ats2026-dpp1-inhibitors-phase-ii-final-pooled-data-verducatib/A study to evaluate the efficacy and safety of CHF10196 tablets (florensocatib) compared with placebo in male and female participants 12 to 85 years of age with bronchiectasis. Updated August 4, 2026. Accessed October 19, 2026. https://clinicaltrials.gov/study/NCT07577804