New CHEST Guidelines Offer a Road Map for Bronchiectasis

For years, pulmonologists treating non-cystic fibrosis (CF) bronchiectasis had little formal guidance and only off-label tools. That has changed in 2025 and 2026. Brensocatib (Brinsupri; Insmed) was approved,¹ the European Respiratory Society (ERS) revised its guideline,² and this month the American College of Chest Physicians (CHEST) published its first clinical practice guideline on managing adult bronchiectasis.³

Sunday’s session at the CHEST 2026 annual meeting in Phoenix, Arizona, "Bronchiectasis 2026: Guidance for the General Pulmonologist," took clinicians through what the guideline says and how to use it, as speakers followed a single patient case from diagnosis through refractory disease.

The Case and the Workup

Ashwin Basavaraj, MD, section chief of pulmonary, critical care, and sleep medicine at NYC Health + Hospitals and associate professor at NYU Grossman School of Medicine, was a member of the guideline panel. He opened with the case of a 49-year-old teacher who had a nonproductive cough for several years and 2 exacerbations in the past year that needed antibiotics and steroids. She also had asthma, gastroesophageal reflux disease, allergic rhinitis, and a history of pneumonia. Spirometry showed mild obstruction, with an FEV₁/FVC ratio of about 64%. CT imaging showed bronchiectasis mainly in the lower lobes, with significant mucoid impaction.

Basavaraj described the baseline workup the ERS guideline recommends: a full blood count, evaluation for allergic bronchopulmonary aspergillosis, immunoglobulins, and sputum cultures that include testing for NTM. Further testing depends on the clinical picture. Chronic sinusitis should raise the possibility of CF or primary ciliary dyskinesia, localized disease suggests obstruction, and systemic symptoms suggest autoimmune disease.

"It's really important to undergo a thorough evaluation for potential etiologies, because if we find an etiology that's causing the bronchiectasis, we want to try to treat that appropriately and try to prevent further bronchiectasis from developing," he said.

His team tests aggressively for CF and CFTR-related disease, using genetic sequencing, a sweat chloride test, or both. The patient's workup did not identify a cause. Her antinuclear antibody titer was mildly elevated, which he said is common in chronic lung disease. Two findings would shape her treatment, however: several sputum cultures grew Pseudomonas aeruginosa, and 1 grew Mycobacterium avium complex (MAC).

Inside the 13 Recommendations

The panel began work in June 2023. It drafted 8 questions in the population, intervention, comparator, and outcome (PICO) format, ran a systematic review of 47 studies, and required 80% agreement for each recommendation.³ The members were international and multidisciplinary. The chairs were Rachel Thomson, MBBS, PhD, of Australia and Christina Thornton, MD, PhD, of Canada, and the panel included infectious disease specialists and chest physiotherapists.

Basavaraj summarized the main recommendations:³

• Acute exacerbations. Choose antibiotics based on prior sputum culture results, and set treatment length by clinical response. Courses can be shorter than 10 days for patients who improve quickly or extended to 14 days for patients who respond slowly.
• Pseudomonas eradication. Here the guideline departs from the ERS, which supports eradication. The CHEST panel found the evidence insufficient to recommend for or against eradication after a first P aeruginosa isolate.
• Prevention. For patients with 2 or more exacerbations a year, the guideline suggests long-term inhaled antibiotics (low certainty), long-term macrolides (moderate certainty), and brensocatib (moderate certainty). It suggests against atorvastatin.
• Hemoptysis. The guideline suggests tranexamic acid.
• Airway clearance. The guideline recommends specific techniques: oscillatory positive expiratory pressure (PEP), nebulized hypertonic saline, active cycle of breathing or ELTGOL breathing techniques, a French acronym that stands for L'Expiration Lente Totale Glotte Ouverte en décubitus latéral, and translates to “expiration with an open glottis in the lateral position.” Also recommended ishigh-frequency chest wall oscillation (HFCWO). It suggests against recombinant human DNase.
• Surgery. Resection can be considered for localized disease that remains refractory despite optimized medical care.

Basavaraj urged caution with macrolides in the United States because, he said, “More than half of our patients with bronchiectasis are colonized with NTM infection, so we don't want to develop resistance by exposing them to macrolide monotherapy." The guideline states that chronic macrolide use is contraindicated when NTM is cultured from sputum, and it calls for NTM screening before starting therapy.³

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.³
• Inhaled 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.^4,5
• Inhaled 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.

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

1. 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-bronchiectasis
2. Chalmers 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.
3. 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.2026.06.057
4. Chalmers 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/NEJMoa2411664
5. Akhtar 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:10.1080/17512433.2026.2739561
6. Yamamoto 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.
7. #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/
8. 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