108. Journal Club with BMJ Thorax – Bronchiectasis

We’re back with our 4th episode in our collaborative series with BMJ Thorax. This week’s episode covers four articles related to bronchiectasis and covers a range of topics in this domain including novel therapeutics, registry data to understand risk, and health related quality of life.

Our mission at Pulm PEEPs is to disseminate and promote pulmonary and critical care education, and we highly value the importance of peer reviewed journals in this endeavor. Each month in BMJ Thorax, a journal club is published looking at high yield and impactful publications in pulmonary medicine. We will be putting out quarterly episodes in association with Thorax to discuss a journal club publication and synthesize four valuable papers.

Meet Our Guests

Chris Turnbull is an Associate Editor for Education at Thorax. He is an Honorary Researcher and Respiratory Medicine Consultant at Oxford University Hospitals. In addition to his role as Associate Editor for Education at BMJ Thorax, he is also a prominent researcher in sleep-related breathing disorders.

Dr. George Doumat completed his medical school at the American University of Beirut and now is an internal medicine resident at UT south western in his second year of training. Prior to starting residency he was a research fellow at MGH studying chronic lung disease.

Journal Club Papers

• Journal club paper from BMJ Thorax
• Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis
• Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study
• Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients
• Anxiety, depression, physical disease parameters and health-related quality of life in the BronchUK national bronchiectasis cohort

To submit a journal club article of your own to Thorax, you can contact Chris directly – christopher.turnbull@ouh.nhs.uk

To engage with Thorax, please use the social media channels (Twitter – @ThoraxBMJ; Facebook – Thorax.BMJ) and subscribe on your preferred platform, to get the latest episodes directly on your device each month.

Key Learning Points

• Four recent papers (2 RCTs, 2 large cohorts) chosen to show both new therapeutics and real-world comorbidities/outcomes, pushing toward precision medicine.

1) ASPEN trial – brensocatib (DPP-1 inhibitor)

• Design: Phase 3, ~1,700 pts, 35 countries, 52 weeks; stratified randomization by region.
• Results: ↓ annualized exacerbation rate (~1.0 vs 1.3/yr; RR≈0.8), longer time to first exacerbation, ~10% absolute ↑ in “exacerbation-free” patients at 1 year, QoL improved, modest FEV1 decline difference (~40 mL/yr).
• Take: First targeted therapy with consistent benefit; effect on lung function small but directionally supportive.
• Gaps: Need long-term durability, adolescent data, and comparisons/positioning in pts with asthma/COPD overlap.

2) AIRLEAF (BI 1291583) – reversible cathepsin C inhibitor

• Design: Phase 2, 4 arms (3 doses + placebo), model-based dose–response analysis to optimize dose selection.
• Results: Overall dose–response signal; individual low-dose arms trended to fewer exacerbations but not statistically significant; skin events more common at higher doses.
• Take: Promising class targeting neutrophil pathway, but needs Phase 3 before clinical use.

3) U.S. Bronchiectasis & NTM Registry – 5-year outcomes

• Cohort: >2,600 CT-confirmed; ~59% with baseline NTM identified.
• Results: 5-yr mortality ~12%; no mortality difference with vs without NTM; predictors = lower baseline FEV1, older age, male sex, prior hospitalization. FEV1 decline ~38 mL/yr. Baseline NTM group had fewer exacerbations (counterintuitive).
• Interpretation cautions: Likely mix of colonization vs active disease; referral/management effects in specialized centers; registry strengths (size, real-world, longitudinal) vs pitfalls (confounding, data quality, causality).

4) Bronch-UK cohort – anxiety & depression

• Cohort: 1,340 adults; HADS screening.
• Prevalence: Anxiety ~33%, depression ~20%; many undiagnosed (≈26%/16%).
• Impact: Worse QoL, more severe disease; depression ~1.8× higher hospitalization risk and shorter time to severe exacerbation.
• Caveat: Association ≠ causation; sicker patients may have more mental health burden.

Practical takeaways for clinic

• Consider brensocatib for appropriate non-CF bronchiectasis patients once accessible; frame benefits around fewer exacerbations and QoL, not big lung function gains.
• Do not introduce cathepsin C inhibitors outside trials yet; discuss as pipeline only.
• Risk stratify using FEV1, age, sex, and prior hospitalizations; expect ~40 mL/yr average FEV1 decline.
• Screen mental health routinely (HADS, PHQ-9, GAD-7). Build multidisciplinary pathways; consider brief CBT-style supports embedded in bronchiectasis clinics, with targeted referrals.
• Registry data ≠ RCTs: Use for counseling and service design, but avoid causal claims.

Research/implementation gaps highlighted

• Long-term safety/efficacy and subgroup effects for brensocatib (adolescents, asthma/COPD overlap).
• Phase 3 confirmation for cathepsin C inhibition and dose selection.
• Granular NTM phenotyping (colonization vs disease) to reconcile paradoxical exacerbation signals.
• Scalable mental-health interventions integrated into respiratory clinics; trials to test impact on exacerbations/hospitalizations.

Pro tip from the episode

When appraising trials, check the CONSORT diagram for generalizability and look for stratification methods in multinational RCTs; in phase 2 programs, expect model-based dose–response designs that trade breadth for power.