PulmPEEPs

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.

Dr. Vishwajit Hegde, a second-year Pulmonary and Critical Care fellow, shares a captivating case of a 26-year-old with chronic cough and pulmonary nodules. Dr. Sahil Pandya, an Associate Professor and program director, dives into diagnostic strategies, emphasizing a Bayesian approach to avoid premature conclusions. They discuss interpreting intricate imaging patterns and the decision-making process for bronchoscopic tissue sampling. The big reveal? A diagnosis of miliary lung adenocarcinoma leading to a targeted therapy breakthrough. Insights into KU's fellowship culture shine as both guests emphasize mentorship and trainee education.

Dive into the complexities of Immune Checkpoint Inhibitor Pneumonitis, a growing concern in oncology due to increased immunotherapy usage. Discover essential diagnostic strategies, including how to identify respiratory symptoms in patients on immunotherapy. Learn about the varying CT findings and the importance of ruling out infections. The hosts break down treatment protocols for different severity levels and explore alternative options when steroids aren't enough. This engaging discussion sheds light on emerging therapies and the need for teamwork in managing these cases.

Join Jim Devanney, a physiatrist transitioning to a role at the University Health Network, and Kalilah Pais, a third-year internal medicine resident passionate about critical care. They dive into the often-overlooked issue of ICU Acquired Weakness, detailing its clinical presentation and potential causes. A compelling case study reveals the significant challenges faced by a sepsis patient experiencing muscle weakness. The duo emphasizes the importance of systematic diagnosis and early intervention strategies to improve recovery in critical care settings.

Chris Kapp, an interventional pulmonologist at Northwestern, shares invaluable insights on managing pleural effusions. He discusses the importance of thoracentesis and pleural fluid analysis, emphasizing accurate diagnosis with the LIGHTS criteria. Kapp clarifies the distinctions between transudative and exudative effusions and explains the role of pleural pH and cell counts in clinical assessment. He also delves into diagnostic challenges like eosinophilic effusions and the significance of adenosine deaminase in identifying tuberculosis pleuritis.

In this fascinating discussion, Matt Freedman, a pulmonary fellow at UVA, presents the complex case of an immunocompromised patient suffering from respiratory failure. Joining him are fellow doctors John Popovich, who discusses diagnostic strategies, and Tim Scialla, who offers insights on bronchoscopy and shock assessment. They delve into challenges of diagnosing ARDS in immunosuppressed patients, weighing the risks of steroids against potential infections, and the intricacies of shock evaluation using POCUS. Their expert commentary reveals the nuances of critical care management.

Today is our third episode in our collaborative series with BMJ Thorax. 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. This week’s episode covers four articles related to obstructive sleep apnea therapies, and the use of non-invasive ventilation and high flow nasal cannula for intubation and COPD exacerbations. 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. Natalie McLeod is  a resident in respiratory medicine and is currently doing a clinical fellowship in sleep and ventilation at Oxford University Hospitals. Journal Club Papers Journal club article from Thorax Effect of CPAP therapy on blood pressure in patients with obstructive sleep apnoea: a worldwide individual patient data meta-analysis Hypoglossal nerve stimulation for obstructive sleep apnea in adults: An updated systematic review and meta-analysis Noninvasive Ventilation for Preoxygenation during Emergency Intubation Nasal high flow or noninvasive ventilation? navigating hypercapnic COPD exacerbation treatment: A randomized noninferiority clinical trial 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.

Dive into the NAVIGATOR trial as experts discuss tezepelumab, a game-changing monoclonal antibody for treating non-allergic asthma. Learn about the trial's design, significant outcomes, and the challenges of asthma exacerbation management. The conversation shifts to the importance of phenotyping patients to tailor treatments based on their unique inflammatory pathways. Discover the drug’s safety profile and the mild adverse effects reported, primarily among those on placebo. It’s a fascinating look at improving asthma therapies!

We are podcasting today directly from ATS 2025 in San Francisco! Every year, in collaboration with the ATS Critical Care Assembly, we highlight some of the scientific symposium programming from the conference. Today, Furf and Monty sit down with the three chairs of the scientific symposium entitled: Mechanical Ventilation of the Future: New Foundations For Ventilator Strategies. Meet Our Guests Juliana Ferreira is an Associate Professor at the University of Sao Paulo, Brazil where she is also co-director of the pulmonary and critical care fellowship program. She is an MD, PhD, and a physician scientist with specific interests in mechanical ventilation and medical education. Finally, she serves ATS as the ATS MECOR Latin America Director. Bhakti Patel is an Assistant Professor Medicine at the University of Chicago. She is a dedicated researcher and educator. Her research focuses on non-invasive ventilator support. Akram Khan is an Associate Professor of Medicine at Oregon Health and Science University. Akram is a pulmonary, critical care, and sleep provider with specific clinical interests in critical illness, pulmonary vascular disease and sleep apnea. Additionally, he is an accomplished translational science researcher.

We’re back with another edition of Fellows’ Case Files! Today, we’re virtually visiting Rutgers University, Robert Wood Johnson Medical School to work through a fascinating pulmonary case. Enjoy, and let us know your thoughts. Meet Our Guests Khalil El Gharib completed his residency training at Northwell at Staten Island University Hospital Program and is currently a first year fellow at Rutgers Robert Wood Johnson Medical School. Sabiha Hussain completed her residency training at Robert Wood Johnson Medical School and her fellowship training at Columbia Presbyterian Medical Center in New York. She is currently a Professor of Medicine and the fellowship Program Director. Case Presentation Patient: 28-year-old male with Asperger’s syndrome and IgA nephropathy. Symptoms: 3-month history of progressive dry cough and dyspnea on exertion; later developed mild hemoptysis. Notable exposure: Questionable black mold in the patient’s apartment. Initial Workup and Diagnostic Reasoning Vital signs: Hypoxemia (SpO₂ 91% on room air). Exam: Inspiratory crackles. ABG findings: Elevated A–a gradient (~50), indicating a gas exchange problem. Chest X-ray: Bilateral, patchy infiltrates without specific lobar preference. Initial management: Discharged with empiric antibiotics for presumed multifocal pneumonia. Re-Presentation and Further Testing Symptoms worsened; now with blood-tinged sputum. Chest CT: Showed diffuse ground-glass opacities (GGOs) without fibrosis, consolidation, or lymphadenopathy. Imaging and Pathology Pathology images a courtesy to Dr Isago Jerrett, pathology resident at RWJMS Key Learning Points Diagnostic Framework for Hypersensitivity Pneumonitis (HP) New classification: Based on fibrotic vs. non-fibrotic phenotype (not acute/chronic). CT features of HP: GGOs with lobular air trapping. “Three-density sign” (normal lung, low-density air-trapping, and ground-glass opacities). BAL: Typically shows lymphocytic predominance in chronic HP, neutrophilic in early stages. Serum IgG testing: Helps identify antigen exposure but doesn’t confirm disease alone. Lung biopsy (VATS): Revealed poorly formed granulomas and airway-centered inflammation—consistent with HP. Differential Diagnosis of Granulomatous Disease Infectious: TB, fungal (must rule out with stains/cultures). Non-infectious: Sarcoidosis, HP, granulomatosis with polyangiitis. Key pathology clues for HP: Loosely formed granulomas, airway inflammation, giant cells. Management and Outcome Primary treatment: Antigen avoidance (patient moved out of mold-exposed apartment). Adjunct therapy: Oral prednisone with a slow taper. Outcome: Symptomatic and radiographic improvement over six months. Teaching Pearls Always take a detailed environmental and occupational exposure history. Hypoxemia with an elevated A–a gradient in a young adult should trigger concern for interstitial/parenchymal lung disease. CT and history are often enough to diagnose HP—biopsy is reserved for uncertain cases. Remember evolving terminology: think fibrotic vs. non-fibrotic HP, not acute/chronic.