PulmPEEPs

Today we have another Pulm PEEPs Pearls episode about a core critical care topic. Furf and Monty will be giving a high level overview of the use of steroids in sepsis including a review of the relevant literature and recent guidelines, and pragmatic bedside points. Contributors This episode was prepared with research by Pulm PEEPs Associate Editor George Doumat. Dustin Latimer, another Pulm PEEPs Associate Editor, assisted with audio and video editing. Key Learning Points Why Steroids in Sepsis? Steroids do not treat the infection — antimicrobials are always first and remain the cornerstone. The goal is addressing critical illness–related corticosteroid insufficiency (CIRCI), where cortisol production cannot keep up with the overwhelming inflammatory demand of septic shock. Hydrocortisone helps in two main ways: Blunts the dysregulated inflammatory response — tempers the excessive vasodilation and febrile response that drive harm beyond the infection itself. Restores vascular sensitivity to catecholamines — sepsis downregulates adrenergic receptors; steroids turn that responsiveness back on. Clinical takeaway: The first thing you notice is vasopressor weaning (or a bend in the escalation curve) — not a rapid improvement in fever or white count. Caveat: These trials predate modern sepsis phenotyping. None distinguish hyperinflammatory vs. hypoinflammatory responders — they treat all comers. The Evidence: Four Landmark Trials Every IM resident and critical care fellow will eventually journal-club these four. The most consistent signal across all of them is faster shock reversal and reduced vasopressor use; the mortality question remains unsettled. Trial (Year)NRegimenKey FindingAnnane (2002)~300Hydrocortisone + fludrocortisoneMortality benefit in ACTH non-responders; criticized methodology and messy cortisol-response testing; not cleanly replicated.CORTICUS (2008)~500Hydrocortisone aloneFaster shock reversal but no mortality benefit, regardless of cortisol responsiveness. Raised (later allayed) superinfection concern. Cornerstone for abandoning routine cort-stim testing.ADRENAL (2018)~3,800Hydrocortisone aloneFaster vasopressor weaning; no 90-day mortality benefit.APROCCHSS (2018)~1,200Hydrocortisone + fludrocortisoneMortality benefit at 90 days. Bottom line: Faster shock reversal is consistent. Mortality benefit appears in 2 of 4 trials (both used fludrocortisone) but not the others. A 2026 meta-analysis showed benefit for hydrocortisone + fludrocortisone vs. placebo, but not for hydrocortisone + fludrocortisone vs. hydrocortisone alone — suggesting hydrocortisone drives the main effect. Who Gets Steroids, and When? 2021 Surviving Sepsis: Consider steroids for norepinephrine or epinephrine ≥ 0.25 mcg/kg/min for ≥ 4 hours despite adequate resuscitation — a reasonable bedside trigger. Early 2026 update: Moved away from a specific numeric trigger — consider steroids when a septic patient is not responding well to vasopressors or has escalating requirements. Make a clinical decision. (Quality of evidence: low to moderate.) Go faster than the threshold when: Known/suspected adrenal insufficiency or home steroids, or florid pressor-requiring shock on arrival. A practical escalation sequence: escalating norepinephrine → add vasopressin (per VASST) → then add steroids if requirements keep climbing. Do NOT wait for an ACTH stimulation test. It does not reliably predict who responds and only delays treatment. Sepsis is an elevated-cortisol state but can dissociate ACTH and cortisol, and cortisol-binding globulin is depleted — the test is too messy to guide care. What to Give: The Regimen Standard dose: Hydrocortisone 200 mg/day, typically 50 mg IV Q6H. (Original trials often used continuous infusions, rarely used in the U.S.) Some start with a 100 mg bolus to gain control. Higher dose: If chronically on steroids / adrenally insufficient, consider ~300 mg/day (e.g., 100 mg Q8H). Fludrocortisone: Unsettled. The two mortality-benefit trials added it (50 mcg PO/NG/OG daily), but hydrocortisone already has mineralocorticoid activity and meta-analyses don’t show added benefit over hydrocortisone alone. Most clinicians omit it — adding it is reasonable and safe, just be honest about the uncertainty. Duration & Tapering Typical course: ~7 days is most common. Trial practices varied (ADRENAL ~7 days; VANISH used a taper after 6 days; some continue until pressors are off). No taper needed. You do not need to taper for adrenal insufficiency after a short course — just stop. If pressors dramatically rebound, you can restart, but most patients have gained the benefit they’ll get by day 7. Pitfalls & Safety Hyperglycemia: Expected and must be managed (monitor closely; insulin drip if needed). No signal for major DKA / severe complications in the trials. Superinfection / fungal infection: The most-quoted concern, but the overall literature does not show a convincing, statistically significant increase. Be disciplined about stopping on schedule. Muscle weakness: Steroids can worsen critical illness myopathy; a short 7-day course likely has limited effect, but be aware. Other: GI bleeding (follow general PPI prophylaxis guidance) and sodium disturbances (watch for hyper-/hyponatremia). Two things we know: (1) steroids shorten duration of vasopressor support, and (2) they are relatively safe in sepsis. Whether they improve mortality — and in whom — remains open. The Five Pulm PEEPs Pearls Mechanism: Steroids restore catecholamine vascular sensitivity and blunt dysregulated inflammation. The clinical target is vasopressor weaning, not infection treatment. Evidence: Faster shock reversal is the most consistent finding. Mortality benefit is seen in 2 of 4 trials but not the others — still controversial. Some patients likely benefit; we don’t yet know who. Trigger: A practical 2021 threshold is levo/epi ≥ 0.25 mcg/kg/min for ≥ 4 hours. Newer guidance drops the strict number — make a clinical decision based on poor pressor response or escalation. Dose: Hydrocortisone 200 mg/day (e.g., 50 mg Q6H). Adding fludrocortisone mirrors two trials, but meta-analyses find no benefit over hydrocortisone alone. Safety: Steroids appear safe in sepsis. Monitor and treat hyperglycemia; no marked increase in superinfection. References and Further Reading Annane, Djillali et al. “Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.” JAMA vol. 288,7 (2002): 862-71. doi:10.1001/jama.288.7.862 Sprung, Charles L et al. “Hydrocortisone therapy for patients with septic shock.” The New England journal of medicine vol. 358,2 (2008): 111-24. doi:10.1056/NEJMoa071366 Venkatesh, Balasubramanian et al. “Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.” The New England journal of medicine vol. 378,9 (2018): 797-808. doi:10.1056/NEJMoa1705835 Annane, Djillali et al. “Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.” The New England journal of medicine vol. 378,9 (2018): 809-818. doi:10.1056/NEJMoa1705716 Sun, Alin et al. “Correction: Hydrocortisone combined with fludrocortisone for treatment of adults with septic shock: an updated meta-analysis and systematic review.” Frontiers in medicine vol. 13 1811616. 2 Mar. 2026, doi:10.3389/fmed.2026.1811616 Prescott, Hallie C et al. “Executive Summary: Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026.” Critical care medicine vol. 54,4 (2026): 715-724. doi:10.1097/CCM.0000000000007089

We’re excited today to launch our first episode in collaboration with the Irish Thoracic Society and their podcast series. The Irish Thoracic Society represents respiratory professionals throughout Ireland and is dedicated to championing excellence in the prevention, diagnosis, and clinical care of respiratory disease through its work in advocacy, education and research. In today’s episode, we explore the complex and often overlooked world of refractory chronic cough — a condition that can significantly impact patients’ quality of life but is frequently misunderstood or underdiagnosed. With insights from leading respiratory specialists in Ireland and the United States, we discuss the latest thinking on diagnosis, management, and emerging treatments aimed at improving outcomes for patients and helping clinicians navigate this challenging area of respiratory medicine. Joining us are renowned experts Professor Lorcan McGarvey and Professor Brendan Canning, both internationally recognised leaders in respiratory medicine and cough research. Together, they share their perspectives on the neurobiology of chronic cough, the considerable morbidity experienced by patients, and how clinicians can approach diagnostic investigations more effectively. We also explore current treatment strategies and promising new therapies on the horizon as chronic cough increasingly gains recognition as a disease in its own right — rather than simply a symptom. Whether you’re a clinician, researcher, or simply interested in advances in respiratory medicine, this episode offers valuable insights into a condition that is finally receiving the attention it deserves. Meet Our Co-Hosts Marissa O’Callaghan is an Irish trained Respiratory fellow currently undertaking a post-doc fellow working in Erasmus MC Rotterdam in the Netherlands. She finished her Irish respiratory and Internal medicine training and Phd in 2025. Her areas of interest are interstitial and rare lung diseases. She enjoys clinical research, Med Ed, and dreaming up new medical innovations. Together with cohost Sandra Green, she founded the ITS podcast series in June 2024. Marissa O’Callaghan –LinkedIn Sandra Green is an Irish-trained respiratory fellow with a strong track record in climate advocacy and multidisciplinary sustainable initiatives, as co-founder of Irish Doctors for the Environment. She has an MSc in Leadership and Innovation in Healthcare at the Royal College of Surgeons Ireland (2023–2025). With Marisssa, she co-founded the Irish Thoracic Society Podcast Productions, launching the platform in 2024 to share knowledge, insights, and innovations in respiratory care. Sandra Green – LinkedIn Meet Our Guests Lorcan McGarvey is a professor of respiratory medicine at the University of Belfast, with a focus on the neurobiology of cough. His research has significantly contributed to the understanding of cough hypersensitivity syndrome and the development of new therapeutic strategies. Lorcan is a respected voice in the field, known for his collaborative work and dedication to advancing respiratory health. Brendan Canning is a distinguished researcher at Johns Hopkins University, specializing in the mechanisms of cough and airway diseases. His pioneering studies on neural pathways and receptor targets have paved the way for novel treatments in refractory chronic cough. Brendan’s expertise and innovative approach make him a key figure in the ongoing efforts to redefine chronic cough management. In This Episode The definitions and classifications of chronic cough, including unexplained, refractory, and unexplained refractory cough The importance of a thorough clinical history and focused diagnostics over exhaustive testing Common causes of chronic cough The role of personalized, multidisciplinary management—combining pharmacologic, speech therapy, and psychological support—to improve quality of life for even the most challenging patients. The concept of cough hypersensitivity syndrome and its role in refractory cases Evidence-based approach to treatment, including pharmacologic and non-pharmacologic options Emerging therapies on the horizon, including novel receptor modulators and neuromodulatory agents and ongoing clinical trials in this rapidly evolving field The impact of chronic cough on mental health, social life, and overall quality of life The importance of reframing chronic cough as a disease entity in its own right References and Further Reading Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008;371(9621):1364-1374. Gibson PG, Vertigan AE. Management of chronic refractory cough. BMJ. 2015;351:h5590. Matsumoto H, Kanemitsu Y, Ohe M, Tanaka H, Terada K, Nishi K, et al. Real-world usage and response to gefapixant in refractory chronic cough. ERJ Open Res. 2025;11(4):01037-2024. doi:10.1183/23120541.01037-2024. McGarvey LP, Birring SS. Cough hypersensitivity syndrome: a novel paradigm for understanding cough. Lancet Respir Med. 2014;2(8):647-656. Morice AH, Millqvist E, Bieksiene K, Birring SS, Dicpinigaitis P, Ribas CD, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J. 2020;55(1):1901136. Parker SM, Smith JA, Birring SS, Chamberlain-Mitchell S, Gruffydd-Jones K, Haines J, et al. British Thoracic Society clinical statement on chronic cough in adults. Thorax. 2023;78(Suppl 1):S3-S19. Smith JA, Woodcock A. Chronic cough. N Engl J Med. 2006;354(2):136-144. Song WJ, Dupont L, Birring SS, Chung KF, Dąbrowska M, Dicpinigaitis P, et al. Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study. ERJ Open Res. 2023;9(6):00618-2023. doi:10.1183/23120541.00618-2023. Song WJ, McGarvey L, Cho PSP, Mazzone SB, Chung KF, editors. Chronic cough. Sheffield: European Respiratory Society; 2025.

Furf and Monty are back with another Pulm PEEPs Pearls episode. The topic of today’s discussion is an often discussed, but often misunderstood, test; the methacholine challenge. They’ll review when to utilize this test, how it should be performed, and the appropriate interpretation. Contributors This episode was prepared with research by Pulm PEEPs Associate Editor George Doumat. Dustin Latimer, another Pulm PEEPs Associate Editor, assisted with audio and video editing. Key Learning Points What the Test Measures Methacholine challenge is a direct bronchial provocation test of airway hyperresponsiveness (AHR), a core physiologic feature of asthma. Anyone will bronchoconstrict at high enough concentrations — the test looks for an abnormal threshold. The key endpoint is the PC20: the methacholine concentration causing a 20% fall in FEV1. Abnormal in adults: PC20 ≤ 8–16 mg/mL Test Performance Meta-analyses: pooled sensitivity ~60%, specificity ~90%. Real-world cohorts: sensitivity 55–62%, specificity 56–100% (varies by population, protocol, and threshold used). Not a standalone yes/no test — best used as part of a broader diagnostic pathway. Where It Fits in the Asthma Workup The test belongs in a stepwise approach: Step 1: Spirometry + bronchodilator response Step 2: Add FeNO and/or peak flow variability (if available) Step 3: If the picture is still unclear → methacholine challenge It is most useful for symptomatic patients with normal spirometry and no bronchodilator reversibility. Given its cost, mild risk, and discomfort, it should not be a first-line test — most asthma diagnoses do not require it. Technique and Medication Prep Technique ERS guidelines favor tidal breathing over deep inspiratory maneuvers. Deep breaths can be bronchoprotective and blunt the response, reducing sensitivity — especially in mild or well-controlled asthma. Medication Washout (to Avoid False Negatives) Medication ClassWashout PeriodShort-acting beta-agonists (SABA)≥ 6 hoursLong-acting beta-agonists (LABA)~24 hoursUltra-long-acting beta-agonists~48 hoursShort-acting anticholinergics (e.g., ipratropium)~12 hoursLong-acting muscarinic antagonists (LAMA, e.g., tiotropium)7 days Inhaled corticosteroids, leukotriene blockers, and antihistamines do not significantly affect the test acutely — continue these. Withdrawing ICS also carries its own risk for asthma patients. Practical tip: Spell out exactly what to hold and when — for both the patient and the PFT lab — at the time the test is ordered. Interpreting Results Negative Test (PC20 > 16 mg/mL) Very high negative predictive value in symptomatic adults. Makes current asthma quite unlikely (assuming proper test conduct). This is the test’s greatest strength: it is an excellent rule-out test. Positive Test (PC20 ≤ 8–16 mg/mL) More nuanced — airway hyperresponsiveness is not unique to asthma. Can be positive in: chronic cough, allergic rhinitis, COPD, and even some healthy asymptomatic individuals. A positive result raises probability but must be interpreted alongside the clinical story, variable respiratory symptoms, peak flow variability, FeNO, and ICS response. Safety and Risks Overall, the test is quite safe; significant adverse effects are rare. Temporary breathing discomfort is expected (bronchoconstriction is being induced). Severe bronchospasm is possible: A trained clinician should be available; SABA inhaler/nebulizer must be immediately on hand; a physician should be reachable in the facility. Contraindications / cautions: Avoid if FEV1 < 70% predicted or < 1–1.5 L (baseline obstruction greatly increases risk). Avoid within 3 months of an acute cardiac event (rare risk of cardiac events with unstable cardiac disease). Five Pearls — Quick Recap What it tests: Methacholine challenge is a direct test of AHR with high specificity but variable sensitivity — it belongs inside a diagnostic pathway, not as a standalone asthma test. When to use it: Most useful for symptomatic patients with normal spirometry and no bronchodilator response, after FeNO and peak flow variability have been considered. Technique and meds matter: Use tidal breathing protocol; respect washout intervals — especially the 7-day LAMA washout and 24–48 hour LABA window — to avoid false negatives. Safety: Generally safe, but can induce significant bronchoconstriction. Have a SABA available and avoid the test in patients with FEV1 < 70% predicted. Interpretation: A negative test (PC20 > 16 mg/mL) strongly argues against current asthma. A positive test raises probability but is not specific — interpret alongside the full clinical picture. References and Further Reading Coates AL, Wanger J, Cockcroft DW, Culver BH; Bronchoprovocation Testing Task Force: Kai-Håkon Carlsen; Diamant Z, Gauvreau G, Hall GL, Hallstrand TS, Horvath I, de Jongh FHC, Joos G, Kaminsky DA, Laube BL, Leuppi JD, Sterk PJ. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J. 2017 May 1;49(5):1601526. doi: 10.1183/13993003.01526-2016. PMID: 28461290. Lee, J., & Song, J. U. (2021). Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis. Journal of Asthma, 58(7), 883–891. https://doi.org/10.1080/02770903.2020.1739704 Davis BE, Blais CM, Cockcroft DW. Methacholine challenge testing: comparative pharmacology. J Asthma Allergy. 2018 May 14;11:89-99. doi: 10.2147/JAA.S160607. PMID: 29785128; PMCID: PMC5957064.

On this week’s episode, we’re continuing our Guidelines Series exploring the 2022 ESC/ERS Guidelines for the diagnosis and treatment of Pulmonary Hypertension. If you missed our first episode in the series, give it a listen to hear about the most recent recommendations regarding Pulmonary Hypertension definitions, screening, and diagnostics. Today, we’re talking about the next steps after diagnosis. Specifically, we’ll be discussing risk stratification, establishing treatment goals, and metrics for re-evaluation. We’ll additionally introduce the mainstays of pharmacologic therapy for Pulmonary Hypertension. Meet Our Co-Hosts Rupali Sood grew up in Las Vegas, Nevada and made her way over to Baltimore for medical school at Johns Hopkins. She then completed her internal medicine residency training at Massachusetts General Hospital before returning back to Johns Hopkins, where she is currently a pulmonary and critical care medicine fellow. Rupali’s interests include interstitial lung disease, particularly as related to oncologic drugs, and bedside medical education. Tom Di Vitantonio is originally from New Jersey and attended medical school at Rutgers, New Jersey Medical School in Newark. He then completed his internal medicine residency at Weill Cornell, where he also served as a chief resident. He currently is a pulmonary and critical care medicine fellow at Johns Hopkins, and he’s passionate about caring for critically ill patients, how we approach the management of pulmonary embolism, and also about medical education of trainees to help them be more confident and patient centered. Key Learning Points 1) Episode Roadmap How to set treatment goals, assess symptom burden, and risk-stratify patients with suspected/confirmed pulmonary arterial hypertension (PAH). What tools to use to re-evaluate patients on treatment Intro to major PAH medication classes and how they map to pathways. 2) Case-based diagnostic reasoning Patient: 37-year-old woman with exertional dyspnea, mild edema, abnormal echo, telangiectasias + epistaxis → raises suspicion for HHT (hereditary hemorrhagic telangiectasia) and/or early connective tissue disease. Key reasoning move: start broad (Groups 2–5) and narrow using history/exam/testing. In a young patient without obvious left heart or lung disease, think more about Group 1 PAH (idiopathic/heritable/associated). HHT teaching point: HHT can cause PH in more than one way: More common: high-output PH from AVMs (often hepatic/pulmonary) Rare (1–2% mentioned): true PAH phenotype (vascular remodeling; associated with ALK1 in some patients), behaving like Group 1 PAH. 3) Functional class assessment WHO Functional Class: Class I: no symptoms with ordinary activity, only with exertion Class II: symptoms with ordinary activity Class III: symptoms with less-than-ordinary activity (can’t do usual chores/shopping without dyspnea) Class IV: symptoms at rest Practical bedside tip they give: Ask if the patient can walk at their own pace or keep up with a similar-age peer/partner. If not, think Class II (or worse). 4) Risk stratification at diagnosis: why, how, and which tools Big principle: treatment choices are driven by risk, and the goal is to move patients to low-risk quickly. ESC/ERS approach at diagnosis (as described): Use a 3-strata model predicting 1-year mortality: Low: <5% Intermediate: 5–20% High: >20% ESC/ERS risk assessment variables (10 domains discussed): Clinical progression, signs of right heart failure, syncope WHO FC Biomarkers (NT-proBNP) Exercise capacity (6MWD) Hemodynamics Imaging (echo; sometimes cardiac MRI) CPET (peak VO₂; VE/VCO₂ slope) They note: even if you don’t have everything, the calculator can still be useful with ≥3 variables. REVEAL 2.0: Builds on similar core variables but adds further patient context (demographics, renal function, BP, DLCO, etc.) Case result: both tools put her in intermediate risk (ESC/ERS ~1.6; REVEAL 2.0 score 8), underscoring that mild symptoms can still equal meaningful mortality risk. 5) Treatment goals and follow-up philosophy What they explicitly prioritize: Help patients feel better, live longer, and stay out of the hospital Use risk tools to communicate prognosis and to track improvement Reassess frequently (they mention ~every 3 months early on) until low risk is achieved “Time-to-low-risk” is an important treatment goal Also emphasized: The diagnosis is psychologically heavy; patients need clear counseling, reassurance about the plan, and connection to support groups. 6) Medication classes for the treatment of PAH Nitric oxide–cGMP pathway PDE5 inhibitors: sildenafil, tadalafil Soluble guanylate cyclase stimulator: riociguat Important safety point: don’t combine PDE5 inhibitors with riociguat (risk of significant hypotension/hemodynamic effects) Endothelin receptor antagonists (ERAs) “-sentan” drugs: bosentan (less used due to side effects/interactions), ambrisentan, macitentan Teratogenicity emphasized Hepatotoxicity that requires LFT monitoring Can cause fluid retention and peripheral edema Prostacyclin pathway Prostacyclin analogs/agonists: Epoprostenol (potent; short half-life; IV administration) Treprostinil (IV/SubQ/oral/inhaled options) Selexipag (oral prostacyclin receptor agonist) 7) Sotatercept (post-guidelines) They note sotatercept wasn’t in 2022 ESC/ERS but is now “a game changer” in practice: Mechanism: ligand trap affecting TGF-β signaling / remodeling biology Positioned as potentially more disease-modifying than pure vasodilators Still evolving: where to place it earlier vs later in regimens is an active question in the field 8) How risk category maps to initial treatment intensity General approach they outline: High risk at diagnosis: parenteral prostacyclin (IV/SubQ) strongly favored, often aggressive early Intermediate risk: at least dual oral therapy (typically PDE5i + ERA); escalate if not achieving low risk Low risk: at least one oral agent; many still use dual oral depending on etiology/trajectory For the case: intermediate-risk → start dual oral therapy (they mention tadalafil + ambrisentan as a typical choice), reassess in ~3 months; add a third agent (e.g., selexipag/prostacyclin pathway) if not low risk. References and Further Reading Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Rådegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. Erratum in: Eur Heart J. 2023 Apr 17;44(15):1312. doi: 10.1093/eurheartj/ehad005. PMID: 36017548. Condon DF, Nickel NP, Anderson R, Mirza S, de Jesus Perez VA. The 6th World Symposium on Pulmonary Hypertension: what’s old is new. F1000Res. 2019 Jun 19;8:F1000 Faculty Rev-888. doi: 10.12688/f1000research.18811.1. PMID: 31249672; PMCID: PMC6584967. Maron BA. Revised Definition of Pulmonary Hypertension and Approach to Management: A Clinical Primer. J Am Heart Assoc. 2023 Apr 18;12(8):e029024. doi: 10.1161/JAHA.122.029024. Epub 2023 Apr 7. PMID: 37026538; PMCID: PMC10227272. Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grünig E, Kopeć G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6. PMID: 36877098. Ruopp NF, Cockrill BA. Diagnosis and Treatment of Pulmonary Arterial Hypertension: A Review. JAMA. 2022 Apr 12;327(14):1379-1391. doi: 10.1001/jama.2022.4402. Erratum in: JAMA. 2022 Sep 6;328(9):892. doi: 10.1001/jama.2022.13696. PMID: 35412560.

This week’s Pulm PEEPs Pearls episode is a focused discussion between Furf and Monty about non-pharmacologic techniques for airway clearance in the non-Cystic Fibrosis bronchiectasis population. This is a focused, high-yield discussion of the key points about airway clearance, including practical tips and a discussion of the evidence. This episode was prepared in conjunction with George Doumat MD. Goerge is an internal medicine resident at UT Southwestern and joined us for a Pulm PEEPs – BMJ Thorax journal club episode. He is now acting as a Pulm PEEPs Editor for the Pulm PEEPs Pearls series. Key Learning Points 1) Why airway clearance matters in non-CF bronchiectasis Non-CF bronchiectasis is defined by irreversible bronchial dilation with impaired mucociliary clearance, leading to mucus retention. Retained sputum drives the classic vicious cycle: mucus → infection → neutrophilic inflammation → airway damage → worse clearance. Airway clearance techniques (ACTs) are meant to interrupt this cycle, primarily by improving mucus mobilization and symptom control. 2) What ACTs are trying to achieve clinically Main benefits are: More effective sputum clearance Reduced cough/dyspnea burden Improved activity tolerance and quality of life Effects on spirometry are usually small. Exacerbation reduction is possible, but evidence is mixed—some longer-term data suggest benefit for specific techniques. 3) The main ACT “families” and when to use them Breathing-based techniques (device-free, flexible) ACBT (Active Cycle of Breathing Technique): breath control → deep breaths with holds → huffing. Pros: portable, adaptable, good first-line option. Key requirement: teaching/coaching to get technique right. Autogenic drainage: controlled breathing at different lung volumes to move mucus from peripheral → central airways. Pros: no device, can work well once learned. Cons: more technically demanding, needs training and practice. PEP / Oscillatory PEP (stents airways + “vibrates” mucus loose) PEP: back-pressure helps prevent small airway collapse during exhalation; often paired with huff/cough. Oscillatory PEP (Flutter/Acapella/Aerobika): adds oscillation that many patients find easy and satisfying to use. Good fit for: people who benefit from airway stenting, want something portable, and prefer a device. Mechanical/manual techniques (help when patient can’t self-clear well) HFCWO (“the vest”): external chest wall oscillation; helpful for high sputum volumes, dexterity limits, or difficulty coordinating breathing maneuvers. Postural drainage/percussion/vibration: caregiver/therapist-assisted options; still useful but consider: GERD/reflux risk with certain positions Hemoptysis risk with vigorous techniques 4) How to choose the “right” technique (the practical framework) There is no one-size-fits-all. Match the tool to the patient: Sputum burden (volume/viscosity) Strength, coordination, cognition, dexterity Comorbidities (GERD, hemoptysis history, severe obstruction/airway collapse) Lifestyle + portability (what they’ll actually do) Cost/access and availability of respiratory therapy/physio support A key mindset from the script: this is not a lifetime contract—reassess and adjust over time with shared decision-making. 5) Evidence takeaways (what improves, what doesn’t) ACTs reliably improve sputum expectoration and often symptoms/QoL. QoL/cough scores (e.g., SGRQ, LCQ) tend to improve modestly, particularly with oscillatory PEP and some vest studies. Lung function: typically minimal change; occasional short-term FEV₁ benefit is reported in some vest trials. Exacerbations: mixed overall; the script highlights a longer-term RCT of ELTGOL showing fewer exacerbations at 12 months vs placebo exercises. Safety: generally excellent; main cautions are hemoptysis and reflux (depending on technique/positioning). 6) Special population pearls Hemoptysis / fragile airways: start with gentle breathing-based ACTs (ACBT, controlled huffing); avoid overly vigorous oscillatory/manual methods if concerned. Severe obstruction or early airway collapse: PEP/oscillatory PEP can help by keeping small airways open on exhalation. Mobility/coordination barriers: consider HFCWO vest or simple oscillatory PEP devices to enable daily adherence. During exacerbations: keep it simple—1–2 reliable techniques, prioritize daily consistency, and re-check technique. 7) The “real” bottom line Start with simple, self-manageable options (often ACBT ± PEP). The “best” ACT is the one the patient will do consistently. Reassess technique and fit over time; education and demonstration are part of the therapy. References and Further Reading Lee AL et al., “Airway clearance techniques for bronchiectasis,” Cochrane Database Syst Rev. 2015; PMC7175838. PMID: 26591003. Athanazio RA et al., “Airway Clearance Techniques in Bronchiectasis,” Front Med (Lausanne). 2020; PMC7674976. PMID: 33251032. Iacono R et al., “Mucociliary clearance techniques for treating non-cystic fibrosis bronchiectasis,” Eur Rev Med Pharmacol Sci. 2015; PMID: 26078380. Polverino E et al., “European Respiratory Society statement on airway clearance techniques in bronchiectasis,” Eur Respir J. 2023; PMID: 37142337. Doumat G, Aksamit TR, Kanj AN. Bronchiectasis: A clinical review of inflammation. Respir Med. 2025 Aug;244:108179. doi: 10.1016/j.rmed.2025.108179. Epub 2025 May 25. PMID: 40425105.

Today we’re kicking off another segment in our Guidelines Series, and doing a deep dive into the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Over a series of episodes we’ll talk about the most recent updates to definitions around pulmonary hypertension, recognizing and diagnosing Group 1 – 5 pulmonary hypertension, risk stratification, and treatments. In this first episode, we will review the most recent definitions, including changes to the definitions that were new in 2022. We’ll then talk about recognizing and diagnosing pulmonary hypertension with tips and insights along the way.   Meet Our Co-Hosts Rupali Sood grew up in Las Vegas, Nevada and made her way over to Baltimore for medical school at Johns Hopkins. She then completed her internal medicine residency training at Massachusetts General Hospital before returning back to Johns Hopkins, where she is currently a pulmonary and critical care medicine fellow alongside Tom. Rupali’s interests include interstitial lung disease, particularly as related to oncologic drugs. And she also loves bedside medical education. Tom Di Vitantonio is originally from New Jersey and attended medical school at Rutgers, New Jersey Medical School in Newark. He then completed his internal medicine residency at Weill Cornell, where he also served as a chief resident. He currently is a pulmonary and critical care medicine fellow at Johns Hopkins, and he’s passionate about caring for critically ill patients, how we approach the management of pulmonary embolism, and also about medical education of trainees to help them be more confident and patient centered in the care they have going forward. Infographic Key Learning Points Why to have a high index of suspicion for pulmonary hypertension (PH) PH often presents subtly with slowly progressive dyspnea on exertion, fatigue, lightheadedness, exertional chest pain, or syncope. There’s often a delay of 1–2+ years from symptom onset to diagnosis, which is associated with worse mortality. Early recognition and treatment, especially for pulmonary arterial hypertension (PAH, WHO group 1), can significantly change outcomes.   When to suspect PH Think PH when: Dyspnea is out of proportion to: CT parenchymal findings (relatively normal lungs) Spirometry (normal FEV₁/FVC, volumes) There are subtle but progressive symptoms over months: Reduced exercise tolerance No obvious alternative explanation (e.g., no overt HF, CAD, big ILD, etc.) Physical exam may show (often late): Elevated JVP, V waves (TR) Peripheral edema, hepatomegaly, ascites Loud P2, RV heave In the case: a woman with systemic sclerosis + slowly progressive exertional dyspnea + relatively normal CT parenchyma and spirometry → high suspicion.   WHO classification: 5 PH groups (big picture + why it matters) Used for pathophysiology, prognosis, and treatment choices: Group 1 – PAH Idiopathic, heritable (e.g., BMPR2), drug-induced (e.g., dasatinib) Connective tissue disease (esp. systemic sclerosis) Portal hypertension (portopulmonary HTN) HIV, HHT, congenital heart disease/shunts Rare: PVOD, PCH Group 2 – PH due to left heart disease HFrEF, HFpEF, valvular disease Most common cause worldwide. Group 3 – PH due to lung disease/hypoxia COPD, ILD, combined pulmonary fibrosis–emphysema OSA/obesity hypoventilation, chronic hypoxemia Group 4 – CTEPH Chronic thromboembolic pulmonary hypertension Group 5 – Multifactorial/unclear Sarcoidosis, myeloproliferative disorders, CKD, sickle cell, etc. Patients can span multiple groups (e.g., systemic sclerosis: group 1 and/or group 3; sickle cell: many mechanisms).   Initial workup & refining pre-test probability Once you suspect PH, you’re trying to answer: Does this patient likely have PH? If yes, what group(s) are most likely? Core non-invasive tests: NT-proBNP (preferred over BNP) Surrogate of RV strain and prognosis. Normal value makes significant RV failure less likely. Oxygenation & exercise Resting SpO₂ plus ambulatory sats; consider 6-minute walk test. Exertional desaturation is common and clinically meaningful. CXR & ECG Low yield but may show RV enlargement, right axis deviation, etc. Pulmonary function tests Full set: spirometry, volumes, DLCO. Clue: isolated or disproportionately low DLCO with relatively preserved FVC suggests pulmonary vascular disease. Imaging High-res CT chest – parenchymal disease (ILD, emphysema). V/Q scan – best screening test for CTEPH; better than CT angiography for chronic disease. Sleep testing / overnight oximetry When OSA/nocturnal hypoxemia suspected.   Echo: estimating PH probability (not diagnosis) TTE is the key screening tool but does not diagnose PH. Main elements: Peak tricuspid regurgitant (TR) velocity Used to estimate pulmonary artery systolic pressure (PASP). Categories: Low probability: TR velocity < 2.8 m/s, no other PH signs. Intermediate: 2.9–3.4 m/s ± other PH signs. High: > 3.4 m/s. The presence and severity of TR ≠ TR velocity. You can have severe TR without PH. “Other signs” of PH/RV dysfunction on echo: RV enlargement or systolic dysfunction (qualitative, TAPSE < ~1.7 cm, S′ ↓) RA enlargement Septal flattening (D-shaped LV; systolic = pressure overload, diastolic + systolic = volume + pressure) Dilated PA Pericardial effusion Interpretation pattern: Low pre-test probability + TR v < 2.8 + no other signs → PH unlikely. Intermediate TR v (2.9–3.4) + high pre-test probability and/or other PH signs → consider RHC. High TR v (>3.4) or clearly abnormal RV → strongly consider RHC if it would change management. Also: Echo is great to follow RV size/function and PASP over time once PH is diagnosed and treated. Case echo: TR velocity 3.1 m/s + mild RA enlargement + moderate RV enlargement + TAPSE 1.6 cm → intermediate probability, consistent with PH and RV involvement.   Right heart cath (RHC): gold standard & updated definitions You cannot definitively diagnose or classify PH without RHC. Key directly measured values: RA, RV, PA pressures Pulmonary capillary wedge pressure (PCWP/PAWP) ≈ LVEDP Oxygen saturations in chambers/vessels Cardiac output (thermodilution) Key derived values: Cardiac output (Fick) Pulmonary vascular resistance (PVR) Updated hemodynamic definitions: Pulmonary hypertension (PH) mPAP ≥ 20 mm Hg (lowered from ≥ 25). Pre-capillary PH (think PAH, group 1; also groups 3, 4, some 5): mPAP ≥ 20 PAWP ≤ 15 PVR > 2 Wood units (new lower threshold) Isolated post-capillary PH (IpcPH) (group 2) mPAP ≥ 20 PAWP > 15 PVR ≤ 2 Combined pre- and post-capillary PH (CpcPH) mPAP ≥ 20 PAWP > 15 PVR > 2 Rationale for the changes: Normal mPAP in healthy people is < ~19; 20 is about 2 SD above normal. Patients with mPAP 20–24 (esp. systemic sclerosis) already have worse outcomes than those < 20. Lowering PVR cutoff from 3 → 2 WU better aligns with these new thresholds and catches earlier precapillary disease. Practical interpretation: You use mPAP + PAWP + PVR to: Confirm PH. Distinguish pre- vs post-capillary. Identify mixed disease. Echo tells you probability; RHC tells you what type and how severe.   Vasoreactivity testing (acute vasodilator testing) Only indicated in: Idiopathic (IPAH) Heritable PAH Drug-induced PAH→ Not routine for all PH patients. Performed in the cath lab with short-acting vasodilator (e.g., inhaled NO). Positive test: ↓ mPAP ≥ 10 mm Hg To an absolute mPAP ≤ 40 mm Hg No fall in cardiac output Why it matters: Identifies a small subset who can be treated with high-dose calcium channel blockers long-term and often have better prognosis. Does not predict response to other PAH therapies (ERA, PDE5i, prostacyclin, etc.).   Screening high-risk populations Some groups warrant systematic screening because of high PAH risk. a) Systemic sclerosis / systemic sclerosis spectrum Annual screening if: Disease duration ≥ 3 years FVC ≥ 40% predicted DLCO < 60% predicted DETECT algorithm (2-step): Step 1: uses labs and simple tests (FVC/DLCO ratio, NT-proBNP, autoantibodies, right axis deviation on ECG, telangiectasias). If positive → Step 2: adds echo (TR velocity, RA size). If high risk after Step 2 → RHC. Goal: catch early PAH before symptoms are severe. b) Other high-risk groups Annual screening (usually with echo ± NT-proBNP, PFTs) for: Known heritable PAH mutations (e.g., BMPR2) Portal hypertension (esp. considering liver transplant or TIPS) HIV Always layer this on top of clinical symptoms and progression.   Big practical takeaways (what to apply on Monday) Don’t label “pulmonary hypertension” off CT or echo alone. Enlarged PA on CT or elevated PASP on echo ≠ diagnosis. RHC is required. Think PH early when: Dyspnea is out of proportion to imaging and spirometry. There is a relevant risk factor (systemic sclerosis, portal HTN, HIV, prior PE, congenital heart disease, etc.). Use the WHO groups to structure your differential and workup: Group 1 vs 2 vs 3 vs 4 vs 5 → drives what tests you order and what treatments you eventually consider. Echo = probability. RHC = truth. Echo gives you low / intermediate / high PH probability. RHC gives you pre- vs post-capillary, PVR, and hemodynamics needed for therapy. Know the new numbers: mPAP ≥ 20 = PH PAWP cutoff = 15 PVR > 2 WU = precapillary component Don’t forget NT-proBNP, DLCO, V/Q scan, and high-risk screening (especially in systemic sclerosis and BMPR2 carriers).   References Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Rådegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. Erratum in: Eur Heart J. 2023 Apr 17;44(15):1312. doi: 10.1093/eurheartj/ehad005. PMID: 36017548. Condon DF, Nickel NP, Anderson R, Mirza S, de Jesus Perez VA. The 6th World Symposium on Pulmonary Hypertension: what’s old is new. F1000Res. 2019 Jun 19;8:F1000 Faculty Rev-888. doi: 10.12688/f1000research.18811.1. PMID: 31249672; PMCID: PMC6584967. Maron BA. Revised Definition of Pulmonary Hypertension and Approach to Management: A Clinical Primer. J Am Heart Assoc. 2023 Apr 18;12(8):e029024. doi: 10.1161/JAHA.122.029024. Epub 2023 Apr 7. PMID: 37026538; PMCID: PMC10227272.

For today’s podcast we have a special episode. We were extremely grateful to be invited to present live at CHEST 2025 this year. Kristina Montemayor, and Pulm PEEPs Associate Editors Luke Hedrick, Tom Di Vitantonio, and Rupali Sood hosted a session entitled “Widened Airways and Narrowed Differentials”. It is a great session around bronchiectasis. Enjoy!   Meet Our Guests Dr. Doreen Addrizzo-Harris is a Professor of Medicine at NYU where she is also Associate Director of Clinical and Academic Affairs for the pulmonary and critical care division. In addition to that, she’s the director of the bronchiectasis and NTM program and also serves as a program director for the pulmonary and critical care fellowship. Case Snapshot 60-year-old with CLL (in remission) → recurrent “pneumonias,” diffuse (not single-lobe), later dx’d with CVID; serial CTs: upper-lobe–predominant bronchiectasis, tree-in-bud, mucus impaction; multiple AFB+ cultures (MAC, later M. abscessus); recurrent bacterial flares (MSSA/MRSA).   CT Images   Key Learning Points Imaging pearls Tree-in-bud = small airways (bronchiolar) impaction/inflammation, not a diagnosis. Differential guided by distribution + chronicity: Acute/diffuse → bacterial/viral/NTM infection Dependent/basal → aspiration Persistent + nodular + bronchiectasis → NTM common Bronchiectasis CT signs (think: “ring, taper, edge”): Broncho-arterial ratio >1 (signet-ring) Lack of normal tapering Visible bronchi within 1 cm of pleura Location matters: Upper lobes → CF, sarcoid, prior TB/radiation Middle lobe/lingula → NTM classic; consider ABPA if central Lower lobes → aspiration, PCD, CTD, immunodeficiency NTM: diagnosis & when to treat Use all three (2020 guideline frame): clinical symptoms, compatible CT, microbiology (≥2 sputum cultures or 1 bronch +, etc.). Not every positive culture = disease needing drugs. If you defer pharmacologic therapy, follow closely (symptoms, sputum, PFTs, interval CT if change). Bug matters: MAC, M. abscessus, kansasii etc. “Low-virulence” species (e.g., M. gordonae) can still flag underlying airway disease. Regimens (MAC, macrolide-susceptible): azithro + ethambutol + rifampin (intermittent for nodular-bronchiectatic; daily ± IV amikacin for fibro-cavitary/advanced). Macrolide is the backbone; the others protect against resistance. M. abscessus: check for inducible macrolide resistance (prolonged in-vitro testing). Monitoring: sputum q1–3 mo; labs (CBC/CMP), vision (ethambutol), hearing (aminoglycosides). Treat ~12 months beyond culture conversion. Anti-inflammatory macrolide for bronchiectasis is contraindicated if macrolide-susceptible NTM is present—risk of resistance. Bronchiectasis management essentials It’s a syndrome: symptoms/exacerbations plus CT changes. Airway clearance is foundational (exercise + devices ± hypertonic saline/DNase when indicated). Expect CT and symptom gains with adherence. Exacerbations often need ~14 days of pathogen-directed antibiotics (short courses may fail). Take the “easy win” when a conventional pathogen explains the flare. Workup framework (start with a core bundle, then target) Core “every patient” bundle CBC with diff (look for eosinophilia/hematologic clues) Quantitative IgG/IgA/IgM (primary/secondary immunodeficiency) ABPA screen: total IgE + Aspergillus-specific IgE/IgG Sputum cultures: routine bacteria + AFB + fungal (if producing) Baseline PFTs Targeted tests (guided by history, distribution, microbes) CF evaluation: sweat chloride and/or CFTR genotyping (especially with upper-lobe disease, chronic sinusitis/nasal polyps, pancreatitis/malabsorption, infertility/CAVD). PCD: nasal NO, genetics, specialized ciliary studies (adult cases may be mild and missed by genetics alone). Alpha-1 antitrypsin (never-smoker emphysema, liver hx) CTD serologies (RA, Sjögren’s, etc.), if suggestive Aspiration/upper-GI assessment when basal-predominant or reflux symptoms For suspected/known CVID: vaccine response assessment if not on replacement (this patient was already on IVIG). Practical diagnostic habits Re-read the CT yourself—radiology may under-call mild bronchiectasis in ED/PE-protocol scans. Use a diagnostic time-out when the course isn’t fitting: name your working dx, list fits/mismatches, consider common diseases with atypical presentations, multi-morbidity, and can’t-miss alternatives; ask for help early; communicate uncertainty. Teach-to-remember pearls from the case Recurrent, geographically scattered pneumonias → think systemic causes (immunodeficiency, CF/PCD), not just focal anatomic problems. Upper-lobe bronchiectasis + CAVD is a CF red flag—even in the 60s. Adult-onset CF is real and actionable. In CF today, MSSA can be more common than Pseudomonas on culture; don’t let absence of Pseudomonas dissuade you. Airway clearance adherence can change CTs; instruct patients to ramp up before surveillance scans for a fair assessment. If symptoms abate with targeted therapy to a conventional pathogen, you may avoid immediate NTM re-treatment—but keep a tight follow-up loop.  

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.

We are so excited to be launching a new series here at Pulm PEEPs! We’ll be talking about high yield topics in 15 minutes or less. In this series, Furf and Monty will tackle core points and provide an overview, key points, and further reading. We’re starting with a key point review of Immune Checkpoint Inhibitor Pneumonitis. Let us know if there are other topics you want to hear about! Key Learning Points Epidemiology & Pathophysiology Increasingly common as immunotherapy use grows in oncology. Caused by immune activation from PD-1, PD-L1, or CTLA-4 inhibitors. Mechanisms: Overactive T cells Autoantibody production Cytokine-mediated inflammation (e.g., ↑IL-1, ↑IL-6) Clinical Suspicion & Diagnosis Any new respiratory symptoms in a patient currently or previously on ICI → consider ICI pneumonitis. CT findings are variable: can mimic organizing pneumonia, NSIP, ARDS, or diffuse ground glass opacities. Imaging pattern does not determine severity grade. Diagnosis is of exclusion — infection and malignancy progression must be ruled out first. Workup: Broad infectious evaluation (cultures, viral panel, fungal markers). Early bronchoscopy with BAL if feasible — typically lymphocyte-predominant in ICI pneumonitis. Screen for TB and hepatitis early (in case infliximab is needed). Severity Grading (Symptom- & O₂-based, not imaging-based) Grade 1: Asymptomatic → monitor, may hold ICI. Grade 2: Symptomatic but not hypoxic → prednisone 1 mg/kg/day PO. Grade 3–4: Hypoxemia or ICU-level care → methylprednisolone 1–2 mg/kg/day IV. Usually hold or permanently stop ICI. Steroid Management Typical taper: over 6 weeks for grade ≥3. Week 1: 1–2 mg/kg/day Gradual step-down to 0.25 mg/kg/day by week 5, then stop week 6. Chronic/recurrent cases may need slower tapers over months. Add GI prophylaxis and PJP prophylaxis during prolonged steroid use. If Steroids Fail (no improvement after 48–72 hrs) Consider adding: IVIG (2 g/kg over 5 days) Infliximab (TNF-α inhibitor — requires TB/hepatitis screening) Mycophenolate mofetil (1–1.5 g/day BID or TID, start at effective dose quickly) IVIG may have lower mortality in some series but comes with risks (volume overload, thrombosis, infusion reactions). Emerging Therapies JAK inhibitors are under investigation as possible future options. Multidisciplinary Care ICU management is a team sport — coordinate with oncology, critical care, infectious disease, and pharmacy.   Infographic   References and Further Reading Managing Immune Checkpoint Inhibitor Pneumonitis in the ICU. Montemayor, Kristina et al.CHEST Critical Care, Volume 3, Issue 1, 100126 Lavalle S, Masiello E, Valerio MR, Aliprandi A, Scandurra G, Gebbia V, Sambataro D. Immune checkpoint inhibitor therapy‑related pneumonitis: How, when and why to diagnose and manage (Review). Exp Ther Med. 2024 Jul 30;28(4):381. doi: 10.3892/etm.2024.12670. PMID: 39113908; PMCID: PMC11304171. Delaunay M, Prévot G, Collot S, Guilleminault L, Didier A, Mazières J. Management of pulmonary toxicity associated with immune checkpoint inhibitors. Eur Respir Rev. 2019 Nov 6;28(154):190012. doi: 10.1183/16000617.0012-2019. PMID: 31694838; PMCID: PMC9488507.

Hi Pulm PEEPs! Today we have a special episode for you. Monty and Furf were invited on the Core IM Podcast to talk about the work up and management of pleural effusions. This is a great overview and we hope you enjoy listening as much as we did recording. If you want a deeper dive into pleural effusions check out our prior series: 36. Top Consults Series: Approach to Pleural Effusions   37. Top Consults: Approach to Parapneumonic Effusions 49. Top Consults: Malignant Pleural Effusions

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.

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.

Today, we continue our review of the Global Initiative for Asthma (GINA) guidelines on asthma. We’ve covered asthma diagnosis and phenotyping, and the initial approach to therapy. On today’s episode we’re talking about biologic therapies for asthma and will cover everything from when to consider starting them, which to choose, and what to monitor for after a patient is started. To help us with this exciting topic we’re joined by an expert in the field. We again have a great infographic prepared along with the episode, and a boards-style question for your review.   Meet Our Guest Megan Conroy is an Assistant Professor of Medicine at The Ohio State University, and is also the associate program director for curriculum and quality in the Pulmonary and Critical Care Medicine Fellowship. Megan’s clinical area of expertise involves asthma and biologic therapies and she was recently recognized for her work in this area as the 2024 CHEST Airway Disorders Network Rising Star Award.  Meet Our Co-Hosts Rupali Sood grew up in Las Vegas, Nevada and made her way over to Baltimore for medical school at Johns Hopkins. She then completed her internal medicine residency training at Massachusetts General Hospital before returning back to Johns Hopkins, where she is currently a second year pulmonary and critical care medicine fellow alongside Tom. Rupali’s interests include interstitial lung disease, particularly as related to oncologic drugs. And she also loves bedside medical education. Tom Di Vitantonio is originally from New Jersey and attended medical school at Rutgers, New Jersey Medical School in Newark. He then completed his internal medicine residency at Weill Cornell, where he also served as a chief resident. He currently is a second year pulmonary and critical care medicine fellow at Johns Hopkins, and he’s passionate about caring for critically ill patients, how we approach the management of pulmonary embolism, and also about medical education of trainees to help them be more confident and patient centered in the care they have going forward.   Key Learning Points   Boards Style Question       References: Mauer Y, Taliercio RM. Managing adult asthma: The 2019 GINA guidelines. Cleve Clin J Med. 2020 Aug 31;87(9):569-575. doi: 10.3949/ccjm.87a.19136. PMID: 32868307. Viswanathan RK, Busse WW. Biologic Therapy and Asthma. Semin Respir Crit Care Med. 2018 Feb;39(1):100-114. doi: 10.1055/s-0037-1606218. Epub 2018 Feb 10. PMID: 29427990. Brusselle GG, Koppelman GH. Biologic Therapies for Severe Asthma. N Engl J Med. 2022 Jan 13;386(2):157-171. doi: 10.1056/NEJMra2032506. PMID: 35020986.