PulmPEEPs

Today we're joined by Dr. Molly Hayes and talking about an upcoming CME course: Principles of Critical Care Medicine for Non-Intensive Care Specialists. This is a wonderful education course covering a wide array of topics in critical care in a case-based, systematic, and peer-reviewed fashion. The course is interactive and all resources will be available for attendees afterwards for their review. You can sign up at https://learn.hms.harvard.edu/criticalmed and save using the discount code "PulmPEEPS50"!

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

Episode Transcript Hey everyone, Dave Furfaro here from Pulm PEEPs. As you may have noticed in the last few weeks and months, we’ve had a little bit of a decrease in the content that we’ve been putting out, and I just wanted to share a couple things with you about why that is and the future of Pulm PEEPs coming up. In December of 2025, I was diagnosed with a large myxoid liposarcoma in my leg, and since then, I have been undergoing treatment for that. Overall, treatment has been going well, but it’s certainly been a long road that, continues, and I hope that it continues to trend positively. Kristina has been an unbelievable support during this. We have continued to work on some content as a great way and distraction for me at times, but we haven’t been able to keep up the same pace of content that we usually put out. And given everything that is going on, I actually anticipate that will continue for a few months. Ee haven’t said anything so far yet because we were still figuring it out ourselves, but now we just wanted you all to know that, we, love doing Pulm PEEPs. We’re very committed to it. We wanna get back to doing it as consistently as we have been previously, and we plan on doing that, but it likely will be a little bit of time, and this is why. I also may be sharing more about my journey through the medical system as a patient, in the future, but for now, I’m really just focusing on my treatment, my health, and my family. So the summer months will likely be, much slower, maybe even a break off together, and look forward to recovering and getting back to producing more regular Pulm PEEPs content in the Fall. Hope everybody who’s listening is doing well. Thank you all, as always, for being supportive, for listening to the podcast, for reaching out to us on social media, for saying hi to us in person at conferences. It’s been, a true delight, and we can’t wait to get back to business as usual. Okay, everybody. Take good care of patients, be safe, be well, and we’ll see you soon.

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.

We are unbelievably excited this week to be reviewing the hot-off-the-presses 2026 Multi-Society (AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN) Pulmonary Embolism Guidelines with lead author Dr. Mark A. Creager. We will talk about key updates in these guidelines compared to prior practice, including the new risk classification model, and provide an overview from diagnosis to follow-up. Given the clinical importance and prevalence of pulmonary embolism, these guidelines are certainly going to shape practice going forward, so this episode is a can’t miss! Watch the full video of this episode with graphics and helpful teaching visuals on our YouTube channel: https://www.youtube.com/@pulmpeeps Meet Our Guest Dr. Mark Creager is a Professor of Medicine at Dartmouth Hitchcock Medical Center where he specializes in Cardiovascular Medicine with an emphasis on venous thromboembolic disease. He served as the lead author of the 2026 Pulmonary Embolism Guidelines. Article and Reference Creager MA, Barnes GD, Giri J, Mukherjee D, Jones WS, Burnett AE, Carman T, Casanegra AI, Castellucci LA, Clark SM, Cushman M, de Wit K, Eaves JM, Fang MC, Goldberg JB, Henkin S, Johnston-Cox H, Kadavath S, Kadian-Dodov D, Keeling WB, Klein AJP, Li J, McDaniel MC, Moores LK, Piazza G, Prenger KS, Pugliese SC, Ranade M, Rosovsky RP, Russo F, Secemsky EA, Sista AK, Tefera L, Weinberg I, Westafer LM, Young MN. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026 Feb 19:S0735-1097(25)10161-7. doi: 10.1016/j.jacc.2025.11.005. Epub ahead of print. PMID: 41712898. Key Learning Points Why these guidelines matter: This is the first joint AHA/ACC clinical practice guideline specifically on acute PE, bringing together a truly multidisciplinary writing committee (cardiology, pulmonology, hematology, emergency medicine, interventional radiology, surgery, and others). Prior guidelines existed from individual societies, but nothing this comprehensive had been updated in roughly five to six years. New PE clinical categories (A through E): One of the most impactful changes is replacing the old “massive/submassive” and “low/intermediate/high risk” labels with five categories that form a severity continuum. Category A is subclinical (incidental PE found on imaging in asymptomatic patients). Category B covers symptomatic but low-severity patients. Category C is where much of the clinical complexity lives — symptomatic, hemodynamically stable patients subdivided into C1, C2, and C3 based on RV function and biomarkers. Category D represents incipient cardiopulmonary failure (transient hypotension, normotensive shock with end-organ dysfunction). Category E is frank cardiopulmonary failure, with E2 being the sickest — refractory or recurrent cardiac arrest. Respiratory modifiers (hypoxia requiring supplemental oxygen) layer onto C, D, and E. Diagnostic approach: Clinical evaluation comes first — history, exam, and validated decision tools (Wells score, revised Geneva, PERC). If clinical probability is low and D-dimer is normal, imaging can be safely avoided. If either is concerning, imaging is warranted. CTPA remains the preferred imaging modality due to superior sensitivity, specificity, wide availability, and ability to assess clot burden and alternative diagnoses. VQ scanning is still appropriate when CTPA is contraindicated, and VQ SPECT offers better reproducibility and specificity than traditional planar VQ if available. Echocardiography is not a diagnostic test for PE but is important for risk stratification — RV size, TAPSE, and tissue Doppler measures all contribute prognostic information. Anticoagulation updates: Anticoagulation remains the cornerstone of treatment. For patients potentially needing advanced therapies (C3, D, E), parenteral anticoagulation is started first. A notable recommendation: low molecular weight heparin is generally preferred over unfractionated heparin, based on evidence showing more effective VTE risk reduction, more predictable pharmacokinetics, no need for routine monitoring, lower rates of heparin-induced thrombocytopenia, and no increase in major bleeding. The committee acknowledged this may create discomfort for clinicians accustomed to unfractionated heparin’s easy reversibility, but the difficulty of achieving and maintaining therapeutic levels with UFH was a significant concern. Advanced therapies: Catheter-based thrombolysis, mechanical thrombectomy, systemic thrombolysis, and surgical embolectomy all received mostly class 2B recommendations (“can consider”) for C3 and D categories, reflecting that current evidence shows improvement in short-term surrogate measures (RV/LV ratio, hemodynamics) but lacks definitive hard outcome data on mortality. For category E1 patients, recommendations are stronger (class 2A). Multiple trials are expected soon — HI-PEITHO, PEERLESS-2, PE-TRACT, PERSEVERE, TORPEDO, and PROG — that should substantially inform future updates. PERT teams: Pulmonary embolism response teams are encouraged, particularly for C3, D, and E patients. They’ve been shown to reduce length of stay. For institutions without PERT capability, establishing consultation networks with larger centers is recommended. Post-PE follow-up: Patients shouldn’t be “left in the wilderness” after discharge. The guidelines recommend communication within the first week to ensure understanding of diagnosis and treatment, an in-person visit at or before three months to assess for persistent symptoms and discuss anticoagulation duration, ongoing surveillance for chronic thromboembolic pulmonary disease, and periodic reassessment for those on extended anticoagulation. Infographics

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.

This week’s Pulm PEEPs Pearls episode is all about spontaneous breathing trials (SBTs). SBTs are a standard part of the daily practice in the intensive care unit, but the exact methods vary across ICUs and institutions. Listen in to hear about the most common methods of SBTs, the physiology of each method, and what the evidence says. 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 an SBT is really testing An SBT is a stress test for post-extubation work of breathing, not just a ventilator check. The goal is to balance sensitivity and specificity: Too hard → unnecessary failures and delayed extubation Too easy → false positives and higher risk of reintubation Common SBT modalities and how they compare T-piece No inspiratory support and no PEEP Highest work of breathing Most “physiologic” but often too strict Pressure support (PS) + PEEP (e.g., 5/5 or 8/5) Offsets ETT resistance and provides modest assistance Easier to pass than T-piece CPAP (0/5) No inspiratory help, but provides PEEP to counter ETT resistance Sits between PS and T-piece in difficulty Evidence favors pressure-supported SBTs for most patients Large meta-analysis (~6,000 patients, >40 RCTs): Pressure-supported SBTs increase successful extubation (~7% absolute benefit) No increase in reintubation rates Trials (e.g., FAST trial): Patients pass SBTs earlier Leads to earlier extubation and fewer ventilator-associated risks Bottom line: A 30-minute PS 5/5 SBT is evidence-based and appropriate for most stable ICU patients When a T-piece still makes sense T-piece SBTs are useful when: Cost of reintubation is high Difficult airway Prior failed extubation Pretest probability of success is low Prolonged or difficult weaning Tracheostomy vs extubation decisions Need to mimic physiology without positive pressure In LV dysfunction or pulmonary edema even small amounts PEEP may significantly improve physiology Some centers use a hybrid approach: PS SBT → short confirmatory T-piece before extubation CPAP as a middle ground Rationale: Allows full patient effort while compensating for ETT resistance Evidence: Fewer and smaller trials Possible modest improvement in extubation success No clear mortality or LOS benefit Reasonable option based on patient physiology, institutional protocols, and clinician comfort No single “perfect” SBT mode Across PS, T-piece, CPAP, and newer methods (e.g., high-flow via ETT) there are no consistent differences in mortality or length of stay What matters most: Daily protocolized screening Thoughtful bedside clinical judgment Matching SBT difficulty to patient-specific risk Institutional variation is normal—and acceptable Examples: PS 10/5 in postoperative surgical ICU patients PS 5/0 as an intermediate difficulty option Key question clinicians should ask: What does passing or failing this specific SBT tell me about this patient’s likelihood of post-extubation success? Take-home pearls SBTs are stress tests of post-extubation physiology. PS 5/5 for 30 minutes is a strong default for most ICU patients. T-piece trials are valuable when false positives are costly or physiology demands it. CPAP is reasonable but supported by less robust data. Consistency, daily screening, and judgment matter more than the exact mode. References and Further Reading Burns KEA, Khan J, Phoophiboon V, Trivedi V, Gomez-Builes JC, Giammarioli B, Lewis K, Chaudhuri D, Desai K, Friedrich JO. Spontaneous Breathing Trial Techniques for Extubating Adults and Children Who Are Critically Ill: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2024 Feb 5;7(2):e2356794. doi: 10.1001/jamanetworkopen.2023.56794. PMID: 38393729; PMCID: PMC10891471. Burns KEA, Sadeghirad B, Ghadimi M, Khan J, Phoophiboon V, Trivedi V, Gomez Builes C, Giammarioli B, Lewis K, Chaudhuri D, Desai K, Friedrich JO. Comparative effectiveness of alternative spontaneous breathing trial techniques: a systematic review and network meta-analysis of randomized trials. Crit Care. 2024 Jun 8;28(1):194. doi: 10.1186/s13054-024-04958-4. PMID: 38849936; PMCID: PMC11162018. Subirà C, Hernández G, Vázquez A, Rodríguez-García R, González-Castro A, García C, Rubio O, Ventura L, López A, de la Torre MC, Keough E, Arauzo V, Hermosa C, Sánchez C, Tizón A, Tenza E, Laborda C, Cabañes S, Lacueva V, Del Mar Fernández M, Arnau A, Fernández R. Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2019 Jun 11;321(22):2175-2182. doi: 10.1001/jama.2019.7234. Erratum in: JAMA. 2019 Aug 20;322(7):696. doi: 10.1001/jama.2019.11119. PMID: 31184740; PMCID: PMC6563557. Burns KEA, Wong J, Rizvi L, Lafreniere-Roula M, Thorpe K, Devlin JW, Cook DJ, Seely A, Dodek PM, Tanios M, Piraino T, Gouskos A, Kiedrowski KC, Kay P, Mitchell S, Merner GW, Mayette M, D’Aragon F, Lamontagne F, Rochwerg B, Turgeon A, Sia YT, Charbonney E, Aslanian P, Criner GJ, Hyzy RC, Beitler JR, Kassis EB, Kutsogiannis DJ, Meade MO, Liebler J, Iyer-Kumar S, Tsang J, Cirone R, Shanholtz C, Hill NS; Canadian Critical Care Trials Group. Frequency of Screening and Spontaneous Breathing Trial Techniques: A Randomized Clinical Trial. JAMA. 2024 Dec 3;332(21):1808-1821. doi: 10.1001/jama.2024.20631. PMID: 39382222; PMCID: PMC11581551. Mahul M, Jung B, Galia F, Molinari N, de Jong A, Coisel Y, Vaschetto R, Matecki S, Chanques G, Brochard L, Jaber S. Spontaneous breathing trial and post-extubation work of breathing in morbidly obese critically ill patients. Crit Care. 2016 Oct 27;20(1):346. doi: 10.1186/s13054-016-1457-4. PMID: 27784322; PMCID: PMC5081985. Yi LJ, Tian X, Chen M, Lei JM, Xiao N, Jiménez-Herrera MF. Comparative Efficacy and Safety of Four Different Spontaneous Breathing Trials for Weaning From Mechanical Ventilation: A Systematic Review and Network Meta-Analysis. Front Med (Lausanne). 2021 Nov 22;8:731196. doi: 10.3389/fmed.2021.731196. PMID: 34881255; PMCID: PMC8647911.​

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.

Luke Hedrick, Dave Furfaro, and recurrent RFJC guest Robert Wharton are joined again today by Nicole Ng to discuss the FIBRONEER-IPF trial investigating Nerandomilast in patients with IPF. This trial was published in NEJM in 2025 and looked at Neradomilast vs placebo for treating patients with IPF, on or off background anti-fibrotic therapy. This agents is now FDA approved for pulmonary fibrosis, and understanding the trial results is essential for any pulmonary physician treating patients with IPF or progressive pulmonary fibrosis.   Article and Reference  Today’s episode discusses the FIBRONEER-IPF trial published in NEJM in 2025. Richeldi L, Azuma A, Cottin V, Kreuter M, Maher TM, Martinez FJ, Oldham JM, Valenzuela C, Clerisme-Beaty E, Gordat M, Wachtlin D, Liu Y, Schlecker C, Stowasser S, Zoz DF, Wijsenbeek MS; FIBRONEER-IPF Trial Investigators. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2025 Jun 12;392(22):2193-2202. doi: 10.1056/NEJMoa2414108. Epub 2025 May 18. PMID: 40387033. https://www.nejm.org/doi/abs/10.1056/NEJMoa2414108 Meet Our Guests Luke Hedrick is an Associate Editor at Pulm PEEPs and runs the Rapid Fire Journal Club Series. He is a senior PCCM fellow at Emory, and will be starting as a pulmonary attending at Duke University next year. Robert Wharton is a recurring guest on Pulm PEEPs as a part of our Rapid Fire Journal Club Series. He completed his internal medicine residency at Mt. Sinai in New York City, and is currently a pulmonary and critical care fellow at Johns Hopkins. Dr. Nicole Ng is an Assistant Profess of Medicine at Mount Sinai Hospital, and is the Associate Director of the Interstitial Lung Disease Program for the Mount Sinai National Jewish Health Respiratory Institute. Infographic Key Learning Points Why this trial mattered IPF therapies remain limited: nintedanib and pirfenidone slow (but do not stop) decline and often cause GI side effects. Nerandomilast is a newer agent (a preferential PDE4B inhibitor) with antifibrotic + immunomodulatory effects. Phase 2 data (NEJM 2022) looked very promising (suggesting near-“halt” of FVC decline), so this phase 3 trial was a big test of that signal. Trial design essentials Industry-sponsored, randomized, double-blind, placebo-controlled, large multinational study (332 sites, 36 countries). Population: IPF diagnosed via guideline-aligned criteria with central imaging review and multidisciplinary diagnostic confirmation. Intervention: nerandomilast 18 mg BID, 9 mg BID, or placebo; stratified by background antifibrotic use. Primary endpoint: change in FVC at 52 weeks, analyzed with a mixed model for repeated measures. Key secondary endpoint: time to first acute exacerbation, respiratory hospitalization, or death (composite). Who was enrolled Typical IPF trial demographics: ~80% male, mean age ~70, many former smokers. Many were already on background therapy (~45% nintedanib, ~30–33% pirfenidone). Notable exclusions included significant liver disease, advanced CKD, recent major cardiovascular events, and psychiatric risk (suicidality/severe depression), reflecting class concerns seen with other PDE4 inhibitors. Efficacy: what the primary endpoint showed Nerandomilast produced a statistically significant but modest reduction in annual FVC decline vs placebo (roughly 60–70 mL difference). Importantly, it did not halt FVC decline the way the phase 2 data suggested; patients still progressed. Important nuance: interaction with pirfenidone Patients on pirfenidone had ~50% lower nerandomilast trough levels. Clinically: 9 mg BID looked ineffective with pirfenidone, so 18 mg BID is needed if used together. In those not on background therapy or on nintedanib, 9 mg and 18 mg looked similar—suggesting the apparent “dose-response” might be partly driven by the pirfenidone drug interaction Secondary and patient-centered outcomes were neutral No demonstrated benefit in the composite outcome (exacerbation/resp hospitalization/death) or its components. Quality of life measures were neutral and declined in all groups, emphasizing that slowing FVC alone may not translate into felt improvement without a disease-reversing therapy. The discussants noted this may reflect limited power/duration for these outcomes and mentioned signals from other datasets/pooling that might suggest mortality benefit—but in this specific trial, the key secondary endpoint was not positive. Safety and tolerability Diarrhea was the main adverse event: Higher overall with the 18 mg dose, and highest when combined with nintedanib (up to ~62%). Mostly mild/manageable; discontinuation due to diarrhea was relatively uncommon (but higher in those on nintedanib). Reassuringly, there was no signal for increased depression/suicidality/vasculitis despite psychiatric exclusions and theoretical class risk. How to interpret “modest FVC benefit” clinically The group framed nerandomilast as another tool that adds incremental slowing of progression. They emphasized that comparing absolute FVC differences across trials (ASCEND/INPULSIS vs this trial) is tricky because populations and “natural history” in placebo arms have changed over time (earlier diagnosis, improved supportive care, etc.). They highlighted channeling bias: patients already on antifibrotics may be sicker (longer disease duration, lower PFTs, more oxygen), complicating subgroup comparisons. Practical takeaways for real-world use All three antifibrotics are “fair game”; choice should be shared decision-making based on goals, tolerability, dosing preferences, and logistics. Reasons they favored nerandomilast in practice: No routine lab monitoring (major convenience advantage vs traditional antifibrotics). Generally better GI tolerability than nintedanib. BID dosing (vs pirfenidone TID). Approach to combination therapy: They generally favor add-on rather than immediate combination to reduce confusion about side effects—while acknowledging it may slow reaching “maximal therapy.” Dosing guidance emphasized: Start 18 mg BID for IPF, especially if combined with pirfenidone (since dose reduction may make it ineffective). 9 mg BID may be considered if dose reduction is needed and the patient is not on pirfenidone (e.g., monotherapy or with nintedanib).

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, Dave Furfaro, Luke Hedrick, and Robert Wharton discuss the PREDMETH trial published in The New England Journal of Medicine in 2025. This was a non-inferiority trial comparing prednisone to methotrexate for upfront therapy in treatment-naive sarcoidosis patients. Listen in for a break down of the trial, analysis, and clinically applicable pearls. Article and Reference Todays’ episode discusses the PREDMETH trial published in NEJM in 2025. Kahlmann V, Janssen Bonás M, Moor CC, Grutters JC, Mostard RLM, van Rijswijk HNAJ, van der Maten J, Marges ER, Moonen LAA, Overbeek MJ, Koopman B, Loth DW, Nossent EJ, Wagenaar M, Kramer H, Wielders PLML, Bonta PI, Walen S, Bogaarts BAHA, Kerstens R, Overgaauw M, Veltkamp M, Wijsenbeek MS; PREDMETH Collaborators. First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate. N Engl J Med. 2025 Jul 17;393(3):231-242. doi: 10.1056/NEJMoa2501443. Epub 2025 May 18. PMID: 40387020. https://www.nejm.org/doi/full/10.1056/NEJMoa2501443 Meet Our Hosts Luke Hedrick is an Associate Editor at Pulm PEEPs and runs the Rapid Fire Journal Club Series. He is a senior PCCM fellow at Emory, and will be starting as a pulmonary attending at Duke University next year. Robert Wharton is a recurring guest on Pulm PEEPs as a part of our Rapid Fire Journal Club Series. He completed his internal medicine residency at Mt. Sinai in New York City, and is currently a first year pulmonary and critical care fellow at Johns Hopkins. Key Learning Points Clinical context Prednisone remains the traditional first-line treatment for pulmonary sarcoidosis when treatment is indicated, with evidence for short-term improvements in symptoms, radiographic findings, and pulmonary function—but with substantial, familiar steroid toxicities (weight gain, insomnia, HTN/DM, infection risk, etc.). Despite widespread use, glucocorticoids haven’t been robustly tested head-to-head against many alternatives as initial therapy, and evidence for preventing long-term decline (especially in severe disease) is limited. Immunosuppressants (like methotrexate) are often used as steroid-sparing agents, but guideline recommendations are generally conditional/low-quality evidence, and practice varies. Why PREDMETH matters It addresses a real-world question: Can methotrexate be an initial alternative to prednisone in pulmonary sarcoidosis, rather than being reserved only for steroid-sparing later? It also probes a common clinical belief: MTX has slower onset than prednisone (often assumed, not well-proven). Trial design (what to know) Open-label, randomized, noninferiority trial across 17 hospitals in the Netherlands. Included patients with pulmonary sarcoidosis who had a clear pulmonary indication to start systemic therapy (moderate/severe symptoms plus objective risk features like reduced FVC/DLCO or documented decline, plus parenchymal abnormalities). Excluded: non–treatment-naïve patients and those whose primary indication was extrapulmonary disease. Treat-to-tolerability with escalation: both drugs started low and were slowly increased; switch/add-on allowed for inadequate efficacy or unacceptable side effects. Primary endpoint: change in FVC (with the usual caveat that FVC is “objective-ish,” but effort-dependent and not always patient-centered). Noninferiority margin: 5% FVC, justified as within biologic/measurement variation and “not clinically relevant.” Outcomes assessed at weeks 4, 16, 24; powered for ~110 patients to detect the NI margin. Patient population (who this applies to) Mostly middle-aged (~40s) with mild-to-moderate physiologic impairment on average (FVC ~77% predicted; DLCO ~70% predicted). Netherlands-based cohort with limited Black representation (~7%), which matters for generalizability. Would have been helpful to know more about comorbidities (e.g., diabetes), which can strongly influence prednisone risk. Main findings (what happened) Methotrexate was noninferior to prednisone at week 24 for FVC: Between-group difference in least-squares mean change at week 24: −1.17 percentage points (favoring prednisone) with CI −4.27 to +1.93, staying within the 5% NI margin. Timing mattered: Prednisone showed earlier benefit (notably by week 4) in FVC and across quality-of-life measures. By week 24, those early differences largely washed out—possibly because MTX “catches up,” and/or because crossover increased over time. In their reporting, MTX didn’t meet noninferiority for FVC until week 24, supporting the practical message that prednisone works faster. Crossover and analysis nuance (important for interpretation) Crossover was fairly high, which complicates noninferiority interpretation: MTX arm: some switched to prednisone for adverse events and others had prednisone added for disease progression/persistent symptoms. Prednisone arm: some had MTX added. In noninferiority trials, heavy crossover can bias intention-to-treat analyses toward finding “no difference” (making noninferiority easier to claim). Per-protocol analyses avoid some of that but introduce other biases. They reported both. Safety signals (what to remember clinically) Adverse events were very common in both arms (almost everyone), mostly mild. Side-effect patterns fit expectations: Prednisone: more insomnia (and classic steroid issues). MTX: more headache/cough/rash, and notably liver enzyme elevations (about 1 in 4), with a small number discontinuing. Serious adverse events were rare; numbers were too small to confidently separate “signal vs noise,” but overall known risk profiles apply. Limitations (why you shouldn’t over-read it) Open-label design, and FVC—while objective-ish—is still effort-dependent and can be influenced by expectation/behavior. Small trial, limiting subgroup conclusions (e.g., severity strata, different phenotypes). Generalizability issues (Netherlands demographics; US populations have higher rates of obesity/metabolic syndrome, which may tilt the steroid risk-benefit equation). Crossover reduces precision and interpretability of between-group differences over time. Practice implications (the “so what”) For many patients with pulmonary sarcoidosis needing systemic therapy, MTX is a reasonable initial alternative to prednisone when thinking long-term tolerability and steroid avoidance. Prednisone likely provides faster symptom/QoL relief in the first weeks—so it may be preferable when rapid improvement is important. The trial strengthens the case for a patient-centered discussion: short-term relief vs side-effect tradeoffs, and the possibility of early combination therapy in more severe cases (suggested, not proven).

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.

Furf and Monty are back today with another Pulm PEEPs Pearls episode, and discussing the use of methylene blue for patients with septic shock. They review the clinical scenarios when this comes up, the mechanism, some key data, and some take aways, all in 15 minutes! Let us know any other topics you’d like covered on the show and make sure to like, give us 5 stars, and subscribe wherever you’re listening to this podcast. 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 Clinical context: when does methylene blue even come up? This is not a first-line sepsis drug. It’s considered in catecholamine-refractory vasoplegic septic shock, typically when: Norepinephrine is at high dose Vasopressin is on board Often a 3rd or 4th vasopressor is being used (e.g., phenylephrine, angiotensin II) The phenotype is strongly vasodilatory/vasoplegic (warm, distributive shock) rather than primarily cardiogenic. Mechanism of action (why it might help) Methylene blue: Inhibits inducible nitric oxide synthase and guanylate cyclase. Blunts excess nitric oxide and cyclic GMP–mediated vasodilation, which are key in vasoplegic sepsis. Practical translation: It restores vascular tone and can make the vasculature more responsive to catecholamines. It’s also used in post-CPB vasoplegia (e.g., after cardiac surgery, especially in patients on ACE inhibitors) and has migrated from that world into ICU sepsis practice. Typical dosing strategy (as described in the episode) Common approach: 1–3 mg/kg IV bolus, then Reassess hemodynamics (MAP, dynamic perfusion markers). If there’s a response, consider a continuous infusion or repeat bolus. Key nuance: unlike other pressors that start as drips, methylene blue is often trialed as a bolus first to see if it’s doing anything. What does the evidence suggest? Most data are from small, single-center, heterogeneous studies, so evidence quality is low. Meta-analyses and systematic reviews (through ~2024–25) suggest: Hemodynamics Can increase MAP (roughly 1–10 mmHg across studies). May shorten total vasopressor duration (one meta-analysis ~30 hours less, though this is not definitive). Secondary physiologic effects Some small improvements in PaO₂/FiO₂ (P/F) ratio in certain studies. Clinical outcomes Possible reduction in hospital length of stay (≈ up to 2 days in some pooled analyses). Some signal toward lower short-term mortality, but: Studies are small Heterogeneous Evidence is very low certainty Bottom line: There’s a repeatable signal that methylene blue: Raises MAP Helps reduce catecholamine requirements But hard clinical outcomes (mortality, LOS, ventilator days) remain uncertain. Safety profile & important adverse effects Things to watch for: Methemoglobinemia Serotonin syndrome Especially in patients on SSRIs, though in life-threatening refractory shock the hosts still lean toward using it with caution. Pulse oximeter artifact Can distort SpO₂ readings. Urine discoloration Blue/green urine—benign but striking. Notably: Methylene blue is both a treatment for and a potential cause of methemoglobinemia, depending on context and dosing. Guidelines & where it fits in practice Surviving Sepsis Campaign 2021: Does not recommend methylene blue for routine use in septic shock. No major critical care society includes it in standard septic shock bundles or protocols. The hosts frame methylene blue as: A rescue therapy, not guideline therapy. Something to consider only in refractory vasoplegic shock, ideally with: Multidisciplinary discussion (intensivist, pharmacist, etc.). Clear documentation that this is off-guideline, salvage use. Practical bedside framing (“2 a.m. in the ICU”) They emphasize three pillars of practice: Physiology – mechanism makes sense (NO / cGMP / vasodilation). Empiric evidence – small studies and meta-analyses show a signal but low-quality data. Bedside reality – at 2 a.m., with a patient in multi-pressor, refractory vasoplegic shock, you sometimes reach for imperfect tools. So, the practical take: You should NOT: Use methylene blue early. Treat it as part of standard sepsis care. You may consider it when: Shock is clearly vasoplegic and refractory. Norepi + vasopressin + at least one more vasopressor are maxed. Team agrees this is salvage therapy and understands the limited evidence and side effects.

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.  

In this episode, we’re concluding our review of the Global Initiative for Asthma (GINA) guidelines on asthma today with a cased based episode on special considerations in asthma care. We’ve covered asthma diagnosis and phenotyping, the approach to therapy inhaler and oral medical therapy, and biologic therapy. On today’s episode we’re talking about complex cases that are at the edges of the guidelines, or may be in future guidelines. To help us with this exciting topic we’re joined by an expert in the field. Enjoy!  Meet Our Guest Dr. Meredith McCormack is a Professor of Medicine at Johns Hopkins, where she leads multiple NIH funded endeavors at understanding lung health and disease. She is the Division Director for Pulmonary and Critical Care Medicine, while also directing the Asthma Precision Medicine Center of Excellence, and the BREATHE Center, which focuses on understanding the effects of the environment on lung health and disease through research and community engagement.  She is an internationally recognized expert in asthma management and is a dedicated member of the faculty who is committed to the trainees. 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 Episode themesBuilt on GINA 2024: final capstone focusing on evolving topics + case-based application.Three focal areas: (1) obesity/metabolic health (GLP-1s, metformin), (2) dual biologics vs switching, (3) de-escalating inhalers while on biologics.Emphasis throughout on personalized care, shared decision-making, and multidisciplinary collaboration.Obesity & metabolic health in asthmaObesity affects mechanics, inflammation, and treatment response; tackling metabolic dysfunction can improve asthma control.GLP-1 receptor agonists may provide additive benefit beyond weight loss for some patients (early clinical signals; trials ongoing).Metformin is being studied as a potential adjunct targeting metabolic-inflammatory pathways.Practical approach: screen/counsel on weight, activity, and metabolic disease; partner with primary care/endocrine/sleep clinics; consider GLP-1/other agents when indicated for comorbidities, with potential asthma “bonus.”Biologics: switching vs dual therapyConsider switching/adding when control is not achieved or sustained on a biologic despite adherence.Upstream vs downstream targets:Upstream: anti-TSLP (e.g., tezepelumab) may help when multiple pathways/biomarkers (e.g., high IgE + eos) suggest broader blockade.Downstream: IL-5/IL-4/13/IgE agents selected to match phenotype/endotypes.Comorbidities can drive choice:Nasal polyps or upper airway syndromes: there are biologic options that improve upper airway symptoms in addition to asthmaAtopic dermatitis: agents with dual indications can be life-changing.Logistics matter: injection burden/needle phobia and dosing cadence (e.g., every 2 vs 4–8 weeks) can determine real-world success.De-escalating inhalers on biologicsDon’t step down immediately. Ask patients to maintain their full regimen for ~3 months after starting a biologic to gauge true benefit.Set expectations early and share a step-down plan to prevent unsupervised discontinuation.Typical order (individualize):Remove non-essential add-ons first (e.g., antihistamines, leukotriene modifiers).Reduce ICS dose gradually (high → medium → low).Keep ICS/LABA combination among the last therapies to taperTargets while stepping down: “normal” lung function when feasible, minimal/no day or night symptoms, full activity, no exacerbations.When patients don’t respond to biologicsRe-check the fundamentals:Adherence/technique for inhalers and biologic.Biomarkers behaving as expected (e.g., eosinophils falling on anti-IL-5).Revisit the diagnosis and contributors/mimics (e.g., vocal cord dysfunction, upper-airway disease). Consider moving upstream (e.g., to TSLP) if a downstream agent underperforms.Communication & practical pearlsUse visual aids to verify what patients actually take and how (e.g., Asthma & Allergy Network inhaler pictogram).Needle issues are common; home vs clinic administration and family support can make or break adherence.Biologics are transformative for the right patient—consider them early in steroid-dependent or poorly controlled severe asthma.Think longitudinally: plan for monitoring, comorbidity management, and timely adjustments. 

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 – [email protected] 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.

After a brief hiatus, we are excited to be back today with another Fellows’ Case Files! Today we’re virtually visiting the University of Kansas Medical Center (KUMC) to hear about a fascinating pulmonary presentation. There are some fantastic case images and key learning points. Take a listen and see if you can make the diagnosis along with us. As always, let us know your thoughts and definitely reach out if you have an interesting case you’d like to share. Meet Our Guests Dr. Vishwajit Hegde completed his internal medicine residency at University of Kansas Medical Center where he stayed for fellowship and is currently a second year Pulmonary and Critical Care medicine fellow.  Dr. Sahil Pandya is an Associate Professor of Medicine and Program Director of the PCCM Fellowship at KUMC. Case Presentation Imaging Infographic Key Learning Points 1) Initial frame & diagnostic mindset Young (26), subacute → chronic dyspnea/cough with diffuse pulmonary nodules; avoid premature closure on TB. Use a Bayesian approach: combine pre-test probability (epidemiology, exposures, tempo) with targeted tests to decide next steps. Always confirm TB when possible (micro/path + resistance testing); empiric RIPE may be reasonable but shouldn’t replace tissue when stakes are high. 2) Imaging pearls—nodular pattern recognition Ask three things: craniocaudal distribution, symmetry, central vs peripheral. Centrilobular (spares pleura/fissures): airway-centered (e.g., NTM, bronchiolitis, tree-in-bud). Perilymphatic (tracks fissures/pleura & septa): sarcoid, lymphangitic spread. Random/diffuse (involves pleural surfaces): hematogenous spread → think miliary TB, disseminated fungal, septic emboli, metastatic disease. Interval change matters: new cavitation and confluence can upweight infection or aggressive malignancy. 3) Neuro findings—ring-enhancing lesions Differential: septic emboli/abscess, nocardia, fungal, TB, parasites, metastases, vasculitis, sarcoid. Partner with neuroradiology for pattern nuances; treat seizures but keep searching for the unifying diagnosis. 4) Lab/serology strategy Broad infectious workup (AFB × multiple, fungal serologies), HIV and basic immune screen. Negative/indeterminate tests don’t end the search—revisit history (e.g., Ohio travel → histo/blasto risk). 5) “Tissue is the issue”—choosing the procedure For diffuse nodules with mediastinal adenopathy and stable patient: EBUS-TBNA + BAL, consider transbronchial or cryobiopsy. Cryobiopsy pros: larger, less crush artifact, better for molecular testing; cons: ↑ bleeding/pneumothorax vs forceps. VATS still best for certain ILD questions or if less invasive routes are non-diagnostic—but weigh patient preference and stage/likelihood of yield. 6) ROSE (rapid on-site evaluation) in bronchoscopy Confirms adequacy in real time, steers you away from necrotic zones, helps decide when you’ve got enough for molecular studies, and when to pivot sites—reduces anesthesia time and repeat procedures. 7) Final diagnosis & management Path: TTF-1+, CK7+, napsin A → pulmonary adenocarcinoma with a fusion driver. Therapy: Targeted TKI (crizotinib) → dramatic radiographic response of miliary lung disease and CNS lesions. Teaching point: even “miliary TB-like” lungs + CNS lesions in a 20-something can be driver-positive lung cancer—don’t let age or pattern blind you. References and Further Reading Desai, S., Devaraj, A., Lynch, D., & Sverzellati, N. (2020). Webb, Müller and Naidich’s high-resolution CT of the lung (6th ed.). Lippincott Williams & Wilkins. Rajeswaran, G., Becker, J. L., Michailidis, C., Pozniak, A. L., & Padley, S. P. G. (2006). The radiology of IRIS (immune reconstitution inflammatory syndrome) in patients with mycobacterial tuberculosis and HIV co-infection: appearances in 11 patients. Clinical radiology, 61(10), 833-843 Poletti, V., Ravaglia, C., & Tomassetti, S. (2016). Transbronchial  cryobiopsy in diffuse parenchymal lung diseases. Current opinion in pulmonary medicine, 22(3), 289-296. Norman, G. R., Monteiro, S. D., Sherbino, J., Ilgen, J. S., Schmidt, H. G., & Mamede, S. (2017). The causes of errors in clinical reasoning: cognitive biases, knowledge deficits, and dual process thinking. Academic Medicine, 92(1), 23-30.

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.

Today we’re talking about a topic that is relevant for all critical care physicians but under-examined: ICU Acquired Weakness. We are joined by two excellent guests to walk through a case and discuss the diagnosis, pathophysiology, prevention, and treatment of ICU Acquired Weakness. Check out our associated infographics and key learning points below. Meet Our Guests Jim Devanney is a Physiatrist who just completed a neurocritical care fellowship at BIDMC. He is transitioning to a clinical associate position at University Health Network – University of Toronto where he will be working as a PM&R consultant within the ICU. Kalaila Pais is a third year internal medicine resident at BIDMC, interested in pulmonary and critical care and medical education and is returning for her third Pulm PEEPs episode. Key Learning Points Definition & Clinical PresentationICU-AW refers to new-onset, generalized muscle weakness that arises during critical illness, not explained by other causes.It typically presents as:Symmetric, proximal > distal weaknessRespiratory muscle involvementPreserved cranial nerve functionNo sensory deficits in myopathy (sensory loss points toward neuropathy)Differential Diagnosis Using Neuroanatomical ApproachAn anatomical approach (central → peripheral) helps localize the etiology weaknessCNS: trauma, stroke, encephalitis, seizuresAnterior horn cells: viral myelitis, motor neuron diseasePeripheral nerves: Guillain-Barré, vasculitis, critical illness polyneuropathy (CIP)Neuromuscular junction: myasthenia gravis, botulism, Lamber EatonMuscle: rhabdomyolysis, inflammatory or drug-induced myopathies, critical illness myopathy (CIM)Subtypes of ICU-AWCritical Illness Myopathy (CIM):Muscle dysfunctionEarly onset (within 48 hrs)Sensation intactproximal > distal weaknessCritical Illness Polyneuropathy (CIP):Nerve involvementDistal > proximal weakness, sensory deficits Critical Illness Polyneuromyopathy (CIPNM): Combination of bothDiagnosisMedical Research Council Score (MRC-SS):Score < 48: ICU-AWScore < 36: severe ICU-AWHandgrip dynamometry: <11 kg (men), <7 kg (women)Electrophysiology: EMG/NCS to distinguish CIM vs CIPMuscle ultrasound: bedside monitoringMRI/CT/Muscle biopsy: rarely used due to practical limitationRisk FactorsModifiable:Hyper/hypoglycemiaElectrolyte derangementParenteral nutritionImmobilityMedications (steroids, NM blockers, sedatives, aminoglycosides)Non-modifiable:Age, female sex, comorbiditiesSeverity of illness, prolonged ventilationSepsis, multi-organ failure Management & PreventionPrevention is key:Early treatment of sepsis and inflammationGlycemic controlEarly enteral nutritionMinimize sedation (A-F bundle)Early mobilization and physical therapyNMES (neuromuscular electrical stimulation): emerging therapy, needs more evidenceOutcomesShort-term: increased LOS, ventilation duration, mortalityLong-term: decreased function, discharge to rehab, prolonged recoveryFinal TakeawaysPrevention is crucial — start interventions early.Systematic approach to ICU weakness helps rule out dangerous mimics.ICU-AW is common but often under-recognized — awareness and early rehab can significantly impact recovery. Infographics References and Further Reading Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/­Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Devlin JW, Skrobik Y, Gélinas C, et al. Critical Care Medicine. 2018;46(9):e825-e873. doi:10.1097/CCM.0000000000003299. The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families. Ely EW. Critical Care Medicine. 2017;45(2):321-330. doi:10.1097/CCM.0000000000002175. Caring for Critically Ill Patients With the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Pun BT, Balas MC, Barnes-Daly MA, et al. Critical Care Medicine. 2019;47(1):3-14. doi:10.1097/CCM.0000000000003482. Delirium in Critical Illness: Clinical Manifestations, Outcomes, and Management. Stollings JL, Kotfis K, Chanques G, et al. Intensive Care Medicine. 2021;47(10):1089-1103. doi:10.1007/s00134-021-06503-1. ICU-acquired Weakness. Vanhorebeek I, Latronico N, Van den Berghe G. Intensive Care Medicine. 2020;46(4):637-653. doi:10.1007/s00134-020-05944-4. Clinical Review: Intensive Care Unit Acquired Weakness. Hermans G, Van den Berghe G. Critical Care (London, England). 2015;19:274. doi:10.1186/s13054-015-0993-7. Best Practices for Conducting Interprofessional Team Rounds to Facilitate Performance of the ICU Liberation (ABCDEF) Bundle. Stollings JL, Devlin JW, Lin JC, et al. Critical Care Medicine. 2020;48(4):562-570. doi:10.1097/CCM.0000000000004197. ABCDE and ABCDEF Care Bundles: A Systematic Review of the Implementation Process in Intensive Care Units. Moraes FDS, Marengo LL, Moura MDG, et al. Medicine. 2022;101(25):e29499. doi:10.1097/MD.0000000000029499.

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, we’re virtually visiting the University of Virginia for another Fellows’ Case Files. This is a fantastic case that covers ARDS, the infectious work up of an immunosuppressed patient, and the evaluation of undifferentiated shock. Please let us know what you think of the episode and always feel free to reach out with interesting cases!   Meet Our Guests John Popovich completed his residency training and chief year at UVA and has stayed on there for his pulmonary and critical care fellowship. Tim Scialla is an associate professor of medicine at UVA. He completed his residency and fellowship at Johns Hopkins Hospital where he was also an ACS. His clinical and research focuses are advanced airways disease. He is also the program director of the PCCM fellowship. Matt Freedman completed his residency training at Virginia Commonwealth University and is currently a second year fellow at University of Virginia.   Case Presentation Patient: 52-year-old male with psoriasis, HIV/AIDS (CD4 count: 71), presenting with progressive shortness of breath, fever, non-productive cough, and weight loss. Vital signs: Febrile (103°F), tachycardic (HR 110), hypoxemic on 6L O₂ (SpO₂ 90–92%). Exam: Diffuse crackles, ill-appearing. Imaging: CXR and CT showed bilateral upper lobe infiltrates, ground-glass opacities, septal thickening, and peripheral cystic changes.   Infographics POCUS algorithms for investigating shock Shock physiology:   Key Learning Points Diagnostic Reasoning in Immunocompromised Hosts Framework: Anchor the differential based on type of immunosuppression. HIV/AIDS → T-cell dysfunction, affecting susceptibility to PCP, TB, CMV, fungi (e.g. histo/blasto), and common CAP organisms. PCP considerations: PCP can occur despite prophylaxis (e.g. Bactrim), especially if adherence or resistance issues exist. Classic symptoms in AIDS: acute, febrile, hypoxemic respiratory failure. Use of Serum Markers and Imaging LDH: Elevated in PCP, but non-specific. High negative predictive value when normal. 1,3-β-D-glucan: Elevated in PCP and other fungal infections. Very sensitive for PCP (up to 95%). Imaging: Ground-glass opacities with cystic changes support PCP diagnosis. Role of Bronchoscopy and Diagnostic Yield BAL studies to obtain: DFA for PCP (rapid, high specificity, lower sensitivity) PCR for PCP (higher sensitivity, slower turnaround) Cultures: bacterial, fungal, mycobacterial Cytology, galactomannan, histo/blasto urine antigens Bronch Risk-Benefit: Can change management in 40–60% of cases. Complication rate: ~10–15%, most often hypoxemia. Heuristic for pre-bronch ABG on non-rebreather: PaO₂ >150 → likely safe 100–150 → ~25% risk of intubation <100 → high risk of decompensation Steroids in PCP and Severe CAP Steroids indicated in PCP with significant hypoxemia (PaO₂ <70 mmHg). With new CAP guidelines (Cape Cod trial), steroids may also be considered in severe bacterial CAP. Shock Evaluation in ICU Framework: Simplify into likely causes — distributive most common, but rule out cardiogenic, obstructive, hypovolemic. Physical exam + POCUS essential early. POCUS: cardiac views, IVC, lung US, abdominal free fluid. Low EF doesn’t exclude distributive shock. PA catheter (Swan) utility: Useful when physiology unclear or when tracking response to therapy is critical. Swan data in this patient: low CVP and wedge, high SVR → distributive shock, not cardiogenic despite low EF.

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 – [email protected] 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’re back with another Rapid Fire Journal Club. Luke Hedrick and Dave Furfaro discuss the NAVIGATOR trial published in NEJM in 2021 evaluating tezepelumab for adults with asthma. Article and Reference We are talking today about the NAVIGATOR trial evaluating the use of tezepelumab in adults with asthma. Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, Brightling CE, Griffiths JM, Hellqvist Å, Bowen K, Kaur P, Almqvist G, Ponnarambil S, Colice G. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021 May 13;384(19):1800-1809. doi: 10.1056/NEJMoa2034975. PMID: 33979488. https://www.nejm.org/doi/full/10.1056/NEJMoa2034975 Key Learning Points Background & Rationale Asthma biologics already exist, targeting IgE and type 2 cytokines (IL-4, IL-5, IL-13), but there’s an unmet need for patients with non-allergic or non-eosinophilic phenotypes. Tezepelumab is a monoclonal antibody targeting TSLP (thymic stromal lymphopoietin), an upstream mediator of both T2 and non-T2 inflammation, offering a potentially broader therapeutic effect.   Study Design (Navigator Trial) Phase 3, double-blind, placebo-controlled RCT Conducted in 18 countries from 2017-2020 N = 1,061 patients, aged 12-80 with moderate to severe asthma All were on medium/high-dose ICS + controller med Required ≥2 exacerbations in prior year   Outcomes Primary Outcome: Annualized rate of asthma exacerbations (events per patient-year) Secondary Outcomes: Change in pre-bronchodilator FEV₁ Symptoms & quality of life (with predefined MCIDs) Subgroup analyses by eosinophil count, FeNO, and perennial allergen sensitivity   Key Inclusion/Exclusion Inclusion: 12-80 years, guideline-based therapy, ≥2 exacerbations Exclusion: recent biologic use, mild/asymptomatic asthma, no reversibility on spirometry   Patient Population (Table 1 Summary) Middle-aged, predominantly white, female Poorly controlled severe asthma despite high-intensity therapy ~75% on high-dose ICS, ~10% on oral steroids ~40% had normal FeNO ~60% had eosinophils <300 Median IgE ~195    Results Efficacy: Annualized exacerbation rate: 0.93 (tezepelumab) vs. 2.1 (placebo) Rate ratio: 0.44, p<0.001 (very positive) In eosinophils <300 group: rate ratio 0.59, still effective FEV₁ improved by ~+0.25 L (vs. +0.09 L placebo), significant & sustained from week 2 onward Quality of life: statistically improved but did not meet MCID, so unclear clinical impact Severity of exacerbations reduced: fewer hospitalizations & ED visits in the treatment arm ~40% of treated patients still had some exacerbations → not a cure, but improves severity Safety: Very well tolerated 77% reported adverse events (more common in placebo) No anaphylaxis, no GBS, no cancer signal Most common AEs: URTI, headache, nasopharyngitis Injection site reactions: 3.6% Serious AEs were lower in drug arm than placebo   Overall Takeaway Tezepelumab significantly reduces asthma exacerbations (including in patients with low eosinophils), improves lung function, and is safe and well tolerated. Provides a broad-acting biologic option even for patients who may not be eligible for existing T2-high biologics. Now widely used as part of the asthma biologic armamentarium for poorly controlled asthma despite maximal inhaled therapy. Infographic:  

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.

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.

In this episode, we add another article to our Rapid Fire Journal Club. Luke Hedrick and Dave Furfaro discuss the MIST 2 trial published in NEJM in 2011 evaluating enzymatic therapy for complex parapneumonic effusions and empyemas.   Article and Reference We are talking today about the MIST 2 trial evaluating the use of intrapleural tPa and DNase for intrapleural infections. Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740. PMID: 21830966. Key Learning Points     Background: Infections in the pleural space are common and morbid, often requiring surgical intervention. Unfortunately, antibiotics and chest tube drainage often fail. The MIST1 trial (NEJM, 2005) of intrapleural streptokinase showed no benefit. MIST2 studied intrapleural tPA and DNase to ease drainage by breaking down septations and thinning pleural fluid. Study Design (design, primary outcome, participants, etc) Design: Double-blind, double-dummy, 2×2 factorial RCT at 11 UK hospitals from 12/2005 to 11/2008 By double dummy, we mean that there was a sham placebo for each of the study drugs Primary Outcome Change in the percent of the hemithorax taken up by effusion on CXR at day 7 compared to day 1 Key secondary outcomes: Referral for surgery Hospital LOS All cause 3 month and 12 month mortality AEs Participants Inclusion: Clinical evidence of infection (assessed by recruiting MD; EG, fever, CRP, WBC) and Pleural fluid with any of: Grossly purulent Positive pleural fluid culture or gram stain pH < 7.2 Exclusion: aiming to exclude patients with increased bleeding risk or who can’t re-expand the lung after drainage Age < 18 Previous intrapleural fibrinolytics, DNase, or both for empyema Allergy to tPA or DNase Coincidental stroke (hemorrhage risk) Major hemorrhage or trauma Major surgery in the last 5 days Previous pneumonectomy on the infected side Pregnancy, lactation Expected survival < 3 months from something other than what caused the pleural problem Summary: Middle-aged, mostly male patients with complicated pleural effusion or empyema occupying 1/3 to 2/5 hemithorax with mostly small-bore CDs for mostly community-acquired infections Small-bore here meant < 15 Fr Intervention/Limitations N = 210 (193 analyzed) randomized approximately 1:1 to one of the following 4 arms: tPA/Dnase (10mg and 5mg) tPA and placebo DNase and placebo Double placebo Medications were given BID for 3 days with clamping of the CD for 1 hour after each dose (to keep the drug in the pleural space) Outcomes/Safety Power: with N = 210 (actual analysis = 193), 80% power to detect 1 in 5 more patients with a 50% reduction in pleural opacity on CXR We’ll discuss the outcomes of tPA/DNase in combination because there was a highly significant interaction between the two (P = 0.002) for the primary outcome Efficacy: Primary (pleural effusion size reduction): -29.5% hemithorax vs baseline and -7.9% effusion size vs placebo (P = 0.005) Neither drug worked on their own Secondary: Referral for surgery: 4% vs 16% (OR 0.17, P = 0.03) Hospital LOS (excluding 391d outlier in placebo group): mean 11.8 vs 17 days (P = 0.006) Mortality: no difference Safety: No difference in AE between groups 6 serious events across all groups, mostly related to bleeding (intra-pleural, GI, hemoptysis); other AE were made up of pain with drug administration, transient AMS, rash Takeaway Combination intrapleural enzyme therapy (IET) with tPA and DNase improves drainage of infected pleural fluid, and reduces need for surgery and hospital LOS Infographic  

We’re back with our second episode in our guideline initiative, and continuing our review of the Global Initiative for Asthma (GINA) guidelines on asthma. In our first episode of this series, we talked about making the diagnosis of asthma, the importance of appropriate phenotyping, and doing an initial assessment of asthma severity. Today, we’re discussing the initial management of asthma and discussing but pharmacologic and non-pharmacologic treatments. We have a great infographic prepared along with the episode, and a boards-style question for your review. 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 Introduction to Asthma Guidelines The podcast continues a guideline series on asthma, focusing on the Global Initiative for Asthma (GINA) 2024 guidelines. Emphasizes practical applications for clinicians managing asthma in different settings. Importance of Evidence-Based Asthma Management Asthma treatment must be systematic and personalized, considering recent clinical evidence. Previous reliance on short-acting beta agonists (SABAs) as rescue inhalers has shifted towards inhaled corticosteroid (ICS)-containing therapies. Over-reliance on SABAs is linked to increased exacerbations, airway inflammation, and poor long-term outcomes. Stepwise Approach to Asthma Management (GINA 2024) The Track 1 approach (preferred) centers around ICS-formoterol as both maintenance and reliever therapy (MART). Track 2 (alternative approach) includes daily ICS or ICS-LABA with a separate SABA as a reliever. Stepwise Therapy Step 1-2 (Mild asthma): Low-dose ICS-formoterol as needed for symptom relief. Step 3 (Moderate asthma): Low-dose maintenance ICS-formoterol (MART therapy). Step 4 (Persistent symptoms): Medium-dose ICS-formoterol (MART) with additional inhaler adjustments. Step 5 (Severe asthma): Consider biologic therapies, phenotyping, and additional controllers. MART Therapy as a Game-Changer Maintenance and Reliever Therapy (MART): Uses a single inhaler for both daily maintenance and symptom relief. Reduces overuse of SABAs. Provides real-time up-titration of ICS during exacerbations. Leads to better adherence and control. Supporting Evidence from Trials: SIGMA 1 & 2, Novel Start, Practical (2018-2019): Showed ICS-formoterol reduces exacerbations and steroid exposure compared to SABAs. MANDALA (2022): Showed ICS-SABA improves outcomes over SABA alone, though not a true MART study. Practical Considerations in Asthma Management Patient adherence is critical—educate on proper inhaler use and symptom monitoring. Insurance and cost barriers may require prescribing alternative inhalers. Review and adjust treatment regularly using the “Assess, Adjust, Review” framework. Avoid high-dose ICS without exploring additional controller therapies like LAMAs, leukotriene receptor antagonists (Montelukast), and azithromycin. Non-Pharmacologic Interventions Smoking cessation (including vaping/marijuana). Weight management and physical activity. Avoiding triggers (allergens, occupational exposures, pollution). Air purifiers and HEPA filters. Vaccinations (flu, COVID-19) to prevent viral exacerbations. Managing comorbidities (GERD, sleep apnea, anxiety/depression). Case Discussion & Real-World Application Patient with recurrent asthma symptoms post-viral illness. Started on low-dose ICS-formoterol as needed. Symptoms persisted, leading to maintenance ICS-formoterol (MART therapy). Regular follow-up to monitor and adjust therapy. Looking Ahead Next episode will focus on biologic therapies for severe asthma. Emphasis on ongoing education, practical application, and patient-centered care. Infographic   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. Matera MG, Rinaldi B, Annibale R, De Novellis V, Cazzola M. The pharmacological management of asthma in adults: 2023 update. Expert Opin Pharmacother. 2024 Mar;25(4):383-393. doi: 10.1080/14656566.2024.2332627. Epub 2024 Mar 20. PMID: 38497368. Arismendi E, Ribo P, García A, Torrego A, Bobolea I, Casas-Saucedo R, Palomino R, Picado C, Muñoz-Cano R, Valero A. Asthma Control According to GINA 2023: Does Changing the Criteria Improve Asthma Control? J Clin Med. 2024 Nov 6;13(22):6646. doi: 10.3390/jcm13226646. PMID: 39597790; PMCID: PMC11594371. http://ginasthma.org/2023-gina-main-report/ https://www.uptodate.com/contents/an-overview-of-asthma-management-in-children-and-adults https://onlinelibrary.wiley.com/doi/full/10.1111%2Fresp.14782 Dubin S, Patak P, Jung D. Update on Asthma Management Guidelines. Mo Med. 2024 Sep-Oct;121(5):364-367. PMID: 39421468; PMCID: PMC11482852.  

Today we have a mini-episode / clinical pearl. We previously discussed the PROSEVA trial and the evidence for prone positioning in ARDS. In that trial, patients with elevated intracranial pressure (ICP) were excluded. We are joined now by Dr. Jon Rosenberg, a neuro intensivist, to discuss his how prone positioning can still be employed for patients with neurologic injuries and elevated ICP.   Meet Our Guest Dr. Jon Rosenberg is an assistant professor of neurology and neurosurgery at Westchester Medical Center, New York Medical College. He’s also the associate program director of the Neurocritical Care Fellowship at Westchester Medical Center and a frequent contributor to the Neurocritical Care Society podcast.   Key Learning Points Elevated Intracranial Pressure (ICP) and Proning: A Common Misconception Elevated ICP is often considered a contraindication to proning, but this is more of a relative caution rather than an absolute contraindication. Many neuro ICUs have successfully proned patients with elevated ICP, particularly since the COVID-19 pandemic, when critical care units had to manage both respiratory failure and neurological conditions simultaneously. Patient Selection for Proning with Elevated ICP Most patients with elevated ICP can still be proned, including those with: Global cerebral edema (e.g., post-anoxic brain injury, liver failure) Focal lesions (e.g., traumatic brain injury, large ischemic strokes, intracerebral hemorrhage) Situations where proning might be more concerning: Severe hemodynamic instability (multi-pressor shock) Morbid obesity (e.g., >300 lbs), where physically flipping the patient is a major challenge Theoretical Concerns with Proning in Elevated ICP Loss of neurological exam access (sedation + flipped position makes pupil and motor exam difficult) Jugular venous compression (especially if the head is turned to one side) Cerebrospinal fluid (CSF) flow obstruction, depending on the lesion Risk of increased ICP if venous outflow is impaired or head positioning is not optimized Best Practices for Proning Patients with Elevated ICP Patients with invasive ICP monitors vs. without monitors: If possible, placing an ICP monitor (EVD or parenchymal bolt) before proning provides better guidance. Without a monitor, providers must rely on other practices like maintaining strict MAP goals and sodium targets, and indirect signs of increased ICP. Positioning considerations: Keep the head midline to prevent jugular venous compression. If head positioning is not neutral, place the dominant/internal jugular facing upward to maintain venous drainage. Maintain the head of the bed elevated even while prone (reverse Trendelenburg positioning). Hemodynamic management: Target a higher MAP (e.g., 70–75 mmHg, sometimes 75–80 mmHg) to ensure adequate cerebral perfusion pressure (CPP) if there is no ICP monitor Avoid hypotension, as MAP – ICP = CPP, and low MAP could critically reduce cerebral perfusion. A normal intracranial pressure is 7 – 15 mmHg The recommended CPP is between 60 – 70 mmHg Sedation & Sodium Management: Consider deep sedation (RASS -5) to reduce metabolic demand and intracranial blood volume. Consider keeping sodium >145 mmol/L prophylactically to mitigate brain swelling if no ICP monitor in place When to Reconsider Proning (i.e. when to supinate) If a patient’s ICP spikes significantly (e.g., from 20 to 60 mmHg) despite medical management (hypertonic saline, sedation, paralysis, etc.). If new signs of neurological deterioration emerge (e.g., changes in pupil exam once patient is repositioned). Hemodynamic instability that is unmanageable in the prone position. Literature and Future Considerations Small case series have demonstrated success in proning patients with traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage. While more formal research is needed, the neurocritical care community has begun embracing proning for neuro patients, provided that proper precautions are taken. Bottom Line Proning is not an absolute contraindication for patients with elevated ICP—it can be done safely with proper monitoring, patient selection, and precautions. Having an ICP monitor makes the process more controlled and allows clinicians to adjust treatment in real time. Key considerations: Maintain cerebral perfusion, optimize head positioning, monitor hemodynamics, and have a plan for reversing if ICP becomes unmanageable.  

On February 7, 2025 it was announced that the National Institutes of Health (NIH) would be capping indirect cost payments for research grants at 15%. This is a massive reduction from the current standard, and will have widespread impacts on research, healthcare delivery, and trainee and young faculty development throughout the United States. We have a special episode today to try to explain what this change really means, the broad impact it will have on the healthcare system and scientific research, and what we as a the healthcare community can / should be doing. Please feel free to reach out to us with any thoughts or questions from the episode.  Meet Our Guests Dr. Theodore “Jack” Iwashyna is a Bloomberg Distinguished Professor at Johns Hopkins School of Medicine and the Johns Hopkins Bloomberg School of Public Health. Jack is a critical care physician and focuses on research to understand the broader context of critical illness, and the long term impact on patients’ lives. He is an enormously productive and successful researcher with numerous publications in the field of critical care, and is a pioneer in the field of ICU survivorship. He is a devoted mentor and has received accolades from numerous societies Dr. Kathryn Hibbert is an Assistant Professor of Medicine at Harvard Medical School and a pulmonary and critical care physician at Massachusetts General Hospital. She is the MICU Director at MGH, as well at the Vice Chair for Critical Care. Summary of Key Points Overview of NIH Funding NIH research funding is divided into direct costs (salaries, supplies, specific project expenses) and indirect costs (infrastructure, utilities, administrative support). Indirect costs support shared research resources like lab space, IT infrastructure, and institutional overhead. Recent Policy Change & Impact A sudden 15% cap on indirect cost reimbursement for NIH grants was announced late on a Friday, catching the academic community off guard. Many universities typically receive 50-60% in indirect cost reimbursements, making this a drastic cut. This change could severely affect research institutions by reducing available funding for shared infrastructure, education, and clinical care. Broader Ramifications Threat to Medical Research: Loss of funding for essential research infrastructure could slow or halt key medical advancements, such as cancer therapies, CF treatments, and more. Impact on Education & Clinical Care: Reduced research funding could lead to cuts in trainee programs, fewer job opportunities, and diminished support for clinical services, particularly those serving vulnerable populations. Economic Consequences: Academic medical centers are often major employers in states across the U.S. A reduction in funding could lead to job losses and economic downturns in affected regions. Political and Institutional Response Legal challenges were quickly filed, resulting in a temporary restraining order against the policy change. The administration’s actions were seen as an attack on academic freedom and scientific independence. The impact extends beyond select universities or states. States like Texas, Ohio, Florida, and Iowa stand to lose millions in research funding. Advice for Early-Career Researchers Continue applying for NIH grants as normal, following institutional guidance. Stay informed about evolving policies. Engage in advocacy—contact representatives, raise awareness, and contribute to public discussions. Call to Action The speakers urge medical professionals, researchers, and the public to share knowledge about what the impact of these changes would be, and prevent them from becoming permanent. They emphasize the critical role of NIH-funded research in improving healthcare outcomes worldwide and encourage continued engagement in the conversation. References and Further Reading https://www.al.com/news/2025/02/katie-britt-vows-to-work-with-rfk-jr-after-nih-funding-cuts-cause-concern-in-alabama.html https://www.forbes.com/sites/michaeltnietzel/2025/02/10/what-the-nih-cut-to-indirect-cost-payments-could-cost-red-states https://www.npr.org/2025/02/12/nx-s1-5292359/what-cuts-to-nih-funding-could-mean-for-american-universities https://www.press.jhu.edu/books/title/53759/transformation-american-health-insurance?srsltid=AfmBOoqvR5-TrqcsIC6ELO3AdZgjFWkIJ9jdlawJpyxJDus1cM–LxLr https://global.oup.com/academic/product/time-to-heal-9780195181364?cc=us&lang=en& https://www.africa.upenn.edu/Articles_Gen/Letter_Birmingham.html

Today we are launching a new Pulm PEEPs initiative! We are going to be reviewing some of the major guidelines that are available in pulmonary and critical care. We are starting by diving into the Global Initiative for Asthma (GINA) guidelines on asthma. The goal of this initiative is to breakdown the guidelines into digestible and helpful discussions, and to talk about key issues that are pointed out by the guideline authors. Our first episode will be the start of the GINA guidelines and we’re discussing the initial diagnosis and evaluation of patients with asthma. 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 Understanding Asthma & the GINA Guidelines Asthma is a heterogeneous disease characterized by recurring respiratory symptoms (breathlessness, wheezing, cough, chest tightness) with variable airflow limitation. The 2023 & 2024 Global Initiative for Asthma (GINA) guidelines emphasize phenotyping asthma to improve diagnosis and treatment. Asthma differs from other obstructive lung diseases due to reversible airway obstruction, which can be demonstrated through diagnostic testing. Diagnosing Asthma Clinical history is crucial, particularly identifying symptom triggers (cold air, exercise, allergens). Spirometry is the standard diagnostic tool, looking for an increase in FEV1 or FVC ≥12% and 200 mL after bronchodilator use. Alternative tests include: Peak expiratory flow monitoring over time. Bronchoprovocation tests (e.g., methacholine challenge) to assess airway hyperresponsiveness. Fractional exhaled nitric oxide (FENO) and blood eosinophils as markers of type 2 inflammation. Asthma Phenotypes & Precision Medicine Different asthma phenotypes guide personalized treatment approaches: Type 2  inflammation: Characterized by eosinophilic inflammation, high FeNO, good steroid responsiveness, and potential for biologic therapy. Non-Type 2 inflammation: Associated with neutrophilic inflammation, poor steroid responsiveness, and potential benefit from macrolides or bronchodilators. Asthma-COPD overlap requires a distinct treatment approach due to persistent obstruction. Imaging & Adjunctive Tests Imaging is not routinely needed in asthma but can be useful for: Bronchiectasis (suspected allergic bronchopulmonary aspergillosis – ABPA). Asthma-COPD overlap (CT chest for emphysema). Chronic sinusitis or nasal polyps (CT sinus imaging). Assessing Asthma Control Asthma is not a one-time diagnosis; continuous reassessment is crucial. Asthma control is assessed at every visit, considering: Symptom frequency Exacerbations Inhaler technique Comorbidities Rule of Twos: Asthma is not well-controlled if: Symptoms occur >2 times per week. Nighttime awakenings >2 times per month. Rescue inhaler use >2 times per week (excluding pre-exercise use). Peak flow meters are valuable for self-monitoring and guiding asthma action plans. Conclusion Asthma assessment is a continuous process, incorporating history, spirometry, biomarkers, and patient-reported symptoms. Future episodes will cover asthma treatment, including biologics and inhaler therapy. Infographics and questions will accompany this series for further learning. Infographic Board Style Questions 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. Matera MG, Rinaldi B, Annibale R, De Novellis V, Cazzola M. The pharmacological management of asthma in adults: 2023 update. Expert Opin Pharmacother. 2024 Mar;25(4):383-393. doi: 10.1080/14656566.2024.2332627. Epub 2024 Mar 20. PMID: 38497368. Arismendi E, Ribo P, García A, Torrego A, Bobolea I, Casas-Saucedo R, Palomino R, Picado C, Muñoz-Cano R, Valero A. Asthma Control According to GINA 2023: Does Changing the Criteria Improve Asthma Control? J Clin Med. 2024 Nov 6;13(22):6646. doi: 10.3390/jcm13226646. PMID: 39597790; PMCID: PMC11594371. http://ginasthma.org/2023-gina-main-report/ 2024 GINA Main Report

Today is our second 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 lung health, COPD, and emphysema. 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.  Ewan Mackay is a Respiratory Clinical Research Fellow who has started his PhD in London. His research focus is on chronic cough and in the development of new patient-reported outcome measures as well as respiratory physiology, particularly in relation to exercise and disease. Journal Club Papers Journal club article from Thorax Estimated health effects from domestic use of gaseous fuels for cooking and heating in high-income, middle-income, and low-income countries: a systematic review and meta-analyses Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry Association of Ground-Glass Opacities with Systemic Inflammation and Progression of Emphysema Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results To submit a journal club article of your own to Thorax, you can contact Chris directly – [email protected] 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.

This week we’re talking about a case as a lens for discussing Tylenol toxicity and Acute Liver Failure. These relatively common critical care presentations are essential knowledge for anyone practicing in the ICU. Listen in for some key discussion both about toxicology and the diagnosis and management of acute livery injury and failure.   Meet Our Guests Kalaila Pais received her MD from Howard University College of Medicine and is currently a second year internal medicine resident at BIDMC. She is interested in pulmonary and critical care, as well as medical education. She also had the idea for this episode and was essential in its writing and production. Hima Veeramachaneni received her MD from University of Missouri-Kansas City School of Medicine, and her residency at Emory where she was also a Chief Resident at Grady Memorial Hospital. She is a gastroenterologist and completed her GI and transplant hepatology training at Emory. She is also now doing a critical care medicine fellowship year.   Case Presentation Presentation: Patient found down, surrounded by liquor bottles, with coffee-ground emesis, hemodynamic instability, scleral icterus, and metabolic derangements. Key Lab Findings: Severe transaminitis (AST >10,000, ALT ~3,000). Elevated bilirubin (5.8), lactate (16), and INR (>2). Metabolic acidosis with a pH of 7.04. Tylenol level: 41 (slightly elevated but inconclusive without ingestion timing).   Key Learning Points Infographic: Acute Liver Injury vs. Acute Liver Failure Acute Liver Injury (ALI): Elevated liver enzymes without encephalopathy or significant synthetic dysfunction. Acute Liver Failure (ALF): Defined by: Presence of encephalopathy. Coagulopathy (elevated INR). Rapid onset (<26 weeks) in patients without pre-existing liver disease. ALF often leads to complications such as cerebral edema, which necessitates aggressive management. Tylenol Toxicity and Interpretation Pathophysiology: Tylenol overdose overwhelms liver glutathione, leading to accumulation of NAPQI, which causes hepatocyte necrosis. Interpretation of Tylenol Levels: Timing of ingestion is critical to interpreting levels. The Rumack-Matthew Nomogram is used for acute ingestions but requires a known ingestion time. Management: N-acetylcysteine (NAC): Standard of care; acts as a glutathione precursor and mitigates liver damage. Early use is recommended in suspected cases of Tylenol toxicity, even if ingestion timing is unclear. Critical Management Principles Stabilization: Focus on airway, hemodynamics, and perfusion. Monitor for signs of cerebral edema (e.g., pupillary changes, seizures). In select patients, use hypertonic saline to maintain sodium levels (145–150 mmol/L) to mitigate cerebral edema risks. CRRT and Plasma Exchange: Continuous renal replacement therapy (CRRT) for hyperammonemia and acidosis. Plasma exchange (PLEX) may stabilize cytokine storms and improve survival. Organ-Specific Considerations: Renal failure: Common due to hepatorenal syndrome; requires CRRT. Coagulopathy: Managed with blood products as needed but indicates worsening liver synthetic dysfunction. Prognosis and Transplant Considerations King’s College Criteria: Guides transplant listing for ALF patients. Factors: Encephalopathy severity, INR, lactate, bilirubin trends. Ethical considerations for liver transplant in patients with substance use or overdose: Emphasis on assessing social support and addressing psychiatric needs. Efforts are made to ensure equitable access to transplant when warranted. Takeaways for Clinical Practice Broad Differential Diagnosis: Keep a wide perspective for acute liver presentations, considering toxins, infections, and systemic conditions. Early Use of NAC: Err on the side of initiating NAC when Tylenol toxicity is suspected. CNS Focus in ALF: Monitor and manage cerebral edema aggressively. CRRT & PLEX: Advanced liver support techniques are critical in select cases. Interdisciplinary Collaboration: Psychiatrists, neurocritical care, and hepatologists play pivotal roles in management.  

We are excited to be back with a Rapid Fire Journal Club. Today’s episode is hosted by PulmPEEPs Associate Editor, Luke Hedrick, and will delve into the ANDROMEDA-SHOCK trial published in JAMA in 2019. Meet our Guests Jose Meade Aguilar is a second year Internal Medicine resident at Boston University Medical Campus (BUMC). Article and Reference Today the discussion highlights the ANDROMEDA-SHOCK trial (JAMA, 2019) which evaluated whether resuscitation guided by capillary refill time (CRT) is superior to lactate-guided resuscitation in reducing mortality in patients with septic shock. Hernández G, Ospina-Tascón GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegría L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernández P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernández G, Ospina-Tascón G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegría L, Teboul JL, Cecconi M, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernández P, Barahona D, Cavalcanti AB, Bakker J, Hernández G, Alegría L, Ferri G, Rodriguez N, Holger P, Soto N, Pozo M, Bakker J, Cook D, Vincent JL, Rhodes A, Kavanagh BP, Dellinger P, Rietdijk W, Carpio D, Pavéz N, Henriquez E, Bravo S, Valenzuela ED, Vera M, Dreyse J, Oviedo V, Cid MA, Larroulet M, Petruska E, Sarabia C, Gallardo D, Sanchez JE, González H, Arancibia JM, Muñoz A, Ramirez G, Aravena F, Aquevedo A, Zambrano F, Bozinovic M, Valle F, Ramirez M, Rossel V, Muñoz P, Ceballos C, Esveile C, Carmona C, Candia E, Mendoza D, Sanchez A, Ponce D, Ponce D, Lastra J, Nahuelpán B, Fasce F, Luengo C, Medel N, Cortés C, Campassi L, Rubatto P, Horna N, Furche M, Pendino JC, Bettini L, Lovesio C, González MC, Rodruguez J, Canales H, Caminos F, Galletti C, Minoldo E, Aramburu MJ, Olmos D, Nin N, Tenzi J, Quiroga C, Lacuesta P, Gaudín A, Pais R, Silvestre A, Olivera G, Rieppi G, Berrutti D, Ochoa M, Cobos P, Vintimilla F, Ramirez V, Tobar M, García F, Picoita F, Remache N, Granda V, Paredes F, Barzallo E, Garcés P, Guerrero F, Salazar S, Torres G, Tana C, Calahorrano J, Solis F, Torres P, Herrera L, Ornes A, Peréz V, Delgado G, López A, Espinosa E, Moreira J, Salcedo B, Villacres I, Suing J, Lopez M, Gomez L, Toctaquiza G, Cadena Zapata M, Orazabal MA, Pardo Espejo R, Jimenez J, Calderón A, Paredes G, Barberán JL, Moya T, Atehortua H, Sabogal R, Ortiz G, Lara A, Sanchez F, Hernán Portilla A, Dávila H, Mora JA, Calderón LE, Alvarez I, Escobar E, Bejarano A, Bustamante LA, Aldana JL. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):654-664. doi: 10.1001/jama.2019.0071. PMID: 30772908; PMCID: PMC6439620. Infographic

Our episode today is diving into a broader initiative to discuss the management of interstitial lung disease. In this episode we will be talking about the treatment of Idiopathic Pulmonary Fibrosis through the lens of a journal club discussion of the NEJM 2014 INPULSIS trial. Today’s episode is hosted by Pulm PEEPs Associate Editor Luke Hedrick. Meet Our Guests Robert Wharton is a recurring guest on Pulm PEEPs as a part of our Rapid Fire Journal Club Series. He completed his internal medicine residency at Mt. Sinai in New York City, and is currently a first year pulmonary and critical care fellow at Johns Hopkins. Dr. Nicole Ng is an Assistant Profess of Medicine at Mount Sinai Hospital, and is the Associate Director of the Interstitial Lung Disease Program for the Mount Sinai National Jewish Health Respiratory Institute. Article and Reference Today the discussion of IPF treatment centers around the 2014 NEJM publication of the INPULSIS trials investigating the efficacy of Nintedanib for the treatment of IPF. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2071-82. doi: 10.1056/NEJMoa1402584. Epub 2014 May 18. Erratum in: N Engl J Med. 2015 Aug 20;373(8):782. doi: 10.1056/NEJMx150012. PMID: 24836310. Infographic Summary of Key Discussion Points Background and Challenges in ILD Treatment: Interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), had historically poor treatment outcomes, with numerous therapies showing either no benefit or even harm. Prior to 2014, effective treatments were extremely limited, and lung transplantation was the primary management option. INPULSIS I and II Trials: These 2014 trials examined nintedanib, an antifibrotic drug initially tested for cancer, in patients with moderate IPF. The studies were well-structured, involving strict criteria to ensure accurate diagnoses and excluding younger patients or those with more advanced disease. Nintedanib’s Mechanism and Design of the Trials: Nintedanib acts by blocking multiple tyrosine kinases that mediate fibrotic growth factors. Patients were monitored over a year, with primary endpoints focusing on forced vital capacity (FVC) decline—a common surrogate measure for disease progression in ILD trials due to its correlation with survival. Outcomes: Both trials showed that nintedanib significantly reduced the rate of FVC decline compared to placebo, suggesting that it slowed disease progression. Secondary endpoints included reduced acute exacerbations (significant only in one trial) and minor improvements in quality of life, though these weren’t statistically or clinically significant. Adverse Effects: Nintedanib’s side effects included gastrointestinal issues (diarrhea, nausea, vomiting) and, less commonly, liver enzyme elevations and cardiovascular events. While post-marketing data suggested some improvements in tolerability, clinicians still monitor for these side effects closely. Application in Clinical Practice: The trials support nintedanib as an option for slowing IPF progression, though no cure or disease reversal is achieved. Clinicians weigh the choice between nintedanib and pirfenidone (another antifibrotic) based on each drug’s side effect profile and individual patient needs. Future Directions: The trials paved the way for further research into multi-therapy approaches for ILD, targeting multiple disease pathways, similar to strategies in asthma or COPD. Upcoming therapies and trials aim to provide more targeted and effective options for IPF and other ILDs.

We are joined today by two amazing educators from NYU for our latest Fellows’ Case Files Episode. Listen today as we go through a great case with some fantastic teaching points highlighted throughout the episode. Meet Our Guests Dr. Jeremy Grossman completed his Medicine-Pediatrics residency at Stony Brook Medicine where he was also a Chief Resident. He is currently a second-year PCCM fellow at NYU. Dr. Shari Brosnahan is an Assistant Professor of Medicine and one of the Assistant Program Directors for the NYU Langone’s Division of Pulmonary, Critical Care, and Sleep Medicine. Her clinical and research interests are focused on pulmonary embolism and thrombosis in critically ill patients. Case Presentation An 80-year-old male presents with shortness of breath. At home, his oxygen saturation was 82% on room air, improving only to 86% on 4L nasal cannula. Over the past month, he has experienced worsening symptoms, including a dry cough, fatigue, and difficulty speaking or ambulating due to shortness of breath at rest. He denies recent fever, sputum production, chest pain, or lower extremity swelling and presents to the ED for further evaluation. Key Learning Points 1.In any patient with a history of malignancy and hypoxia, clinicians should keep pulmonary tumor emboli (PTE) on the differential as early intervention may alter outcomes. 2.PTE contributes to hypoxia via mechanisms of mechanical obstruction of pulmonary arteries leading to shunting, VQ Mismatch, and in some cases pulmonary hypertension due to increased PVR. 3.A wedged aspirate can be used to diagnose PTE ante-mortem

Here at Pulm PEEPs we have always loved the CHEST Annual Meetings. We have enjoyed learning at them, reuniting with and meeting colleagues, and having conference specific episodes the past two years. This year, we had the opportunity to podcast live at CHEST 2024 and it was a real thrill! We talked to Maria Smilios about her wonderful book The Black Angels: The Untold Story of the Nurses Who Helped Cure Tuberculosis. . The book covers a range of fascinating topics including how treatments for tuberculosis were developed, the successes and plights of Black nurses working in this endeavor, an exploration of health care in New York City, and a discussion of Racism and civil rights in American healthcare. We were also thrilled that Virginia Allen, the last surviving Black Angel is at the conference and her and her colleagues (posthumously) are receiving an honorary FCCP. Meet Our Guests Maria Smiios is a native New Yorker but completed her master of arts in religion and literature right here in Boston. She completed her masters at Boston University, where she was a Luce scholar, and taught in the religion and writing program. Through her work, she found a love for history, medicine and women’s narratives. While working at Springer Publishing as a science book editor, she learned about the story of the Black Angels and was determined to tell their story. She spent years deeply engaged in the lives and stories of those who were closest to these remarkable women.

We are excited to be back with our colleagues from CHEST to be previewing the CHEST 2024 Annual Meeting. CHEST his year is in Boston, MA from October 5th to October 9th. Listen in to hear about some great new features at CHEST this year, some old favorites, and to learn how to optimize your conference experience. See you all in two weeks! Meet Our Guests Sandhya Khurana is a  Professor of medicine at University of Rochester school of medicine and Director of the Mary Parkes Asthma Center. Her clinical and research interest is in asthma. She is the Vice-Program Chair for CHEST 2024 and will be the program Chair for CHEST 2025 next year in Chicago. Gabe Bosslet is the Program Chair for CHEST this year. In addition he is a Professor of Clinical Medicine at Indiana University School of Medicine. He is also an Assistant Dean at IU, and the Director of Mentoring and Faculty Development for the Division Pulmonary, Critical Care, Allergy and Occupational Medicine. Huzaifah Salat is a clinician educator who is currently working as a consultant pulmonologist and intensivist at Advocate Aurora Health in Wisconsin. He completed his Pulmonary and Critical Care Fellowship at the University of Oklahoma Health Sciences Center

We are extremely excited today to announce a new collaboration 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. We hope you enjoy! 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.  Imran Howell is an Asthma Fellow at the Nuffield Department of Medicine, University of Oxford Journal Club Papers Journal club article from Thorax Blood eosinophil-guided oral prednisolone for COPD exacerbations in primary care in the UK (STARR2): a non-inferiority, multicentre, double-blind, placebo-controlled, randomised controlled trial Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial The airway microbiome mediates the interaction between environmental exposure and respiratory health in humans Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): a population-based, prospective birth cohort study To submit a journal club article of your own to Thorax, you can contact Chris directly – [email protected] 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.

In this podcast episode, we continue our summer series reviewing landmark ARDS studies. Today, Dave and Luke discuss the Driving Pressure trial (published in NEJM in 2015) which evaluated the impact of driving pressure on survival in patients with ARDS. Article and Reference We are talking about the Driving Pressure trial today which evaluated the impact of driving pressure, as an independent variable, on survival in patients with ARDS. Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639. PMID: 25693014. Infographic

In the penultimate episode in our ARDS Rapid Fire Journal Club Summer Series we are talking about the DEXA-ARDS trial (published in Lancet Respiratory Medicine in 2020). This trial evaluated the impact of dexamethasone in the treatment of ARDS.   Article and Reference Today we’re discussing the DEXA-ARDS trial published in Lancet Respiratory Medicine in 2020. This trial evaluated the impact of dexamethasone on mortality and duration of mechanical ventilation for patients with ARDS. Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, Aguilar G, Alba F, González-Higueras E, Conesa LA, Martín-Rodríguez C, Díaz-Domínguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Añón JM, Fernández RL, González-Martín JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7. PMID: 32043986.   Infographic   Article Notes DEXA-ARDS; Lancet Respiratory Medicine, 2020 DOI:10.1016/S2213-2600(19)30417-5 Link: https://doi.org/10.1016/s2213-2600(19)30417-5 Background: ARDS is an intense inflammatory process without proven, specific pharmacotherapies. Previous work and a recent meta-analysis demonstrated improvements in inflammation, gas exchange, and ventilator and ICU liberation but did not adequately address mortality. Study Design (design, primary outcome, participants, etc) Design: investigator-initiated, multicenter, unblinded, randomized controlled trial in 17 academic ICUs in Spain, conducted from 3/2013 to 12/2018 Primary Outcome VFD at 28d Secondary: 60d mortality Actual duration of ventilation in ICU survivors ICU acquired infections Participants Inclusion ARDS with P/F < 200 for < 24hr on LTVV Exclusion: Already receiving steroids or immunosuppression CHF Severe COPD DNR Summary: Middle aged, mostly male patients with < 24hr of moderate to severe ARDS receiving LPV without chronic heart or lung disease Like many ARDS trials, just over 3/4 of patients’ ARDS was caused by PNA or sepsis. Mean P/F was ~140 Intervention/Limitations N = 277, stratified by center and then randomized Intervention: dexamethasone 20mg qd for 5d followed by 10mg qd for 5d Stopped early for extubation before day 10 First dose given no more than 30 hours after P/F < 200 Control: no placebo, just SOC All patients received LTVV Outcomes/Safety Power: with N = 314 (actual N = 277), 80% power to detect 2 additional VFD and 15% mortality reduction As an aside, this seems to be a theme in ICU trials: massively ambitious proposed benefits during power calculations and then under-enrolling for that power calculation ultimately resulting with a point estimate that favors the intervention but is not statistically significant. Efficacy: 60d mortality: 21% vs 36%, P = 0.0047 NNT of just < 7! VFD at 28d: 12.3 vs 7.5, P < 0.0001 Actual duration of ventilation in ICU survivors: 14.2d vs 19.5d (P = 0.0009) Safety: Hyperglycemia: 76% vs 70%, P = 0.33 Always interesting in steroid trials when no change in glucose control is seen. This isn’t the most EBM thing I’ll ever say, but frankly I disregard this and assume steroids will cause hyperglycemia regardless of the trial results. ICU acquired infections: 24% vs 25%, P = 0.75 Takeaway In a narrowly selected population of patients without chronic heart or severe lung disease and with early, moderate ARDS (mostly from sepsis or pneumonia), dexamethasone reduced mortality and duration of mechanical ventilation. If time, insert soap-box about etiology of ARDS being very important (EG, flu, fungal, parasitic, mycobacterial infections)  

We have another great case in our Fellows’ Case Files coming today from UMass Chan. Listen in for a great discussion about a fascinating case with interesting physical exam and radiographic findings. Meet Our Guests Dr. Jen Kodela completed her residency training at UMass Memorial Medical Center and is currently a third year PCCM fellow at UMass Chan. Dr. Ariel McKenna completed her residency training at Maine Medical Center and is also currently a third year PCCM fellow at UMass Chan. Dr. Will Wong is an Assistant Professor of Medicine and is the Program Director of the PCCM fellowship at UMass Chan Case Presentation A 75 y/o F presenting with acute on chronic SOB, cough, L sided chest pain and rash. She has had ~7 months of progressive dyspnea, now a/w 2 months of productive cough, and several weeks of L sided chest pain and rash. She has been seen multiple times in the past two months for these sxs. During that time she received multiple antibiotic courses (urgent care, outpatient providers), including augmentin, azithromycin and levaquin, and asthma directed therapy (no steroids). Imaging throughout that time (CXRs, CTPE) show progression from a LLL infiltrate to bibasilar infiltrates. Despite these interventions, sxs continue to worsen. One month prior she was admitted to an OSH w/ continued worsening, vitals stable, exam nonfocal, mild leukocytosis but infectious w/u bland. Received broad spectrum abx. Bronch w/ BAL offers negative cultures, cytology, cell count w/ 66% neutrophils, 14% eosinophils. Discharged w/ dx of PNA on a 10 day course of levaquin and new exertional oxygen requirement of 2L. She then presents to Umass ~1 month later w/ continued progression of sxs Key Learning Points 1. Formulate a differential diagnosis for non-resolving pneumonia 2. Evaluate the utility of transbronchial biopsy in the workup of undifferentiated ILD 3. Describe the clinical manifestations of antisynthetase syndrome and identify the differences in presentation associated with PL-12 positivity References and Further Reading 1. Kuru T, Lynch JP 3rd. Nonresolving or slowly resolving pneumonia. Clin Chest Med. 1999 Sep;20(3):623-51. doi: 10.1016/s0272-5231(05)70241-0. PMID: 10516909. 2. Troy LK, Grainge C, Corte TJ, Williamson JP, Vallely MP, Cooper WA, Mahar A, Myers JL, Lai S, Mulyadi E, Torzillo PJ, Phillips MJ, Jo HE, Webster SE, Lin QT, Rhodes JE, Salamonsen M, Wrobel JP, Harris B, Don G, Wu PJC, Ng BJ, Oldmeadow C, Raghu G, Lau EMT; Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease alliance (COLDICE) Investigators. Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med. 2020 Feb;8(2):171-181. doi: 10.1016/S2213-2600(19)30342-X. Epub 2019 Sep 29. PMID: 31578168. 3. Hallowell RW, Danoff SK. Diagnosis and Management of Myositis-Associated Lung Disease. Chest. 2023 Jun;163(6):1476-1491. doi: 10.1016/j.chest.2023.01.031. Epub 2023 Feb 9. PMID: 36764512. 4. Hallowell RW, Paik JJ. Myositis-associated interstitial lung disease: a comprehensive approach to diagnosis and management. Clin Exp Rheumatol. 2022 Feb;40(2):373-383. doi: 10.55563/clinexprheumatol/brvl1v. Epub 2021 Mar 25. PMID: 33769263; PMCID: PMC8855729. 5. Marie I, Josse S, Decaux O, Dominique S, Diot E, Landron C, Roblot P, Jouneau S, Hatron PY, Tiev KP, Vittecoq O, Noel D, Mouthon L, Menard JF, Jouen F. Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev. 2012 Aug;11(10):739-45. doi: 10.1016/j.autrev.2012.01.006. Epub 2012 Feb 3. PMID: 22326685.

In this podcast episode, we continue our summer series reviewing landmark ARDS studies. Today, Dave and Luke discuss the PROSEVA trial (published in NEJM in 2013) which evaluated the impact of early, prolonged proning in patients with severe ARDS. Article and Reference We are talking about the PROSEVA trial today which evaluated the patients with severe ARDS (P/F < 150) to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20. PMID: 23688302. Infographic

In this podcast episode, we continue our summer series reviewing landmark ARDS studies. Today, Dave and Luke discuss the ROSE trial (published in NEJM in 2019) which investigated use of continuous neuromuscular blockade in moderate to severe ARDS. Article and Reference We are talking about the ROSE trial today which was a comparison of early continuous neuromuscular blockade in patients with ARDS who were receiving mechanical ventilation. Reference: National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 10.1056/NEJMoa1901686. Epub 2019 May 19. PMID: 31112383; PMCID: PMC6741345. Infographic

In this podcast episode, we continue our summer series reviewing landmark ARDS studies. Today, Dave and Luke discuss the FACTT trial, which investigated fluid management strategies in ARDS. This was published in the NEJM in 2006. Article and Reference We’re talking about the FACTT trial today which was a “Comparison of Two Fluid-Management Strategies in Acute Lung Injury” Reference: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21. PMID: 16714767. Infographic Summary of discussion: Background: The FACT trial aimed to address fluid balance in ARDS, given the complexity of managing pulmonary edema and systemic organ failure. The challenge has been finding the right balance between managing fluid to optimize cardiac function and avoiding exacerbation of pulmonary edema. Study Design: Randomized Controlled Trial: Conducted at 20 North American medical centers from 2000 to 2005. Participants: Included intubated ARDS patients who required or were planned to receive a central venous catheter. Excluded patients with chronic diseases, recent MI, or irreversible conditions. Shock was not an exclusion criterion. Interventions: Patients were randomly assigned to either a liberal or conservative fluid management strategy, and also received either a PA catheter or a central line. Fluid Management Protocol: Liberal Strategy: Aimed for higher filling pressures (CVP of 10-14 or wedge pressure of 14-18). Conservative Strategy: Aimed for lower filling pressures (CVP less than 4 or wedge pressure under 14). Fluid Balance: The liberal group had a net positive fluid balance of around 7 liters, while the conservative group had a net negative balance of about 130 cc. Results: Mortality: No statistically significant difference in 60-day mortality between the liberal and conservative groups (25.5% vs. 28.4%, respectively). Ventilator and ICU-Free Days: The conservative strategy resulted in more ventilator-free and ICU-free days. Shock and Dialysis: There was no difference in shock rates, but the conservative group had a trend toward fewer dialysis requirements (10% vs. 14%, p=0.06). Conclusion: The trial indicated that a conservative fluid management strategy in ARDS patients can reduce ventilator dependence and ICU length of stay without worsening shock or end-organ function. It underscores the benefit of managing fluid conservatively to protect lung function, even though it didn’t significantly reduce mortality. Overall, the FACT trial supports the practice of conservative fluid management in ARDS, advocating that “dry lungs are happy lungs” for improving patient outcomes.

Today, we’re going to be talking about pre-oxygenation methods for endotracheal intubation and the PREOXI Trial which is hot off the presses in the New England Journal of Medicine in June of 2024. This trial has potentially widespread, practice changing results and we’re lucky enough to be joined by two of the authors to discuss.     Meet Our Guests Dr. Kevin Gibbs is an Associate Professor of Medicine at Wake Forest University School of Medicine. He obtained his MD at George Washington University School of Medicine, and completed his residency and fellowship training at Johns Hopkins. He is an active researcher in critical care, ARDS, mechanical ventilation, and pragmatic trial design. Dr. Jon Casey is an Assistant Professor of Medicine for the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University Medical Center. He obtained his MD from the University of Louisville School of Medicine, and completed his residency training at Brigham and Women’s Hospital before going to Vanderbilt for fellowship training. He is a physician scientist and also has his Masters of Science in Clinical Investigation. His research is focused on comparative effectiveness of ICU treatments and he also has a focus on pragmatic trials. He is supported with NIH funding and is active in the American Thoracic Society Critical Care Assembly. Summarized Key Points Significance of the Problem: Tracheal intubation in emergency and ICU settings is common, with significant risks such as hypoxemia (10-20% incidence) and cardiac arrest (2% incidence) associated with the procedure. This makes effective pre-oxygenation crucial.Methods of Pre-oxygenation: Common methods include face mask oxygen (e.g., non-rebreather, bag-mask devices) and more advanced techniques like non-invasive ventilation (used in about 15% of cases globally). Each method has pros (e.g., simplicity, no risk of aspiration for face masks; 100% oxygen delivery, positive pressure for non-invasive ventilation) and cons (e.g., potential for gastric insufflation with non-invasive ventilation).Study Design: The study discussed in the podcast is a pragmatic trial aiming to optimize pre-oxygenation strategies to prevent peri-intubation hypoxemia. Eligibility criteria were broad, encompassing most patients undergoing tracheal intubation in the ED or ICU, with exclusions mainly for safety reasons.Primary Outcome: The primary outcome of the trial was hypoxemia, defined as oxygen saturation < 85%. This threshold was chosen because it signifies a critical point on the oxygen dissociation curve, where patients are at higher risk of further desaturation and adverse outcomes.Secondary Outcomes: Secondary exploratory outcomes included more severe levels of hypoxemia (oxygen saturation < 80% and < 70%), aiming to capture varying degrees of oxygenation failure during intubation. Rates of cardiac arrest during intubation were an additional outcome.Intervention Comparison:The trial compared two methods of pre-oxygenation: non-invasive ventilation (NIV) and oxygen mask (face mask)Both methods aimed to provide at least three minutes of pre-oxygenation before intubation.NIV group specifics: Expiratory pressure of 5 cm H2O, Inspiratory pressure of 10 cm H2O, respiratory rate of 10 breaths per minute, and 100% oxygen deliveryOxygen mask group specifics: Non-rebreather or bag mask device with at least 15 liters per minute oxygen flow.Nasal cannulas and HFNC could be used in both groups.Logistics and Equipment Use:The trial allowed flexibility in using available equipment (invasive ventilator capable of NIPPV vs. dedicated BiPAP machine).Sites were encouraged to use the same ventilator for both pre-oxygenation and subsequent ventilation to streamline workflow and reduce logistical challenges.Primary and Secondary Outcomes:Results showed a significant reduction in hypoxemia incidents in the NIV group compared to the oxygen mask group.There was also a reduction in severe hypoxemia and a notable decrease in cardiac arrest incidents in the NIV group.Aspiration Safety:There was no statistical difference in aspiration-related outcomes between the NIV and oxygen mask groups, indicating that NIV did not increase the risk of aspiration.Conclusions:The trial concluded that NIV for pre-oxygenation significantly reduced the incidence of hypoxemia and possibly cardiac arrest during tracheal intubation.It also dispelled concerns about increased aspiration risk with NIPPV as pre-oxygenation, suggesting it can be safely used in clinical practice. Reference Gibbs KW, Semler MW, Driver BE, Seitz KP, Stempek SB, Taylor C, Resnick-Ault D, White HD, Gandotra S, Doerschug KC, Mohamed A, Prekker ME, Khan A, Gaillard JP, Andrea L, Aggarwal NR, Brainard JC, Barnett LH, Halliday SJ, Blinder V, Dagan A, Whitson MR, Schauer SG, Walker JE Jr, Barker AB, Palakshappa JA, Muhs A, Wozniak JM, Kramer PJ, Withers C, Ghamande SA, Russell DW, Schwartz A, Moskowitz A, Hansen SJ, Allada G, Goranson JK, Fein DG, Sottile PD, Kelly N, Alwood SM, Long MT, Malhotra R, Shapiro NI, Page DB, Long BJ, Thomas CB, Trent SA, Janz DR, Rice TW, Self WH, Bebarta VS, Lloyd BD, Rhoads J, Womack K, Imhoff B, Ginde AA, Casey JD; PREOXI Investigators and the Pragmatic Critical Care Research Group. Noninvasive Ventilation for Preoxygenation during Emergency Intubation. N Engl J Med. 2024 Jun 20;390(23):2165-2177. doi: 10.1056/NEJMoa2313680. Epub 2024 Jun 13. PMID: 38869091.

This episode is launching our 2024 Rapid Fire Journal Club summer series on ARDS! This summer we will be talking about landmark ARDS trials that have defined the literature and shaped patient care. Journal clubs often focus on new trials, and so learners may have a less thorough understanding of the baseline literature that defines many of our ICU practices. The goal of this series is to provide a quick, but in-depth look at these papers so that learners understand the modern landscape of ARDS. Today, we’re kicking this initiative off by looking at the ARMA or ARDSNet Trial published in the NEJM in 2000. Enjoy! Article and Reference We’re talking about the ARMA trial today which examined “Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome.” Reference: Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801. PMID: 10793162. Infographic Correction: We mention a step-wise titration of tidal volume in the control group to achieve Pplats of 45-50. To clarify, there was no adjustment of Vt in the traditional Vt group unless Pplat > 50. If Vt had been decreased in the traditional Vt group because Pplat was > 50, it would not be subsequently increased back to 12 unless Pplat < 45 (to avoid a cycle of corrections and re-adjustments). Similarly in the lower Vt group, there was no adjustment (“titration”) of Vt unless Pplat > 30, and there was a similar protocol in place not to increase the Vt again unless the Pplat was < 25.

Today we’re back with another stop on our Fellows’ Case Files journey and making our way to the University of Rochester. Tune in to hear about this fascinating case and learn some key teaching points along the way. Meet Our Guests Dr. Shiv Patel completed his IM residency and a Chief year at the California Pacific Medical Center- Van Ness Campus and is currently a second-year PCCM fellow at the University of Rochester. Dr. Mary Anne Morgan is an Associate Professor of Medicine and the Fellowship Program Director for the PCCM Fellowship at the University of Rochester. Her clinical interests range from the care of critically ill patients in the ICU to the diagnosis and management of rare lung disease in her role as Director of the University of Rochester LAM Clinic. She loves unwrapping clinical reasoning with trainees, exploring issues around communication and teamwork in the ICU, and is excited about curriculum revitalization in the growing URMC PCCM fellowship program. Case Presentation  A 75 y.o. female with a history of Hypertension, Hyperlipidemia, and Type 2 Diabetes presented for evaluation of hypoglycemia and generalized fatigue. She had felt poorly for about a week with symptoms of back pain, generalized weakness, and dyspnea, all of which acutely worsened on the day of presentation.  She was found to be hypoglycemic with a blood glucose level in the to 40’s. Initial vital signs included a heart rate of 56, blood pressure of 70/40, respiratory rate of 30, and temperature of 28.5 degrees Celsius. Key Learning Points Lactic Acidosis: Type A, Type B and Type D Type A: Typically secondary to conditions that impair oxygen delivery (respiratory failure, PE) to tissues or decrease tissue perfusion (severe anemia, shock). Patients typically present with hypotension, tachycardia, tachypnea, altered mental status, and signs of organ dysfunction. Type B: Typically secondary to conditions that directly affect cellular metabolism or lactate clearance and characterized by the presence of hyperlactatemia without evidence of tissue hypoperfusion or hypoxia. Conditions associated include liver dysfunction (e.g., liver failure, cirrhosis), malignancies (especially hematological malignancies), medications/toxins (e.g., metformin, cyanide poisoning), inborn errors of metabolism, and mitochondrial disorders. Type D: Less common presentation and can be seen in patients with short gut syndrome. References 1.Blough B, Moreland A, Mora A Jr. Metformin-induced lactic acidosis with emphasis on the anion gap. Proc (Bayl Univ Med Cent). 2015 Jan;28(1):31-3. doi: 10.1080/08998280.2015.11929178. PMID: 25552792; PMCID: PMC4264704. 2.Callelo et al. Extracorporeal Treatment for Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workgroup. DOI: 10.1097/CCM.0000000000001002 3.Friesecke, S., Abel, P., Roser, M. et al. Outcome of severe lactic acidosis associated with metformin accumulation. Crit Care 14, R226 (2010). https://doi.org/10.1186/cc9376 4.Madias NE. Lactic acidosis. Kidney Int. 1986 Mar;29(3):752-74. doi: 10.1038/ki.1986.62. PMID: 3702227. 5. Stiller RH, Luks AM, Çoruh B. All That Raises Lactate Is Not Sepsis. ATS Sch. 2023 Jun 12;4(3):385-386. doi: 10.34197/ats-scholar.2023-0032OT.

We’re back with our Rapid Fire Journal Club, and talking about the NEJM 2023 STELLAR Trial of Sotatercept in Pulmonary Arterial Hypertension. This is a landmark trial that is actively changing the face of PAH treatment today. Listen to hear the details of the trial and how its findings can be utilized to help patients. Article and Reference We’re looking at the STELLAR Trial today which is a Phase 3 trial of Sotatercept in Pulmonary Arterial Hypertension. Reference: 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. Infographic

We have had a number of episodes on Acute Respiratory Distress Syndrome or ARDS. These episodes have ranged from how to titrate PEEP, subphenotypes in ARDS, and the future of ARDS research. Today, we are talking about how we all think about and define ARDS, and work that has highlighted a newer global definition of ARDS.  Meet our Guests Dr. Elisabeth Riviello is an Assistant Professor of Medicine at Harvard Medical School, and a PCCM physician at Beth Israeal Deconess Medical Center. She is also an Affiliate of the HMS Department of Global Health and Social Medicine and an honorary Associate Professor of Emergency Medicine and Critical Care at the University of Rwanda. She is passionate about improving critical care delivery in resource limited settings and has served on Committees for the World Health Organization. She is the Principal Investigator of BREATHE or the (Building Respiratory Support in East Africa Through High flow versus standard flow oxygen Evaluation); a RCT looking at HFNC in five sites in Kenya, Malawi, and Rwanda. Dr. Theogen Twagirumugabe is an Anesthesiologist and Intensivist at the College of Medicine and Health Sciences, and a Professor at the University of Rwanda. In addition to clinical work, he has his PhD in Medical Sciences. He is a widely succesful researcher with over 70 publications in critical care and anesthesia delivery and is also a lead investigator in the BREATHE initiative. References Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, Calfee CS, Combes A, Daniel BM, Ferguson ND, Gong MN, Gotts JE, Herridge MS, Laffey JG, Liu KD, Machado FR, Martin TR, McAuley DF, Mercat A, Moss M, Mularski RA, Pesenti A, Qiu H, Ramakrishnan N, Ranieri VM, Riviello ED, Rubin E, Slutsky AS, Thompson BT, Twagirumugabe T, Ware LB, Wick KD. A New Global Definition of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2024 Jan 1;209(1):37-47. doi: 10.1164/rccm.202303-0558WS. PMID: 37487152; PMCID: PMC10870872. Riviello ED, Buregeya E, Twagirumugabe T. Diagnosing acute respiratory distress syndrome in resource limited settings: the Kigali modification of the Berlin definition. Curr Opin Crit Care. 2017 Feb;23(1):18-23. doi: 10.1097/MCC.0000000000000372. PMID: 27875408. ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. PMID: 22797452.