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

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:

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.

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.

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.

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.

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.

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

Test Performance

Where It Fits in the Asthma Workup

The test belongs in a stepwise approach:

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

Medication Washout (to Avoid False Negatives)

Interpreting Results

Negative Test (PC20 > 16 mg/mL)

Positive Test (PC20 ≤ 8–16 mg/mL)

Safety and Risks

Five Pearls — Quick Recap

References and Further Reading

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

T-piece SBTs are useful when:

References and Further Reading

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

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.

HHT teaching point: HHT can cause PH in more than one way:

3) Functional class assessment

WHO Functional Class:

Practical bedside tip they give:

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):

ESC/ERS risk assessment variables (10 domains discussed):

They note: even if you don’t have everything, the calculator can still be useful with ≥3 variables.

REVEAL 2.0:

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:

Also emphasized:

6) Medication classes for the treatment of PAH

Nitric oxide–cGMP pathway

Endothelin receptor antagonists (ERAs)

Prostacyclin pathway

7) Sotatercept (post-guidelines)

They note sotatercept wasn’t in 2022 ESC/ERS but is now “a game changer” in practice:

8) How risk category maps to initial treatment intensity

General approach they outline:

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

Trial design essentials

Who was enrolled

Efficacy: what the primary endpoint showed

Important nuance: interaction with pirfenidone

Secondary and patient-centered outcomes were neutral

Safety and tolerability

How to interpret “modest FVC benefit” clinically

Practical takeaways for real-world use

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

2) What ACTs are trying to achieve clinically

3) The main ACT “families” and when to use them

Breathing-based techniques (device-free, flexible)

PEP / Oscillatory PEP (stents airways + “vibrates” mucus loose)

Mechanical/manual techniques (help when patient can’t self-clear well)

4) How to choose the “right” technique (the practical framework)

There is no one-size-fits-all. Match the tool to the patient:

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)

6) Special population pearls

7) The “real” bottom line

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

Why PREDMETH matters

Trial design (what to know)

Patient population (who this applies to)

Main findings (what happened)

Crossover and analysis nuance (important for interpretation)

Safety signals (what to remember clinically)

Limitations (why you shouldn’t over-read it)

Practice implications (the “so what”)