PulmPEEPs

Dr. Mark Creager, Professor of Medicine at Dartmouth Hitchcock and lead author of the 2026 multisociety pulmonary embolism guideline, walks through the new guideline framework. He explains the new A–E clinical categories and respiratory modifiers. The conversation covers updated risk assessment, diagnostic approaches including imaging and D-dimer use, role of echocardiography, anticoagulation choices, advanced therapies, and follow-up strategies.

They dig into the methacholine challenge: what it measures and why PC20 matters. They discuss test accuracy, real-world sensitivity and specificity. They explain where the test fits in a stepwise asthma workup. They cover technique tips like tidal breathing and medication washout. They review safety considerations, contraindications, and practical interpretation caveats.

A concise tour of spontaneous breathing trials and why they matter for extubation decisions. Short comparisons of T-piece, pressure support plus PEEP, and CPAP highlight how each changes work of breathing. A look at the evidence favoring pressure-supported trials for most patients. Practical scenarios when a T-piece still makes sense and tips on institutional variation and daily screening.

Discussion of how to stratify risk in pulmonary arterial hypertension and which tools guide prognosis. Conversation about setting treatment goals, measuring symptom burden, and timing for reassessment. Overview of major medication classes, mapping therapies to physiologic pathways and when to escalate care. Case-based walkthrough illustrates application of guidelines and risk calculators.

In this engaging discussion, Robert Wharton, a pulmonary and critical care fellow, and Nicole Ng, an Assistant Professor specialized in interstitial lung disease, dive into the FIBRONEER-IPF trial examining the new treatment, Nerandomilast, for idiopathic pulmonary fibrosis (IPF). They highlight the trial's design, enrollment criteria, and how it compares to previous studies. The duo debates the clinical implications of the trial's findings, particularly the modest FVC benefit, while addressing safety concerns and the need for better patient management strategies.

Dive into the essential role of airway clearance in non-CF bronchiectasis, where mucus retention creates a vicious cycle of infection and inflammation. Discover practical tips on various non-pharmacologic techniques designed to improve sputum clearance and enhance quality of life. Learn about the different families of airway clearance techniques, from breathing-focused methods to device-assisted options, and how to personalize these approaches based on patient needs and circumstances. Gain insights from the latest evidence to navigate treatment choices effectively!

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).

A deep dive into updated 2022 definitions and lowered diagnostic thresholds for pulmonary hypertension. Practical tips for when to suspect the condition and which noninvasive tests to use. Clear explanation of echocardiographic signs of right heart strain and how to interpret key right heart catheter numbers. Guidance on screening high-risk groups and the streamlined diagnostic pathway.

Dive into the intriguing world of methylene blue and its potential role in managing septic shock. The hosts unravel its mechanism, showing how it inhibits nitric oxide synthase to restore vascular tone. Discover the specific clinical scenarios where it shines, especially in vasodilatory shock. They discuss the evidence from meta-analyses, showing improved MAP and shorter vasopressor duration, though the mortality benefit remains murky. Plus, learn about practical dosing strategies and important safety considerations. It's a concise yet enlightening discussion!

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.