109. Guidelines Series: GINA Guidelines – Special Considerations in Asthma Care

Posted on October 28, 2025 by Pulm PEEPs

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 themes

Built 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 asthma

Obesity 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 therapy

Consider 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 biologics

Don’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 taper

Targets while stepping down: “normal” lung function when feasible, minimal/no day or night symptoms, full activity, no exacerbations.

When patients don’t respond to biologics

Re-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 pearls

Use 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.

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108. Journal Club with BMJ Thorax – Bronchiectasis

Posted on October 7, 2025 by Pulm PEEPs

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

To submit a journal club article of your own to Thorax, you can contact Chris directly – christopher.turnbull@ouh.nhs.uk

To engage with Thorax, please use the social media channels (Twitter – @ThoraxBMJ; Facebook – Thorax.BMJ) and subscribe on your preferred platform, to get the latest episodes directly on your device each month.

Key Learning Points

Four recent papers (2 RCTs, 2 large cohorts) chosen to show both new therapeutics and real-world comorbidities/outcomes, pushing toward precision medicine.

1) ASPEN trial – brensocatib (DPP-1 inhibitor)

Design: Phase 3, ~1,700 pts, 35 countries, 52 weeks; stratified randomization by region.
Results: ↓ annualized exacerbation rate (~1.0 vs 1.3/yr; RR≈0.8), longer time to first exacerbation, ~10% absolute ↑ in “exacerbation-free” patients at 1 year, QoL improved, modest FEV1 decline difference (~40 mL/yr).
Take: First targeted therapy with consistent benefit; effect on lung function small but directionally supportive.
Gaps: Need long-term durability, adolescent data, and comparisons/positioning in pts with asthma/COPD overlap.

2) AIRLEAF (BI 1291583) – reversible cathepsin C inhibitor

Design: Phase 2, 4 arms (3 doses + placebo), model-based dose–response analysis to optimize dose selection.
Results: Overall dose–response signal; individual low-dose arms trended to fewer exacerbations but not statistically significant; skin events more common at higher doses.
Take: Promising class targeting neutrophil pathway, but needs Phase 3 before clinical use.

3) U.S. Bronchiectasis & NTM Registry – 5-year outcomes

Cohort: >2,600 CT-confirmed; ~59% with baseline NTM identified.
Results: 5-yr mortality ~12%; no mortality difference with vs without NTM; predictors = lower baseline FEV1, older age, male sex, prior hospitalization. FEV1 decline ~38 mL/yr. Baseline NTM group had fewer exacerbations (counterintuitive).
Interpretation cautions: Likely mix of colonization vs active disease; referral/management effects in specialized centers; registry strengths (size, real-world, longitudinal) vs pitfalls (confounding, data quality, causality).

4) Bronch-UK cohort – anxiety & depression

Cohort: 1,340 adults; HADS screening.
Prevalence: Anxiety ~33%, depression ~20%; many undiagnosed (≈26%/16%).
Impact: Worse QoL, more severe disease; depression ~1.8× higher hospitalization risk and shorter time to severe exacerbation.
Caveat: Association ≠ causation; sicker patients may have more mental health burden.

Practical takeaways for clinic

Consider brensocatib for appropriate non-CF bronchiectasis patients once accessible; frame benefits around fewer exacerbations and QoL, not big lung function gains.
Do not introduce cathepsin C inhibitors outside trials yet; discuss as pipeline only.
Risk stratify using FEV1, age, sex, and prior hospitalizations; expect ~40 mL/yr average FEV1 decline.
Screen mental health routinely (HADS, PHQ-9, GAD-7). Build multidisciplinary pathways; consider brief CBT-style supports embedded in bronchiectasis clinics, with targeted referrals.
Registry data ≠ RCTs: Use for counseling and service design, but avoid causal claims.

Research/implementation gaps highlighted

Long-term safety/efficacy and subgroup effects for brensocatib (adolescents, asthma/COPD overlap).
Phase 3 confirmation for cathepsin C inhibition and dose selection.
Granular NTM phenotyping (colonization vs disease) to reconcile paradoxical exacerbation signals.
Scalable mental-health interventions integrated into respiratory clinics; trials to test impact on exacerbations/hospitalizations.

Pro tip from the episode

When appraising trials, check the CONSORT diagram for generalizability and look for stratification methods in multinational RCTs; in phase 2 programs, expect model-based dose–response designs that trade breadth for power.

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107. Fellows’ Case Files: University of Kansas Medical Center KUMC

Posted on October 1, 2025 by Pulm PEEPs

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.

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Radiology Rounds – 9/24/25

Posted on September 24, 2025 by Pulm PEEPs

We’re back with another Pulm PEEPs Radiology Rounds!

That’s right! All of the findings are present

History and physical exam are essential. Here are a few can’t miss diagnoses when working up a young adult with bilateral hilar adenopathy.

Pathology is consistent with a non-caseating granuloma. What is the most likely diagnosis?

Imaging and pathology were consistent with sarcoidosis and after negative work-up for alternative causes. The patient will follow-up with outpatient pulmonary for sarcoidosis management. Don’t forget about the Sarcoid 1-2-3 sign!

106. Pulm PEEPs Pearls: ICI Pneumonitis

Posted on August 12, 2025 by Pulm PEEPs

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:
  1. Overactive T cells
  2. Autoantibody production
  3. 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

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105. ICU Acquired Weakness

Posted on July 29, 2025 by Pulm PEEPs

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 Presentation

ICU-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 weakness

CNS: 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-AW

Critical Illness Myopathy (CIM):

Muscle dysfunctionEarly onset (within 48 hrs)Sensation intactproximal > distal weakness

Critical Illness Polyneuropathy (CIP):

Nerve involvementDistal > proximal weakness, sensory deficits

Critical Illness Polyneuromyopathy (CIPNM): Combination of both

Diagnosis

Medical Research Council Score (MRC-SS):
- Score < 48: ICU-AW
- Score < 36: severe ICU-AW
Handgrip dynamometry: <11 kg (men), <7 kg (women)
Electrophysiology: EMG/NCS to distinguish CIM vs CIP
Muscle ultrasound: bedside monitoring
MRI/CT/Muscle biopsy: rarely used due to practical limitation

Risk Factors

Modifiable:

Hyper/hypoglycemia
Electrolyte derangement
Parenteral nutrition
Immobility
Medications (steroids, NM blockers, sedatives, aminoglycosides)

Non-modifiable:

Age, female sex, comorbidities
Severity of illness, prolonged ventilation
Sepsis, multi-organ failure

Management & Prevention

Prevention is key:
- Early treatment of sepsis and inflammation
- Glycemic control
- Early enteral nutrition
- Minimize sedation (A-F bundle)
- Early mobilization and physical therapy
NMES (neuromuscular electrical stimulation): emerging therapy, needs more evidence

Outcomes

Short-term: increased LOS, ventilation duration, mortality
Long-term: decreased function, discharge to rehab, prolonged recovery

Final Takeaways

Prevention 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.

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104. Pulm PEEPs on Core IM – Pleural Effusions

Posted on July 9, 2025 by Pulm PEEPs

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

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103. Fellows’ Case Files: University of Virginia

Posted on July 1, 2025 by Pulm PEEPs

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.

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102. Journal Club with BMJ Thorax – Sleep and Non-Invasive Ventilation

Posted on June 17, 2025 by Pulm PEEPs

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

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

To submit a journal club article of your own to Thorax, you can contact Chris directly – christopher.turnbull@ouh.nhs.uk

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101. RFJC – NAVIGATOR

Posted on June 3, 2025 by Pulm PEEPs

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.

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