35. The Future of ARDS Research Roundtable

We are extremely excited for another PulmPEEPs Roundtable table discussion today. We have spent multiple episodes talking about different aspects of ARDS and respiratory failure. Today, multiple expert guests return, as well as a new guest to the show, to discuss the future of ARDS research. This is a can’t miss discussion that is so jam-packed with pearls you’ll have to listen twice!

Meet Our Guests

Carolyn Calfee is a Professor of Medicine and Anesthesia at the University of California, San Francisco. She is a world-renowned ARDS researcher and has authored multiple landmark studies in the field. She previously joined us for a discussion on ARDS precision medicine and phenotypes.

Ewan Goligher is an Assistant Professor at the University of Toronto and University Health Network. He has published many practice-changing papers in ARDS. These have included prospective studies and some fantastic retrospective analyses that have fundamentally shaped our interpretation of trial results.  He previously came on the show discussing lung and diaphragm protection.

Sarina Sahetya is an Assistant Professor of Medicine at Johns Hopkins. She is a funded researcher in ARDS and respiratory physiology and has published multiple studies on lung protection and ARDS. She last helped us understand how to titrate PEEP in ARDS.

Matthew Semler is an Assistant Professor of Medicine and Biomedical Informatics at Vanderbilt University Medical Center, where he is also the Associate MICU Director and the co-director of the Inpatient Division of the Learning Healthcare System at Vanderbilt. Through his role as Chair of the Steering Committee for the Pragmatic Critical Care Research Group, he has helped lead more than two dozen randomized trials leading to multiple high-impact publications.

Radiology Rounds – 1/31/23

For today’s #RadiologyRounds we have a combined Radiology and Ventilator imaging rounds! You’re in the ICU caring for a young patient on a ventilator when you are called to the bedside for a desaturation.

You perform an inspiratory hold and see that the PIP, plateau, and difference between peak and plateau have all increased. On exam you hear bilateral mechanical breath sounds anteriorly. You order a CXR and the student asks a question about the waveforms

There are pressure deviations corresponding to the flow deviations.

There is no clear patient effort The fact that the PIP and plat have changed makes water in the tubing or cardiac oscillations less likely.

You think this is mucus, with a plug ball-valving in a bronchus

The CXR arrives and shows right lower lobe collapse.

A bedside bronchoscopy is performed with large mucus plugs suctioned out of the RLL and RML. Afterward, the patient’s oxygenation is improved, the flow deviations resolve, and the plateau pressure drops to 19

33. Lung and Diaphragm Protective Ventilation Roundtable

Today the PulmPEEPs are discussing Lung and Diaphragm Protective Ventilation with two experts in the field. We are joined by Dr. Jose Dianti and Dr. Ewan Goligher.

Meet Our Guests

Dr. Jose Dianti is a clinical and research fellow at the University of Toronto and University Health Network. He completed his residency in Critical Care and worked as a critical care attending previously at the Hospital Italiano in Buenos Aires, Argentina. He is particularly interested in ventilator induced lung injury and personalized ventilation strategies. Dr. Ewan Goligher is an Assistant Professor at the University of Toronto and University Health Network, and is a world renowned researcher in the mechanisms of ventilator induced lung and diaphragm injury.

32. VV-ECMO Roundtable

For the first Pulm PEEPs episode of 2023, we are starting off with a bang and a Roundtable discussion about venovenous extracorporeal membrane oxygenation (VV-ECMO). VV-ECMO has been increasing in use in the intensive care unit for patients with severe respiratory failure, especially during the COVID-19 pandemic. We are joined by experts in the field, Cara Agerstrand, Eddy Fan, and Nida Qadir, to discuss the basics of how ECMO works, physiologic goals, when to use ECMO for patients with ARDS, and much more. Let us know your thoughts and stay tuned for more great content in 2023.

Meet Our Guests

Cara Agerstrand is an Associate Professor of Medicine at Columbia University Irving Medical Center / NewYork-Presbyterian Hospital, where she is also the Director of the Medical ECMO Program. She is an international renown ECMO expert and is the current Conference Chair for the Extracorporeal Life Support Organization (or ELSO). Finally, she is a lauded educator and has received the American College of Chest Physicians Distinguished Educator Award.

Eddy Fan is an Associate Professor at the University of Toronto, and the University Health Network / Mount Sinai Hospital. He is also the Director of Critical Research and the Medical Director of the Extracorporeal Life Support Program. He has literally 100s of publications about ARDS, ECMO, and critical care, chairs the ELSO Research Committee, and spearheads multiple international collaborative studies.

Nida Qadir is an Associate Professor at the University of California Los Angeles and is an Associate Director of the MICU, as well as the co-director of the Post-ICU Recovery Clinic. Nida is also on the Critical Care Editorial Board for CHEST and is a highly regarded pulmonary and critical care educator.

Key Learning Points

VV- ECMO Basic Components and Core Physiology

Oxygenation Delivery on VV-ECMO

Carbon Dioxide Removal on VV-ECMO

Flows and Line Pressures on VV-ECMO

ECMO for ARDS

  • Should be considered after conventional therapies have failed (including ventilator optimization and proning)
  • Allows for ultra-lung protective ventilation
  • Lung rest means settings that minimize ventilator-induced lung injury
  • EOLIA Trial (see below) shows that ECMO can be delivered safely, and likely has a benefit in severe ARDS, although the magnitude of that benefit remains uncertain. A Bayesian re-analysis showed a high likelihood of benefit even if skeptical of ECMO

ECMO For Bridge to Lung Transplant

  • Allows for patients to maintain gas exchange while awaiting transplant
  • Ideally done with patient extubated
  • Can allow for patients to maintain nutrition and mobility while awaiting transplant

References and Further Reading

  1. Brodie D, Bacchetta M. Extracorporeal Membrane Oxygenation for ARDS in Adults. N Engl J Med. 2011;365(20):1905-1914. doi:10.1056/NEJMct1103720
  2. Munshi L, Brodie D, Fan E. Extracorporeal Support for Acute Respiratory Distress Syndrome in Adults. NEJM Evidence. 2022;1(10):EVIDra2200128. doi:10.1056/EVIDra2200128
  3. Combes A, Hajage D, Capellier G, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. New England Journal of Medicine. 2018;378(21):1965-1975. doi:10.1056/NEJMoa1800385
  4. Goligher EC, Tomlinson G, Hajage D, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome and Posterior Probability of Mortality Benefit in a Post Hoc Bayesian Analysis of a Randomized Clinical Trial. JAMA. 2018;320(21):2251-2259. doi:10.1001/jama.2018.14276
  5. Erdeneochir E, Strunina S. Analysis of blood flow in extracorporeal membrane oxygenation circuit. Published online 2017.
  6. Schmidt M, Pham T, Arcadipane A, et al. Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. An International Multicenter Prospective Cohort. Am J Respir Crit Care Med. 2019;200(8):1002-1012. doi:10.1164/rccm.201806-1094OC
  7. Tonna JE, Abrams D, Brodie D, et al. Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO Journal. 2021;67(6):601-610. doi:10.1097/MAT.0000000000001432
  8. Hayanga JWA, Hayanga HK, Holmes SD, et al. Mechanical ventilation and extracorporeal membrane oxygenation as a bridge to lung transplantation: Closing the gap. J Heart Lung Transplant. 2019;38(10):1104-1111. doi:10.1016/j.healun.2019.06.026

31. Last Night in the ICU

Today we have a Pulm PEEPs special episode! Dave and Kristina chat post-call about their respective nights in the ICU. Hear about clinical reasoning on the fly, some crucial learning points, insights on procedural troubleshooting, and about the value of end-of-life discussions. The post-call brain fog and jokes only add to the learning fun!

References and Further Reading

Stein PD, Yaekoub AY, Matta F, Kleerekoper M. Fat embolism syndrome. Am J Med Sci. 2008 Dec;336(6):472-7. doi: 10.1097/MAJ.0b013e318172f5d2. PMID: 19092320.

Kainoh T, Iriyama H, Komori A, Saitoh D, Naito T, Abe T. Risk Factors of Fat Embolism Syndrome After Trauma: A Nested Case-Control Study With the Use of a Nationwide Trauma Registry in Japan. Chest. 2021 Mar;159(3):1064-1071. doi: 10.1016/j.chest.2020.09.268. Epub 2020 Oct 13. PMID: 33058815.

Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest. 2010 May;137(5):1164-71. doi: 10.1378/chest.08-2084. PMID: 20442117.

30. Fellows’ Case Files: University of Mississippi Medical Center

We’re excited to be back with another episode in our Pulm PEEPs Fellows’ Case Files series! This is a particularly exciting case since it is our first episode where some intrepid fellows reached out to us with an interesting case they had encountered. If you have a great case, please let us know and you can follow in their footsteps! Pack your bags, and let’s head to Mississippi to learn about another great pulmonary and critical care case.

Meet our Guests

Meredith Sloan is a pulmonary and critical care fellow at the University of Mississippi. She completed her medical school at the Medical University of South Carolina College of Medicine, and her residency at the University of Mississippi.

Kevin Kinloch is a senior fellow at the University of Mississippi Medical Center where he also completed his internal medicine residency. He completed medical school at Meharry Medical College.

Jessie Harvey is an Associate professor of Medicine at the University of Mississippi and is the Pulmonary and Critical Care Program Director. She is also the Director of the MICU, and has been at MMC since medical school. She is a dedicated educator and leads the POCUS curriculum for IM residents and PCCM fellows

Patient Presentation

A 65-year-old man presented to the ED with worsening hemoptysis over the last several days after a recent lung biopsy. The patient is an active smoker with at least a 50-pack-year history, and he had been having a cough with small-volume hemoptysis. He ultimately had a chest CT that revealed a large LUL mass (10.3 x 6.4 cm). Given this suspicious mass, three days prior to his ED presentation, he was taken for bronchoscopy with BAL, transbronchial biopsies, endobronchial biopsy, EBUS guided TBNA of 11L, along with TBNA, brushing and radial EBUS TBNA of his left upper lobe mass.

Key Learning Points

**Spoilers Ahead** If you want to think through the case on your own we advise listening to the episode first before looking at these points.

Staging procedures for masses

  • Enough tissue so we can make a diagnosis and do molecular testing
  • Highest staging when getting your biopsy

POCUS for respiratory failure

  • Absence of lung slidings
    • Especially post procedure
  • The presence of a new pleural effusion after a procedure could indicate hemothorax
    • Hematocrit sign – an echogenic layering of material in an effusion
  • New B-lines, especially if prior there were only A-lines
    • Cardiogenic or non-cardiogenic pulmonary edema, alveolar hemorrhage, or infection
  • Diaphragmatic function
    • Excursion
    • Diaphragm thickness

References and Further Reading

1.Scorsetti M, Leo F, Trama A, D’Angelillo R, Serpico D, Maerelli M, Zucali P, Gatta G, Garassino MC. Thymoma and thymic carcinomas. Critical Reviews in Oncology/Hematology. 2016; 99:332-350.

2. Singh TD, Wijdicks EFM. Neuromuscular respiratory failure. Neurol Clin 2021; 39:333-353.

26. A Case of AMS, Renal Failure, and Hemolysis

This week on Pulm PEEPs, we have another great case episode. We’re switching up the format a bit, and instead of introducing our guests in the beginning, we’ll bring them in consultants as we need to. Luckily, we’re joined by Pulm PEEPs Associated Editor Luke Hedrick to walk us through the case. Let us know your thoughts and if you have any other pearls to add!

Meet Our Guests

Rakhi Naik an Associate Professor of Medicine at Johns Hopkins Hospital and the Associate Director for the Hematology / Oncology Fellowship program. She also has a Masters in Health Sciences from the Johns Hopkins Bloomberg School of Public Health. She has expertise in an array of non-malignant hematology disorders and focuses specifically on sickle cell in her research. She is also an outstanding and dedicated educator and serves as the Chair of the American Society of Hematology Hematology-Focused Training Program Consortium to develop innovative training pathways for non-malignant heme.

Patient Presentation

A 60-year-old woman with a past medical history of hypertension, diabetes, stage 4 chronic kidney disease, COPD, HFpEF, chronic pain on methadone, hyperparathyroidism s/p parathyroidectomy that was c/b hypothyroidism now on thyroid hormone replacement, and a recent admission for nonconvulsive status epilepticus is brought to an outside hospital by EMS with encephalopathy and shaking. 

When EMS gets her to the other hospital her GCS was 5, so she was intubated for airway protection and started on fentanyl and midazolam drips. Details of labs and imaging are scarce, but we know that she had a CT head that was normal, a CXR with a report of pulmonary edema, and labs with a Cr of 2.4, serum bicarbonate of 14, and a pH from a VBG of 7.1 with pCO2 of 38.

Key Learning Points

*Spoilers ahead* The infographic below highlighting key points gives away the diagnosis in this case so if you want to work through the case on your own, we recommend listening to the episode first.

References and further reading

  1. George JN. Thrombotic Thrombocytopenic Purpura. New England Journal of Medicine. 2006;354(18):1927-1935. doi:10.1056/NEJMcp053024
  2. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. doi:10.1182/blood-2016-10-709857
  3. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017;3(1):1-17. doi:10.1038/nrdp.2017.20
  4. Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. New England Journal of Medicine. 2019;380(4):335-346. doi:10.1056/NEJMoa1806311
  5. Sukumar S, Lämmle B, Cataland SR. Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. J Clin Med. 2021;10(3):536. doi:10.3390/jcm10030536

25. ARDS Precision Medicine & Phenotypes Roundtable

We’re very excited this week on Pulm PEEPs to be resuming our Roundtable series. We are joined by two outstanding critical care doctors to discuss precision medicine in the ICU, specifically ARDS phenotypes. This is a topic of increasing clinical and research interest, and personalized medicine in the ICU will certainly change the landscape of how care is delivered in the coming years and decades. We are honing in on ARDS today and how phenotyping can influence future research and clinical care.

Meet Our Guests

Carolyn Calfee is a Professor of Medicine and Anesthesia at the University of California, San Francisco. She is a leader in the field of ARDS research and a pioneer in the field of ARDS phenotyping research. She has received numerous NIH grants and has literally 100s of publications on ARDS and other topics. She is also a previous ATS CC Assembly chair, and in 2022 received the ATS Recognition Award for Scientific Accomplishments.

Annette Esper is an Associate Professor of Medicine at Emory University School of Medicine. She works clinically in critical care and is the Medical Director of the stepdown Intensive Care Unit at Grady Memorial Hospital. In addition to her clinical activities, Annette does both clinical and translational research in ARDS, and was the Assembly Chair for the ATS Critical Care Assembly from 2021 – 2022.

Key Learning Points

Berlin Criteria of ARDS:

— Acute symptoms developing within 7 days of a known insult

— Bilateral airspace opacites on chest imaging

— Hypoxemia not fully explained by cardiogenic pulmonary edema

— P:F ratio < 300 on a PEEP of 5

Heterogeneity in ARDS

— ARDS has a broad definition so it is comprised of people with a wide range of disease characteristics and severity

— There is heterogeneity in clinical characteristics, but also underlying biological drivers of disease

— Heterogeneity stymies research efforts to identify effective therapies in ARDS

Phenotyping in ARDS

— There are many ways of phenotyping for critical illness and ARDS

1. Etiology. Examples: COVID vs non-COVID, pulmonary vs non-pulmonary, bacterial vs viral

2. Physiologic phenotypes: Severity (Berlin criteria P:F ratio); Compliance, Ventilatory ratio

3. Biological phenotypes: Different underlying drivers of disease

— The motivation for phenotyping is to find treatment-responsive subgroups within the broader heterogeneous subgroups

— Phenotyping embodies more than risk factors, because it includes information about the host response, not just predictors of outcome

Biomarkers in ARDS

— There is probably a role for biomarkers in ARDS clinically and in research

> Prognostication

> Identify who will be responsive to specific therapies

> May not be one biomarker, will likely be a panel

— What is the perfect ARDS biomarker?

> Specific: identify a group of patients that are at risk, or respond to therapies differently

> Easily measurable at the bedside

> Reliable

> Reproducible

— Challengers in identifying useful biomarkers

> Heterogeneity of disease

> Real world applicability. For example, can you get IL-6 back in real-time? Can you apply it consistently when labs have different testing techniques and scales?

> Temporal stability – how do biomarkers change over the time course of ARDS?

— Biomarkers of interest

> Inflammatory markers (IL-6, IL-8, TNF)

> sRAGE – Soluble receptor for advanced glycation end products

> Highest levels on type 1 alveolar epithelial cells

> Seems to be a marker of alveolar epithelial injuries

> Meta-genomic sequencing of patients in a real-time environment

Latent class analysis

— Clustering technique that, agnostic to outcomes, looks for existing groups within the data

— Ideally, identifies biologically distinct phenotypes that may have different prognoses or response to therapy

Omics in ARDS

— Existing risk scores are quite limited, so using biological data to distinguish patients seems promising.

— Unbiased approach to identifying subgroups to identify patients that behave similarly biologically

— Omics is really thinking about endotyping patients and identifying the biological processes that are driving phenotypes

Hypo and hyperinflammatory phenotypes in ARDS

— Described by LCA incorporating demographics, clinical data, labs, vital signs, 6-8 plasma protein biomarkers

— Importantly, the groups were identified agnostically to outcomes.

— Distinguished by:

> Inflammatory biomarkers (IL-6, IL-8, TNF 1)

> Acidosis

> Shock, vasopressor requirement, and multi-system organ failure

— Consistently across 8 different data sets

— Both RCTs and observational cohorts

— Hyperinflammatory phenotype has dramatically worse clinically outcomes (higher mortality, fewer VFD)

— The different phenotypes respond differently to therapies retrospectively in RCTs

— The phenotypes did respond differently to PEEP, fluids conservative therapy, and simvastatin.

— This was not seen universally (rosuvastatin did not have differential treatment response)

— Note: We don’t really know that inflammation is at the heart of the pathogenesis of what distinguishes these two groups. The “hypoinflammatory” phenotype still has elevated levels of inflammatory biomarkers compared to controls.

What is next?

— This is all just subgroup analysis.

— These hypotheses still need to be tested prospectively

— Need to be able to easily identify the phenotypes quickly and easily

— Working on biomarker-based and non-biomarker-based clinical classifications

Key Quote:

Dr. Calfee “My takeaway point would be, there is no one best or one right way to phenotype these patients. I think there are numerous different approaches that we’re probably going to be using over the years. But I would say that what we want to focus on is what has the potential to change outcomes for our patients and to really identify individual patients or groups of patients that respond differently to therapies. And I think if we can keep that goal in mind and start testing some of these hypotheses prospectively we’re going to make progress.”

References and links for further reading

  1. Sinha P, Calfee CS. Phenotypes in ARDS: Moving Towards Precision Medicine. Curr Opin Crit Care. 2019;25(1):12-20. doi:10.1097/MCC.0000000000000571
  2. Calfee CS, Delucchi KL, Sinha P, et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018;6(9):691-698. doi:10.1016/S2213-2600(18)30177-2
  3. Matthay MA, Arabi YM, Siegel ER, et al. Phenotypes and personalized medicine in the acute respiratory distress syndrome. Intensive Care Med. 2020;46(12):2136-2152. doi:10.1007/s00134-020-06296-9
  4. Wilson JG, Calfee CS. ARDS Subphenotypes: Understanding a Heterogeneous Syndrome. Crit Care. 2020;24(1):102. doi:10.1186/s13054-020-2778-x
  5. Yang P, Esper AM, Martin GS. The Future of ARDS Biomarkers: Where Are the Gaps in Implementation of Precision Medicine? In: Vincent JL, ed. Annual Update in Intensive Care and Emergency Medicine 2020. Annual Update in Intensive Care and Emergency Medicine. Springer International Publishing; 2020:91-100. doi:10.1007/978-3-030-37323-8_7

23. Fellows’ Case Files: University of Washington

We’re very excited for the second episode in our Pulm PEEPs Fellows’ Case Files series! For a reminder, the purpose of this series is to highlight and amplify the incredible clinical work that is done by pulmonary and critical care fellows, share fascinating cases, and assemble a diverse network of pulmonary and critical care educators. This week, we’re visiting the Pacific Northwest and headed to the University of Washington to meet two passionate educators, and hear about an incredible teaching case.

Meet Our Guests

Robin Stiller is a third-year pulmonary and critical care fellow at the University of Washington. Robin completed internal medicine residency training at the University of Washington and her clinical and research interests include procedural education and curriculum development.

Başak Çoruh Associate Professor of Medicine at the University of Washington School of Medicine and is the Program Director for the Pulmonary and Critical Care Fellowship. She completed her fellowship and the Teaching Scholars Program at UW. Başak has received numerous teaching and mentoring awards throughout her career and has leadership roles with ATS, CHEST as well as the APCCMPD.

Patient Presentation

A 56-year-old woman with a history of alcohol use and depression presents after being found down at home by her boyfriend with an unknown downtime. She was found to be unresponsive and in the supine position. Her physical exam did not show any obvious trauma but the paramedics did note vomitus on her face. She received 1 L of crystalloids in the field and was intubated and brought to the ED for further management. A  bag of pill bottles was found and brought with her. Her home medications include amlodipine, baclofen, buspirone, and hydroxyzine.

Key Learning Points

**Spoilers Ahead** If you want to think through the case on your own we advise listening to the episode first before looking at the infographic below

References and Further Reading

  1. Boyer EW, Shannon M. Treatment of calcium-channel-blocker intoxication with insulin infusion. N Engl J Med. 2001;344(22):1721-1722. doi:10.1056/NEJM200105313442215
  2. Cole JB, Arens AM, Laes JR, Klein LR, Bangh SA, Olives TD. High dose insulin for beta-blocker and calcium channel-blocker poisoning. Am J Emerg Med. 2018;36(10):1817-1824. doi:10.1016/j.ajem.2018.02.004
  3. Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J Emerg Med. 1995;13(4):444-450. doi:10.1016/0735-6757(95)90137-X
  4. St-Onge M, Dubé PA, Gosselin S, et al. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol (Phila). 2014;52(9):926-944. doi:10.3109/15563650.2014.965827

22. Fellows’ Case Files: University of Maryland

This week we are absolutely thrilled to be launching a new series here at Pulm PEEPs. This is the first episode in our new Fellows’ Case Files series. The purpose of this series is to highlight the incredible clinical work that is done by pulmonary and critical care fellows everywhere, share fascinating cases from across the world, and assemble a diverse network of pulmonary and critical care educators. For each episode, we will visit a different institution, and be joined by a current fellow and the Pulmonary and Critical Care Fellowship Program Director. Our aim is to learn from them, amplify some incredible teaching points, and hear about their program. We hope you enjoy it, and if you have a case you want to bring on the series reach out to us on Twitter or at our email pulmpeeps@gmail.com.

Meet Our Guests

Fahid Alghanim is a senior pulmonary and critical care fellow at the University of Maryland. He attended medical school at the Lebanese American University Gilbert and Rose-Marie Chagoury School of Medicine and completed his internal medicine residency at Johns Hopkins Bayview. He has published on topics ranging from lung transplants to patient navigators in the ICU.

Dr. Van Holden is an Associate Professor of  Medicine at the University of Maryland School of Medicine and the Pulmonary and Critical Care Fellowship Program director. Clinically, she specializes in interventional pulmonology. She is also an accomplished educator and is very active with the American Thoracic Society. She helped write the 2021 Critical Care Core Curriculum and helped coordinate the 2022 Resident Boot Camp.

Patient Presentation

A 26-year-old man presents to his primary care doctor with 1.5 months of intermittent dyspnea, cough, chest tightness, and fatigue. His dyspnea was initially exertional, and he noticed he could do less at the gym. However, in the past 3-4 weeks it has progressed to being even with mild movement. His brother was recently diagnosed and treated for acute bronchitis so he thought this could be similar. In the office, he is noted to be tachypneic with an oxygen saturation of 83% breathing ambient air. A chest X-ray is obtained and he is sent urgently to the emergency department.

Key Learning Points

**Spoilers Ahead** If you want to think through the case on your own we advise listening to the episode first before looking at the infographics below

  1. Crazy Paving is a radiological term describing ground glass opacities with superimposed interlobular septal thickening. The differential diagnosis is broad and includes infectious, neoplastic, and autoimmune processes. It is not limited to just Pulmonary alveolar proteinosis (PAP) but is suggestive in an appropriate clinical setting.
  2. PAP is a disorder of surfactant production or clearance and its etiology is divided into three major subgroups. Primary or autoimmune; Secondary such as from toxic inhalations, hematological disorders, or medications; and Congenital
  3. PAP is diagnosed by positive Periodic acid-Schiff (PAS) staining of lipo-proteinaceous material in the distal bronchioles and alveoli on lung biopsy. The diagnosis can be made with PAS-positive BAL staining, but this has limited sensitivity and lung biopsy is necessary for the diagnosis in up to 30 – 35% of cases.
  4. It is important not to anchor on a diagnosis when a patient presents to you for re-evaluation even if seen by a prior expert. This was pivotal in this case!
  5. Please don’t put anything in your lung. Any toxic inhalation exposure could result in significant damage to lung parenchyma and morbidity as a result.

References and Further Reading

  1. Borie R, Danel C, Debray MP, et al. Pulmonary alveolar proteinosis. Eur Respir Rev. 2011;20(120):98-107. doi:10.1183/09059180.00001311
  2. Carey B, Trapnell BC. The molecular basis of pulmonary alveolar proteinosis. Clin Immunol. 2010;135(2):223-235. doi:10.1016/j.clim.2010.02.017
  3. Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med. 2008;177(7):752-762. doi:10.1164/rccm.200708-1271OC
  4. Kavuru MS, Malur A, Marshall I, et al. An open-label trial of rituximab therapy in pulmonary alveolar proteinosis. Eur Respir J. 2011;38(6):1361-1367. doi:10.1183/09031936.00197710
  5. Michaud G, Reddy C, Ernst A. Whole-lung lavage for pulmonary alveolar proteinosis. Chest. 2009;136(6):1678-1681. doi:10.1378/chest.09-2295
  6. Smith BB, Torres NE, Hyder JA, et al. Whole-lung Lavage and Pulmonary Alveolar Proteinosis: Review of Clinical and Patient-centered Outcomes. J Cardiothorac Vasc Anesth. 2019;33(9):2453-2461. doi:10.1053/j.jvca.2019.03.047
  7. Tazawa R, Ueda T, Abe M, et al. Inhaled GM-CSF for Pulmonary Alveolar Proteinosis. New England Journal of Medicine. 2019;381(10):923-932. doi:10.1056/NEJMoa1816216
  8. Tung AH, Grace J, O’Kane GM, Kumar K. Transbronchial lung biopsy (TBLB) in diagnosing pulmonary alveolar proteinosis (PAP): forgotten role in Australia? Respirology Case Reports. 2015;3(4):145-147. doi:10.1002/rcr2.129
  9. Werner AK, Koumans EH, Chatham-Stephens K, et al. Hospitalizations and Deaths Associated with EVALI. New England Journal of Medicine. 2020;382(17):1589-1598. doi:10.1056/NEJMoa1915314