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

24. Fellows’ Case Files: Baylor College of Medicine

Welcome to another episode in our Pulm PEEPs Fellows’ Case Files series! 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. Today we’re headed to Baylor College of Medicine to hear about a fascinating case. Tune in, let us know what you think on Twitter, and let us know if you have a great case to share!

Meet Our Guests

Benjamin Moss completed his internal medicine residency training at Baylor College of Medicine in Houston, Texas, and is currently a senior pulmonary and critical care fellow there.

Philip Alapat is an Assistant Professor of Medicine and the Program Director of the Pulmonary and Critical Care Fellowship at Baylor. He completed his residency and fellowship training all at Baylor.

Patient Presentation

A 60s-year-old man with seropositive RA on Rituximab presents with dyspnea and cough, and overall “not feeling well.”  For the past week, he has had malaise, body aches, and subjective fever. For the past 3 days, he has had acutely worsening dyspnea that is worse with exertion, but present at rest and a cough with scant sputum production. He had been on Methotrexate previously but within the last year developed pancytopenia and MTX was stopped and he was switched to adalimumab/Humira. His pancytopenias did not resolve, and he was ultimately diagnosed with Felty syndrome (a triad of RA, neutropenia, and splenomegaly) and switched to rituximab every 6 months with his last dose being 4 months ago. During the last week, he tried taking prednisone 10 mg a day but his symptoms did not improve.

X-ray on presentation (L) X-ray 8 months ago (R)

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.

Image Source: Reference 1: https://doi.org/10.1007/s00134-019-05906-5

References and Further Reading

  1. Azoulay E, Russell L, Van de Louw A, et al. Diagnosis of severe respiratory infections in immunocompromised patients. Intensive Care Med. 2020;46(2):298-314. doi:10.1007/s00134-019-05906-5
  2. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12):e405-e421. doi:10.1016/S1473-3099(19)30312-3
  3. Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis. 2012;54 Suppl 1:S16-22. doi:10.1093/cid/cir865

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

21. Post Intensive Care Syndrome (PICS)

Today on Pulm PEEPs, we are joined by two pioneers in the field of post-intensive care outcomes and delirium research. Drs. Dale Needham and Wes Ely talk to us all about the Post Intensive Care Syndrome (PICS) and cover everything from how it was first recognized, to the impact it has, and, most importantly, what we can do to prevent it. This is a huge topic in the field of critical care and we’re thrilled to be delving into it with such knowledgeable guides.

Meet Our Guests

Wes Ely is the Grant W. Liddle Chair in Medicine and a Professor of Medicine at Vanderbilt University Medical Center. He is also the Associate Director of Aging Research at the VA Tennessee Valley Geriatric Research and Education Clinical Center and the co-director of the Critical, Illness, Brain Dysfunction and Survivorship Center. He has published 100s of manuscripts on critical illness survivorship and delirium. He also published a book called “Every Deep-Drawn Breath” about his and his patients’ experiences in the ICU and about the ramifications of critical illness. All net proceeds for the book are going to the CIBS Center Endowment for Survivorship

Dale Needham is a Professor of Medicine at Johns Hopkins, where he is also the Medical Director of the Critical Care Physical Medicine and Rehabilitation Program and the Director of the Outcomes After Critical Illness and Surgery Group. He is the author of 100s of publications focusing on post-ICU outcomes and has received numerous research grants from the NIH and other organizations.

Key Learning Points

Visit our website www.pulmpeeps.com to see the key learning points from this episode summarized in two infographics.

References and links for further reading

  1. Devlin JW, Skrobik Y, Gélinas C, et al. Executive Summary: Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Critical Care Medicine. 2018;46(9):1532-1548. doi:10.1097/CCM.0000000000003259
  2. Ely EW. The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families. Crit Care Med. 2017;45(2):321-330. doi:10.1097/CCM.0000000000002175
  3. Mikkelsen ME, Still M, Anderson BJ, et al. Society of Critical Care Medicine’s International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness. Crit Care Med. 2020;48(11):1670-1679. doi:10.1097/CCM.0000000000004586
  4. Needham DM, Sepulveda KA, Dinglas VD, et al. Core Outcome Measures for Clinical Research in Acute Respiratory Failure Survivors. An International Modified Delphi Consensus Study. Am J Respir Crit Care Med. 2017;196(9):1122-1130. doi:10.1164/rccm.201702-0372OC
  5. Needham DM, Wozniak AW, Hough CL, et al. Risk Factors for Physical Impairment after Acute Lung Injury in a National, Multicenter Study. Am J Respir Crit Care Med. 2014;189(10):1214-1224. doi:10.1164/rccm.201401-0158OC
  6. Semler MW, Bernard GR, Aaron SD, et al. Identifying Clinical Research Priorities in Adult Pulmonary and Critical Care. NHLBI Working Group Report. Am J Respir Crit Care Med. 2020;202(4):511-523. doi:10.1164/rccm.201908-1595WS
  7. Spruit MA, Holland AE, Singh SJ, Tonia T, Wilson KC, Troosters T. COVID-19: Interim Guidance on Rehabilitation in the Hospital and Post-Hospital Phase from a European Respiratory Society and American Thoracic Society-coordinated International Task Force. Eur Respir J. Published online August 13, 2020:2002197. doi:10.1183/13993003.02197-2020
  8. Turnbull AE, Sepulveda KA, Dinglas VD, Chessare CM, Bingham CO, Needham DM. Core Domains for Clinical Research in Acute Respiratory Failure Survivors: An International Modified Delphi Consensus Study. Crit Care Med. 2017;45(6):1001-1010. doi:10.1097/CCM.0000000000002435
  9. Ward DS, Absalom AR, Aitken LM, et al. Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations From Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III. Crit Care Med. 2021;49(10):1684-1693. doi:10.1097/CCM.0000000000005049
  10. Ozga D, Krupa S, Witt P, Mędrzycka-Dąbrowska W. Nursing Interventions to Prevent Delirium in Critically Ill Patients in the Intensive Care Unit during the COVID19 Pandemic—Narrative Overview. Healthcare. 2020;8:578. doi:10.3390/healthcare8040578

20. Top Consults: Pulmonary Hypertension Diagnosis

This week on Pulm PEEPs, we are continuing our Top Consults series with a discussion on the work-up and diagnosis of Pulmonary Hypertension. See our prior Radiology Rounds on signs of PAH on CT scan, and listen to our follow-up episode on right heart catheterizations for some background before this episode… or dive right in! We’ll cover everything from history and physical, to recent guideline changes in the definition of PH, and much, much more!

Meet Our Guests

Erika Berman Rosenzweig is a Professor of Pediatrics and the Director of the Pulmonary Hypertension Center and CTEPH Program at Columbia University Medical Center / New-York Presbyterian Hospital. She is an active member of the Pulmonary Hypertension Association, was the Editor-in-Chief of Advances in Pulmonary Hypertension and is on the Scientific Board of the World Symposium on PH.

Catherine Simpson is an Assistant Professor of Medicine at Johns Hopkins Hospital and is one of the faculty members in our Pulmonary Hypertension group. Her clinical and research areas of expertise are in pulmonary vascular disease and right heart function. Her research is focused on novel biomarker discovery and metabolomics in pulmonary vascular disease.

Cyrus Kholdani is an Instructor in Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School. He is also the director of the Pulmonary Hypertension Program at BIDMC, and is actively involved in clinical care and clinical research in a variety of pulmonary vascular disease domains.

Consult Patient

Ms. Pamela Harris (PH) is a 47-year-old woman with PMH of migraines, obesity s/p gastric sleeve (BMI now 33), and a history of remote DVT in her 20s while on OCP s/p 6 months of AC who is referred to pulmonary hypertension clinic for evaluation of dyspnea on exertion. She has actually had dyspnea for some time and previously it has been attributed to her weight. Based on this, she pursued a gastric sleeve and has lost 55 pounds, but continues to have shortness of breath. She has no cough, and does not get dyspnea at rest, but notes that after 1 flight of stairs, or 2-3 blocks on flat ground she has shortness of breath. She saw her PCP and had basic labs, basic spirometry, and an echocardiogram. He did not note anything significant on examination in the notes.


The labs had no anemia, and normal renal and liver function. Her serum bicarbonate was 25 and there was no blood gas. Spirometry showed an FVC 82% predicted, FEV1 83% predicted, and FEV1/FVC was 99% predicted. The echocardiogram had normal LVEF, mild LVH, normal RV size and function qualitatively. There was mild TR with tricuspid valve peak regurgitant velocity of 3.4 m/sec. The estimated PASP + RA pressure (based on normal IVC diameter 2.1 cm) was 46 mmHg.

RHC: Systemic BPs 140s/90s, with O2 saturations 97-98% on RA throughout. RA mean pressure was 9, RV was 48 with an RVEDP of 17, PA was 48/27 with mean of 34, and PCWP mean was 11. CO/CI by Fick was 5.56 / 2.42, and by thermo was similar, 5.8 / 2.52. Her PA sat was 62%, and PVR was 3.97 WU.

Key Learning Points

History

  • Understand the constellation of symptoms and the functional limitation
    • The goal is to assign a WHO functional class by the end of the visit
  • Evaluate the time course and evolution of the symptoms
  • Concerning symptoms that need to be addressed
    • Palpitations
    • Pre-syncope
    • Syncope
    • Chest pain
    • LE edema
  • Evaluate for risk factors to explain or contribute to pulmonary hypertension
    • Signs or symptoms of OSA
    • Signs or symptoms of auto-immune disease
      • Raynauds
      • Skin changes
    • Family history
      • Heritable lung disease
      • Clotting disorders
      • Auto-immune disease
    • Social history
      • Exposure history
      • Smoking

Physical Exam

  • Look for signs that confirm PH
    • Loud P2
      • Accentuated with elevated PVR
      • Can hear pretty early on. Could be one of the earliest findings
    • TR murmur – pansystolic murmur at RUSB
    • Diastolic murmur if severe pulmonary insufficiency
  • Look for signs of right heart failure
    • JVD
    • S4 gallop – later in course
    • RV heave – later in course
    • Peripheral edema
    • Pulsatile liver or hepatosplenomegaly
  • Look for signs of other secondary causes of PH
    • Mitral regurgitation or aortic stenosis murmur
    • Asymmetric lower extremity edema
    • Pulmonary edema
    • Skin findings concerning for auto-immune disease or liver disease
    • Arthritis

Work up for etiology of PH

  • CBC with diff – myeloproliferative and hemolytic anemia
  • CMP – renal function, liver function
  • Serologies – lupus, scleroderma, vasculitis – broad evaluation
  • HIV, hepatitis
  • Liver duplex if concerned
  • ECHO with bubble
  • Consider cardiac MRI
  • History of toxin and anorexigenic use
  • CT scan of the chest
  • PFTs including lung volumes and DLCO to evaluate for lung disease
  • Pulse oximetry at rest and with exercise
  • A sleep study or nocturnal oximetry
  • V/Q scan for all patients

References and links for further reading

  1. Bonno EL, Viray MC, Jackson GR, Houston BA, Tedford RJ. Modern Right Heart Catheterization: Beyond Simple Hemodynamics. Advances in Pulmonary Hypertension. 2020;19(1):6-15. doi:10.21693/1933-088X-19.1.6
  2. Augustine DX, Coates-Bradshaw LD, Willis J, et al. Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography. Echo Res Pract. 2018;5(3):G11-G24. doi:10.1530/ERP-17-0071
  3. Callan P, Clark AL. Right heart catheterisation: indications and interpretation. Heart. 2016;102(2):147-157. doi:10.1136/heartjnl-2015-307786
  4. Chokkalingam Mani B, Chaudhari SS. Right Heart Cardiac Catheterization. In: StatPearls. StatPearls Publishing; 2022. Accessed April 18, 2022. http://www.ncbi.nlm.nih.gov/books/NBK557404/
  5. D’Alto M, Dimopoulos K, Coghlan JG, Kovacs G, Rosenkranz S, Naeije R. Right Heart Catheterization for the Diagnosis of Pulmonary Hypertension: Controversies and Practical Issues. Heart Failure Clinics. 2018;14(3):467-477. doi:10.1016/j.hfc.2018.03.011
  6. Galiè N, McLaughlin VV, Rubin LJ, Simonneau G. An overview of the 6th World Symposium on Pulmonary Hypertension. European Respiratory Journal. 2019;53(1). doi:10.1183/13993003.02148-2018
  7. Rosenkranz S, Preston IR. Right heart catheterisation: best practice and pitfalls in pulmonary hypertension. European Respiratory Review. 2015;24(138):642-652. doi:10.1183/16000617.0062-2015

19. Severe COPD and Lung Volume Reduction

We are extremely excited for the third and final installment in our Pulm PEEPs and ATS Clinical Problems Assembly collaborative series on COPD. Today, we are joined by Drs. Jessica Bon, Michael Lester, and Niru Putcha to discuss severe COPD management and the role of lung volume reduction procedures. If you missed the first two parts of our series, make sure to check out episode 1 on COPD diagnosis and initial management, and episode 2 on COPD exacerbations.

Meet our Guests

Jessica Bon is an Associate Professor of Medicine at the University of Pittsburgh School of Medicine where she is also the Program Director for the Pulmonary and Critical Care Medicine Fellowship. Her research and clinical interests focus on lung disease progression in COPD and she manages patients with difficult-to-treat and severe COPD and evaluates patients for lung volume reduction surgery. Jessica was the chair of the ATS Clinical Problems Assembly Programming Committee from 2021 – 2022.

Michael Lester is an Assistant Professor of Medicine at Vanderbilt University Medical Center. Michael’s interests span both pulmonary and critical care medicine. He specializes in patients with advanced COPD and evaluation for bronchoscopic lung volume reduction surgery.

Niru Putcha is an Associate Professor of Medicine at Johns Hopkins School of Medicine and is an integral member and mentor in the Obstructive Lung Disease Group. Her research and clinical interests focus on the role of comorbidities on clinical outcomes in individuals with COPD. She also manages patients with difficult-to-treat and severe COPD and evaluates patients for lung volume reduction surgery. Niru is also the new chair of the ATS  Clinical Problems Assembly Programming Committee.

Key Learning Points

Patients with advanced COPD should also be considered for lung transplantation. We will have an episode on lung transplant coming up soon!

References

  1. Criner GJ, Sternberg AL. A Clinician’s Guide to the Use of Lung Volume Reduction Surgery. Proc Am Thorac Soc. 2008;5(4):461-467. doi:10.1513/pats.200709-151ET
  2. A Randomized Trial Comparing Lung-Volume–Reduction Surgery with Medical Therapy for Severe Emphysema. New England Journal of Medicine. 2003;348(21):2059-2073. doi:10.1056/NEJMoa030287
  3. Valipour A, Slebos DJ, Herth F, et al. Endobronchial Valve Therapy in Patients with Homogeneous Emphysema. Results from the IMPACT Study. Am J Respir Crit Care Med. 2016;194(9):1073-1082. doi:10.1164/rccm.201607-1383OC
  4. Sciurba FC, Ernst A, Herth FJF, et al. A Randomized Study of Endobronchial Valves for Advanced Emphysema. New England Journal of Medicine. 2010;363(13):1233-1244. doi:10.1056/NEJMoa0900928
  5. Klooster K, Slebos DJ. Endobronchial Valves for the Treatment of Advanced Emphysema. Chest. 2021;159(5):1833-1842. doi:10.1016/j.chest.2020.12.007
  6. Choi M, Lee WS, Lee M, et al. Effectiveness of bronchoscopic lung volume reduction using unilateral endobronchial valve: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015;10:703-710. doi:10.2147/COPD.S75314

18. A Case of Severe Weakness in the ICU

We are thrilled here @PulmPEEPS to have our first episode with one of our new Associate Editors Luke Hedrick, and our first nephrology consultant Jeff William. Luke will walk us through an interesting case presentation, and we will discuss an approach to severe weakness in our patient in the ICU.

Meet Our Guests

Jeff William is an Assistant Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, where he is also the Associate Director of the Nephrology Fellowship Program. He completed a Medical Education Research Fellowship at Harvard Medical School, and is very involved in residency, fellowship and medical student education.

Patient Presentation

We have a man in his 40s with a past medical history of asthma, hypertension, and acid reflux who was brought in by EMS with back pain and profound proximal lower extremity weakness. He reports mild weakness in his legs which started 2 days ago, but this morning his weakness acutely worsened to the point that he can’t lift his legs out of the bed. He also has some cramping pain in his thighs. He additionally has had mild shortness of breath and yesterday went to an urgent care where he was given steroids and swabbed for COVID (which was negative).

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

Although our patient’s etiology of severe hypokalemia was thought to be secondary to thiazide diuretic use, it is important to be familiar with hypokalemic periodic paralysis.

References

  1. Knochel JP, Schlein EM. On the mechanism of rhabdomyolysis in potassium depletion. J Clin Invest. 1972 Jul;51(7):1750-8. doi: 10.1172/JCI106976.
  2. Wang X, Han D, Li G. Electrocardiographic manifestations in severe hypokalemia. J Int Med Res. 2020 Jan;48(1):300060518811058. doi: 10.1177/0300060518811058.
  3. Venance SL, Cannon SC, Fialho D, Fontaine B, Hanna MG, Ptacek LJ, Tristani-Firouzi M, Tawil R, Griggs RC; CINCH investigators. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006 Jan;129(Pt 1):8-17. doi: 10.1093/brain/awh639.
  4. Lin SH, Lin YF, Halperin ML. Hypokalaemia and paralysis. QJM. 2001 Mar;94(3):133-9. doi: 10.1093/qjmed/94.3.133. 
  5. Lin SH, Lin YF, Chen DT, Chu P, Hsu CW, Halperin ML. Laboratory tests to determine the cause of hypokalemia and paralysis. Arch Intern Med. 2004 Jul 26;164(14):1561-6. doi: 10.1001/archinte.164.14.1561.

17. Top Consults: Pneumothorax

This week on Pulm PEEPs we are resuming our Top Consults series with a common pulmonary presentation that can range from incidental to life-threatening: pneumothorax. We will talk through three different cases and review assessments and common management strategies. Make sure to subscribe to our show wherever you listen to podcasts, rate and review us, and visit our website to catch up on all our old content.

Meet Our Guests

Christine Argento is an Associate Professor of Medicine at Johns Hopkins Hospital and specializes in Interventional Pulmonology.

Charlie Murphy received his medical degree from LSU School of Medicine in New Orleans and completed his internal medicine residency at the Montefiore-Einstein Internal Medicine Residency Program. He is currently a Pulmonary and Critical Care fellow at New York-Presbyterian Hospital / Columbia University Medical Center, where he is one of the chief fellows.

Consult Patients

Barry is a 26-year-old man who came to the emergency department with acute onset of shortness of breath. He is tachypneic to 26, saturating 88% on RA so he was put on NC and is now 95% at 4L, HR 120, BP 145/85. There is only limited history but he reports he has never had anything like this before. His CXR shows a pneumothorax 5cm from the apex.

Larry is a 22-year-old man with normal HR and BP, saturating 96% on RA and breathing 14 x a minute. He has a CXR that shows a small pneumothorax. He has no past medical history and has never had a pneumothorax before, but he is a 1 PPD smoker and smokes marijuana.

Carrie is a 54-year-old woman who has been admitted with a COPD exacerbation. She has a history of emphysema, is not on home oxygen, and came in 2 days ago with worsening dyspnea and increased productive cough. She has been being treated with nebulizers every 4 hours, azithromycin, steroids, and supplemental O2 at 2L NC/ minute and never required NIPPV. This morning she had a coughing spell and significant chest pain and a CXR shows a moderate-sized left-sided pneumothorax. She is on 10L NC now with tachypnea to 26, and HR 105 but stable blood pressure.

Key Learning Points

Management options for a persistent air leak

— Conservative management: continue chest tube to suction

— Heimlich valve – can discharge a patient with this valve if they are stable to water seal, but don’t tolerate clamping

— Blood patch – inject the patient’s own blood into the chest tube to try to heal any pleural defect

— Chemical pleurodesis – inject talc powder, doxycycline, or another substance through the chest tube to cause pleural irritation and closure of the pleural space

— Endobronchial valve – off-label use

— VATS – surgical pleurodesis, resection of blebs

References and links for further reading

  1. Baumann MH, Strange C, Heffner JE, et al. Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement. Chest. 2001;119(2):590-602. doi:10.1378/chest.119.2.590
  2. Bintcliffe OJ, Hallifax RJ, Edey A, et al. Spontaneous pneumothorax: time to rethink management? Lancet Respir Med. 2015;3(7):578-588. doi:10.1016/S2213-2600(15)00220-9
  3. Brown SGA, Ball EL, Perrin K, et al. Conservative versus Interventional Treatment for Spontaneous Pneumothorax. New England Journal of Medicine. 2020;382(5):405-415. doi:10.1056/NEJMoa1910775
  4. MacDuff A, Arnold A, Harvey J. Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(Suppl 2):ii18-ii31. doi:10.1136/thx.2010.136986
  5. Sahn SA, Heffner JE. Spontaneous pneumothorax. N Engl J Med. 2000;342(12):868-874. doi:10.1056/NEJM200003233421207
  6. Tschopp JM, Bintcliffe O, Astoul P, et al. ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax. Eur Respir J. 2015;46(2):321-335. doi:10.1183/09031936.00219214
  7. Zarogoulidis P, Kioumis I, Pitsiou G, et al. Pneumothorax: from definition to diagnosis and treatment. J Thorac Dis. 2014;6(Suppl 4):S372-S376. doi:10.3978/j.issn.2072-1439.2014.09.24

16. A Case of Hemoptysis and Hypertension

We are thrilled here at Pulm PEEPs to have our first episode with our new Associate Editor Tess Litchman. Tess will walk us through an interesting case presentation of hemoptysis and we’ll use the approach from our Top Consults episode on hemoptysis to come to a key pulmonary and critical care diagnosis.

Meet Our Guests

Tess Litchman is a second-year internal medicine resident at Beth Israel Deaconess Medical Center. She received her undergraduate degree from Wesleyan University in Middletown, CT where she studied neuroscience and internal relations. She attended medical school at the Yale School of Medicine in New Haven, CT. She is currently completing her internal medicine residency at BIDMC. She is interested in medical education and pulmonary and critical care medicine.

Patient Presentation

A young man in his 20s presented to the emergency department with one week of cough and small volume hemoptysis. He has been experiencing several episodes of hemoptysis per day during this time. He says he coughs up about 1/4 cup of blood with each episode. He also adds that for the past 2 weeks he also has noticed worsening nausea, vomiting, headaches, and fatigue. He saw his primary care doctor and he was diagnosed with new hypertension and started on clonidine 0.1 mg three times a day, and provided cough medication. However, his symptoms continued. Given the increasing frequency of the hemoptysis and worsening nausea, he presented 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

References and links for further reading

  1. Radchenko C, Alraiyes AH, Shojaee S. A systematic approach to the management of massive hemoptysis. J Thorac Dis. 2017;9(Suppl 10):S1069-S1086. doi:10.21037/jtd.2017.06.41
  2. Lara AR, Schwarz MI. Diffuse Alveolar Hemorrhage. CHEST. 2010;137(5):1164-1171. doi:10.1378/chest.08-2084
  3. Gallagher H, Kwan JTC, Jayne DRW. Pulmonary renal syndrome: A 4-year, single-center experience. American Journal of Kidney Diseases. 2002;39(1):42-47. doi:10.1053/ajkd.2002.29876
  4. Sanders JSF, Rutgers A, Stegeman CA, Kallenberg CGM. Pulmonary-Renal Syndrome with a Focus on Anti-GBM Disease. Semin Respir Crit Care Med. 2011;32(3):328-334. doi:10.1055/s-0031-1279829
  5. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med. 2003;348(25):2543-2556. doi:10.1056/NEJMra022296
  6. McAdoo SP, Pusey CD. Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol. 2017;12(7):1162-1172. doi:10.2215/CJN.01380217
  7. Maxwell AP, Nelson WE, Hill CM. Reversal of renal failure in nephritis associated with antibody to glomerular basement membrane. BMJ. 1988;297(6644):333-334. doi:10.1136/bmj.297.6644.333