This week’s #RadiologyRounds and tutorial is authored by Huzaifah Salat, our newest PulmPEEPs contributor! See if you can figure out the case and check out our high-yield points at the end. Follow us on Twitter to answer live polls about the case.
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
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This week’s #RadiologyRounds is authored by Leon Mirson, one of our amazing Associate Editors. Follow us on Twitter to answer live polls about the case and future Radiology Rounds cases!
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.
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.
References and Further Reading
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Time for another #RadiologyRounds! This case is authored by PulmPEEPs associate editor @TessLitchman. Great teaching ahead!
Trick question (sorry)! All of these features are present.
A bronchoscopy was performed and the patient was diagnosed with PCP. Additional testing confirmed a new diagnosis of HIV.
This patient was treated with high-dose Bactrim and IV steroids, in addition to being started on ART.
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
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It is Tuesday and we have another Radiology Rounds we can’t wait to share with you. Follow along and see if you select the right answer as we go through different presentations of sarcoidosis and pick your answer! What stage is it?!
A middle-aged man presents to you after he was found to have hilar adenopathy on a routine chest x-ray.
A middle-age man presents with dyspnea on exertion, night sweats and weight loss. You see evidence of bilateral apical disease, and fibrosis with evidence of honeycombing on chest CT.
A young woman presents with dyspnea on exertion and was found to have hilar adenopathy with parenchymal disease.
An elderly man presents with dyspnea on exertion and was found to have nodular parenchymal disease without extensive lymphadenopathy.
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
References and Further Reading
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It is Tuesday and time for another #RadiologyRounds!! This is a patient who presented to the emergency department with symptoms of cough, dyspnea, malaise, and weight loss. A PA and lateral CXR was obtained.
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
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