89. Idiopathic Pulmonary Fibrosis Treatment: RFJC – INPULSIS

Our episode today is diving into a broader initiative to discuss the management of interstitial lung disease. In this episode we will be talking about the treatment of Idiopathic Pulmonary Fibrosis through the lens of a journal club discussion of the NEJM 2014 INPULSIS trial. Today’s episode is hosted by Pulm PEEPs Associate Editor Luke Hedrick.

Robert Wharton is a recurring guest on Pulm PEEPs as a part of our Rapid Fire Journal Club Series. He completed his internal medicine residency at Mt. Sinai in New York City, and is currently a first year pulmonary and critical care fellow at Johns Hopkins.

Dr. Nicole Ng is an Assistant Profess of Medicine at Mount Sinai Hospital, and is the Associate Director of the Interstitial Lung Disease Program for the Mount Sinai National Jewish Health Respiratory Institute.

Today the discussion of IPF treatment centers around the 2014 NEJM publication of the INPULSIS trials investigating the efficacy of Nintedanib for the treatment of IPF.

Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2071-82. doi: 10.1056/NEJMoa1402584. Epub 2014 May 18. Erratum in: N Engl J Med. 2015 Aug 20;373(8):782. doi: 10.1056/NEJMx150012. PMID: 24836310.

Infographic

Background and Challenges in ILD Treatment: Interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), had historically poor treatment outcomes, with numerous therapies showing either no benefit or even harm. Prior to 2014, effective treatments were extremely limited, and lung transplantation was the primary management option.

INPULSIS I and II Trials: These 2014 trials examined nintedanib, an antifibrotic drug initially tested for cancer, in patients with moderate IPF. The studies were well-structured, involving strict criteria to ensure accurate diagnoses and excluding younger patients or those with more advanced disease.

Nintedanib’s Mechanism and Design of the Trials: Nintedanib acts by blocking multiple tyrosine kinases that mediate fibrotic growth factors. Patients were monitored over a year, with primary endpoints focusing on forced vital capacity (FVC) decline—a common surrogate measure for disease progression in ILD trials due to its correlation with survival.

Outcomes: Both trials showed that nintedanib significantly reduced the rate of FVC decline compared to placebo, suggesting that it slowed disease progression. Secondary endpoints included reduced acute exacerbations (significant only in one trial) and minor improvements in quality of life, though these weren’t statistically or clinically significant.

Adverse Effects: Nintedanib’s side effects included gastrointestinal issues (diarrhea, nausea, vomiting) and, less commonly, liver enzyme elevations and cardiovascular events. While post-marketing data suggested some improvements in tolerability, clinicians still monitor for these side effects closely.

Application in Clinical Practice: The trials support nintedanib as an option for slowing IPF progression, though no cure or disease reversal is achieved. Clinicians weigh the choice between nintedanib and pirfenidone (another antifibrotic) based on each drug’s side effect profile and individual patient needs.

Future Directions: The trials paved the way for further research into multi-therapy approaches for ILD, targeting multiple disease pathways, similar to strategies in asthma or COPD. Upcoming therapies and trials aim to provide more targeted and effective options for IPF and other ILDs.

88. Fellows’ Case Files: NYU

We are joined today by two amazing educators from NYU for our latest Fellows’ Case Files Episode. Listen today as we go through a great case with some fantastic teaching points highlighted throughout the episode.

Dr. Jeremy Grossman completed his Medicine-Pediatrics residency at Stony Brook Medicine where he was also a Chief Resident. He is currently a second-year PCCM fellow at NYU.

Dr. Shari Brosnahan is an Assistant Professor of Medicine and one of the Assistant Program Directors for the NYU Langone’s Division of Pulmonary, Critical Care, and Sleep Medicine. Her clinical and research interests are focused on pulmonary embolism and thrombosis in critically ill patients.

An 80-year-old male presents with shortness of breath. At home, his oxygen saturation was 82% on room air, improving only to 86% on 4L nasal cannula. Over the past month, he has experienced worsening symptoms, including a dry cough, fatigue, and difficulty speaking or ambulating due to shortness of breath at rest. He denies recent fever, sputum production, chest pain, or lower extremity swelling and presents to the ED for further evaluation.

1.In any patient with a history of malignancy and hypoxia, clinicians should keep pulmonary tumor emboli (PTE) on the differential as early intervention may alter outcomes.

2.PTE contributes to hypoxia via mechanisms of mechanical obstruction of pulmonary arteries leading to shunting, VQ Mismatch, and in some cases pulmonary hypertension due to increased PVR.

3.A wedged aspirate can be used to diagnose PTE ante-mortem

87. Live from CHEST 2024 – Black Angels with Maria Smilios

Here at Pulm PEEPs we have always loved the CHEST Annual Meetings. We have enjoyed learning at them, reuniting with and meeting colleagues, and having conference specific episodes the past two years. This year, we had the opportunity to podcast live at CHEST 2024 and it was a real thrill! We talked to Maria Smilios about her wonderful book The Black Angels: The Untold Story of the Nurses Who Helped Cure Tuberculosis. . The book covers a range of fascinating topics including how treatments for tuberculosis were developed, the successes and plights of Black nurses working in this endeavor, an exploration of health care in New York City, and a discussion of Racism and civil rights in American healthcare.

We were also thrilled that Virginia Allen, the last surviving Black Angel is at the conference and her and her colleagues (posthumously) are receiving an honorary FCCP.

Maria Smiios is a native New Yorker but completed her master of arts in religion and literature right here in Boston. She completed her masters at Boston University, where she was a Luce scholar, and taught in the religion and writing program. Through her work, she found a love for history, medicine and women’s narratives. While working at Springer Publishing as a science book editor, she learned about the story of the Black Angels and was determined to tell their story. She spent years deeply engaged in the lives and stories of those who were closest to these remarkable women.

86. CHEST 2024 Preview

We are excited to be back with our colleagues from CHEST to be previewing the CHEST 2024 Annual Meeting. CHEST his year is in Boston, MA from October 5th to October 9th. Listen in to hear about some great new features at CHEST this year, some old favorites, and to learn how to optimize your conference experience. See you all in two weeks!

Sandhya Khurana is a  Professor of medicine at University of Rochester school of medicine and Director of the Mary Parkes Asthma Center. Her clinical and research interest is in asthma. She is the Vice-Program Chair for CHEST 2024 and will be the program Chair for CHEST 2025 next year in Chicago.

Gabe Bosslet is the Program Chair for CHEST this year. In addition he is a Professor of Clinical Medicine at Indiana University School of Medicine. He is also an Assistant Dean at IU, and the Director of Mentoring and Faculty Development for the Division Pulmonary, Critical Care, Allergy and Occupational Medicine.

Huzaifah Salat is a clinician educator who is currently working as a consultant pulmonologist and intensivist at Advocate Aurora Health in Wisconsin. He completed his Pulmonary and Critical Care Fellowship at the University of Oklahoma Health Sciences Center

85. Journal Club with BMJ Thorax – Airway Disease

We are extremely excited today to announce a new collaboration 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. We hope you enjoy!

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.

 Imran Howell is an Asthma Fellow at the Nuffield Department of Medicine, University of Oxford

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.

82. Fellows’ Case Files: UMass Chan

We have another great case in our Fellows’ Case Files coming today from UMass Chan. Listen in for a great discussion about a fascinating case with interesting physical exam and radiographic findings.

Dr. Jen Kodela completed her residency training at UMass Memorial Medical Center and is currently a third year PCCM fellow at UMass Chan.

Dr. Ariel McKenna completed her residency training at Maine Medical Center and is also currently a third year PCCM fellow at UMass Chan.

Dr. Will Wong is an Assistant Professor of Medicine and is the Program Director of the PCCM fellowship at UMass Chan

A 75 y/o F presenting with acute on chronic SOB, cough, L sided chest pain and rash. She has had ~7 months of progressive dyspnea, now a/w 2 months of productive cough, and several weeks of L sided chest pain and rash. She has been seen multiple times in the past two months for these sxs. During that time she received multiple antibiotic courses (urgent care, outpatient providers), including augmentin, azithromycin and levaquin, and asthma directed therapy (no steroids). Imaging throughout that time (CXRs, CTPE) show progression from a LLL infiltrate to bibasilar infiltrates. Despite these interventions, sxs continue to worsen. One month prior she was admitted to an OSH w/ continued worsening, vitals stable, exam nonfocal, mild leukocytosis but infectious w/u bland. Received broad spectrum abx. Bronch w/ BAL offers negative cultures, cytology, cell count w/ 66% neutrophils, 14% eosinophils. Discharged w/ dx of PNA on a 10 day course of levaquin and new exertional oxygen requirement of 2L. She then presents to Umass ~1 month later w/ continued progression of sxs

1. Formulate a differential diagnosis for non-resolving pneumonia

2. Evaluate the utility of transbronchial biopsy in the workup of undifferentiated ILD

3. Describe the clinical manifestations of antisynthetase syndrome and identify the differences in presentation associated with PL-12 positivity

1. Kuru T, Lynch JP 3rd. Nonresolving or slowly resolving pneumonia. Clin Chest Med. 1999 Sep;20(3):623-51. doi: 10.1016/s0272-5231(05)70241-0. PMID: 10516909.

2. Troy LK, Grainge C, Corte TJ, Williamson JP, Vallely MP, Cooper WA, Mahar A, Myers JL, Lai S, Mulyadi E, Torzillo PJ, Phillips MJ, Jo HE, Webster SE, Lin QT, Rhodes JE, Salamonsen M, Wrobel JP, Harris B, Don G, Wu PJC, Ng BJ, Oldmeadow C, Raghu G, Lau EMT; Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease alliance (COLDICE) Investigators. Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med. 2020 Feb;8(2):171-181. doi: 10.1016/S2213-2600(19)30342-X. Epub 2019 Sep 29. PMID: 31578168.

3. Hallowell RW, Danoff SK. Diagnosis and Management of Myositis-Associated Lung Disease. Chest. 2023 Jun;163(6):1476-1491. doi: 10.1016/j.chest.2023.01.031. Epub 2023 Feb 9. PMID: 36764512.

4. Hallowell RW, Paik JJ. Myositis-associated interstitial lung disease: a comprehensive approach to diagnosis and management. Clin Exp Rheumatol. 2022 Feb;40(2):373-383. doi: 10.55563/clinexprheumatol/brvl1v. Epub 2021 Mar 25. PMID: 33769263; PMCID: PMC8855729.

5. Marie I, Josse S, Decaux O, Dominique S, Diot E, Landron C, Roblot P, Jouneau S, Hatron PY, Tiev KP, Vittecoq O, Noel D, Mouthon L, Menard JF, Jouen F. Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev. 2012 Aug;11(10):739-45. doi: 10.1016/j.autrev.2012.01.006. Epub 2012 Feb 3. PMID: 22326685.

78. PREOXI Trial

Today, we’re going to be talking about pre-oxygenation methods for endotracheal intubation and the PREOXI Trial which is hot off the presses in the New England Journal of Medicine in June of 2024. This trial has potentially widespread, practice changing results and we’re lucky enough to be joined by two of the authors to discuss.

 

 

Dr. Kevin Gibbs is an Associate Professor of Medicine at Wake Forest University School of Medicine. He obtained his MD at George Washington University School of Medicine, and completed his residency and fellowship training at Johns Hopkins. He is an active researcher in critical care, ARDS, mechanical ventilation, and pragmatic trial design.

Dr. Jon Casey is an Assistant Professor of Medicine for the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University Medical Center. He obtained his MD from the University of Louisville School of Medicine, and completed his residency training at Brigham and Women’s Hospital before going to Vanderbilt for fellowship training. He is a physician scientist and also has his Masters of Science in Clinical Investigation. His research is focused on comparative effectiveness of ICU treatments and he also has a focus on pragmatic trials. He is supported with NIH funding and is active in the American Thoracic Society Critical Care Assembly.

Summarized Key Points


  • Significance of the Problem: Tracheal intubation in emergency and ICU settings is common, with significant risks such as hypoxemia (10-20% incidence) and cardiac arrest (2% incidence) associated with the procedure. This makes effective pre-oxygenation crucial.

  • Methods of Pre-oxygenation: Common methods include face mask oxygen (e.g., non-rebreather, bag-mask devices) and more advanced techniques like non-invasive ventilation (used in about 15% of cases globally). Each method has pros (e.g., simplicity, no risk of aspiration for face masks; 100% oxygen delivery, positive pressure for non-invasive ventilation) and cons (e.g., potential for gastric insufflation with non-invasive ventilation).

  • Study Design: The study discussed in the podcast is a pragmatic trial aiming to optimize pre-oxygenation strategies to prevent peri-intubation hypoxemia. Eligibility criteria were broad, encompassing most patients undergoing tracheal intubation in the ED or ICU, with exclusions mainly for safety reasons.

  • Primary Outcome: The primary outcome of the trial was hypoxemia, defined as oxygen saturation < 85%. This threshold was chosen because it signifies a critical point on the oxygen dissociation curve, where patients are at higher risk of further desaturation and adverse outcomes.

  • Secondary Outcomes: Secondary exploratory outcomes included more severe levels of hypoxemia (oxygen saturation < 80% and < 70%), aiming to capture varying degrees of oxygenation failure during intubation. Rates of cardiac arrest during intubation were an additional outcome.

  • Intervention Comparison:

    • The trial compared two methods of pre-oxygenation: non-invasive ventilation (NIV) and oxygen mask (face mask)

    • Both methods aimed to provide at least three minutes of pre-oxygenation before intubation.

    • NIV group specifics: Expiratory pressure of 5 cm H2O, Inspiratory pressure of 10 cm H2O, respiratory rate of 10 breaths per minute, and 100% oxygen delivery

    • Oxygen mask group specifics: Non-rebreather or bag mask device with at least 15 liters per minute oxygen flow.

    • Nasal cannulas and HFNC could be used in both groups.



  • Logistics and Equipment Use:

    • The trial allowed flexibility in using available equipment (invasive ventilator capable of NIPPV vs. dedicated BiPAP machine).

    • Sites were encouraged to use the same ventilator for both pre-oxygenation and subsequent ventilation to streamline workflow and reduce logistical challenges.



  • Primary and Secondary Outcomes:

    • Results showed a significant reduction in hypoxemia incidents in the NIV group compared to the oxygen mask group.

    • There was also a reduction in severe hypoxemia and a notable decrease in cardiac arrest incidents in the NIV group.



  • Aspiration Safety:

    • There was no statistical difference in aspiration-related outcomes between the NIV and oxygen mask groups, indicating that NIV did not increase the risk of aspiration.



  • Conclusions:

    • The trial concluded that NIV for pre-oxygenation significantly reduced the incidence of hypoxemia and possibly cardiac arrest during tracheal intubation.

    • It also dispelled concerns about increased aspiration risk with NIPPV as pre-oxygenation, suggesting it can be safely used in clinical practice.


Gibbs KW, Semler MW, Driver BE, Seitz KP, Stempek SB, Taylor C, Resnick-Ault D, White HD, Gandotra S, Doerschug KC, Mohamed A, Prekker ME, Khan A, Gaillard JP, Andrea L, Aggarwal NR, Brainard JC, Barnett LH, Halliday SJ, Blinder V, Dagan A, Whitson MR, Schauer SG, Walker JE Jr, Barker AB, Palakshappa JA, Muhs A, Wozniak JM, Kramer PJ, Withers C, Ghamande SA, Russell DW, Schwartz A, Moskowitz A, Hansen SJ, Allada G, Goranson JK, Fein DG, Sottile PD, Kelly N, Alwood SM, Long MT, Malhotra R, Shapiro NI, Page DB, Long BJ, Thomas CB, Trent SA, Janz DR, Rice TW, Self WH, Bebarta VS, Lloyd BD, Rhoads J, Womack K, Imhoff B, Ginde AA, Casey JD; PREOXI Investigators and the Pragmatic Critical Care Research Group. Noninvasive Ventilation for Preoxygenation during Emergency Intubation. N Engl J Med. 2024 Jun 20;390(23):2165-2177. doi: 10.1056/NEJMoa2313680. Epub 2024 Jun 13. PMID: 38869091.

76. Fellows’ Case Files: University of Rochester

Today we’re back with another stop on our Fellows’ Case Files journey and making our way to the University of Rochester. Tune in to hear about this fascinating case and learn some key teaching points along the way.

Dr. Shiv Patel completed his IM residency and a Chief year at the California Pacific Medical Center- Van Ness Campus and is currently a second-year PCCM fellow at the University of Rochester.

Dr. Mary Anne Morgan is an Associate Professor of Medicine and the Fellowship Program Director for the PCCM Fellowship at the University of Rochester. Her clinical interests range from the care of critically ill patients in the ICU to the diagnosis and management of rare lung disease in her role as Director of the University of Rochester LAM Clinic. She loves unwrapping clinical reasoning with trainees, exploring issues around communication and teamwork in the ICU, and is excited about curriculum revitalization in the growing URMC PCCM fellowship program.

 A 75 y.o. female with a history of Hypertension, Hyperlipidemia, and Type 2 Diabetes presented for evaluation of hypoglycemia and generalized fatigue. She had felt poorly for about a week with symptoms of back pain, generalized weakness, and dyspnea, all of which acutely worsened on the day of presentation. 

She was found to be hypoglycemic with a blood glucose level in the to 40’s. Initial vital signs included a heart rate of 56, blood pressure of 70/40, respiratory rate of 30, and temperature of 28.5 degrees Celsius.

Lactic Acidosis: Type A, Type B and Type D

Type A: Typically secondary to conditions that impair oxygen delivery (respiratory failure, PE) to tissues or decrease tissue perfusion (severe anemia, shock). Patients typically present with hypotension, tachycardia, tachypnea, altered mental status, and signs of organ dysfunction.


Type B: Typically secondary to conditions that directly affect cellular metabolism or lactate clearance and characterized by the presence of hyperlactatemia without evidence of tissue hypoperfusion or hypoxia. Conditions associated include liver dysfunction (e.g., liver failure, cirrhosis), malignancies (especially hematological malignancies), medications/toxins (e.g., metformin, cyanide poisoning), inborn errors of metabolism, and mitochondrial disorders.

Type D: Less common presentation and can be seen in patients with short gut syndrome.

1.Blough B, Moreland A, Mora A Jr. Metformin-induced lactic acidosis with emphasis on the anion gap. Proc (Bayl Univ Med Cent). 2015 Jan;28(1):31-3. doi: 10.1080/08998280.2015.11929178. PMID: 25552792; PMCID: PMC4264704.

2.Callelo et al. Extracorporeal Treatment for Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workgroup. DOI: 10.1097/CCM.0000000000001002

3.Friesecke, S., Abel, P., Roser, M. et al. Outcome of severe lactic acidosis associated with metformin accumulation. Crit Care 14, R226 (2010). https://doi.org/10.1186/cc9376

4.Madias NE. Lactic acidosis. Kidney Int. 1986 Mar;29(3):752-74. doi: 10.1038/ki.1986.62. PMID: 3702227.

5. Stiller RH, Luks AM, Çoruh B. All That Raises Lactate Is Not Sepsis. ATS Sch. 2023 Jun 12;4(3):385-386. doi: 10.34197/ats-scholar.2023-0032OT.

73. PulmPEEPs and ATS Critical Care Assembly: Dying in the ICU

Welcome to our second episode of ATS 2024 highlighting content featured through the ATS Critical Care Assembly. Today we are going to be talking about one of the Critical Care Assembly Symposiums entitled: “Care of Dying in the ICU: End of Life Care in 2024 and Beyond”

Dr. Theodore “Jack: Iwashyna is a Bloomberg Distinguished Professor at Johns Hopkins School of Medicine and the Johns Hopkins Bloomberg School of Public Health. Jack is a critical care physician and has a broad focus on research that understands the broader context of critical illness, and the long term impact on patients’ lives. He is an enormously productive and successful researcher with numerous publications in the field of critical care, and is a pioneer in the field of ICU survivorship. He is a devoted mentor and has received accolades from numerous societies

Dr. Molly Hayes is an Associate Professor of Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, the Director of the MICU at BIDMC, and the Director of External Education at the Carl J Shapiro Institute for Education and Research. She additionally is a co-founder of the BIDMC Center for Humanizing the ICU. Molly has been extensively involved with ATS with leadership roles in the Critical Care Assembly, and the newly minted Steering Committee on the Advancement of Learning.

The American Thoracic Society Critical Care Assembly is the largest Assembly in the American Thoracic Society. Their members include a diverse group of intensivists and care providers for both adult and pediatric critically ill patients. The primary goal of the Critical Care Assembly is to “improve the care of the critically ill through education, research, and professional development.”

71. Fellows’ Case Files: University of New Mexico

Today we’re visiting the University of New Mexico for another interesting entry in our Fellows’ Case Files.

 

Neel Vahil is a second-year internal medicine resident at the University of New Mexico. He completed medical school at New York Medical College and is planning on applying to pulmonary critical care fellowship programs.

Ishan Patel is a third year PCCM fellow at the University of New Mexico and will be pursuing a second fellowship in clinical informatics this year. He completed medical school and residency in Internal Medicine at Oregon Health & Science University. His fellowship research has focused on clinical outcomes of intensivist-led ECMO programs.

Dr. Lucie Griffin completed her internal medicine residency and PCCM fellowship at the University of New Mexico and is currently the Director of the Albuquerque VA medical intensive care unit.

 

A 69 year old male veteran who presents with 6 weeks of weight loss, cough, and malaise. He has ongoing tobacco use, and history of rheumatoid arthritis on HCQ and weekly MTX with etanercept, which he had stopped taking in the three prior months. Vitals: Afebrile, mildly tachycardic to 101, BP of 93/59, saturating appropriately on room air without any signs of respiratory distress

 

Komarla A, Yu GH, Shahane A. Pleural effusion, pneumothorax, and lung entrapment in rheumatoid arthritis. J Clin Rheumatol. 2015;21(4):211-215.

Boddington MM, Spriggs AI, Morton JA, Mowat AG. Cytodiagnosis of rheumatoid pleural effusions. J Clin Pathol. 1971;24(2):95-106.

Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y. Rheumatoid pleural effusion. Semin Arthritis Rheum. 2006;35(6):368-378