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High-dimensional analysis reveals a pathogenic role of inflammatory monocytes in experimental diffuse alveolar hemorrhage.

ABSTRACT: Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication associated with systemic lupus erythematosus, vasculitis, and stem cell transplant. Little is known about the pathophysiology of DAH, and no targeted therapy is currently available. Pristane treatment in mice induces systemic autoimmunity and lung hemorrhage that recapitulates hallmark pathologic features of human DAH. Using this experimental model, we performed high-dimensional analysis of lung immune cells in DAH by mass cytometry and single-cell RNA sequencing. We found a large influx of myeloid cells to the lungs in DAH and defined the gene expression profile of infiltrating monocytes. Bone marrow-derived inflammatory monocytes actively migrated to the lungs and homed adjacent to blood vessels. Using 3 models of monocyte deficiency and complementary transfer studies, we established a central role of inflammatory monocytes in the development of DAH. We further found that the myeloid transcription factor interferon regulatory factor 8 is essential to the development of both DAH and type I interferon-dependent autoimmunity. These findings collectively reveal monocytes as a potential treatment target in DAH.

SUBMITTER: Lee PY

PROVIDER: S-EPMC6693829 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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High-dimensional analysis reveals a pathogenic role of inflammatory monocytes in experimental diffuse alveolar hemorrhage.

Lee Pui Y PY Nelson-Maney Nathan N Huang Yuelong Y Levescot Anaïs A Wang Qiang Q Wei Kevin K Cunin Pierre P Li Yi Y Lederer James A JA Zhuang Haoyang H Han Shuhong S Kim Edy Y EY Reeves Westley H WH Nigrovic Peter A PA

JCI insight 20190808 15

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication associated with systemic lupus erythematosus, vasculitis, and stem cell transplant. Little is known about the pathophysiology of DAH, and no targeted therapy is currently available. Pristane treatment in mice induces systemic autoimmunity and lung hemorrhage that recapitulates hallmark pathologic features of human DAH. Using this experimental model, we performed high-dimensional analysis of lung immune cells in DAH by ...[more]

PMID: 31391335

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Project description:AudienceThis scenario was developed to educate junior and senior emergency medicine (EM) residents.IntroductionEM Model of Practice recommends that the residents are able to manage patients in a critical condition from massive hemoptysis. Mild to moderate hemoptysis can be self-limiting and often can be managed with conservative measures; however, massive hemoptysis is a life-threatening emergency that needs to be managed promptly. Mortality from massive hemoptysis is about 13%-18%.1 There are several causes for hemoptysis ranging from pulmonary to vascular causes. Diffuse alveolar hemorrhage (DAH) causes hemoptysis only 0.2% which makes it a very rare but devastating disease.2 Hemoptysis from DAH can present a significant challenge to an EM physician since it can present in various ways including chest pain, shortness of breath or hemoptysis. Up to 40% of the patients can present without hemoptysis which makes it a diagnostic dilemma.3 Patients presenting with massive hemoptysis from DAH require management for hypovolemic shock, hypoxic respiratory arrest and potential cardiac arrest. The physicians also need to perform adequate ventilator management to help with alveolar recruitment. This simulation case can help discuss some of the nuances of the management of hemoptysis and DAH.ObjectivesBy the end of this simulation session, learners will be able to: (1) recognize worsening respiratory status of a patient with hemoptysis and intervene appropriately, (2) manage a patient with severe hemoptysis and perform appropriate ventilator management, (3) manage sinus tachycardia with QT prolongation on the ECG caused by cocaine and hypomagnesemia, (4) address various etiologies of hemoptysis, (5) discuss the causes of massive hemoptysis and management options, and (6) review ventilation strategies in an intubated hypoxic patient.Educational methodsThis session was conducted using high-fidelity simulation, which was immediately followed by an in-depth debriefing session. Each session had 3 EM residents from various levels of training on the team and 7 observers. There was 1 simulation instructor running the session and 1 simulation technician who acted as a nurse.Research methodsAfter the simulation and debriefing session was complete, an online survey was sent via surveymonkey.com to all the participants. The survey collected responses to the following questions: (1) the case was believable, (2) the case had right amount of complexity, (3) the case helped in improving medical knowledge and patient care, (4) the simulation environment gave me a real-life experience and, (5) the debriefing session after simulation helped improve my knowledge. A Likert scale was used to collect the responses.ResultsSeven learners responded to the survey. One hundred percent of them either agreed or strongly agreed that the case was beneficial in learning and improving patient care. They also agreed that it helped in improving medical knowledge. The post-session debrief was found to be very helpful by all the learners.DiscussionHigh-fidelity simulation was a cost-effective yet realistic way to manage severe hemoptysis, PEA (pulseless electrical activity), and persistent hypoxia in patients with diffuse alveolar hemorrhage. Starting the case with severe hypoxia that quickly progresses to PEA helps the learner to manage the patient quickly and effectively. Overall, learners enjoyed managing the patient, followed by discussing the various management strategies.TopicsHemoptysis, diffuse alveolar hemorrhage, medical simulation, respiratory.

Dataset Information

High-dimensional analysis reveals a pathogenic role of inflammatory monocytes in experimental diffuse alveolar hemorrhage.

Publications

High-dimensional analysis reveals a pathogenic role of inflammatory monocytes in experimental diffuse alveolar hemorrhage.

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