Dataset Information

Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.

ABSTRACT: Secondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event for individuals infected with influenza A virus (IAV). How IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs, is not known. We addressed this issue using real-time determinations of alveolar responses to IAV in live, intact, perfused lungs. Our findings show that IAV infection blocked defensive alveolar wall liquid (AWL) secretion and induced airspace liquid absorption, thereby reversing normal alveolar liquid dynamics and inhibiting alveolar clearance of inhaled SA. Loss of AWL secretion resulted from inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in the alveolar epithelium, and airspace liquid absorption was caused by stimulation of the alveolar epithelial Na+ channel (ENaC). Loss of AWL secretion promoted alveolar stabilization of inhaled SA, but rescue of AWL secretion protected against alveolar SA stabilization and fatal SA-induced lung injury in IAV-infected mice. These findings reveal a central role for AWL secretion in alveolar defense against inhaled SA and identify AWL inhibition as a critical mechanism of IAV lung pathogenesis. AWL rescue may represent a new therapeutic approach for IAV-SA coinfection.

SUBMITTER: Tang S

PROVIDER: S-EPMC10541650 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.

Tang Stephanie S De Jesus Ana Cassandra AC Chavez Deebly D Suthakaran Sayahi S Moore Sarah Kl SK Suthakaran Keshon K Homami Sonya S Rathnasinghe Raveen R May Alison J AJ Schotsaert Michael M Britto Clemente J CJ Bhattacharya Jahar J Hook Jaime L JL

The Journal of clinical investigation 20231002 19

Secondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event for individuals infected with influenza A virus (IAV). How IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs, is not known. We addressed this issue using real-time determinations of alveolar responses to IAV in live, intact, perfused lungs. Our findings show that IAV infection blocked defensive alveolar wall liquid (AWL) secretion and induced airspace liquid ...[more]

PMID: 37581936

Similar Datasets

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

Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.

Publications

Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets