Acute Respiratory Distress Syndrome Clinical Trial
Official title:
Immune Alveolar Alterations During Pneumonia-Associated Acute Respiratory Distress Syndrome
Sepsis is a dysregulated host response to severe life-threatening infections, leading to
organ failure and death in up to 40% of patients with septic shock. Pulmonary infections are
the main cause of community-acquired sepsis and frequently lead to the development of acute
respiratory distress syndrome(ARDS). Features of immunosuppression, including diminished cell
surface monocyte human leukocyte antigen DR (mHLA-DR) expression, are strongly associated
with hospital mortality. Such decrease in HLA-DR expression on antigen-presenting cells has
been associated with impairment of microbial antigens to Tcells. Septic patients also show
elevated expression of inhibitory receptors associated with cell exhaustion.. Yet,
biochemical, flow cytometric and immunohistochemical findings consistent with
immunosuppression have been observed in lungs and spleen of patients died of sepsis and
multiple organ failure, demonstrating the relevance of studying these defects directly in
organ tissues. A novel approach aimed to characterize the role and prognostic value of
alveolar biomarkers measured directly in the injured lungs is warranted and supported by:
-disappointing results of previous clinical trials attempting to restore the level of
biomarkers measured on circulating cells; -evidences of regional immunosuppression in lungs
of ARDS patients; -lung is the main site of hospital-acquired infections with a prevalence of
ventilator-associated pneumonia in 30% over the course of Intensive Care Unit(ICU) stay in
ARDS patients.
Investigators speculate that biomarkers measured on alveolar leukocytes (AL) surface, are
important predictors of outcome and potential therapeutic targets in ICU patients with
pneumonia-associated ARDS.
Investigators aim to explore whether biomarkers measured directly on AL from patients with
pneumonia-associated ARDS are associated to regional pulmonary immunosuppression using
leukocyte functional tests; and predictors of outcomes.
Bronchoalveolar lavage fluid(BALF) and blood samples will be collected in ARDS patients.
Leukocyte populations and cell membrane biomarkers will be quantified using flow cytometry.
Leukocyte functional tests will be performed ex vivo on leukocytes collected from BALF and
blood samples. Pharmacological interventions will be performed ex vivo.
This project aims to identify biomarkers associated with outcomes and potential therapeutic
targets.
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