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A2981 - Circulating Monocyte Responses Are Associated with Development of ARDS
Author Block: R. E. Abdulnour1, T. Gunderson2, I. Barkas1, J. Y. Timmons1, C. Barnig3, M. N. Gong4, D. Kor5, O. Gajic5, D. S. Talmor6, R. E. Carter2, B. D. Levy7; 1Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, MA, United States, 2Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, United States, 3Chest Disease, University Hospital of Strasbourg and FMTS, STRASBOURG, France, 4Montefiore Med Ctr, Bronx, NY, United States, 5Mayo Clinic, Rochester, MN, United States, 6Beth Israel Deaconess Medical Ctr, Boston, MA, United States, 7Brigham and Womens Hosp, Boston, MA, United States.
RATIONALE: The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. METHODS: Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin (325-mg loading dose followed by 81 mg daily) or placebo. We compared the association of biochemical and cellular responses to treatment regime and ARDS outcome. MEASUREMENTS AND MAIN RESULTS: Nine subjects developed ARDS after randomization and prior to study drug initiation, including 7 prior to aspirin (77.8%), and 24 of 367 at-risk patients (6.5%) developed ARDS, including 10 patients after initiation of aspirin (41.7%). Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. In patients without ARDS at the time of first dose of study medication, plasma TxB2 significantly increased over time, and peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio in plasma, and did not significantly impact leukocyte responses. CONCLUSIONS: Patients at-risk for ARDS demonstrated intravascular platelet and leukocyte activation with increased leukocyte-platelet aggregates. Aspirin treatment effects were present in several biochemical parameters. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain secondary to low ARDS event rates and the development of ARDS in some subjects prior to the administration of the first study medication dose. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.