DESCRIPTION (provided by applicant): The goal of this project is to employ novel therapies in patients who are at risk for or who have early ARDS in order to reduce the significant attributable mortality and to improve both short term and long term morbidities (1,2). As a participant in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, our specific aims are: 1. The creation of a two site multi-disciplinary network for recruitment into PETAL studies. Principal Investigators and Co-investigators from the Divisions of Pulmonary and Critical Care Medicine, Acute Care Surgery, and the Emergency Department Intensive Care Unit (ED-ICU) at the University of Michigan will collaborate to insure early identification and robust recruitment o study subjects. Additionally, investigators from the Emergency Department and the Division of Pulmonary and Critical Care Medicine of Henry Ford Health System, our second site in this network, have joined to create a rich environment in which to recruit patients for PETAL studies. This environment is strengthened by the inclusion of a fully integrated ED-ICU, providing a unique continuum of care for critically ill patients at these institutions, permitting early recruitment and intervention in these patients. 2. The annual recruitment of at least 40 high quality enrollees into PETAL protocols through the continuation and initiation of multiple overlapping recruitment strategies, including a novel alert mechanism through the electronic medical record, calculation of lung injury prevention scores, targeted capture of select at risk populations and traditional coordinator screening. 3. Prevention of ARDS: To determine the effect of GM-CSF administration on relevant clinical outcomes in patients with severe sepsis who are at risk for ARDS. The primary outcome measures are 28- and 90-day mortality. Major secondary end-points include the development/progression of ARDS and other organ failures, resolution of sepsis, duration of ICU and hospital stay, and long term functional recovery. Biological outcomes include monocyte innate responses and systemic inflammatory responses. 4. Early intervention in ARDS: To determine the effect of azithromycin administration on relevant clinical outcomes in patients with early onset ARDS. The primary outcome measures are 28- and 90-day mortality. Major secondary end-points include ventilator-free days, organ failure free days, infectious complications, duration of ICU and hospital stay, and long term functional recovery. An important biological outcome to be assessed is the influence of azithromycin therapy on temporal changes in the lung microbiome. These highly novel studies are to be led by a Co-Investigator with outstanding expertise in this arena.