Morrell ED, Bhatraju PK, Mikacenic CR, et al. - Researchers investigated if there exists a link between alveolar macrophage (AM) transcriptional programs and prolonged mechanical ventilation and 28-day mortality in people with acute respiratory distress syndrome (ARDS). AMs purified from BAL fluid obtained from 35 individuals with ARDS were put to genome-wide transcriptional profiling. They collected cells at baseline (Day 1), Day 4, and Day 8 following ARDS onset (N  =  68 total samples). In participants alive and extubated within 28 days following ARDS onset (alive/extubated_Day28) vs those dead or persistently supported on mechanical ventilation at Day 28 (dead/intubated_Day28), they looked for biological pathways that were enriched at each time point. In AMs isolated on Day 1 in alive/extubated_Day28 vs dead/intubated_Day28 individuals, significant enrichment with “M1-like” (classically activated) and proinflammatory gene sets such as IL-6/Janus kinase/signal transducer and activator of transcription 5 signaling was identified. In contrast, several of these same proinflammatory gene sets were enriched in AMs solicited from dead/intubated_Day28 vs alive/extubated_Day28 individuals, by Day 8. Overall, findings revealed a link between clinical results in ARDS and highly distinct AM transcriptional programs.