Rationale: Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes. Objectives: To determine whether AM transcriptional programs are associated with prolonged mechanical ventilation and 28-day mortality in individuals with ARDS. Methods: We performed genome-wide transcriptional profiling of AMs purified from BAL fluid collected from 35 subjects with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset (N = 68 total samples). We identified biological pathways that were enriched at each time point in subjects alive and extubated within 28 days after ARDS onset (alive/extubatedDay28) versus those dead or persistently supported on mechanical ventilation at Day 28 (dead/intubatedDay28).Measurements and Main Results: "M1-like" (classically activated) and proinflammatory gene sets such as IL-6/JAK/STAT5 (Janus kinase/signal transducer and activator of transcription 5) signaling were significantly enriched in AMs isolated on Day 1 in alive/extubatedDay28 versus dead/intubatedDay28 subjects. In contrast, by Day 8, many of these same proinflammatory gene sets were enriched in AMs collected from dead/intubatedDay28 compared with alive/extubatedDay28 subjects. Serially sampled alive/extubatedDay28 subjects were characterized by an AM temporal expression pattern of Day 1 enrichment of innate immune programs followed by prompt downregulation on Days 4 and 8. Dead/intubatedDay28 subjects exhibited an opposite pattern, characterized by progressive upregulation of proinflammatory programs over the course of ARDS. The relationship between AM expression profiles and 28-day clinical status was distinct in subjects with direct (pulmonary) versus indirect (extrapulmonary) ARDS.Conclusions: Clinical outcomes in ARDS are associated with highly distinct AM transcriptional programs.
Rationale: Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes. Objectives: To determine whether AM transcriptional programs are associated with prolonged mechanical ventilation and 28-day mortality in individuals with ARDS. Methods: We performed genome-wide transcriptional profiling of AMs purified from BAL fluid collected from 35 subjects with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset (N = 68 total samples). We identified biological pathways that were enriched at each time point in subjects alive and extubated within 28 days after ARDS onset (alive/extubatedDay28) versus those dead or persistently supported on mechanical ventilation at Day 28 (dead/intubatedDay28).Measurements and Main Results: "M1-like" (classically activated) and proinflammatory gene sets such as IL-6/JAK/STAT5 (Janus kinase/signal transducer and activator of transcription 5) signaling were significantly enriched in AMs isolated on Day 1 in alive/extubatedDay28 versus dead/intubatedDay28 subjects. In contrast, by Day 8, many of these same proinflammatory gene sets were enriched in AMs collected from dead/intubatedDay28 compared with alive/extubatedDay28 subjects. Serially sampled alive/extubatedDay28 subjects were characterized by an AM temporal expression pattern of Day 1 enrichment of innate immune programs followed by prompt downregulation on Days 4 and 8. Dead/intubatedDay28 subjects exhibited an opposite pattern, characterized by progressive upregulation of proinflammatory programs over the course of ARDS. The relationship between AM expression profiles and 28-day clinical status was distinct in subjects with direct (pulmonary) versus indirect (extrapulmonary) ARDS.Conclusions: Clinical outcomes in ARDS are associated with highly distinct AM transcriptional programs.
Authors: Kara J Mould; Lea Barthel; Michael P Mohning; Stacey M Thomas; Alexandra L McCubbrey; Thomas Danhorn; Sonia M Leach; Tasha E Fingerlin; Brian P O'Connor; Julie A Reisz; Angelo D'Alessandro; Donna L Bratton; Claudia V Jakubzick; William J Janssen Journal: Am J Respir Cell Mol Biol Date: 2017-09 Impact factor: 6.914
Authors: Carolyn S Calfee; David R Janz; Gordon R Bernard; Addison K May; Kirsten N Kangelaris; Michael A Matthay; Lorraine B Ware Journal: Chest Date: 2015-06 Impact factor: 9.410
Authors: Matthew E Long; William E Eddy; Ke-Qin Gong; Lara L Lovelace-Macon; Ryan S McMahan; Jean Charron; W Conrad Liles; Anne M Manicone Journal: J Immunol Date: 2016-12-21 Impact factor: 5.422
Authors: Stacey L Fanning; Thaddeus C George; Di Feng; Steven B Feldman; Nicholas J Megjugorac; Alexander G Izaguirre; Patricia Fitzgerald-Bocarsly Journal: J Immunol Date: 2006-11-01 Impact factor: 5.422
Authors: Robert Paine; Theodore J Standiford; Ronald E Dechert; Marc Moss; Gregory S Martin; Andrew L Rosenberg; Victor J Thannickal; Ellen L Burnham; Morton B Brown; Robert C Hyzy Journal: Crit Care Med Date: 2012-01 Impact factor: 7.598
Authors: Eric D Morrell; Alice Wiedeman; S Alice Long; Sina A Gharib; T Eoin West; Shawn J Skerrett; Mark M Wurfel; Carmen Mikacenic Journal: JCI Insight Date: 2018-05-17
Authors: Yale Jiang; Brian R Rosborough; Jie Chen; Sudipta Das; Georgios D Kitsios; Bryan J McVerry; Rama K Mallampalli; Janet S Lee; Anuradha Ray; Wei Chen; Prabir Ray Journal: JCI Insight Date: 2020-07-09
Authors: Matthew E Long; Ke-Qin Gong; William E Eddy; Joseph S Volk; Eric D Morrell; Carmen Mikacenic; T Eoin West; Shawn J Skerrett; Jean Charron; W Conrad Liles; Anne M Manicone Journal: JCI Insight Date: 2019-12-05
Authors: Thomas R Martin; Rachel L Zemans; Lorraine B Ware; Eric P Schmidt; David W H Riches; Lisa Bastarache; Carolyn S Calfee; Tushar J Desai; Susanne Herold; Catherine L Hough; Mark R Looney; Michael A Matthay; Nuala Meyer; Samir M Parikh; Troy Stevens; B Taylor Thompson Journal: Am J Respir Cell Mol Biol Date: 2022-09 Impact factor: 7.748
Authors: Rod A Rahimi; Josalyn L Cho; Claudia V Jakubzick; Shabaana A Khader; Bart N Lambrecht; Clare M Lloyd; Ari B Molofsky; Sebastien Talbot; Catherine A Bonham; Wonder P Drake; Anne I Sperling; Benjamin D Singer Journal: Am J Respir Cell Mol Biol Date: 2022-07 Impact factor: 7.748