title: Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study.
abstract: OBJECTIVE
  To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis.
  
  
  METHODS
  Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively.
  
  
  RESULTS
  Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48-3.39, P = 1.24 × 10-4(derivation); HR = 2.16, 95% CI 1.33-3.51, P = 1.95 × 10-3(validation); and HR = 2.00, 95% CI 1.47-2.72, P = 1.10 × 10-5(combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16-2.48, P = 6.62 × 10-3(derivation); HR = 1.78, 95% CI 1.15-2.75, P = 9.80 × 10-3(validation); and HR = 1.59, 95% CI 1.20-2.10, P = 1.22 × 10-3(combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04-2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03-2.02, P = 0.0313).
  
  
  CONCLUSIONS
  Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 665 Hunting Avenue, Building I Room 1401, Boston, MA, 02115, USA.|Department of Biostatistics, Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Joint Laboratory of Health and Environmental Risk Assessment (HERA), Nanjing Medical University School of Public Health/Harvard School of Public Health, Nanjing, China.
authors.forename: Ruyang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 665 Hunting Avenue, Building I Room 1401, Boston, MA, 02115, USA.
authors.forename: Zhaoxi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 665 Hunting Avenue, Building I Room 1401, Boston, MA, 02115, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Tejera
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Frank
authors.affiliation: Department of Biostatistics, Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Joint Laboratory of Health and Environmental Risk Assessment (HERA), Nanjing Medical University School of Public Health/Harvard School of Public Health, Nanjing, China.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 665 Hunting Avenue, Building I Room 1401, Boston, MA, 02115, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 665 Hunting Avenue, Building I Room 1401, Boston, MA, 02115, USA.
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 665 Hunting Avenue, Building I Room 1401, Boston, MA, 02115, USA.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Biostatistics, Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Joint Laboratory of Health and Environmental Risk Assessment (HERA), Nanjing Medical University School of Public Health/Harvard School of Public Health, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Ednan K
authors.initials: EK
authors.lastname: Bajwa
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 665 Hunting Avenue, Building I Room 1401, Boston, MA, 02115, USA. dchris@hsph.harvard.edu.|Joint Laboratory of Health and Environmental Risk Assessment (HERA), Nanjing Medical University School of Public Health/Harvard School of Public Health, Nanjing, China. dchris@hsph.harvard.edu.|Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. dchris@hsph.harvard.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000401:mortality*; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors
keywords: ARDS; Cox proportional hazards model; Early and late onset; Logistic regression model; Mortality rate; Overall survival time