title: Acute respiratory distress syndrome in patients with and without diffuse alveolar damage: an autopsy study.
abstract: OBJECTIVE
  To demonstrate that among patients with acute respiratory distress syndrome (ARDS), the presence of diffuse alveolar damage (DAD) at histological examination, as compared to its absence, defines a specific subphenotype.
  
  
  METHODS
  We studied 149 patients who died in our ICU with the clinical diagnosis of ARDS according to the Berlin Definition (BD) and who had autopsy examination. We compared the change over time of different clinical variables in patients with (n = 49) and without (n = 100) DAD. A predictive model for the presence of DAD was developed and validated in an independent cohort of 57 patients with ARDS and postmortem examination (21 of them with DAD).
  
  
  RESULTS
  Patients with DAD, as compared to patients without DAD, had a lower PaO₂/FiO₂ ratio and dynamic respiratory system compliance, and a higher SOFA score and INR, and were more likely to die of hypoxemia and less likely to die of shock. In multivariate analysis, variables associated with DAD [odds ratio, 95% confidence interval (CI)] were PaO₂/FiO₂ ratio [0.988 (0.981-0.995)], dynamic respiratory system compliance [0.937 (0.892-0.984)] and age [0.972 (0.946-0.999)]. Areas under the ROC curve (95 % CI) for the classification of DAD using the regression model or the BD were, respectively, 0.74 (0.65-0.82) and 0.64 (0.55-0.72) (p = 0.03). In the validation cohort, the areas under the ROC curve for the diagnosis of DAD were 0.73 (0.56-0.90) and 0.67 (0.54-0.81) for the regression model and the BD, respectively.
  
  
  CONCLUSIONS
  The presence of DAD appears to define a specific subphenotype in patients with ARDS. Targeting patients with DAD within the population of patients with the clinical diagnosis of ARDS might be appropriate to find effective therapies for this condition.
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario de Getafe, 28905, Madrid, Spain. joseangel.lorente@salud.madrid.org.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. joseangel.lorente@salud.madrid.org.|Universidad Europea, Madrid, Spain. joseangel.lorente@salud.madrid.org.
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.affiliation: Hospital Universitario de Sanchinarro, Madrid, Spain. pablocardinal@hotmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cardinal-Fernández
authors.affiliation: Hospital Pablo Tobón Uribe, Universidad CES, Medellín, Colombia.
authors.forename: Diego
authors.initials: D
authors.lastname: Muñoz
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario de Getafe, 28905, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Frutos-Vivar
authors.affiliation: Medical ICU, CHU de Poitiers, Poitiers, France.
authors.forename: Arnaud W
authors.initials: AW
authors.lastname: Thille
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario de Getafe, 28905, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Jaramillo
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario de Getafe, 28905, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Ballén-Barragán
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario de Getafe, 28905, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Rodríguez
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario de Getafe, 28905, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Peñuelas
authors.affiliation: Universidad del Bosque, Bogotá, Colombia.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ortiz
authors.affiliation: Universidad del Bosque, Bogotá, Colombia.
authors.forename: José
authors.initials: J
authors.lastname: Blanco
authors.affiliation: Division of Respiratory and Critical Care Medicine, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
authors.forename: Bruno Valle
authors.initials: BV
authors.lastname: Pinheiro
authors.affiliation: Hospital Español Juan José Crottoggini, Montevideo, Uruguay.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Nin
authors.affiliation: Intensive Care Service, Hospital Regional 1º de Octubre, ISSSTE, Mexico DF, Mexico.
authors.forename: María
authors.initials: M
authors.lastname: del Carmen Marin
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario de Getafe, 28905, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Esteban
authors.affiliation: Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Thompson
mesh_terms: D001344:Autopsy; D001938:Brazil; D003105:Colombia; D006801:Humans; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000473:pathology*; D012128:Respiratory Distress Syndrome / Q000145:classification / Q000473:pathology*; D012189:Retrospective Studies
keywords: Adult respiratory distress syndrome; Autopsy; Diffuse alveolar damage; Histology; Hyaline membranes; Subphenotype