title: Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies.
abstract: BACKGROUND
  Diffuse alveolar damage is the histological hallmark of acute respiratory distress syndrome (ARDS). However, the chronology of histological lesions is not well established. We aimed to determine the time to onset of exudative or proliferative changes and end-stage fibrosis in ARDS.
  
  
  METHODS
  We analysed all patients who died between Jan 1, 1991, and Dec 31, 2010, in the intensive-care unit at the Hospital Universitario de Getafe, Madrid, Spain, and who had a clinical autopsy. Patients had to have clinical criteria for ARDS at time of death and histological features of diffuse alveolar damage at autopsy examination. Capillary congestion and intra-alveolar oedema characterised the exudative phase whereas proliferation of alveolar cell type 2 or fibroblasts, or fibrosis characterised the proliferative phase.
  
  
  RESULTS
  We analysed 159 patients. The prevalence of exudative changes decreased over time, being reported in 74 (90%) of 82 patients with ARDS of less than 1 week duration, 40 (74%) of 54 patients with disease of 1-3 week duration, and only four (17%) of 23 patients with disease of longer than 3 weeks' duration (p<0·0001). The incidence of proliferative changes increased over time, and was reported in 44 (54%) of 82 patients with ARDS of less than 1-week duration, 42 (78%) of 54 patients with disease duration of 1-3 weeks, and 23 (100%) of 23 patients with disease duration longer than 3 weeks (p<0·0001). Fibrosis was noted in three (4%) of 82 patients with disease of less than 1 week duration, 13 (24%) of 54 patients with disease of 1-3-weeks' duration, and 14 (61%) of 23 patients with disease longer than 3-week duration (p<0·0001). Fibrosis was more frequent in ARDS of pulmonary origin than in that of extrapulmonary origin.
  
  
  CONCLUSIONS
  Histological features of the lungs were related to duration of ARDS. Within the first week of evolution, exudative changes were predominant and fibrosis was rarely noted. Beyond the third week of evolution, proliferative changes were noted in all patients and fibrosis in two-thirds of them. Treatments with a potential effect on inflammation or fibrosis, or both, should probably focus on the first week after the onset of ARDS.
  
  
  BACKGROUND
  None.
authors.affiliation: Departamento de Cuidados Intensivos, Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain; Medical Intensive Care Unit, University Hospital of Poitiers, Poitiers, France.
authors.forename: Arnaud W
authors.initials: AW
authors.lastname: Thille
authors.affiliation: Departamento de Cuidados Intensivos, Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain. Electronic address: aesteban@ucigetafe.com.
authors.forename: Andrés
authors.initials: A
authors.lastname: Esteban
authors.affiliation: Departamento de Anatomía Patología, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Fernández-Segoviano
authors.affiliation: Departamento de Anatomía Patología, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: José-María
authors.initials: JM
authors.lastname: Rodriguez
authors.affiliation: Departamento de Anatomía Patología, Hospital Universitario de Getafe, Madrid, Spain.
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Aramburu
authors.affiliation: Departamento de Cuidados Intensivos, Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Patricio
authors.initials: P
authors.lastname: Vargas-Errázuriz
authors.affiliation: Departamento de Cuidados Intensivos, Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martín-Pellicer
authors.affiliation: Departamento de Cuidados Intensivos, Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain; European University of Madrid, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.affiliation: Departamento de Cuidados Intensivos, Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain; European University of Madrid, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Frutos-Vivar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D002196:Capillaries / Q000473:pathology*; D004487:Edema / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000473:pathology*; D012128:Respiratory Distress Syndrome / Q000473:pathology*; D013997:Time Factors