Intensive Care Medicine

, Volume 41, Issue 11, pp 1921–1930 | Cite as

Acute respiratory distress syndrome in patients with and without diffuse alveolar damage: an autopsy study

  • José A. Lorente
  • Pablo Cardinal-Fernández
  • Diego Muñoz
  • Fernando Frutos-Vivar
  • Arnaud W. Thille
  • Carlos Jaramillo
  • Aida Ballén-Barragán
  • José M. Rodríguez
  • Oscar Peñuelas
  • Guillermo Ortiz
  • José Blanco
  • Bruno Valle Pinheiro
  • Nicolás Nin
  • María del Carmen Marin
  • Andrés Esteban
  • Taylor B. Thompson



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.


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).


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.


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.


Adult respiratory distress syndrome Diffuse alveolar damage Subphenotype Histology Autopsy Hyaline membranes 



Instituto de Salud Carlos III FIS PI 12/02898, and FIS PI 12/02451. European Network (7th FP) ITN 264864.

Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

134_2015_4046_MOESM1_ESM.docx (5 mb)
Supplementary material 1 (DOCX 5153 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • José A. Lorente
    • 1
    • 2
    • 3
  • Pablo Cardinal-Fernández
    • 4
  • Diego Muñoz
    • 5
  • Fernando Frutos-Vivar
    • 1
    • 2
  • Arnaud W. Thille
    • 6
  • Carlos Jaramillo
    • 1
  • Aida Ballén-Barragán
    • 1
    • 2
  • José M. Rodríguez
    • 1
    • 2
  • Oscar Peñuelas
    • 1
    • 2
  • Guillermo Ortiz
    • 7
  • José Blanco
    • 7
  • Bruno Valle Pinheiro
    • 8
  • Nicolás Nin
    • 9
  • María del Carmen Marin
    • 10
  • Andrés Esteban
    • 1
    • 2
  • Taylor B. Thompson
    • 11
  1. 1.Servicio de Medicina IntensivaHospital Universitario de GetafeMadridSpain
  2. 2.CIBER de Enfermedades Respiratorias (CIBERES)MadridSpain
  3. 3.Universidad EuropeaMadridSpain
  4. 4.Hospital Universitario de SanchinarroMadridSpain
  5. 5.Hospital Pablo Tobón UribeUniversidad CESMedellínColombia
  6. 6.Medical ICU, CHU de PoitiersPoitiersFrance
  7. 7.Universidad del BosqueBogotáColombia
  8. 8.Division of Respiratory and Critical Care MedicineFederal University of Juiz de ForaJuiz de ForaBrazil
  9. 9.Hospital Español Juan José CrottogginiMontevideoUruguay
  10. 10.Intensive Care ServiceHospital Regional 1º de Octubre, ISSSTEMexico DFMexico
  11. 11.Pulmonary and Critical Care UnitMassachusetts General HospitalBostonUSA

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