Intensive Care Medicine

, Volume 44, Issue 11, pp 1859–1869 | Cite as

Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

  • Pratik SinhaEmail author
  • Kevin L. Delucchi
  • B. Taylor Thompson
  • Daniel F. McAuley
  • Michael A. Matthay
  • Carolyn S. Calfee
  • for the NHLBI ARDS Network



Using latent class analysis (LCA), we have consistently identified two distinct subphenotypes in four randomized controlled trial cohorts of ARDS. One subphenotype has hyper-inflammatory characteristics and is associated with worse clinical outcomes. Further, within three negative clinical trials, we observed differential treatment response by subphenotype to randomly assigned interventions. The main purpose of this study was to identify ARDS subphenotypes in a contemporary NHLBI Network trial of infection-associated ARDS (SAILS) using LCA and to test for differential treatment response to rosuvastatin therapy in the subphenotypes.


LCA models were constructed using a combination of biomarker and clinical data at baseline in the SAILS study (n = 745). LCA modeling was then repeated using an expanded set of clinical class-defining variables. Subphenotypes were tested for differential treatment response to rosuvastatin.


The two-class LCA model best fit the population. Forty percent of the patients were classified as the “hyper-inflammatory” subphenotype. Including additional clinical variables in the LCA models did not identify new classes. Mortality at day 60 and day 90 was higher in the hyper-inflammatory subphenotype. No differences in outcome were observed between hyper-inflammatory patients randomized to rosuvastatin therapy versus placebo.


LCA using a two-subphenotype model best described the SAILS population. The subphenotypes have features consistent with those previously reported in four other cohorts. Addition of new class-defining variables in the LCA model did not yield additional subphenotypes. No treatment effect was observed with rosuvastatin. These findings further validate the presence of two subphenotypes and demonstrate their utility for patient stratification in ARDS.


ARDS Subphenotypes Latent class analysis Statins 



HL131621, HL133390, HL140026 (CSC), 2T32GM008440-21 (PS); SAILS was supported by a grant from the National Heart, Lung, and Blood Institute, National Institutes of Health (HHSN268200 536165C-536179C), and the Investigator-Sponsored Study Program of AstraZeneca.

Supplementary material

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Supplementary material 1 (JPEG 31 kb)
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Supplementary material 3 (DOC 94 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature and ESICM 2018

Authors and Affiliations

  • Pratik Sinha
    • 1
    Email author
  • Kevin L. Delucchi
    • 2
  • B. Taylor Thompson
    • 3
  • Daniel F. McAuley
    • 4
    • 5
  • Michael A. Matthay
    • 1
    • 6
    • 7
  • Carolyn S. Calfee
    • 1
    • 6
    • 7
  • for the NHLBI ARDS Network
  1. 1.Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep MedicineUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Department of PsychiatryUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Department of Medicine, Division of Pulmonary and Critical CareMassachusetts General HospitalBostonUSA
  4. 4.Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical SciencesQueen’s University of BelfastBelfastUK
  5. 5.Regional Intensive Care UnitRoyal Victoria HospitalBelfastUK
  6. 6.Department of AnesthesiaUniversity of California, San FranciscoSan FranciscoUSA
  7. 7.Cardiovascular Research Institute, University of California, San FranciscoSan FranciscoUSA

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