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Original research
Six-month and 12-month patient outcomes based on inflammatory subphenotypes in sepsis-associated ARDS: secondary analysis of SAILS-ALTOS trial
  1. Mohamed D Hashem1,
  2. Ramona O Hopkins2,3,
  3. Elizabeth Colantuoni4,5,
  4. Victor D Dinglas5,6,
  5. Pratik Sinha7,
  6. Lisa Aronson Friedman5,6,
  7. Peter E Morris8,
  8. James C Jackson9,10,
  9. Catherine L Hough11,
  10. Carolyn S Calfee12,
  11. Dale M Needham5,6
  1. 1 Department of Medicine, Marshfield Clinic Health System, Marshfield, Wisconsin, USA
  2. 2 Center for Humanizing Critical Care, Intermountain Medical Center, Murray, Utah, USA
  3. 3 Psychology Department and Neuroscience Center, Brigham Young University, Provo, Utah, USA
  4. 4 Department of Biostatistics, Johns Hopkins University - Bloomberg School of Public Health, Baltimore, Maryland, USA
  5. 5 Outcomes After Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, Maryland, USA
  6. 6 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  7. 7 Division of Critical Care, Department of Anesthesia, Washington University in St Louis, Saint Louis, Missouri, USA
  8. 8 Division of Pulmonary, Critical Care & Sleep Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, USA
  9. 9 Center for Critical Illness, Brain Dysfunction, and Survivorship (CIBS Center), Nashville, Tennessee, USA
  10. 10 Department of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  11. 11 Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA
  12. 12 Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco Department of Medicine, San Francisco, California, USA
  1. Correspondence to Dr Dale M Needham, Outcomes After Critical Illness and Surgery (OACIS) Group, Johns Hopkins University School of Medicine, Baltimore, MD 21201, USA; dale.needham{at}


Background Prior acute respiratory distress syndrome (ARDS) trials have identified hypoinflammatory and hyperinflammatory subphenotypes, with distinct differences in short-term outcomes. It is unknown if such differences extend beyond 90 days or are associated with physical, mental health or cognitive outcomes.

Methods 568 patients in the multicentre Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo were included and assigned a subphenotype. Among 6-month and 12-month survivors (N=232 and 219, respectively, representing 243 unique survivors), subphenotype status was evaluated for association with a range of patient-reported outcomes (eg, mental health symptoms, quality of life). Patient subsets also were evaluated with performance-based tests of physical function (eg, 6 min walk test) and cognition.

Findings The hyperinflammatory versus hypoinflammatory subphenotype had lower overall 12-month cumulative survival (58% vs 72%, p<0.01); however, there was no significant difference in survival beyond 90 days (86% vs 89%, p=0.70). Most survivors had impairment across the range of outcomes, with little difference between subphenotypes at 6-month and 12-month assessments. For instance, at 6 months, in comparing the hypoinflammatory versus hyperinflammatory subphenotypes, respectively, the median (IQR) patient-reported SF-36 mental health domain score was 47 (33–56) vs 44 (35–56) (p=0.99), and the per cent predicted 6 min walk distance was 66% (48%, 80%) vs 66% (49%, 79%) (p=0.76).

Interpretation Comparing the hyperinflammatory versus hypoinflammatory ARDS subphenotype, there was no significant difference in survival beyond 90 days and no consistent findings of important differences in 6-month or 12-month physical, cognitive and mental health outcomes. These findings, when considered with prior results, suggest that inflammatory subphenotypes largely reflect the acute phase of illness and its short-term impact.

  • ARDS
  • critical care

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Contributors DMN, VDD, EC, CLH, ROH, CSC and PS contributed to the conception and design of the manuscript; VDD, CLH, ROH, PEM, JCJ and DMN contributed to acquisition of data; all authors contributed to data interpretation and analysis; MDH drafted the manuscript and all other authors critically revised it and gave final approval.

  • Funding National Heart, Lung and Blood Institute funded this follow-up study (N01HR56170, R01HL091760 and 3R01HL091760-02S1) and the SAILS trial (contracts HHSN268200536165C to HHSN268200536176C and HHSN268200536179C), along with the Johns Hopkins Institute for Clinical and Translational Research (ICTR) (UL1 TR 0 00 424–06). Additionally, the SAILS trial was supported by the Investigator-Sponsored Study Programme of AstraZeneca. CSC was supported by HL140026.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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