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.
- critical care
Data availability statement
Data are available on reasonable request.
Statistics from Altmetric.com
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.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.