Identifying how acute respiratory distress syndrome (ARDS) subphenotypes respond differently to various ARDS treatments may lead to better outcomes, an article recently published in CHEST suggested.  The article concluded that heterogeneity of treatment effect may have contributed to the indeterminate results of studies of various ARDS treatments.

Investigators sought evidence showing that the effectiveness of a particular ARDS treatment modality might depend upon a patient’s particular ARDS subphenotype. Toward that end, they reviewed research identifying different subphenotypes of ARDS as well as the research on various ARDS treatment modalities that had demonstrated no overall benefit in patients with ARDS. Treatments investigated included open lung ventilation, prone positioning, fluid therapy, invasive mechanical ventilation, and statins.

When subtypes were determined based on ARDS severity, both prone positioning and statins were identified as therapies that may have different effects in different patient populations. Patients with a PaO2/FIO2 ratio less than 150 mm Hg and undergoing prone positioning for at least 16 hours per day had decreased 28- and 90-day mortality. Patients with PaO2/FIO2 ratio less than 100 mm Hg and who were treated with statins had less occurrence of sepsis-associated ARDS mortality.

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Additionally, when subtypes were determined based on inflammation, both open lung ventilation and fluid therapy were identified as potentially having different effects on different patient populations. Among those in the hyperinflammatory subphenotype, open lung ventilation with higher positive end-expiratory pressure (PEEP) was associated with lower mortality compared with the low PEEP strategy; however, the opposite was true within the hypoinflammatory subphenotype. For fluid therapy, a conservative fluid strategy (as opposed to a liberal fluid strategy) was associated with lower 90-day mortality in the hyperinflammatory subphenotype group.

The study authors wrote, “Recognizing different subphenotypes among patients with ARDS and understanding how they can modify the effects of different treatments has important implications for the study of these therapies.” They added, “The studies reviewed here suggest that many treatments that were previously considered to be ineffective, might in fact reduce mortality under certain circumstances, when they are applied to the appropriate patients.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Khan YA, Fan E, Ferguson ND. Precision medicine and heterogeneity of treatment effect in therapies for acute respiratory distress syndrome. Chest. July 13, 2021;S0012-3692(21)01327-1. doi:10.1016/j.chest.2021.07.009