Cholestenoic Acid: A Potential Biomarker for Acute Respiratory Distress Syndrome

Cholestenoic acid (CA) may represent a unique and clinically important biomarker for acute respiratory distress syndrome (ARDS), according to a study published in the Journal of Allergy and Clinical Immunology.

Researchers theorized that declines in CA would coincide with increasing severity of ARDS, primarily attributed to mitochondrial dysfunction or other cytotoxicities. In the ALVEOLI study cohort, 144 patients with acute lung injury/ARDS were randomly assigned to mechanical ventilation with either lower or higher positive end-expiratory pressure levels. At time of enrollment, the researchers calculated the APACHE (Acute Physiology and Chronic Health Evaluation) III scores and classified sepsis according to the Society of Critical Care Medicine clinical definition.

In the fish oil study cohort, patients were randomly assigned to either enteral fish oil or saline placebo. Both treatments were administered for 14 days in mechanically ventilated patients with acute lung injury.

In the National Institute of Environmental Health Sciences bronchoscopy cohort, nonsmoking healthy adults underwent bronchoalveolar lavage with 250 mL saline in the right middle lobe. In all patients, plasma samples were collected and used to measure CA.

Robust expression of CYP27A1 was found in the alveolar macrophages of healthy participants, and mean alveolar macrophage lysates contained a mean CA of approximately 6.4 ng per million cells. In the ALVEOLI trial, each increase in plasma CA by 1 ng/mL was associated with up to a 1% reduction in mortality at 90 days, according to the adjusted regression analysis. In addition, for each 1 ng/mL increase in plasma CA, there was an associated increase in ventilator-free days (P =.04) and an increase in organ failure-free days (P <.001).

The fish oil study demonstrated that lower CYP27A1 mRNA in monocytes and alveolar macrophages was primarily observed in participants with fewer ventilator-free days, suggesting “that the reduced plasma CA in patients with severe ARDS may derive, at least in part, from CYP27A1 downregulation.”

In their conclusion, the researchers speculated “that plasma CA may represent a valuable new peripheral blood indicator of [alveolar macrophage] mitochondrial function,” while proposing “that it [plasma CA] should now be measured in a wider range of lung diseases, and, potentially, in emerging studies of cell-based mitochondrial rescue in the lung.”

Reference

Madenspacher JH, Stapleton RD, Suratt BT, et al. Cholestenoic acid is a prognostic biomarker in acute respiratory distress syndrome [published online October 5, 2018]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2018.09.017