Ceramide as a Novel Biomarker in Acute Respiratory Distress Syndrome

Introduction: Acute respiratory distress syndrome (ARDS) describes a syndrome of acute onset, bilateral, inflammatory pulmonary infiltrates and impaired oxygenation. ARDS results in a life threatening, rapidly progressive illness and occurs in critically ill patients. Severity can be quantified by the ratio of the partial pressure of oxygen to the fraction of inspired oxygen, or PaO2/FiO2. ARDS can be caused by several diseases, including but not limited to infection or injury. Despite increased understanding of ARDS, we still lack good biomarkers for diagnosis and treatment.


Methods: Our lab is examining the role of ceramide in lung disease. Ceramide serves a pivotal role in regulating cell structure and cellular mechanical properties which are especially important in the lung. Our hypothesis is than an increase in ceramide concentration levels in ARDS patients would be a predictor of disease severity and/or mortality. In a small cohort of patients, we examined levels of sphingolipid species in the bronchoalveolar lavage fluid (BALF) by liquid chromatography electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS).


Results: We compared different length ceramide chains to clinical variables such as severity of illness, ICU length of stay, mortality, Acute Physiology and Chronic Health Evaluation (APACHE) and Sequential Organ Failure Assessment score (SOFA). Furthermore, there was a statistical significance between the APACHE score and 5 different ceramide compositions. Additionally, there was statistical significance between the SOFA score and 4 different sphingolipid compositions. We show a statistically significant correlation to APACHE and SOFA scores thus highlighting a potential novel role for ceramide in ARDS.


Conclusions: This work, albeit with a limited data population, potentially highlights to us a new diagnostic and prognostic biomarker ARDS. Furthermore, this also shows us that there could be a new pathway for ARDS management, encouraging others to formulate or to repurpose new and existing medications. Future work includes elucidating a more in-depth understanding of the potential pathway, continuing to enroll patients to collect and analyze samples; moreover, we need to determine if blocking ceramide pathway has any intrapulmonary effects in an in vivo model.