Alcohol use is common in the United States with up to 7% of Americans meeting diagnostic criteria for alcohol use disorder (AUD). AUD is a significant risk factor for poor health outcomes and up to 1.5 million AUD patients require intensive care annually. However, little is known regarding the overall impact of AUD on intensive care unit (ICU) survivorship. Muscle wasting is the most common organ manifestation of alcohol abuse and contributes to respiratory compromise. Yet, no studies to date have investigated the impact of muscle disease on outcomes from respiratory failure in AUD patients. Currently, the diagnosis of neuromuscular dysfunction (NMD) relies on a combination of electrophysiology (EP) testing and muscle biopsy, both of which are often impractical in routine ICU care. Recent data suggest that measurement of muscle specific microRNAs (myomiRs) may accurately reflect ongoing myogenesis. We posit that specific myomiRs might provide an easily measurable, specific biomarker for alcohol-related muscle injury that may differentiate alcohol-related muscle disease and NMD in patients with acute respiratory failure (ARF). We hypothesize that alcohol is an independent risk factor for NMD in respiratory failure patients and that circulating myomiRs (c-myomiRs), miR-1, -133a/133b, -206, will accurately identify muscle injury in AUD patients with ARF. To test this hypothesis, subjects will undergo serial EP testing and muscle ultrasound (Aim 1) to identify prevalent alcohol-related muscle disease and incident NMD. Subjects will undergo serial c-miRNA measurement (Aim 3) followed by a percutaneous muscle biopsy at day 7 of mechanical ventilation to determine the concordance between muscle and circulating miRNA expression. Finally, this cohort will be followed longitudinally (Aim 2) with functional testing and detailed alcohol assessment at hospital discharge, 2 weeks and 6 months post-hospitalization to determine the long-term impact of alcohol- related muscle disease on functional impairment. These assessments will provide the applicant with training in 1) the pathophysiology of muscle injury and the regulation of muscle repair, 2) minimally invasive techniques for assessing muscle mass and function, 3) molecular techniques for identifying muscle injury, and 4) integrative approaches to the evaluation of AUD. This will advance the applicant towards her expressed goal of becoming an independent investigator studying the long-term impacts of alcohol-related muscle disease on critical illness.
Alcohol use disorders are associated with increased mortality and morbidity after critical illness. No studies examine the impact of alcohol-related muscle disease on outcomes after critical illness. This study aims to test whether neuromuscular dysfunction is more common and associated with worse outcomes in patients with an alcohol use disorder and determine the utility of circulating muscle-specific microRNAs as biomarkers of alcohol-related muscle injury.
