Participants with AUDs will undergo single time point or longitudinal sampling at the University of Colorado and Emory University. Denver is home to a large population of racially and ethnically diverse AUD participants, including Hispanics, while Atlanta has a sizable African-American population. Denver investigators have enrolled participants with AUDs through regular screening at Denver Comprehensive Addictions Rehabilitation and Evaluation Services (CARES), while Emory investigators have enrolled participants at the Atlanta Veteran’s Affairs (VA) Hospital. The majority of participants with AUDs will undergo a single bronchoscopy, while 30% will have two sequential bronchoscopies performed. The performance of two bronchoscopies in AUD patients will support investigations seeking to establish the persistence of alcohol-related abnormalities. Longitudinal sampling will occur after 1 week of observed alcohol abstinence in an inpatient setting (Denver site), or after 2 or 3 weeks’ outpatient abstinence (Emory site).Inclusion and exclusion criteria for AUD participants:
Clinical protocol. Detailed screening exams will be performed including a full history (demographic, alcohol, tobacco use), physical exam, blood work, chest radiograph, simple spirometry, urine toxicology and cotinine testing, and pregnancy tests (in women). Cigarette and/or cannabis use, if present, will be quantified with validated methods. Abnormal findings (denoted in exclusion criteria) will result in a participant’s exclusion. Participants will undergo research sampling, including bronchoscopy with BAL and bronchial brushings the morning following admission to ensure active alcohol withdrawal has been addressed if present. Along with participants who smoke (majority of AUDparticipants) active recruitment of AUD paricipants who do not smoke either cigarettes or cannabis will also occur to support focused investigations of AUDs.
The University of Colorado investigators currently have IRB approval to enroll healthy control participants who are smoking-, age- and sex- matched to complement AUD participant recruitment. Control participants will be pair-matched to AUD participants based on smoking (yes or no, cigarettes or cannabis), age, sex, and whenever possible, race. Non-AUD controls will undergo a single bronchoscopy.
Clinical Protocol. A detailed history, physical, and screening exam will be performed as described for AUD participants. Both cigarette and/or cannabis use will be verified by point of care urine testing, and quantified when present with validated methods. Abnormal findings will result in exclusion.
Patients will be recruited and enrolled from ICUs at the University of Colorado Hospital, including patients both at risk for, and with, the acute respiratory distress syndrome (ARDS). AUDs are expected to be present in 25-40% of enrolled patients, and approximately 45% of enrolled patients are expected to develop frank ARDS. As of 2020, a percentage of these patients have ARDS due to infection with SARS-CoV-2. A small percentage of patients are mechanically ventilated for non-pulmonary indications (e.g. airway protection in stroke) to serve as a separate "control" group that will enable investigators to account for effects of mechanical ventilation on experimental variables. Detailed alcohol, smoking, and drug use history will be obtained on all enrolled patients, and phosphotidylethanol levels will be measured to provide an objective alcohol history. It is anticipated that 50% will have tracheal aspirate samples available.
A percentage of ICU survivors will follow up in a designated post-ICU clinic where longitudinal measures of respiratory health, neuromuscular weakness, and mental health will be obtained, including on-going assessments of alcohol and substance use.
Inclusion and exclusion criteria for respiratory failure patients
Clinical protocol. The designated health care proxy will participate in the informed consent process, and re-consent of patients will occur once capacity is regained. Alternatively, consent may be waived depending on the sample(s) to be collected After consent, demographic information and research sampling will be completed as soon as feasible at designated time points while patient is in the ICU.
Investigators at Loyola University Medical Center and the University of Colorado will enroll burn-injured patients to explore the impact of AUDs on outcomes. Both sites obtain alcohol histories, and 12-25% of burn patients are expected to meet criteria for AUDs. From 1-2 patients will undergo bronchoscopy each month (at each site).
Inclusion and exclusion criteria for burn-injured patients are the same across the Loyola and University of Colorado sites.
Screening protocol. The designated health care proxy will participate in the informed consent process followed by re-consent of patient when capacity is regained. Demographic information, including AUDIT information and research sampling will be completed as soon as feasible while patient is in the ICU.