• Control participants will be pair-matched to AUD participants based on smoking (yes or no, cigarettes or cannabis), age, sex, and whenever possible, race.

Control Sampling Information

• 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 Bronchoscopy Information 

• Non-AUD controls will undergo a single bronchoscopy.
  

• Inclusion criteria: An AUDIT score of ≤ 2 for men, ≤ 1 for women. Participants who acknowledge cigarette smoking or cannabis smoking will also be considered as needed for collaborators’ studies and will complement habits in participants with AUDs.
• Exclusion criteria: Participants will be ineligible to participate if they meet any of the criteria set forth for participants with AUDs.

Clinical Protocol for Controls

• 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.
• Participants will undergo research sampling, including bronchoscopy with BAL and bronchial brushings.

Respiratory Failure Enrollment Information

• 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.
• Detailed alcohol, smoking, and drug use history will be obtained on all enrolled patients, and phosphatidylethanol levels will be measured to provide an objective alcohol history.

Respiratory Failure Sampling Information

• 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

• Inclusion criteria: Patients ≤ 48 hours after ICU admission on mechanical ventilation who are not undergoing attempts at spontaneous breathing or patients on oxygen via HHFNC with a flow rate of  ≥ 30 L/min.
• Exclusion criteria: Age < 18; co-morbid malignancy; tracheostomy; use of immunosuppressive medications; autoimmune or chronic inflammatory diseases; chronic respiratory failure with baseline oxygen use; patients admitted > 48 hours after mechanical ventilation; patients who are expected to require  <48 hours of ICU care; patients unlikely to survive 48 hours from the time of ICU admission 

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.

Burn Injury Participant Enrollment Information

• 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.

Burn Injury Participant Bronchoscopy Information

• From 1-2 patients will undergo bronchoscopy each month (at each site).

Inclusion and Exclusion Criteria for Burn-Injured Patients

*Criteria is the same across the Loyola and University of Colorado sites.

• Inclusion criteria: Patients ≥ 18 years of age, admitted < 24 hours after burn injury with total body surface area burn ≥ 15% or suspected inhalational injury; expected to require hospital care > 48 hours.
• Exclusion criteria: Age < 18; co-morbid malignancy, use of immunosuppressive medications; known autoimmune or chronic inflammatory diseases; and patients who are admitted > 24 hours after injury.

Clinical 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.​

Chronic Cannabis Participant Enrollment Information

• The University of Colorado investigators currently have IRB approval to enroll healthy participants who are solely chronic cannabis users and not poly-substance users. 

Chronic Cannabis Participant Bronchoscopy Information

• From 1-2 patients will undergo bronchoscopy each month (at each site).

Inclusion and Exclusion Criteria for Chronic Cannabis Patients

*Criteria is the same across the Loyola and University of Colorado sites.

• Inclusion criteria: Inclusion criteria: 1) Daily or near daily cannabis use (inhaled via joint/cigarette or pipe) equivalent to AT LEAST 20 "joint years" (number of joints/cigarettes or bowlsper day multiplied by number of years during which cannabis was smoked) by self-report and validated through urine drug screen. 2) Never or limited exposure to inhaled tobacco products (equivalent to LESS THAN one "pack year" in a lifetime) by self-report and validatedthrough negative urine cotinine screen. 

• Exclusion criteria: 1) LESS THAN near daily cannabis use (inhaled via joint/cigarette or pipe) equivalent to LESS THAN 20 "joint years" (number of joints/cigarettes per day multiplied by number of years during which cannabis was smoked) or a negative urine drug screen (for cannabis) 2) Inhaled tobacco product exposure EXCEEDING one "pack year" or a positive urine cotinine screen for illicit substances such as cocaine, meth, heroin. 3) Elevated AUDIT score suggesting alcohol dependence: A 10-itemquestionnaire to identify subjects with alcohol use disorders. Males with AUDIT score ≥ 15, and females with AUDIT score ≥ 13 will be excluded. Exclusion criteria are otherwise the same as criteria described for AUD and control participants.

Clinical protocol

• A detailed history, physical, and screening exam will be performed as described for AUD and Control 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.
• Participants will undergo research sampling, including bronchoscopy with BAL and bronchial brushings.