Effect of Alcohol and Drugs of Abuse on Immune Function in Critically Ill Patients With Respiratory Failure

This study plans to learn more about people who are sick in the hospital with a lung infection, or respiratory failure. Respiratory failure, or severe lung failure, is a life-threatening disease. When it happens, the lungs have trouble carrying out their normal function of getting oxygen into the blood, and removing carbon dioxide from the body. Investigators are conducting this study to see what drinking too much alcohol, using tobacco products, or using drugs (both legal and illegal) may do to lung infections and respiratory failure.

Subjects are asked to be in this research study because they are thought to have a lung infection and may also have respiratory failure. Alcohol, tobacco, and drug use have been linked to lung infections, respiratory failure, and even death, but the reasons for this aren't known. People who use unhealthy amounts of alcohol, tobacco, and or drugs may be more at risk for lung infections, and for severe complications due to lung infection. Subject participation is important whether or not you use alcohol and or drugs.

Study Overview

• Status: Recruiting
• Conditions: Lung Injury; Infection; Alcohol Abuse; Drugs of Abuse
• Intervention / Treatment: Other: Characterize alcohol and drug use

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Ellen L Burnham, MD; Phone Number: 303-724-6078; Email: ellen.burnham@ucdenver.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital
      • Contact: Carrie Higgins, BSN; Phone Number: 720-848-4210; Email: carrie.higgins@ucdenver.edu
      • Contact: Jeff McKeehan, BSN; Phone Number: 303-724-6080; Email: jeffrey.mckeehan@ucdenver.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Specific Aim 1. Adult medical ICU patients admitted to the University of Colorado Hospital for a primary respiratory problem, and who are expected to require ICU care ≥48 hrs

Specific Aim 2. Adult medical ICU patients with respiratory failure (due to underlying lung pathology) and who require endotracheal intubation and mechanical ventilation

Description

Inclusion criteria:

• Specific Aim 1: Adult medical ICU patients admitted to the University of Colorado Hospital for a primary respiratory problem, and who are expected to require ICU care ≥48 hrs
• Specific Aim 2: (1) Adult medical ICU patients with respiratory failure (due to underlying lung pathology) and who require endotracheal intubation and mechanical ventilation. (2) Adult medical and other ICU patients with respiratory failure, not related to a lung condition, and who require endotracheal intubation and mechanical ventilation. (3) Adult ICU patients previously admitted to the University of Colorado Hospital for a primary respiratory problem, and who required care ≥48 hrs.

Exclusion criteria, Specific Aim 1 and 2:

• Patients who are expected to require ICU care <48 hrs
• Patients admitted to the ICU who are not ICU status (being housed for space issues)
• Patient is unlikely to survive 48 hours
• Patient is on comfort care (hospice measures)
• Patients less than 18 or greater than 90 years of age
• Patient is a prisoner
• ICU attending declines enrollment of patient
• Patients who are pregnant
• Patients who have significant anemia, defined as Hgb<8% or Hct<24%, or who have evidence of active bleeding.

For bronchoscopy portion of Specific Aim 2.

• Patients who are on either a fraction of inspired oxygen inspired oxygen fraction (FiO2)>80% or positive end expiratory pressure (PEEP) >10 cm H20
• Patients with platelets less than 30,000(chronically)
• Patients who are expected to undergo a spontaneous breathing trial within the next 4 hours
• Patients with an order or plan to extubate in the next 4 hours
• Patients who have an endotracheal tube (ETT) <7.5 F
• Patients who are currently dangerously agitated
• Pregnant women

Exclusion criteria (outpatients ONLY for SA2 (3)):

1. Patients who required ICU care <48 hrs
2. Patients less than 18 or greater than 90 years of age
3. Patient is a prisoner
4. Patients who are pregnant
5. Residency > 40 miles from UCH clinics
6. non-English or non-Spanish speaking
7. Inability to perform study procedures (i.e. physical disability)
8. unable to perform pulmonary function testing
9. diagnosis of chronic pulmonary disease (e.g. COPD)
10. diagnosis of chronic neurodegenerative disease or severe dementia
11. history of anoxic or traumatic brain injury
12. prior ICU hospitalization at a non-UCH facility.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult ICU patients with respiratory problem; Adult medical ICU patients admitted to the University of Colorado Hospital for a primary respiratory problem, and who are expected to require ICU care ≥48 hrs.	Other: Characterize alcohol and drug use; Characterize alcohol and drug use in patients newly admitted to the medical ICU service, who are expected to stay in the ICU for greater than 48 hours. The investigators will collect blood, exhaled breath condensate, urine and hair samples over the first 10 days of hospitalization. A select subset of subjects will have bronchoalveolar lavage (BAL) obtained.
Intubated Adult ICU patients with respiratory failure; A subset of subjects, adult medical ICU patients with respiratory failure (due to underlying lung pathology) and who require endotracheal intubation and mechanical ventilation.	Other: Characterize alcohol and drug use; Characterize alcohol and drug use in patients newly admitted to the medical ICU service, who are expected to stay in the ICU for greater than 48 hours. The investigators will collect blood, exhaled breath condensate, urine and hair samples over the first 10 days of hospitalization. A select subset of subjects will have bronchoalveolar lavage (BAL) obtained.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of alcohol use disorders (AUDs)	Among medical ICU (MICU) patients who remain in ICU greater than or equal to 48 hours: Prevalence of alcohol use disorders (AUDs), drug use disorders (DUDs), their combination (both), or no AUD/DUDs. Absolute value, and change over 7 days, in serum/urine/exhaled breath condensate/hair cortisol, corticotropin releasing hormone (CRH), adenovirus proteinase (AVP), and adrenocorticotropic hormone (ACTH), stratified by AUD/DUD/both/neither. 3 Month and 6 Month follow up were added to this outcome measure via a protocol amendment after study-start.	prevalence, absolute value and change over 7 days, 3 Month follow up, 6 Month follow up
Incidence and etiology of respiratory failure, stratified by AUD/DUD/both/neither	Among medical ICU (MICU) patients who develop respiratory failure: Incidence and etiology of respiratory failure, stratified by AUD/DUD/both/neither. Length of time on mechanical ventilation stratified by AUD/DUD/both/neither. Inflammatory profile of BAL stratified by AUD/DUD/both/neither: BAL cell count and differential, Pro-inflammatory BAL cytokines; CCL5, TNFa, interferon-gamma (IFNg), interleukin (IL-1b), interleukin (IL-6). Evidence of oxidative stress in BAL (GSH/glutathione disulfide (GSSG) ratio, pH). Alveolar macrophage activation, degree of apoptosis, and inflammatory cytokine production. Confirm in non-invasively collected samples. Development of Acute Respiratory Distress Syndrome (ARDS) stratified by AUD/DUD/both/neither; Berlin criteria, Lung injury score.	participants will be followed for the duration of hospital stay, an expected average of 17 days
Incidence and etiology of respiratory failure, stratified by AUD/DUD/both/neither: Month 3	Among medical ICU (MICU) patients who develop respiratory failure: Incidence and etiology of respiratory failure, stratified by AUD/DUD/both/neither. Length of time on mechanical ventilation stratified by AUD/DUD/both/neither. Inflammatory profile of BAL stratified by AUD/DUD/both/neither: BAL cell count and differential, Pro-inflammatory BAL cytokines; CCL5, TNFa, interferon-gamma (IFNg), interleukin (IL-1b), interleukin (IL-6). Evidence of oxidative stress in BAL (GSH/glutathione disulfide (GSSG) ratio, pH). Alveolar macrophage activation, degree of apoptosis, and inflammatory cytokine production. Confirm in non-invasively collected samples. Development of Acute Respiratory Distress Syndrome (ARDS) stratified by AUD/DUD/both/neither; Berlin criteria, Lung injury score. 3 Month and 6 Month follow up were added to this outcome measure via a protocol amendment after study-start.	3 Month follow up
Incidence and etiology of respiratory failure, stratified by AUD/DUD/both/neither: Month 6	Among medical ICU (MICU) patients who develop respiratory failure: Incidence and etiology of respiratory failure, stratified by AUD/DUD/both/neither. Length of time on mechanical ventilation stratified by AUD/DUD/both/neither. Inflammatory profile of BAL stratified by AUD/DUD/both/neither: BAL cell count and differential, Pro-inflammatory BAL cytokines; CCL5, TNFa, interferon-gamma (IFNg), interleukin (IL-1b), interleukin (IL-6). Evidence of oxidative stress in BAL (GSH/glutathione disulfide (GSSG) ratio, pH). Alveolar macrophage activation, degree of apoptosis, and inflammatory cytokine production. Confirm in non-invasively collected samples. Development of Acute Respiratory Distress Syndrome (ARDS) stratified by AUD/DUD/both/neither; Berlin criteria, Lung injury score. 3 Month and 6 Month follow up were added to this outcome measure via a protocol amendment after study-start.	6 Month follow up

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Ellen L Burnham, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: November 19, 2014
• First Submitted That Met QC Criteria: November 20, 2014
• First Posted (Estimated): November 24, 2014

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Substance-Related Disorders; Alcoholism; Respiratory Insufficiency; Lung Injury
• Other Study ID Numbers: 14-0630; R24AA019661 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO