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

NCT02299921 | Recruiting

• 2 other identifiers: 14-0630R24AA019661
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infection; Alcohol Abuse; Drugs of Abuse; Lung Injury

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

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

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

Interventions

Characterize alcohol and drug use OTHER

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.

Adult ICU patients with respiratory problem; Intubated Adult ICU patients with respiratory failure

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood: serum cortisol, Adrenocorticotropic Hormone (ACTH), Corticotropin-Releasing Hormone (CRH), Arginine Vasopressin (AVP) hair: cortisol urine: Total Protein (TP), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1) exhaled breath condensate: Chemokine ligand 5 (CCL5) Bronchoalveolar lavage (BAL): cell count and differential, total protein, cytokines/chemokines including CCL5, Tumor Necrosis Factor a (TNFa), Interferon Gamma (IFNg), Interleukin 6 (IL-6), IL-8, IL-10, alveoloar macrophage cytokine/chemokine production, alveolar macrophage viability, apoptosis, cytotoxicity, lymphocyte activation.

MeSH Terms

Conditions

Infections; Alcoholism; Substance-Related Disorders; Lung Injury

Interventions

Ethanol

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Lung Diseases; Respiratory Tract Diseases; Thoracic Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Officials

• Ellen L Burnham, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ellen L Burnham, MD

CONTACT

303-724-6078; ellen.burnham@ucdenver.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: November 24, 2014
• Study Start: November 1, 2014
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)