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.

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.

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