Chronic obstructive pulmonary disease (COPD) is a lung disease caused by cigarette smoke that affects millions of people. In the United States, COPD is the 3rd leading cause of death making it one of our most important public health problems. Some people with COPD get disease flares that are called acute exacerbations of COPD - or AECOPDs for short. When people get an AECOPD they experience increased shortness of breath, wheezing and cough; symptoms that often require urgent or emergent treatment by healthcare providers. In the most severe, life-threatening situations, people with AECOPDs are put on a ventilator in the emergency department and admitted to the intensive care unit. Most AECOPDs can be treated with low doses of medications called steroids. This is good because high doses of steroids can cause unwanted side effects. Unfortunately, recent studies suggest that the sickest people, those admitted to the intensive care unit needing ventilator support, need higher doses of steroids because they may have resistance to these important medications. The investigators are studying steroid resistance during very severe AECOPDs so that we can eventually develop better and safer therapies for these vulnerable people.

Chronic obstructive pulmonary disease (COPD) is a cigarette smoke-induced disease of the lungs that affects millions of people in the United States and worldwide. COPD is the 3rd leading cause of death, making it one our most important public health problems. Perhaps most importantly, COPD confines many people to their homes, tethers them to oxygen lines, and destroys their independence. Like many diseases of chronic inflammation, the course of COPD is marred by intermittent disease flares that need more intensive treatment. In COPD, disease flares are called acute exacerbations of COPD (AECOPDs). AECOPDs are characterized by increased shortness of breath, wheezing or cough that leads to urgent, and sometimes emergent, treatment with inhaled bronchodilators, antibiotics and steroids. AECOPDs can be devastating to many because they worsen quality of life and lung function, frequently lead to hospitalization, and increase the risk of death. For instance, the death rate can reach 25-30% when COPD patients are admitted to the intensive care unit with respiratory failure (i.e. needing ventilator support). Accordingly, our research is focused on improving outcomes in the sickest patients admitted to the hospital with an AECOPD.

Oral or intravenous steroids (glucocorticoids) have been the mainstay of treatment for over 40 years, but virtually no research has been done to determine the optimal therapy for the sickest patients who are admitted to the intensive care unit. Results from the few clinical studies suggest that steroid resistance is increased in these critically-ill patients and that many physicians under- or over-dose steroids. For example, patients hospitalized with an AECOPD (without respiratory failure) are effectively treated with steroids (such as prednisone) dosed as low as 40mg/day. In contrast, two recent clinical studies showed that ~80mg/day of prednisone was ineffective for AECOPD patients hospitalized with respiratory failure (those who require ventilatory support), while in a second study ~160mg/day of methylprednisolone improved outcomes. The investigators recent epidemiologic study showed that 66% of patients admitted with an AECOPD and respiratory failure between 2003-2008 were treated with >240mg/day of methylprednisolone, a dose that increases steroid-related side effects. The investigators hypothesize that there is a stepwise increase in steroid resistance with COPD\

Inclusion Criteria for AECOPD with Ventilatory Failure Cohort:

• Emergency Department (ED) or ICU physician diagnosis of an acute exacerbation of COPD
• Age ≥ 40 years of age
• Need for ventilator support in the ED or ICU during the first 24 hours

Inclusion Criteria for Stable COPD Cohort:

• Physician diagnosis of COPD

• Age ≥ 40 years of age

• Frequency matched to AECOPD subjects for:

  • Age (± 10 year increments)
  • Current/Former smoking status (former smoker = no smoking for ≥ 1 month)
  • Lung function (FEV1% predicted by ± 10% increments)

Exclusion Criteria for AECOPD with Ventilatory Failure Cohort:

• Systemic steroid use ≤ 30 days prior to return visit
• Infection requiring antibiotics ≤ 1 month prior to return visit
• Hemoglobin < 8.0 g/dl
• Acute pulmonary embolism
• Diabetes
• History of immunodeficiency, interstitial lung disease, neuromuscular disorder or heart failure with respiratory exacerbation
• Tracheostomy
• Drugs that induce cytochrome P450 3A enzyme activity (e.g. barbiturates, phenytoin or carbamazepine) or drugs that inhibit cytochrome P450 3A activity (e.g. ketoconazole and chronic macrolide antibiotics)
• Age ≥ 90 year of age
• Known pregnancy
• Nursing mothers
• Prisoners

Exclusion Criteria for Stable COPD Cohort:

• Systemic steroid use ≤ 30 days prior to return visit
• Infection requiring antibiotics ≤ 1 month prior to return visit
• Hemoglobin < 8.0 g/dl
• Acute pulmonary embolism
• Diabetes
• History of immunodeficiency, interstitial lung disease, neuromuscular disorder or heart failure with respiratory exacerbation
• Tracheostomy
• Drugs that induce cytochrome P450 3A enzyme activity (e.g. barbiturates, phenytoin or carbamazepine) or drugs that inhibit cytochrome P450 3A activity (e.g. ketoconazole and chronic macrolide antibiotics)
• Age ≥ 90 year of age
• Known pregnancy
• Nursing mothers
• Prisoners

The AECOPD Cohort will be selected from University of Colorado Hospital inpatient units during an exacerbation of their COPD requiring respiratory failure.

The COPD Cohort will be selected from the pulmonary clinics at the University of Colorado Hospital.