Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

Inclusion Criteria:

- Age between 45 and 80 years

- A confirmed diagnosis of advanced stage COPD, using current accepted diagnostic
criteria, including clinical/laboratory findings, pulmonary function tests, and
appropriate history to exclude other disorders that could explain their lung disease.
The accepted range of forced expiratory volume at one second will include 25% ≤ forced
expiratory volume at one second ≤ 60%

- Subjects agree to maintain a stable medication regimen in the absence of a disease
flare

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- carbon dioxide partial pressure < 45 mm Hg, room air oxyhemoglobin saturation > 85%

- A willingness to participate in all portions of the protocol, including serial
bronchoscopy, requisite surveillances, and ancillary immunologic studies in follow-up
visits at this institution

- For woman of childbearing age, a negative pregnancy test, and a willingness to use two
methods of contraception, or abstinence

- An ability and willingness to provide written informed consent

Exclusion Criteria:

- Three, or more exacerbations of lower respiratory disease in the past year requiring
systemic corticosteroids, or one exacerbation requiring hospitalization in the past 6
months

- Intubation for COPD, or other cause of respiratory failure in the past year

- Use of immunosuppressive therapy including oral prednisone > 10mg per day other than
aerosolized corticosteroids, anytime within three months prior to participation

- Evidence for an opportunistic infection/colonization of the airways, i.e.,
non-bacterial

- Evidence for systemic illness including hematologic disorders (defined by an absolute
neutrophil count (ANC) < 4000 /mL and platelets < 120,000/mL), cirrhosis, or hepatic
insufficiency (total bilirubin, or alkaline phosphatase > 1.5 x normal, serum
glutamate oxaloacetate transaminase, or serum glutamate pyruvate transaminase > 1.2 x
normal values), or a coagulopathy (INR > 1.4), seizure disorder

- Evidence for renal insufficiency with a calculated creatinine clearance using the
Cockcroft and Gault's method of < 80 ml/min for males and < 70 ml/min for females, or
serum creatinine > 1.4 mg/dL.

- Evidence of coronary artery disease by history, e.g., angina or history of myocardial
infarction within the past 12 months, unless corrected by coronary artery bypass graft
within < 5 years, and asymptomatic since

- Evidence for systemic abnormal renal function manifested by uncontrolled hypertension
(systolic blood pressure > 160 mmHg or diastolic blood pressure >90 mmHg),
hyperkalemia (serum potassium > 5.0 meq/dl, and/or elevated serum potassium above the
normal range for the subject's age)

- Pregnancy or lactation, or inability to take contraception during and for 6 months
following treatment

- Positive HIV, or hepatitis B or C serology, or another active infection

- Current or past history of cancer excluding basal or squamous cell skin cancer

- Undiagnosed pulmonary nodule requiring diagnostic evaluation

- Weight loss > 10% usual body weight over the past 6 months or a BMI < 18

- Known hypersensitivity or allergy to cyclosporine

- Concurrent participation in other clinical trials within the prior month

- Known medical or psychological condition (severe personality disorder or mental
illness) that would not permit the subject to complete the trial or sign informed
consent

- Autoimmune disorders or other disorders with suspected systemic immune involvement

- Active smoking history or urinary cotinine > 2

- Hypersensitivity to midazolam or narcotics which would not allow bronchoscopy sedation

- Concurrent use of drugs with a known interaction with cyclosporine