Aerosol Cyclosporine in Chronic Obstructive Pulmonary Disease (COPD)

Inclusion criteria

• Age between 45 and 70 years.
• A confirmed diagnosis of COPD, Gold Stage III, 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.
• Subjects agree to maintain a stable medication regimen in the absence of a disease flare
• ECOG performance status of 0, 1, or 2.
• pCO2 < 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, and undergo monthly pregnancy testing.
• Elevated T-cell cytokine gene expression, defined as baseline values > the mean of the pilot Gold 0-1 study population for one variable (CD4+IL-2 >23%, CD8+IFN-g >17%, CD8+MHC > 6%, or CD8 TGF-b).
• 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), other than aerosolized corticosteroids, anytime within three months prior to participation
• Evidence for an opportunistic infection/colonization of the airways, i.e., non-bacterial
• Use of aerosolized corticosteroids with an inability to maintain inhaled corticosteroid therapy dosing without change during the study interval
• Evidence for systemic illness including hematologic disorders (defined by an absolute neutrophil count (ANC) < 4000 /mL and platelets < 120,000/mL), renal insufficiency (serum creatinine > 2.0 mg/dL), cirrhosis, or hepatic insufficiency (total bilirubin, or alkaline phosphatase > 1.5 x normal, SGOT, or SGPT > 1.2 x normal values), or a coagulopathy (INR > 1.4), seizure disorder.
• Evidence for systemic abnormal renal function manifested by uncontrolled hypertension (systolic blood pressure > 160mmHg or diastolic blood pressure >90mmHg), hyperkalemia (serum creatinine > 5.0 meq/dl, and/or elevated serum creatinine above the normal range for the subject's age.
• Evidence of coronary artery disease by history, e.g., angina or history of myocardial infarction within the past 12 months, unless corrected by CABG within < 5 years, and asymptomatic since
• Pregnant or breast feeding females or women of childbearing potential not practicing birth control during and for 6 months following treatment, or fertile and sexually active males unwilling to use contraceptive techniques 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 propylene glycol, CsA, or lidocaine
• Concurrent enrollment or participation within the prior month in other clinical trials
• Greater than 15% or 200 ml reduction in FEV1 post test dose propylene glycol administration
• 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