Asthmatics who are significantly overweight tend to have more severe symptoms, more flare ups, and are more likely to have poorly-controlled asthma when compared to other asthmatics.

Researchers believe this occurs because excess adipose tissue (fat) in the body can cause higher-than-normal levels of leptin and lower-than-normal levels of adiponectin in the blood.

The researchers of this study are testing a medication called pioglitazone in overweight asthmatics because they believe it can help regulate leptin and adiponectin and that this may improve symptoms of asthma.

Participants in this study will be randomly assigned (like the flip of a coin) to pioglitazone or a placebo (an inactive pill). They will be given study medication to take everyday for 12 weeks (3 months).

Participants will complete a number of asthma-related questionnaires and a variety of pulmonary function tests. Participants will undergo physical exams, an electrocardiogram, and blood sampling to measure leptin, adiponectin, markers of inflammation, blood cell counts, glucose levels, BNP hormone levels, and liver function.

To monitor participants throughout the study, follow-up visits will be done at 2, 6, and 12 weeks after starting study drug. At these visits many of the pulmonary function tests and questionnaires will be repeated.

Inclusion Criteria:

• Asthma diagnosed by a physician at least 1 year prior to study enrollment
• Poorly-controlled asthma at study enrollment
• Non smokers (stopped smoking at least 1 year ago) and limited life-time history of smoking
• Body mass index 30-60
• Responds to methacholine challenge test with PC20 of <16 mg/ml
• On a stable dose of inhaled corticosteroid for at least 4 weeks prior to study entry
• FEV1 >60% predicted
• Able to obtain weekly weights at home

Exclusion Criteria:

• Systemic steroids within the past 4 weeks
• Lung pathology other than asthma
• Other significant non-pulmonary co-morbidities such as: coronary artery disease, peripheral vascular disease, cerebrovascular disease, congestive heart failure with an ejection fraction <50%, liver disease or elevated liver enzymes at baseline, malignancy (excluding non-melanoma skin cancers), AIDS, renal failure with serum creatinine >3.0, or disorders requiring steroid treatment such as vasculitis, lupus, rheumatoid arthritis
• B-type natriuretic peptide (BNP) >400 pg/mL
• Pregnant or lactating
• Currently taking a beta blocker, a CYP2C8 inhibitor or inducer such as gemfibrozil or rifampin, a TZD (thiazolidinedione), or allergic to TZD
• Taking antioxidants or nutritional supplements (stable dose of calcium, vitamin D, or multivitamin is OK)
• Illicit drug use within the past year
• Current/active upper respiratory infection (if active URI, wait until asymptomatic for 1 week to enroll)
• Asthma exacerbation within the past 4 weeks (includes ER, urgent care, or hospital visits due to asthma resulting in an increase in asthma-related medications)
• Undergoing evaluation for sleep apnea, or plans to institute treatment for sleep apnea (patients on a stable treatment regimen for sleep apnea for the last 3 months will be allowed to participate)
• Clinically significant abnormalities present on screening 12-lead electrocardiogram
• Women of childbearing potential using oral contraceptives who are not willing to use a second method of contraception during the study