Evaluation of Lovastatin in Severe Persistent Asthma

Inclusion Criteria:

- Age > 18 years to <65 years

- Severe persistent asthma (per 2002 National Asthma Education and Prevention Program
guidelines)

- Treatment with daily fluticasone (500 ug BID) and salmeterol (50 ug BID) during the
past 4 or more weeks

- Pre-bronchodilator FEV1 <80% predicted

- Post-bronchodilator improvement in FEV1 of at least 12% and 200 mL or a PC20 to
methacholine of <8 mg/mL

- Evidence of inadequate asthma control in the past 2 weeks: use of rescue inhaler > 4
days and >8 occasions in the past 2 weeks, daytime asthma symptoms > 4 days in the
past 2 weeks, or 1 or more nocturnal awakening in the past 2 weeks

- No evidence of alternate diagnosis (e.g., sarcoidosis, eosinophilic pneumonia) on
bronchoscopy performed as part of routine care in the Refractory Obstructive Lung
Disorders clinic.

- Completed research bronchoscopy while on current dose of daily fluticasone and
salmeterol within 4 weeks of meeting other inclusion criteria. Note: many patients
in the ROLD clinic require a bronchoscopy to confirm the diagnosis of asthma and
exclude other diagnosis (e.g., sarcoidosis). These patients are asked to participate
in a research protocol (separate from this proposal) that allows investigators to
collect additional samples (endobronchial biopsies, bronchoalveolar lavage fluid,
endobronchial brushings) at the end of the clinical portion of the bronchoscopy {IRB
protocol # 15361A entitled, "Airway inflammation in refractory obstructive lung
disease (ROLD): understanding markers of inflammation and remodeling"}. This
protocol was recently submitted to the IRB in March 2007.

Exclusion Criteria:

- Pregnancy or lactation

- Severe metabolic disease

- Other respiratory or inflammatory disorders (sarcoidosis, emphysema)

- Hypokalemia, dehydration

- Uncontrolled seizure disorder ( 2 or more seizures in last year)

- Major surgery, trauma

- Pre-existing liver disease (AST or ALT >10% above the upper limit of normal)

- Elevated CK (>50% above the upper limit of normal)

- History of alcohol abuse

- Current smokers or ex-smokers with > 10 pack-years of smoking

- Partial ileal bypass surgery

- Concurrent treatment with drugs known to be have potential interactions or associated
with rhabdomyolysis (Cimetadine, danazole, delavaridine, diltiazem, fenofiibrate,
nefazodone, niacin, protease inhibitors, quinipristoline/dalfopristin, ranolazine,
rifampin, telbivudine, telithromycin)

- HIV patients taking protease inhibitors

- History of allergy or intolerance to statin

- Use of 1 or more doses of any cholesterol lowering medication in the previous 12
weeks

- Clinical indication for treatment with statins