Role of the Isomerase Pin-1 in the Development and Treatment of Asthma

The investigators will test their hypothesis that Pin1 regulates TLR/IL-1R signaling
pathways in asthma by examining Pin1 and related pathway activation in BAL-derived
eosinophils after house dust mite allergen challenge. The investigators will perform
segmental allergen challenge. BAL and lung biopsy of the allergen-challenged segments will
be performed 48 hr later and activation of Pin1 and related pathways will be examined.

Inclusion criteria:

- Subjects 18-55 years of age, diagnosed with asthma for at least 1 year;

- And FEV1 > 70% predicted on only short acting beta agonists e.g albuterol

- And methacholine PC20 < 8 mg/ml

- Positive skin prick test to Dermatophagoides pteronyssinus(DerP)

- No prior history of intubation for asthma

- No use of inhaled corticosteroids for 1 month prior to entry

Exclusion criteria:

- Current smoking or smoking history of greater than 10 pack-years

- Any other clinically important comorbidity determined by the principal investigator
to affect subject safety, including uncontrolled diabetes, uncontrolled coronary
artery disease, acute or chronic renal failure, and uncontrolled hypertension that
would increase the risk of significant adverse events during bronchoscopy,

- Worsening of asthma symptoms requiring treatment with steroids within 4 weeks of
screening

- Respiratory infection within four weeks

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant or who are currently pregnant or lactating.

Unless they:

- Are women whose career, lifestyle, or sexual orientation precludes intercourse with a
male partner

- Are women whose partners have been sterilized by vasectomy or other means

- Use one acceptable birth control method. Adequate barrier methods of contraception
include: diaphragm, condom (by the partner), intrauterine device (copper or
hormonal), sponge or spermicide. Hormonal contraceptives include any marketed
contraceptive agent that includes an estrogen and/or a progestational agent.

- Pre-existing lung disease other than asthma

- History of coagulation disorders or abnormal PT/PTT testing at screening

- History of immunodeficiency diseases, including HIV

- A disability that may prevent the patient from completing all study requirements

- Use of other investigational drugs at the time of enrollment, or within 30 days or 5
half-lives of enrollment, whichever is longer

- History of malignancy of any organ system (other than localized basal cell carcinoma
of the skin), treated or untreated, within the past 5 years, regardless of whether
there is evidence of local recurrence or metastases.

- Diagnosis of Hepatitis B or C.

- History of alcohol abuse (as determined by the principal investigator) within 6
months of screening.

- History of illicit drug abuse (as determined by the principal investigator) within 6
months of screening.