Cell Biology of Steroid Resistant Asthma
Cell Biology of Steroid Resistant Asthma
The hypothesis is that patients who demonstrate steroid resistant asthma by showing little or
 no improvement in lung function after a course of oral steroids have different cellular
 responses to steroids than patients who are steroid sensitive. These altered responses are
 the reason they demonstrate steroid resistance.
Current NHLBI guidelines for persistent asthma management recommends the use of steroids for
 treatment of airway inflammation (1,2). However, some asthmatics do not respond to steroids
 (3-6). Unfortunately these patients are subjected to the unwanted side effects (osteoporosis,
 cataracts, etc) of high dose steroid therapy because non-immune tissues remain sensitive to
 steroids. Recent studies suggest that the costs of asthma are largely attributable to
 uncontrolled disease (7). Thus, it is important to understand the mechanism(s) of steroid
 resistance and introduce new forms of therapy for the treatment of these difficult to control
 asthmatics. As a prelude to pharmaceutical studies in steroid resistant asthma, it is
 imperative to develop biomarkers that can robustly identify individuals likely to be poor
 steroid responders so that alternative non-steroid anti-inflammatory therapies, such as
 Xolair®, can be introduced early in the course of asthma therapy.
Inclusion Criteria:

 1. Will meet American Thoracic Society criteria for asthma

 2. Pulmonary function tests consistent with asthma. This includes a baseline FEV1 < 80%
 predicted as well as a 12% improvement in FEV1 following up to 4 puffs of albuterol.

 3. Subjects must be 12 to 65 years old.

 Exclusion Criteria:

 1. Viral infection within four weeks of the starting date.

 2. Abnormal hepatic function.

 3. History of COPD

 4. Pregnancy.

 5. History of smoking.

 6. Anemia (hemoglobin less than 12 gm %)

 7. Concurrent therapy with anticonvulsants, erythromycin, rifampin and any systemic
 asthma medication including Singular®, Xolair® or oral prednisone.

 8. Greater than 500 mcg per day of inhaled corticosteroids

 9. Suspected non-compliance with medical care.

 10. Abnormal prednisone pharmacokinetics (applies to phase 2 of trial)

 11. Patients with severe medical conditions that in the view of the investigator prohibits
 participation in the study (specify as required)

 12. Use of any investigational agent in the last 30 days