Role of microRNAs in T Cell-Driven Inflammation in Asthma (RITA)

This will be a single center study of asthmatic subjects and healthy controls which will investigate mechanisms of asthma through detailed molecular analysis of airway tissues and fluids. The primary goal will be investigate the role of microRNAs in Th2-driven inflammation in asthma. The investigators hypothesize that asthma is associated with abnormal expression of miRNAs in T cells which favors differentiation into Th2-cells. The investigators further hypothesize that asthma is heterogeneous based on the presence and absence of Th2-driven inflammation and that abnormalities in T cell miRNA expression will be most prominent in a subgroup with high levels of Th2-driven inflammation (as assessed using molecular markers that the investigators have previously established). Finally, the investigators hypothesize that inhaled corticosteroids will normalize the T-cell miRNA abnormalities observed in asthma, as corticosteroids treat Th2-driven inflammation. The samples collected will also facilitate the pursuit of secondary analyses designed to investigate mechanisms of inflammation and remodeling in asthma as well as molecular phenotypes of asthma.

Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression.

Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids.

Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids.

Identification of T cell miRNAs which are differentially expressed in asthma as compared to healthy controls. The investigators will measure a panel of ~200 miRNAs by qPCR (yielding normalized copy numbers for each miR) and identify differential expressed based on a false discovery rate <0.05. Normalized copy numbers from this qPCR experiment were established using the "global mean-normalization" approach as described in the paper by Barbara D'haene et al. entitled "miRNA expression profiling - from reference genes to global mean normalization" published in MicroRNA Expression profiling Methods and Protocols, Springer Verlag, Feb 2011.

Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment

Identification of T cell miRNAs which were reduced in asthmatics who were randomized to inhaled corticosteroids as compared to those randomized to no treatment. The investigators will measure the same miRNAs by qPCR as identified in the other Primary Outcome and define a significant change using a multiple comparison adjusted p-value (false discovery rate <0.05).

Group A: Inclusion Criteria: Male and female subjects between the ages of 18 and 70 years Group B: Inclusion Criteria: Male and female subjects between the ages of 18 and 70 years History of asthma No use of oral or inhaled corticosteroids for the treatment of asthma in the past 6 weeks Hyperreactivity to methacholine (PC20FEV1 Methacholine ≤ 8.0 mg/mL) At least one of the following symptoms, beta agonist use, or FEV1 criteria: Asthma symptoms on at least two days per week; OR Beta agonist use on at least two days per week; OR FEV1 < 85% predicted Groups A & B: Exclusion Criteria: Current smokers (smoking within the last 12 months) or former smokers who have a total pack-year smoking history greater than 10 Pregnant women Subjects with a history of lung disease other than asthma Subjects with a history of a medical disease, which in the opinion of the investigator may put the subject at extra risk from study-related procedures or because the disease may influence the results of the study