Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)

Inhaled corticosteroids (ICS) are considered first-line therapy for the management and
control of patients with persistent asthma. Use of inhaled steroids has been associated with
improved lung function, diminished symptoms, and fewer exacerbations. However studies show
considerable inter-subject variability in ICS response. It has also been estimated that
corticosteroid resistance accounts for half of all asthma-related health care costs.
Therefore, identifying factors associated with ICS response is both clinical and economically
important. African-American patients have been understudied with respect to genetic
predictors of asthma controller medication response, and to date there have been no
sufficiently powered genome-wide association studies of ICS treatment response among African
American individuals with asthma. This issue is of particular importance, since
African-American individuals are disproportionately affected by asthma-related complications.
In this proposal, we seek to identify novel genetic loci associated with ICS treatment
responsiveness (defined by the change in Asthma Control Test score) among African American
individuals treated with beclomethasone dipropionate (BD) for 6 weeks. We will attempt to
validate loci identified in the discovery set by 1) reassessing these variants for their
interaction with ICS treatment on asthma exacerbations in a separate group of African
American individuals with asthma, and 2) by reexamining the genetic association with change
in asthma control among similarly treated (i.e., treatment with 6 weeks of BD) European
Americans with asthma.

Inclusion Criteria for Discovery Group:

- Age 12-56 years

- Physician diagnosis of asthma (identified by using encounter data prior to screening
and by the survey administered at the clinic visit)

- Bronchodilator reversibility on pulmonary function testing (i.e., improvement in
baseline FEV1 of >12%)

- African-American/Black self-reported race-ethnicity

Exclusion Criteria for Discovery Group:

- Smoking in the preceding year or <10 pack-year smoking history total

- Pregnant at the time of enrollment or intending to get pregnant during the 6-week
treatment period

- Oral or inhaled corticosteroid use in the 4 weeks preceding enrollment

- Prior diagnosis of chronic obstructive pulmonary disease or emphysema

- Prior diagnosis of congestive heart failure

- Self-reported race not African-American/Black or Hispanic ethnicity (these groups
could be included in Replication/Validation group)