Observational Assessment of Baseline Asthma Control in African-American Children

In the general public, certain sub-populations are at higher risk for adverse health effects
due to air pollution exposure. Asthmatics have been identified as one such susceptible
population due to the observed association of elevated air pollution levels and increased
incidences of acute asthma exacerbations as evidenced by decreased lung function values and
respiratory symptoms, shortness of breath, emergency department (ED) visits, and
hospitalizations (6-13). A study conducted by Mar et al (2004) reported that health outcomes
associated with coarse particulate matter (PM2.5-10) were more notable in children with
asthma than in adults with asthma (14) and a large epidemiological study of asthmatic
children in the Northeastern US showed that asthma morbidity on high ozone days was
consistently highest among children age 6 to 18 years (15). Furthermore, children with
persistent asthma (requiring daily maintenance medication) were shown to be at increased
risk of respiratory symptoms and rescue medication use after ambient ozone exposure compared
to children with mild intermittent asthma (16). Together, these studies demonstrate an
additional level of susceptibility to air pollution in children compared with adults and in
children with persistent asthma compared with mild intermittent asthma.

African-American patients appear to be particularly susceptible to asthma-related
complications, with rates of asthma-related emergency department visits, hospitalizations,
and death approximately 2 to 3 times the rates found in Caucasian subjects (17) .
Furthermore, a higher proportion of African-American asthmatics have poorly-controlled
asthma compared to non-African-American asthmatics (18). In a recent pediatric study, very
poorly controlled asthmatics had an increased risk of asthma-related hospitalization,
emergency department visits, or corticosteroid burst (OR, 6.4; 95% CI, 1.2-34.5) compared
with those whose asthma was under better control over a 2-year period (19).

The goal of this panel study is to determine if African-American children with
poorly-controlled moderate-to-severe persistent asthma are at increased risk for
cardiopulmonary effects as a result of ambient air pollution exposure compared to age- and
race-matched well-controlled moderate-to-severe asthmatic children. The primary cohort for
this panel study will be African-American children between the ages of 12-17 years with
moderate-to-severe asthma (divided between the study populations of poorly-controlled asthma
and well-controlled asthma). Since this study is exclusively focused on an African-American
population, it is not designed to address the effect of race/ethnicity on baseline asthma
control. Volunteers will be recruited primarily from the UNC Pediatric Pulmonary clinic and
the UNC Allergy/Immunology clinic located at Rex Hospital in Raleigh, NC in which Dr.
Hernandez is an attending physician. These volunteers are well-characterized asthmatics
followed regularly by a pediatric pulmonologist (Dr. Ceila Loughlin) and by a pediatric
allergist (Dr. Michelle Hernandez) at the Rex location. In order to ensure that the two
cohorts experience equivalent daily exposures to ambient air pollutants, the study
population will be recruited from a defined geographical region within a reasonable driving
distance of the Rex Hospital and in relative proximity to the state-operated monitoring
station for ambient air pollutants.

Establishing a relationship between asthma control and adverse health outcomes in response
to air pollution exposure will provide health care providers and parents of children with
moderate-to-severe asthma the information necessary to take proactive action on high air
pollution days as they are communicated to the public through color-coded days based on the
National Ambient Air Quality Standards (NAAQS) established by the EPA. If asthma control is
determined in this study to be a risk factor for susceptibility, future work will be
directed toward establishing the mechanism underlying the susceptibility which may then lead
to the potential design of new therapies or intervention strategies.

Inclusion Criteria for all subjects:

1. Self-identified as African-American

2. Ages 12-17 years

3. Live within convenient driving distance of the UNC Rex Clinic in Raleigh, NC.

4. Physician-diagnosis of moderate-to-severe persistent asthma

5. Current treatment with appropriate therapy for moderate-to-severe persistent asthma
symptoms as per the NHLBI guidelines including: Daily controller medication use for
asthma requiring at least a medium-dose inhaled corticosteroids (ICS) or a low dose
ICS + long-acting beta2 agonist (LABA) combination. Subjects may use daily or every
other day oral corticosteroids for control of asthma symptoms

Inclusion criteria for well-controlled asthmatics (from NHLBI guidelines):

1. Nighttime awakening with asthma symptoms ≤ 2x/month over the past 6 months

2. Use of short-acting beta2 agonist for symptom control ≤ 2 days /week over the past 6
months

3. Asthma Control Test score >19. The Asthma Control Test is a standardized clinical
tool to assess asthma control over the previous 4 week period (attached).

4. Baseline FEV1(pre-albuterol) > 80% of that predicted for gender, ethnicity, age and
height (NHANES III predicted set)

Inclusion criteria for poorly-controlled asthmatics (from NHLBI guidelines):

1. Nighttime awakening with asthma symptoms > 2x/month over the past 6 months

2. Use of short-acting beta2 agonist for symptom control > 2 days /week over the past 6
months

3. Asthma Control Test score <19. The Asthma Control Test is a standardized clinical
tool to assess asthma control over the previous 4 week period (attached).

4. Baseline FEV1 (pre-albuterol) < 80% of that predicted for gender, ethnicity, age and
height (NHANES III predicted set)

Exclusion criteria for all subjects:

1. Children younger than age 12 and older than 17

2. Children unable to perform spirometry

3. Medical history or underlying health problems that may preclude participation in the
protocol per the study physician (including but not limited to cystic fibrosis,
chronic bronchitis, recurrent pneumonia, immunodeficiency, hematologic disorders)

4. History of bleeding disorder or anemia

5. Subjects and families unwilling to travel to the clinic for the required 6 visits

6. Unwilling or unable to refrain from the following medications for the week prior to
the study as well as the week of the study including fish oil; anti-inflammatory
agents such as ibuprofen (Advil, Motrin), naproxen (Aleve) or aspirin as needed**.
Acetaminophen (Tylenol) is allowed.**If the child requires anti-inflammatory
medications for a fever or joint/muscle pain, in the week prior to the study visit,
all subsequent visits may be rescheduled.

7. Other uncontrolled health problems

8. Non-English speaking subjects