Molecular Phenotyping of Asthma in Sickle Cell Disease

Asthma recently has been described as a disorder of multiple subphenotypes despite a common
symptom presentation. These subphenotypes have differing molecular pathways and discovering
these differences may lead to better diagnosis strategies and new treatments. Most studies
investigating asthma pathways are driven by the scientist's own theories and experience and
thus, are considered biased. Metabolomics, an exciting and innovative discipline, represents
an unbiased, hypothesis free approach to defining a molecular phenotype of asthma.

Sickle cell disease is a common genetic disorder and there is ample evidence that asthma is
a common co-morbidity with an asthma prevalence of 2% to 45% compared with 12.8% in African
American children without sickle cell disease. Acute chest syndrome (ACS) contributes to the
cause of death in up to 60% of deaths in sickle cell patients and there is a strong
relationship between having asthma and the risk of developing ACS and an increased risk of
death.

Metabolomics is the study of the entire repertoire of small molecules present in cells,
tissues, organs and biological fluids that comprise the metabolome. Metabolomics measures
the downstream products of protein, gene, and environmental interactions and importantly,
comes closest to expressing phenotype, and provides the opportunity to explore gene by
environment and gene by gene interactions. A systems biology approach using metabolomics has
been advocated to better understand pulmonary disease.

Asthma in the sickle cell patient is likely to have a molecular fingerprint which can be
distinguished from asthma in the non-sickle cell patient. The investigator's specific aim is
to compare the urinary metabolomic profile of children with asthma and sickle cell disease
to children without asthma who have sickle cell disease, and to a cohort of African American
children with asthma but without sickle cell disease. The hypothesis is that children with
asthma and sickle cell disease will have a unique metabolomic profile that will discriminate
these patients from children with sickle cell disease who have respiratory dysfunction that
is not asthma, and from children with asthma who do not have sickle cell disease.

The investigators will collect a single saliva, urine and blood specimen from children with
asthma and sickle cell disease, children with sickle cell disease only, and African American
children with asthma only for metabolomic analysis. A single urine sample will be collected
from health African American children without any chronic diseases. Blood will be stored for
a future study to compare metabolomic variability between blood and urine. The
investigator's goal is to use this information to correctly identify children with asthma.
These data will enhance the investigator's understanding of the mechanisms that underlie the
molecular asthma phenotype in sickle cell disease, which should lead to more targeted
treatment of asthma in sickle cell disease. The investigators long-term goal is to reduce
the burden of asthma in the child with sickle cell disease (pain, ACS, and death) by using
this innovative systems biology approach.

Inclusion Criteria:

- Patients are aged 6 years old up to 21 years old

- Children with sickle cell disease with the genotype SS, SC, or S β 0 thal

- African American children with asthma who do not have sickle cell disease or sickle
cell disease trait.

- African American children with no chronic disease

- Physician diagnosed asthma and atopy (of any asthma severity) plus a family history
of asthma 89,90

- Patients whose controller respiratory medications and maintenance medications for
sickle cell disease (e.g. hydroxyurea) have been unchanged for the previous 4 weeks

Exclusion Criteria:

- Patients who are current smokers

- Patients who had an inflammatory event related to sickle cell disease (pain episode,
priapism, acute chest syndrome, urgent medical visit), asthma exacerbation, or
respiratory infection within 1 month prior to the blood, saliva, and urine
collection.

- Patients who are receiving chronic transfusion therapy and who have received a
transfusion within 90 days prior to blood, saliva, and urine collection.

- Patients who have received treatment with a leukotriene synthesis inhibitor or a
leukotriene modifier[montelukast (Singulair®)] within the 2 weeks prior to blood and
urine collection.

- Women who are pregnant or lactating