Molecular Phenotyping of Asthma in Sickle Cell Disease
Molecular Phenotyping of Asthma in Sickle Cell Disease
Asthma and sickle cell disease each are serious medical problems. People with asthma have
 difficulty breathing, wheeze (a whistling noise when breathing), cough, produce sputum or
 phlegm, and have inflammation (swelling, irritation, redness) and narrowing of the bronchial
 tubes.

 When a person has both asthma and sickle cell disease together, more serious medical problems
 can occur such as having acute chest syndrome and pain episodes more often. It is sometimes
 hard to diagnose asthma in a person with sickle cell disease because sickle cell disease can
 also cause lung problems.

 The purpose of this study is to see if the investigators can better understand asthma when it
 occurs in a person who has sickle cell disease. The investigators will do this by taking a
 blood, urine, and saliva sample. The blood and urine samples will be analyzed for chemicals
 and DNA (genes). Certain genes can cause patients to have sickle cell disease or asthma. The
 investigators will use the saliva sample for future studies to compare the results from the
 blood testing with saliva. The investigator's long-term goal is to make sure people who have
 asthma and sickle cell disease are getting the best asthma treatments. The investigator's
 hypothesis is that the analysis of the blood, urine and saliva using a method called,
 metabolomics, may identify a unique asthma signature in children with sickle cell disease
 which may lead to targeted treatments.
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