Molecular Phenotyping of Asthma in Sickle Cell Disease
Condition: Sickle Cell Disease; Asthma
MeSH terms: Asthma; Anemia, Sickle Cell
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Three groups of 30 children each will be studied: Group 1, children with asthma and sickle
        cell disease; Group 2, children with sickle cell disease but without asthma; Group 3,
        control group of 30 African American children with asthma but without sickle cell disease ;
        Group 4, healthy control group of 25 African American children with no chronic disease. All
        children are seen at Nemours Children's Clinics in Jacksonville FL, Orlando FL, or
        Wilmington DE.
      
Biospecimen description: 
      Blood (RBC, WBC, DNA), urine, and saliva
    
Keywords: Sickle cell disease; Asthma; Metabolomics; Gene expression