Characterizing Asthma Sputum Elasticity in the UCSF Severe Asthma Research Program
Condition: Asthma
MeSH terms: Asthma
Study type: Observational

Summary: 
      This study is designed to characterize subjects in terms of their sputum phenotype. The
      purpose of this study is to learn more about the impact of having abnormally elastic sputum
      on asthma severity by comparing subjects with severe as well as mild/moderate asthma to
      healthy controls. The characterization will include medical history, pulmonary function
      testing, imaging of the lungs and biospecimen collection.
    

Detailed description: 
      Asthma is a heterogeneous disease characterized by airway hyperreactivity and chronic airway
      inflammation. Published literature from the last few years has shown that asthma does not
      behave like a single disease but is more of a syndrome with vast heterogeneity in
      pathogenesis, severity, and treatment response. Various clinical phenotypes and endotypes
      have been described that advance our understanding of these differences and the mechanisms
      underlying them. We propose there is a subgroup of asthmatic patients that have sputum with
      abnormal biophysical properties. Healthy airway mucus is composed of a lightly cross-linked
      gel that is easily transported by the mucociliary apparatus, coughed and expectorated or
      swallowed. Pathologic mucus has, in contrast, abnormally high elasticity. This is due to a
      more cross linked structure which gives the sputum the properties of solid and makes sputum
      difficult to mobilize. Increased sputum elasticity makes expectoration of sputum more
      difficult and leads to airflow obstruction. Pathologic mucus contributes to airflow
      obstruction and airway infection in multiple lung diseases, including asthma. Mucus plugs are
      a particular problem in asthmatic patients with allergic bronchopulmonary aspergillosis
      (ABPA)The identification of phenotype of severe asthma with pathologic mucus contributing to
      disease severity may change how we think about severe asthma, moving towards therapies
      targeting mucus clearance such as in other conditions such as cystic fibrosis. Pathologic
      mucus in severe asthma is characterized by cellular inflammation, high concentrations of
      mucins and DNA polymers. Knowledge of specific cellular and biochemical constituents of
      pathologic mucus in severe asthma can guide targeted mucolytic treatment with
      n-acetylcysteine, rhDNAse, or novel mucolytic agents.

      As part of the Severe Asthma Research Program (SARP), UCSF is in a unique position to recruit
      a large number of severe asthmatic subjects within which we expect a portion will demonstrate
      high sputum elasticity. We will also through CAESAR recruit additional subjects with moderate
      to severe airflow obstruction. We will perform rheological measurement on all subjects that
      are recruited to our site and from this identify a group of asthmatic cases that have an
      elastic modulus of ≥1 or <1 and compare properties of sputum from these subjects to healthy
      controls.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        A diverse sample of subjects with asthma is needed to gain better understanding of asthma
        and its endotypes. CAESAR will therefore enroll subjects between 18 and 65 years with a
        physician diagnosis of asthma as well as a group of healthy subjects. The target
        recruitment goal for UCSF is 50 adults with asthma and 25 healthy controls (age 18 and
        older). Within the asthma group, an attempt will be made to enroll 60% of subjects with
        severe with the rest of the subjects mild to moderate asthma.Within the cohort, an attempt
        will be made to enroll at least 50% females and 10% minorities.
      
Biospecimen description: 
      Samples of induced sputum and blood for DNA and RNA extraction, plasma, and serum will be
      banked in the UCSF Airway Tissue Bank.
    
Keywords: Severe asthma; Sputum; Mucolysis