Progression of Airway Obstruction in Childhood Asthma
Condition: Asthma
MeSH terms: Asthma; Airway Obstruction; Disease Progression
Study type: Observational

Summary: 
      Distinct patterns of loss in pulmonary function were identified in children with mild to
      moderate asthma participating in a 10-year observation period during the NHLBI Childhood
      Asthma Management Program. This loss in pulmonary function is likely related to ongoing
      inflammation unresponsive to current therapy. This study will measure indicators of airway
      inflammation which are associated with structural and physiologic changes in the lung and
      provide insight into mechanisms of asthma progression in adolescence and early adulthood.
    

Detailed description: 
      The Childhood Asthma Management Program Continuation Study/Phase 2 is a 3.25 year
      observational follow-up study of the children enrolled in the Childhood Asthma Management
      Program (CAMP) randomized trial. CAMPCS/2 is a multicenter National Heart, Lung and Blood
      Institute program. The objective of the CAMPCS/2 is to determine the consequences of
      childhood asthma and its treatment on asthma outcomes in young adulthood. This separate
      ancillary study will extend the core CAMP/CAMPCS work by focusing on progression of airway
      obstruction in childhood asthma to evaluate mechanisms of progression and describe the
      differences in the four separate patterns in airway obstruction that have evolved over time.
      The four patterns of airway obstruction which have been identified are as follows: (1)
      abnormal obstruction present in early childhood which remained abnormal (Low/Low group) and
      (2) initially normal ratios, which worsened into the abnormal range over time (Normal/Low
      group). These patterns with unfavorable outcomes can be compared to two other patterns with
      favorable outcomes: (3) initially abnormal ratios improving with time (Low/Normal group) and
      (4) normal ratios throughout follow-up (Normal/Normal group).

      Based on these four patterns, three specific hypotheses related to immunology, structure, and
      physiology are identified:

        1. Among school-aged children with mild to moderate asthma, those children with increased
           airflow limitation (i.e. low FEV1/FVC) at the end of CAMPCS (Normal/Low and Low/Low
           groups) have elevated markers of inflammation related to proteolysis (i.e. neutrophil
           elastase, matrix metalloproteinase-9 (MMP9), and tissue inhibitor of metalloproteinase-1
           (TIMP1) and neutrophils in sputum).

        2. Subjects who show a pattern of early progression and failure to resolve (Low/Low group)
           have clinical evidence of steroid insensitivity compared to those with slow progression
           (Normal/Low group). They also have in vitro evidence of steroid resistance compared to
           the Normal/Low or Normal/Normal groups. This pattern of obstruction may be due to
           irreversible changes consistent with airway remodeling and inflammation that are
           relatively refractory to steroid therapy.

        3. Children with ongoing airflow limitation (Normal/Low and Low/Low groups) have more
           prominent structural changes related to increased air trapping and airway thickening
           compared to those with normal FEV1/FVC at the end of CAMPCS (Low/Normal and
           Normal/Normal groups).

      Each participant will be studied at varying times over the 2-year study period. Researchers
      will complete a collection of sputum, blood, urine, and exhaled breath condensate samples;
      exhaled nitric oxide; and spirometry from CAMPCS/3 participants, representing each of the
      four phenotypes (n = 20 for a total of 80).
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Participants enrolled in CAMPCS/3 from various CAMP sites will be invited to participate in
        this study.
      
Biospecimen description: 
      Induced sputum, urine, blood, and exhaled breath condensates
    
Keywords: Asthma Progression; Airway Wall Thickness; Corticosteroid Resistance; Biomarkers; Pulmonary Physiology