Progression of Airway Obstruction in Childhood Asthma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stanley Szefler, National Jewish Health
ClinicalTrials.gov Identifier:
NCT00873873
First received: April 1, 2009
Last updated: January 30, 2012
Last verified: January 2012
  Purpose

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.


Condition
Asthma

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Progression of Airway Obstruction in Childhood Asthma

Resource links provided by NLM:


Further study details as provided by National Jewish Health:

Primary Outcome Measures:
  • Airway Wall Thickness [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]
    Segmental average airway wall thickness


Secondary Outcome Measures:
  • Protease/Antiprotease [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]

    MMP9/TIMP 1 molar ratio MMP9 is matrix metalloproteinse 9 and is a protease enzyme that is responsible for tissue degradation of extracellular matrix and could be a factor in airway remodeling.

    TIMP 1 is an abbreviation for tissue inhibitor of metalloproteinase-1 and is an inhibitor of MMP9 and would serve to balance the activity protease activity of MMP9 and this it is an anti-protease.

    Therefore the ratio of MMP9 and TIMP1 is used to assess the relative balance of protease and antiprotease activity.



Biospecimen Retention:   Samples Without DNA

Induced sputum, urine, blood, and exhaled breath condensates


Enrollment: 55
Study Start Date: September 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Persistent obstruction
(pattern of asthma progression)
Late obstruction
(pattern of asthma progression)
Late normal
(pattern of asthma progression)
Persistent normal
(pattern of asthma progression)

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).

  Eligibility

Ages Eligible for Study:   16 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Participants enrolled in CAMPCS/3 from various CAMP sites will be invited to participate in this study.

Criteria

Inclusion Criteria:

  • Must be enrolled in the CAMPCS/3 study; individuals enrolled in this study will represent four different patterns of asthma progression, as defined by forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) levels

Exclusion Criteria:

  • Unwilling to comply with study procedures
  • Physical state does not allow the study procedures to be performed (e.g., low pulmonary function for induced sputum, pregnancy for computerized tomography [CT] scan)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00873873

Locations
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
Sponsors and Collaborators
National Jewish Health
Investigators
Principal Investigator: Stanley J. Szefler, MD National Jewish Health
  More Information

Publications:
Responsible Party: Stanley Szefler, Head, Pediatric Clinical Pharmacology, National Jewish Health
ClinicalTrials.gov Identifier: NCT00873873     History of Changes
Other Study ID Numbers: 645, R21HL087811-01
Study First Received: April 1, 2009
Results First Received: November 27, 2011
Last Updated: January 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Jewish Health:
Asthma Progression
Airway Wall Thickness
Corticosteroid Resistance
Biomarkers
Pulmonary Physiology

Additional relevant MeSH terms:
Airway Obstruction
Asthma
Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Bronchial Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 21, 2014