CompletedNCT00873873Updated Oct 22, 2020Results posted

Progression of Airway Obstruction in Childhood Asthma

An observational study in Asthma, sponsored by National Jewish Health. Completed at 1 site in United States. Open to participants aged 16 Years to 40 Years. Per ClinicalTrials.gov, last updated 2020-10-22.

Sponsored by National Jewish Health · Observational

Study type: Observational
Model: Cohort
Time perspective: Prospective
Enrollment: 55
Ages: 16 Years to 40 Years
Sex: All

Study 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.

Read the 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:

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).
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.
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).

Conditions studied

Asthma

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Keywords

Asthma Progression
Airway Wall Thickness
Corticosteroid Resistance
Biomarkers
Pulmonary Physiology

In context

Asthma

3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.

This study's enrollment of 55 is below the median of 150 across 970 observational studies indexed under Asthma.

Browse Asthma studies →

Lead sponsor

National Jewish Health is the lead sponsor of 108 studies on the registry; 14 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 16 Years to 40 Years
Sexes eligible: All
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.

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

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)

Study design

Observational model: Cohort
Time perspective: Prospective
Enrollment: 55 participants (actual)
Biospecimen retention: Samples without dna

Groups and 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)

What researchers measure

Primary outcomes

Airway Wall Thickness
Segmental average airway wall thickness
Time frame: Measured at Year 2

Secondary outcomes

Protease/Antiprotease
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.
Time frame: Measured at Year 2

Results

Posted Jan 6, 2012

Limitations and caveats

We had planned to extend invitations to the remaining 55 participants in a streamlined version of this protocol after analyzing the preliminary data and an additional cycle of CAMP was funded in 2007.

Participant flow

The NHLBI Childhood Asthma Management Program (CAMP) and CAMP Continuation Studies afforded a unique opportunity to investigate four newly described, distinct patterns of airway obstruction associated with childhood asthma, including two that have been associated with significant and potentially irreversible loss in pulmonary function.

Participant flow — Overall Study
Milestone	Persistent Obstruction	Late Obstruction in Pulmonary Physiology	Late Normal in Pulmonary Physiology	Persistent Normal in Pulmonary Physiology
Started	20	8	9	18
Completed	20	8	9	18
Not completed	0	0	0	0

Outcome measures

PrimaryAirway Wall Thickness

Segmental average airway wall thickness

Time frame:: Measured at Year 2
Reported as:: Mean · mm

Airway Wall Thickness
mm	Persistent Obstruction	Late Obstruction	Late Normal	Persistent Normal
Airway Wall Thickness	1.5 ± 0.2	1.5 ± 0.2	1.4 ± 0.1	1.6 ± 0.3

Statistical analysis

Persistent Obstruction vs Late Obstruction vs Persistent Normal · ANOVA · p = 0.2

SecondaryProtease/Antiprotease

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.

Time frame:: Measured at Year 2
Reported as:: Mean · ratio

Protease/Antiprotease
ratio	Persistent Obstruction	Late Obstruction	Late Normal	Persistent Normal
Protease/Antiprotease	34.1 ± 58.8	29.3 ± 31.3	9.9 ± 8.4	12.1 ± 9.0

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Persistent Obstruction	—	0/20 (0%)	0/20 (0%)
Late Obstruction in Pulmonary Physiology	—	0/7 (0%)	0/7 (0%)
Late Normal in Pulmonary Physiology	—	0/9 (0%)	0/9 (0%)
Persistent Normal in Pulmonary Physiology	—	0/18 (0%)	0/18 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Persistent Obstruction	Late Obstruction in Pulmonary Physiology	Late Normal in Pulmonary Physiology	Persistent Normal in Pulmonary Physiology	Total
<=18 years	3	2	1	3	9
Between 18 and 65 years	17	6	8	15	46
>=65 years	0	0	0	0	0

Age, Continuous
Age, Continuous(years)	Persistent Obstruction	Late Obstruction in Pulmonary Physiology	Late Normal in Pulmonary Physiology	Persistent Normal in Pulmonary Physiology	Total
Mean	20.0 ± 2.1	18.9 ± 2.0	20.8 ± 2.4	19.9 ± 2.0	20.0 ± 2.1

Sex: Female, Male
Sex: Female, Male(Participants)	Persistent Obstruction	Late Obstruction in Pulmonary Physiology	Late Normal in Pulmonary Physiology	Persistent Normal in Pulmonary Physiology	Total
Female	8	2	6	11	27
Male	12	6	3	7	28

Region of Enrollment
Region of Enrollment(participants)	Persistent Obstruction	Late Obstruction in Pulmonary Physiology	Late Normal in Pulmonary Physiology	Persistent Normal in Pulmonary Physiology	Total
United States	20	8	9	18	55

Study locations

1 site

National Jewish Health
Denver, Colorado 80206, United States

References and documents

Publications

Childhood Asthma Management Program Research Group; Szefler S, Weiss S, Tonascia J, Adkinson NF, Bender B, Cherniack R, Donithan M, Kelly HW, Reisman J, Shapiro GG, Sternberg AL, Strunk R, Taggart V, Van Natta M, Wise R, Wu M, Zeiger R. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000 Oct 12;343(15):1054-63. doi: 10.1056/NEJM200010123431501. PubMed 11027739 ↗
Covar RA, Spahn JD, Murphy JR, Szefler SJ; Childhood Asthma Management Program Research Group. Progression of asthma measured by lung function in the childhood asthma management program. Am J Respir Crit Care Med. 2004 Aug 1;170(3):234-41. doi: 10.1164/rccm.200308-1174OC. Epub 2004 Mar 17. PubMed 15028558 ↗
Strunk RC, Weiss ST, Yates KP, Tonascia J, Zeiger RS, Szefler SJ; CAMP Research Group. Mild to moderate asthma affects lung growth in children and adolescents. J Allergy Clin Immunol. 2006 Nov;118(5):1040-7. doi: 10.1016/j.jaci.2006.07.053. PubMed 17088127 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 22, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00873873
Lead sponsor: National Jewish Health
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Responsible party: Sponsor
First posted: Apr 2, 2009
Start date: Sep 2008
Primary completion: Jun 2011
Completion: Jun 2011
Results posted: Jan 6, 2012
Last update: Oct 22, 2020

Study contacts

Stanley J. Szefler, MD

principal investigator · National Jewish Health

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2020. You cannot join it, but the record below documents what was studied.

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