The Long-term Prognosis of Moderate to Severe Bronchial Hyperresponsiveness (BHR) in Asthmatic Preschool Children

Study Overview
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Brief Summary
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The aim of investigator´s clinical trial is to investigate 52 patients aged three to five years with viral-induced asthma and 52 patients aged three to five years with allergic asthma. Over a time-span of 5 years the investigators will explore lung function and bronchial responsiveness. The investigators plan to evaluate long-term clinical history of moderate to severe bronchial hyperresponsiveness in preschool children with asthma. Therefore factors like atopy in children, parental atopy and bronchial hyperresponsiveness will be explored.

Detailed Description
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A positive family history with prevalence of atopy, eczema, wheezing are well-known factors predicting asthma. Caudri et al. found more important predictors like perinatal transmission, parental use of inhalative medications and wheezing/dyspnea out of viral infections(5). Measurement of BHR in children was in most studies a second outcome parameter. Four visits will be performed, baseline and after 1, 3, and 5 years. At visit 1 the investigators will characterize all patients by a ISAAC survey. At each visit in children a methacholine challenge, a skin Prick test, eNO, RAST and total IgE will be performed. At visit 3 and 4 sputum will be induced. In parents only at the first visit a methacholine challenge will be performed. A genetic identification of ADAM33 gene from EDTA blood shall be provided. ADAMs are multidomain proteins with a metalloprotease domain, associated with airway remodelling. Visits should be kept in a time interval without asthma therapy and respiratory infection. To examine the feasibility of methacholine challenges in preschool children data measured in 2006 will be analysed.

Official Title
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A Prospective, Open Label, Single-center Study of the Long-term Prognosis of Moderate to Severe Bronchial Hyperresponsiveness (BHR) in Asthmatic Preschool Children.

Conditions
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Intrinsic Asthma, Allergic Asthma, Allergy, Bronchial Hyperresponsiveness

Intervention / Treatment
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* Other: methacholine challenge test
* Other: methacholine challenge test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent age 3 to 6 years diagnosis asthma pulmonary function: FEV1 (% pred.)≥ 70% ability to carry out 2 reproducible flow volume loops moderate to severe BHR (PD20 FEV1 ≤ 0,3 mg methacholine) more than 4 weeks interval since last infection 8 hours washout period of Short Acting Beta Agonist 1 week washout period of Ipratropium Bromide 1 week washout period of Long Acting Beta Agonist 4 weeks washout period of Systemic Corticosteroids 4 weeks washout period of Leukotriene Antagonists Exclusion Criteria: Age < 3 and > 6 Years Pulmonary function test: FEV1 (% pred.) < 70% Others chronic diseases or infections (e.g., HIV, tuberculosis, malignancy) Incapability to perform spirometry Current participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BHR non-atopy<br>Patients from the outpatient Department of Allergy, Pneumology and Cystic fibrosis, children's hospital, Goethe-University, Frankfurt, Germany. Over a time-span of 5 years the investigators will explore the lung function and the bronchial hyperresponsiveness. Bronchial methacholine challenges will be performed at baseline and after 1, 3 and 5 years. | Other: methacholine challenge test<br>* 2 ml of liquid-dissolved methacholine in concentration of 16 mg/ml dosed in 5 steps of 0.01 mg, 0.1 mg, 0.4 mg, 0.8 mg, and 1.6 mg. 2 minutes after each step up an impulse oscillometry (IOS) and spirometry will be performed. the challenge will be stopped in case of a ≥ 20% decrease from baseline in FEV1 (PD20) and 0,2 mg Salbutamol will be given.<br>* Other names: There are no other names;|
| BHR atopy<br>Patients from the outpatient Department of Allergy, Pneumology and Cystic fibrosis, children's hospital, Goethe-University, Frankfurt, Germany. Over a time-span of 5 years the investigators will explore the lung function and the bronchial hyperresponsiveness. Bronchial methacholine challenges will be performed at baseline and after 1, 3 and 5 years. | Other: methacholine challenge test<br>* 2 ml of liquid-dissolved methacholine in concentration of 16 mg/ml dosed in 5 steps of 0.01 mg, 0.1 mg, 0.4 mg, 0.8 mg, and 1.6 mg. 2 minutes after each step up an impulse oscillometry (IOS) and spirometry will be performed. the challenge will be stopped in case of a ≥ 20% decrease from baseline in FEV1 (PD20) and 0,2 mg Salbutamol will be given.<br>* Other names: There are no other names.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of severe bronchial hyperresponsiveness over time of five years. | Bronchial hyperresponsiveness will be defined by the provocation dose (PD) of methacholine causing a 20% drop of FEV1 (PD-20FEV1). | five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bronchial responsiveness of parents | In parents at first visit bronchial hyperresponsiveness will be defined by the provocation dose (PD) of methacholine causing a 20% drop of FEV1 (PD-20FEV1). | two years | 
| Impact of atopy | Influence of atopy on the time course of bronchial hyperresponsiveness. | five years | 
| eNO | Influence of the level of exhaled NO on the time course of BHR. | five years | 
| Total-IgE | Influence of the level of total-IgE on the time course of BHR | five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, preschool child, bronchial hyperresponsiveness, methacholine challenge test, atopy