Clinical trial NCT01144910: The Long-term Prognosis of Moderate to Severe Bronchial Hyperresponsiveness (BHR) in Asthmatic Preschool Children
Official title: A Prospective, Open Label, Single-center Study of the Long-term Prognosis of Moderate to Severe Bronchial Hyperresponsiveness (BHR) in Asthmatic Preschool Children.
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Intrinsic Asthma
Allergic Asthma
Allergy
Bronchial Hyperresponsiveness
Keywords: asthma
preschool child
bronchial hyperresponsiveness
methacholine challenge test
atopy
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2010-06-16
Enrollment: 0
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients from the outpatient Department of Allergology, Pneumology and Cystic fibrosis, children's hospital, Goethe-University, Frankfurt, Germany

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of severe bronchial hyperresponsiveness over time of five years.
timeFrame: five years
Secondary outcomes:
measure: Bronchial responsiveness of parents
timeFrame: two years
measure: Impact of atopy
timeFrame: five years
measure: eNO
timeFrame: five years
measure: Total-IgE
timeFrame: five years
Other outcomes:
Locations:
city: Frankfurt am Main
country: Germany
facility: Goethe University
Study officials:
affiliation: Goethe University, Frankfurt, Germany
name: Johannes Schulze, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, Mitchell EA, Pearce N, Sibbald B, Stewart AW, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995 Mar;8(3):483-91. doi: 10.1183/09031936.95.08030483.
citation: Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1403-6. doi: 10.1164/ajrccm.162.4.9912111.
citation: Frank PI, Morris JA, Hazell ML, Linehan MF, Frank TL. Long term prognosis in preschool children with wheeze: longitudinal postal questionnaire study 1993-2004. BMJ. 2008 Jun 21;336(7658):1423-6. doi: 10.1136/bmj.39568.623750.BE. Epub 2008 Jun 16.
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citation: Schulze J, Rosewich M, Riemer C, Dressler M, Rose MA, Zielen S. Methacholine challenge--comparison of an ATS protocol to a new rapid single concentration technique. Respir Med. 2009 Dec;103(12):1898-903. doi: 10.1016/j.rmed.2009.06.007. Epub 2009 Jul 10.
citation: Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan;161(1):309-29. doi: 10.1164/ajrccm.161.1.ats11-99. No abstract available.
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