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

NCT ID: NCT01144910

Last Updated: 2017-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2011-05-31

Study Completion Date

2017-09-30

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.

Conditions

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Intrinsic Asthma Allergic Asthma Allergy Bronchial Hyperresponsiveness

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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BHR non-atopy

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.

methacholine challenge test

Intervention Type OTHER

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.

BHR atopy

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.

methacholine challenge test

Intervention Type OTHER

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.

Interventions

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methacholine challenge test

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.

Intervention Type OTHER

methacholine challenge test

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.

Intervention Type OTHER

Other Intervention Names

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There are no other names There are no other names.

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
Minimum Eligible Age

3 Years

Maximum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johann Wolfgang Goethe University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Johannes Schulze MD

Cosultant, Pediadric Allergy, Pulmonology and Cystic fibrosis

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Johannes Schulze, Dr.

Role: PRINCIPAL_INVESTIGATOR

Goethe University, Frankfurt, Germany

Locations

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Goethe University

Frankfurt am Main, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 7789502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11029352 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18558639 (View on PubMed)

Matricardi PM, Illi S, Gruber C, Keil T, Nickel R, Wahn U, Lau S. Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Eur Respir J. 2008 Sep;32(3):585-92. doi: 10.1183/09031936.00066307. Epub 2008 May 14.

Reference Type BACKGROUND
PMID: 18480107 (View on PubMed)

Caudri D, Wijga A, A Schipper CM, Hoekstra M, Postma DS, Koppelman GH, Brunekreef B, Smit HA, de Jongste JC. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age. J Allergy Clin Immunol. 2009 Nov;124(5):903-10.e1-7. doi: 10.1016/j.jaci.2009.06.045. Epub 2009 Aug 8.

Reference Type BACKGROUND
PMID: 19665765 (View on PubMed)

Pijnenburg MW, Bakker EM, Hop WC, De Jongste JC. Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial. Am J Respir Crit Care Med. 2005 Oct 1;172(7):831-6. doi: 10.1164/rccm.200503-458OC. Epub 2005 Jun 23.

Reference Type BACKGROUND
PMID: 15976380 (View on PubMed)

Illi S, von Mutius E, Lau S, Niggemann B, Gruber C, Wahn U; Multicentre Allergy Study (MAS) group. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet. 2006 Aug 26;368(9537):763-70. doi: 10.1016/S0140-6736(06)69286-6.

Reference Type BACKGROUND
PMID: 16935687 (View on PubMed)

Nuijsink M, Hop WC, Sterk PJ, Duiverman EJ, de Jongste JC. Long-term asthma treatment guided by airway hyperresponsiveness in children: a randomised controlled trial. Eur Respir J. 2007 Sep;30(3):457-66. doi: 10.1183/09031936.00111806. Epub 2007 May 30.

Reference Type BACKGROUND
PMID: 17537770 (View on PubMed)

Beydon N. Pulmonary function testing in young children. Paediatr Respir Rev. 2009 Dec;10(4):208-13. doi: 10.1016/j.prrv.2009.03.001. Epub 2009 Sep 25.

Reference Type BACKGROUND
PMID: 19879511 (View on PubMed)

Beydon N. Assessment of bronchial responsiveness in preschool children. Paediatr Respir Rev. 2006;7 Suppl 1:S23-5. doi: 10.1016/j.prrv.2006.04.016. Epub 2006 Jun 5.

Reference Type BACKGROUND
PMID: 16798575 (View on PubMed)

Holgate ST, Davies DE, Powell RM, Howarth PH, Haitchi HM, Holloway JW. Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms. Eur Respir J. 2007 Apr;29(4):793-803. doi: 10.1183/09031936.00087506.

Reference Type BACKGROUND
PMID: 17400878 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19596563 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10619836 (View on PubMed)

Hagmolen of ten Have W, van den Berg NJ, van der Palen J, Bindels PJ, van Aalderen WM. Validation of a single concentration methacholine inhalation provocation test (SCIPT) in children. J Asthma. 2005 Jul-Aug;42(6):419-23. doi: 10.1081/JAS-67934.

Reference Type BACKGROUND
PMID: 16293536 (View on PubMed)

Other Identifiers

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KGU-317/09

Identifier Type: -

Identifier Source: org_study_id

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