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

Allergy Clinical Trial

— BHR  

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01144910
• Other study ID #: KGU-317/09
• Status: Withdrawn
• Phase: N/A
• First received: June 1, 2010
• Last updated: March 2, 2017
• Start date: May 2011
• Est. completion date: September 2017

Study information

• Verified date: March 2017
• Source: Johann Wolfgang Goethe University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Allergic Asthma
• Allergy
• Asthma
• Bronchial Hyperreactivity
• Bronchial Hyperresponsiveness
• Intrinsic Asthma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Germany	Goethe University	Frankfurt am Main

Sponsors (1)

Lead Sponsor	Collaborator
Johann Wolfgang Goethe University Hospital

Country where clinical trial is conducted

Germany, 

References & Publications (14)

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. — View Citation

Beydon N. Assessment of bronchial responsiveness in preschool children. Paediatr Respir Rev. 2006;7 Suppl 1:S23-5. Review. — View Citation

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. Review. — View Citation

Castro-Rodríguez 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. — View Citation

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. — View 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. — View 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. — View Citation

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. — View Citation

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. Review. — View Citation

Illi S, von Mutius E, Lau S, Niggemann B, Grüber 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. Erratum in: Lancet. 2006 Sep 30;368(9542):1154. — View Citation

Matricardi PM, Illi S, Grüber 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. — View Citation

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. — View Citation

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. — View 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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Impact of atopy	Influence of atopy on the time course of bronchial hyperresponsiveness.	five years
Secondary	eNO	Influence of the level of exhaled NO on the time course of BHR.	five years
Secondary	Total-IgE	Influence of the level of total-IgE on the time course of BHR	five years