Predicting short term response to anti-inflammatory therapy in young children with asthma

Abstract

Background:

Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.

Objective:

To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.

Methods:

A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.

Clinical trial registration:

NCT00543686.

Results:

Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.

Conclusion:

Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma.

Key words::

• Airway reversibility
• Biomarkers
• Childhood asthma
• Inhaled corticosteroids
• Leukotriene receptor antagonist
• Montelukast

Transparency

Declaration of funding

This study has been funded in parts by grants of Dr. Marschner Stiftung and MSD Germany. Stefan Zielen and Martin Christmann as first authors contributed equally to this work.

Declaration of financial and other relationships

S.Z. has disclosed receiving a research grant from MSD; he also received fees for speaking and consulting for Novartis, Allergy Therapeutics, Symbio Vaccines, HAL, MSD, GSK and Wyeth. All the other authors have disclosed that they have no relevant financial interests.

Acknowledgements

Birgit Schinzel from Biostatistical Services performed the statistical analysis.