Histamine challenges discriminate between symptomatic and asymptomatic children. MAS-Study Group. Multicentre Allergy Study.

The aims of this study were to investigate a threshold value for bronchial responsiveness in children aged 7 yrs, which discriminates between symptomatic and asymptomatic children, and to identify determinants of this responsiveness. Titrated bronchial histamine challenges using the reservoir method were performed in 645 children aged 7 yrs, from the birth cohort Multicentre Allergy Study (MAS). When defining a reference population of healthy children within the MAS cohort, the 95th percentile of the provocative concentration causing a 20% fall in forced expired volume in one second PC20 among these asymptomatic study subjects amounted to 0.60 mg x mL(-1). This resulted in a specificity of 93.0% and a sensitivity of 45.9%, for discriminating between "current wheezers" and "non-current wheezers". Determinants of airway responsiveness at this age were pulmonary function, sensitization to indoor allergens, total immunoglobulin E and current wheeze. The results indicate that a very low cut-off provocative concentration causing a 20% fall in forced expired volume in one second (<1.0 mg x mL(-1)) defines airway hyperresponsiveness in children aged 7 yrs using the reservoir method. Provocation protocols for histamine challenges in this age group should therefore start with concentrations markedly below 1.0 mg x mL(-1).

Transient early wheeze is not associated with impaired lung function in 7-yr-old children.

The aim of the present study was to analyse determinants of lung function in 7-yr-old children with different wheezing patterns (early, persistent and late onset) in a prospective cohort study. The German Multicentre Allergy Study (MAS) followed 1,314 children from birth onwards. Annual assessments included clinical check-ups, a structured interview and repeated measurement of specific immunoglobulins Ig(E) directed against food and inhalant allergens. At the age of 7 yrs, lung function was measured by body plethysmography in 800 children. Episodes of wheezing in the past 12 months ("current wheeze") were strongly associated with reduced lung function at age 7 yrs. Children with wheezing episodes only during the first 3 yrs of life showed a slight impairment in maximal expiratory flow when 50% of the forced vital capacity remains to be exhaled (98.9 +/- 24.2 versus 103.2 +/- 22.8% of the predicted value in children who never wheeze). Separate analysis of determinants of pulmonary function within these subgroups resulted in distinctly different patterns. Determinants of impaired lung function in the group of current wheezers were: time in years since first wheeze, a parental history of atopy, current sensitisation to indoor allergens, elevated cord blood IgE levels and a low ponderal index at birth. In the group of transient early wheezers, frequent lower respiratory tract infections early in life and maternal smoking during pregnancy were significant but weak determinants of impaired lung function. The present results indicate that determinants of pulmonary function in 7-yr-old children differ with respect to different wheezing phenotypes, demanding different therapeutic strategies. Although transient early wheezers were found to have normal-to-subnormal lung function, children with asthmatic symptoms (persistent and late-onset disease) at age 7 yrs already show significant impairment of expiratory flow volumes.