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Validated safety predictions of airway responses to house dust mite in asthma


A. J. Ravensberg, Department of Pulmonology, Leiden University Medical Center, Lung Function Laboratory C2-P-62, PO Box 9600, 2300 RC Leiden, the Netherlands.


Background House dust mite (HDM) is the most common aeroallergen causing sensitization in many Western countries and is often used in allergen inhalation challenges. The concentration of inhaled allergen causing an early asthmatic reaction [provocative concentration of inhaled allergen causing a 20% fall of forced expiratory volume in 1 s (FEV1)(PC20 allergen)] needs to be predicted for safety reasons to estimate accurately the severity of allergen-induced airway responsiveness. This can be accomplished by using the degree of non-specific airway responsiveness and skin sensitivity to allergen.

Objective We derived prediction equations for HDM challenges using PC20 histamine or PC20 methacholine and skin sensitivity data obtained from patients with mild to moderate persistent asthma and validated these equations in an independent asthma population.

Methods PC20 histamine or PC20 methacholine, skin sensitivity, and PC20 allergen were collected retrospectively from 159 asthmatic patients participating in allergen challenge trials. Both the histamine and methacholine groups (n=75 and n=84, respectively), were divided randomly into a reference group to derive new equations to predict PC20 allergen, and a validation group to test the new equations.

Results Multiple linear regression analysis revealed that PC20 allergen could be predicted either from PC20 methacholine only (10log PC20 allergen=−0.902+0.741·10log PC20 methacholine) or from PC20 histamine and skin sensitivity (SS) (10log PC20 allergen=−0.494+0.231·10log SS+0.546·10log PC20 histamine). In the validation study, these new equations accurately predicted PC20 allergen following inhalation of HDM allergen allowing a safe starting concentration of allergen of three doubling concentrations below predicted PC20 allergen in all cases.

Conclusion The early asthmatic response to inhaled HDM extract is predominantly determined by non-specific airway responsiveness to methacholine or histamine, whereas the influence of the cutaneous sensitivity to HDM appears to be rather limited. Our new equations accurately predict PC20 allergen and hence are suitable for implementation in HDM inhalation studies.