Validated safety predictions of airway responses to house dust mite in asthma.
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 (FEV(1))(PC(20) 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 PC(20) histamine or PC(20) methacholine and skin sensitivity data obtained from patients with mild to moderate persistent asthma and validated these equations in an independent asthma population.


METHODS
PC(20) histamine or PC(20) methacholine, skin sensitivity, and PC(20) 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 PC(20) allergen, and a validation group to test the new equations.


RESULTS
Multiple linear regression analysis revealed that PC(20) allergen could be predicted either from PC(20) methacholine only ((10)log PC(20) allergen=-0.902+0.741.(10)log PC(20) methacholine) or from PC(20) histamine and skin sensitivity (SS) ((10)log PC(20) allergen=-0.494+0.231.(10)log SS+0.546.(10)log PC(20) histamine). In the validation study, these new equations accurately predicted PC(20) allergen following inhalation of HDM allergen allowing a safe starting concentration of allergen of three doubling concentrations below predicted PC(20) allergen in all cases.


CONCLUSIONS
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 PC(20) allergen and hence are suitable for implementation in HDM inhalation studies.
Ravensberg
A J
AJ
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. a.j.j.ravensberg@lumc.nl
van Rensen
E L J
EL
Grootendorst
D C
DC
de Kluijver
J
J
Diamant
Z
Z
Ricciardolo
F L M
FL
Sterk
P J
PJ
D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000175:diagnosis* / Q000276:immunology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D002986:Clinical Trials as Topic; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D012044:Regression Analysis; D012189:Retrospective Studies; D012449:Safety; D012882:Skin Tests
D039741:Antigens, Dermatophagoides; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D006632:Histamine