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Notes: In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC20 histamine after 24 h. When the group was divided into three subgroups according to baseline PC20 histamine, a significant decrease in PC20 histamine was found only in patients with relatively high baseline PC20 histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC20 and allergen-induced PC20 histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC20 histamine; no further decrease in mean PC20 histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC20 values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.

Notes: To describe the distribution of serum total IgE and specific IgE. to common aeroallergens by sex and age and to study their relationship to each other, we measured serum total IgE and specific IgE (CAP) to house-dust mite, timothy grass, cat, birch, and Cladosporium in a random sample of 2496 subjects, aged 20–70 years from the Dutch general population. We found that total IgE was higher in men, independently of smoking, and that total IgE had no relationship with age after adjustment for specific IgE and smoking in linear regression analysis. At least one positive specific IgE test was found in 32% in both sexes. Men had higher prevalences of specific IgE to house-dust mite and lower prevalences of specific IgE to birch than women. The proportion with positive specific IgE decreased with age. The mean total IgE increased with the number of positive specific IgE tests. Thus, total IgE is higher in men and has no relationship with age if specific IgE is taken into account. The prevalences of specific IgE to aeroallergens are high and decrease with increasing age. We suggest that sex differences in total IgE should be considered when using total IgE.

Notes: Skin reactivity (intracutaneous test) to histamine and allergens was studied cross-sectionally in a Dutch asthmatic patient population from childhood to old age (4–75 years). It was found that the histamine skin reactivity rose significantly (p〈0.05) during childhood, was significantly higher in the 10–15-year age group, and was constant between 20 and 75 years of age. The mean wheal index (histamine ratio) of all allergens was constant during childhood, and decreased after the age of 25 for grass pollen and house-dust mite and after the age of 15 for the other allergens. The prevalence of a positive skin test decreased with age, except for grass pollen. During childhood the indoor allergens, cat dander and house-dust mite, were the most important, while after the age of 15 sensitivity to an outdoor allergen, grass pollen, increased markedly. At all ages house-dust mite was the most important allergen. After the age of 25 the prevalence of every allergen declines. The prevalence of a positive skin test to Cladosporium was unexpectedly high in childhood (10–40%). It can be concluded that the prevalence of a positive skin test declines with age, except for grass pollen. The degree of sensitization in asthmatics peaked in the age groups between 20 and 40 and sensitivity to indoor allergens developed earlier than sensitivity to outdoor allergens.Clinical aspectsSkin tests producing immediate wheal and flare reactions are widely used for the detection of allergy in patients referred for asthmatic prohlems. For good evaluation of a skin test it is important to know the influence of age on skin reactivity. In this study we evaluated the wheal index (histamine ratio) of the skin test and the prevalence of a positive skin test using a set of 6 standardized common aero-allergens and one non-standardized, cross-sectionally, in a Dutch asthmatic patient population (4–75 years). Since standardized allergens were used, the prevalences hetween the different allergens could be compared. It was found that the histamine skin reactivity peaked at the age of 15 and was lower in all other age groups. Therefore, when comparing skin test results in different age groups, it may be important to use wheal indices instead of absolute values. Except for grass pollen the prevalence of a positive skin test decreased with age. During childhood indoor allergens are the most important, while after the age of 15 sensitivity towards outdoor allergens increases. Honse-dust mite is the most important allergen at all ages. Surprisingly, a fungal allergen (Cladosporium herharuni) was found to he of significance in young children (prevalence 10–40%). The prevalence of at least one positive skin test in asthmatics declined with age, while the degree of sensitization (expressed as the mean wheal index) peaked in young adults (20–40 years of age).

Notes: Background:  Most previous epidemiological studies on the relationship between allergy and bronchial hyperresponsiveness (BHR) have made no distinction between sensitization to indoor and outdoor allergens. We studied the relationship between specific sensitization to allergen and BHR and further assessed whether this was different in young adults and older subjects.Methods:  Specific IgE to indoor allergens (house dust mite and cat) and outdoor allergens (timothy grass and birch) were measured using the CAP System. BHR was defined as PD20 ≤ 2 mg methacholine. Multiple logistic regression analysis was performed to study independent relationships between BHR and specific IgE to indoor and outdoor allergens in 1018 young adults (20–44 years) and 909 older subjects (45–70 years).Results:  In the older age group specific IgE to indoor allergens was associated with BHR at a lower level (class 2) than in young adults (class ≥ 3). Young adults with multiple sensitization had the highest risk of BHR. Subjects who were exclusively sensitized to pollen did not show increased BHR in both age groups. Total IgE had, independently of sensitization, only a significant dose–response relationship with BHR in the oldest age group.Conclusions:  The association between sensitization and BHR is dependent on the nature of the allergen and the level of specific IgE. Furthermore, this study shows for the first time that total IgE is associated with BHR at older ages, independently of sensitization.

Notes: Oral disodiumcromoglycate (DSCG) has been used for many years in the prevention of food allergic reactions. The reported effectiveness varies widely and little is known about the mode of action. The aim of this study was to evaluate the effect of DSCG pretreatment (2 x 100 mg) on intestinal permeability (IP), as measured with a sugar absorption test (SAT), in relation to the clinical response during food challenge in 30 children suspected of cow's milk allergy. In the SAT the urinary Lactu-lose/Mannitol (L/M) ratio was measured after oral administration of these compounds. DSCG pretreatment did not alter the number of clinically positive challenges. Children with clinically positive challenges showed a significant increase in the L/M ratio with placebo pretreatment as compared to children with clinically negative challenges (p = 0.0008). This difference was reduced to nonsignificant levels after DSCG pretreatment (p = 0.07). We conclude that DSCG in this dosage probably reduces the local intestinal response but does not prevent the extra-intestinal reactions.

Notes: Standardization of allergen provocation tests of the airways requires standardization of each of the steps involved, including standardization of the extracts used. The value of international standards is emphasized and so is the determination of a clinically relevant potency. The allergen extracts used for bronchial provocation tests must be compared with qualitatively and quantitatively clinically relevant standards using complementary immunochemical and biological methods. Ideally the same extracts should be used for diagnosis (skin test, specific IgE determinations, provocations) and treatment (immuno-therapy). The importance of the biological compared with the non-biological methods is that the biological methods are established in allergenic patients in order to select a clinically relevant potency of the allergen in question, and this potency ought to be confirmed in clinical trials. Once established the biological potency of an in-house preparation can be reproduced by supplementary in vitro methods. Very few commercial allergen preparations are available which fulfil the above-mentioned criteria.

Notes: Background Airway inflammation in asthma is orchestrated by recruitment of T helper (Th)2 lymphocytes to the lung and subsequent production of Th2-like cytokines upon allergen challenge.Objective To examine whether allergen-induced dysfunction of the β2-adrenergic receptor (β2-AR) contributes to the enhanced T(h2) cell activity in asthma.Methods β2-adrenergic regulation of cytokine mRNA expression was studied in α-CD3/α-CD28-activated peripheral blood lymphocytes from seven asthma patients before and 6 h after allergen challenge, in conjunction with the effects of β2-agonist fenoterol on T cell chemotaxis and signalling pathways.Results A complete loss of β2-AR control over expression of the Th2 cytokines IL-4, IL-5 and IL-13, but not of the Th1 cytokine IFN-γ, was observed after allergen challenge. Furthermore, we found impaired β2-AR regulation of T cell migration as well as signal transduction pathways, i.e. the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein and the inhibition of the mitogen-activated protein kinase pathway. The loss of β2-AR control was associated with increased β-adrenergic receptor kinase expression, which might be involved in β2-AR desensitization. In addition, we demonstrate for the first time that T cells exposed to the chemokine thymus and activation-regulated chemokine show hyporesponsiveness to fenoterol.Conclusion Our results suggest that allergen-induced loss of β2-AR control, possibly mediated by chemokine release, plays an important role in enhanced Th2-like activity in asthma.

Notes: Background Anti-allergic mattress encasing may provide clinical benefit in asthmatic patients. However, the effect of mattress encasings on allergen-specific parameters, such as bronchial reactions to house dust mite (HDM) challenge, is not clear.Objective To investigate the effect of anti-allergic mattress encasings on allergen sensitivity in patients with moderate to severe asthma.Methods Twenty-seven patients with asthma and HDM allergy were studied in a double-blind, placebo-controlled study. Concentrations of Dermatophagoides pteronyssinus (Der p 1) were measured in mattress dust before and after 1 year of treatment; bronchial histamine challenge, bronchial challenge with HDM and intradermal skin challenges with HDM were performed. The number of eosinophils in peripheral blood was assessed.Results In the active group, but not in the placebo group, there was a significant reduction in Der p 1 concentration in the dust collected from the mattresses after 1 year of treatment compared to before. There was a significant difference between the groups with respect to HDM-induced early-reaction (ER) in the airways and the number of blood eosinophils, which reflected an increase in ER and eosinophils in the placebo group without significant change in the active group. No significant improvement in PC20 histamine, late-reaction (LR) and skin tests was found in either groups.Conclusion Our data suggest that encasings protect against a further increase in allergen sensitivity in asthmatic patients, so their use should be recommended.

Notes: We investigated whether the association of allergy symptoms with sensitization to inhalant allergens depends on bronchial hyperresponsiveness, blood eosinophil count, or the degree and nature of sensitization.〈section xml:id="abs1-2"〉〈title type="main"〉MethodsData on asthma and rhino-conjunctivitis symptoms were obtained from 1904 subjects from a random sample of the Dutch population, aged 20–70 years by the ECRHS questionnaire. Total IgE and specific IgE to four inhalant allergens were measured using CAP System. Bronchial hyperresponsiveness (BHR) was defined as PD20≤ 2 mg methacholine and ‘high eosinophil count’ as an eosinophil count in the highest quartile.〈section xml:id="abs1-3"〉〈title type="main"〉ResultsForty-three percent of the subjects with specific IgE to inhalant allergens was asymptomatic. These subjects had a lower degree of sensitization than symptomatic sensitized subjects and had ‘normal’ prevalences of BHR and ‘high eosinophil count’. Logistic regression showed that the presence of BHR increased the risk of having symptoms for subjects who were sensitized to indoor allergens. Low levels of specific IgE to indoor allergens were only associated with symptoms when BHR was present. Sensitization to outdoor allergens was associated with symptoms at all levels of specific IgE, independently of BHR or eosinophils.〈section xml:id="abs1-4"〉〈title type="main"〉ConclusionOur epidemiological data suggest that whether low levels of specific IgE to indoor allergens lead to allergic symptoms is probably determined by the concurrent existence of inflammation of the airways.