Christa E. Lopuhaa

The Prevalence of Parasite Infestation and House Dust Mite Sensitization in Gabonese Schoolchildren

Background: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. Methods: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. Results: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. Conclusions: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.

Bronchial allergen challenge with isolated major allergens of Dermatophagoides pteronyssinus : The role of patient characteristics in the early asthmatic response

BACKGROUND The use of allergen extracts will hamper studies into quantitative aspects of allergic responses because the precise amount of relevant allergen for each patient is unknown. OBJECTIVE We applied isolated IgE-binding components (major allergens) in the technique of bronchial allergen challenge to determine the role of patient characteristics in the early asthmatic response (EAR). METHODS In 30 patients with mild-to-moderate asthma, the EAR was investigated after inhalation of an isolated major allergen of Dermatophagoides pteronyssinus (i.e., Der p 1 [n = 16] or Der p 2 [n = 14]). The degree of early-phase bronchial responsiveness to allergen (the cumulated dose of allergen causing a 20% fall in FEV1 [PD20allergen]) was related to the degree of nonspecific bronchial responsiveness (the concentration of histamine causing a 20% fall in FEV1 [PC20histamine]) and the level of specific IgE or allergen thresholds as found in skin tests and basophil histamine release assays. RESULTS Twenty-seven patients with an immediate response during allergen and histamine challenges (deltaFEV1, > or = 20%) were analyzed. In these patients, a strong correlation was found between PD20allergen and PC20histamine (r = 0.81, p < 0.001). Weak correlations were found between PD20allergen and the level of specific IgE (r = -0.36, p = 0.07) or allergen thresholds as found in skin tests (skin prick test, r = 0.36 and p = 0.07; intracutaneous test, r = 0.49 and p = 0.01) or basophil histamine release assays (r = 0.37, p = 0.08). Moreover, no significant contribution of these indices of IgE-mediated hypersensitivity to the prediction of PD20allergen by multilinear regression models with PC20histamine was found. CONCLUSION In asthmatic patients allergic to house dust mites the degree of nonspecific bronchial hyperresponsiveness is the main determinant of early-phase bronchial responsiveness to allergen. In these patients the degree of allergic sensitivity does not contribute to the prediction of the EAR after allergen inhalation.

Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge

Background: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non‐asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen‐induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms.

Lack of correlation between bronchial late allergic reaction to Dermatophagoides pteronyssinus and in vitro immunoglobulin E reactivity to histamine-releasing factor derived from mononuclear cells

BACKGROUND Activity of immunoglobulin (Ig)E-dependent histamine-releasing factor (HRF) is dependent on the IgE molecules bound to the surface of basophils. Sera capable of passively sensitizing basophils to release histamine to HRF were designated IgE+ sera. IgE+ and HRF have been suggested to play a role in late allergic reaction (LAR). OBJECTIVE The working hypothesis was tested that IgE+ induces a LAR. Further, activity of HRF produced by mononuclear cells (HRF(mn)) was compared with that of recombinant HRF p23. METHODS Atopic patients (n = 82) were bronchially provoked with Dermatophagoides pteronyssinus extract and the change in forced expiratory volume in 1 second was monitored. A LAR was defined as forced expiratory volume in 1 second as percentage of baseline < 80% 4 to 10 hours after allergen challenge. The presence of HRF-responsive IgE in serum was determined using basophils sensitized in vitro by serum. RESULTS The presence of HRF(mn)-responsive IgE (IgE(mn+)) in serum was shown not be essential for a LAR: 63% of the patients with a LAR had no IgE(mn+) in their serum. Further, 71% of patients with IgE(mn+) did not have a LAR. HRF(mn) and recombinant HRF p23 were not equivalent in the bioassay: serum of 38 of 82 atopic patients sensitized basophils to release histamine to HRF(mn), whereas this was found with serum of 1 of 82 patients to HRF p23. CONCLUSIONS The results do not support the hypothesis that IgE(mn+) induces a LAR, but do not exclude the alternative hypothesis that HRFs are released during a LAR and contribute to asthma severity.

Comparison of Allergen-Induced Late Inflammatory Reactions in the Nose and in the Skin in House Dust Mite-Allergic Patients with or without Asthma

Background: It remains to be established which factors contribute to the occurrence of asthma in allergic individuals. We hypothesized that differences in the late allergic inflammatory reaction to allergen between asthmatic and non-asthmatic house dust mite-allergic individuals might contribute to the difference in the clinical presentation of allergy. Aim: To compare allergen-induced changes in parameters for cellular inflammation during the phase of the late allergic reaction in the skin and nose, in house dust mite-allergic individuals with or without asthma. Material and Methods: Nasal and dermal allergen challenges with house dust mite (Dermatophagoides pteronyssinus) extract were performed in 52 house dust mite-allergic individuals, of whom 26 had mild to moderate persistent asthma and 26 had perennial rhinitis without current or past asthmatic symptoms. Serial nasal lavage samples were analyzed for the presence of inflammatory cells (eosinophils and neutrophils) and soluble markers associated with cellular inflammation [interleukin-5 (IL-5), interleukin-8 (IL-8), eosinophil cationic protein (ECP) and myeloperoxidase (MPO)]. Macroscopic late phase skin reactions were studied after intracutaneous skin tests with house dust mite extract. Results: Fixed dose nasal allergen provocation elicited a similar degree of immediate allergic reaction as judged by plasma protein exudation and histamine concentrations in asthma and non-asthmatic rhinitis. Subsequently, no differences between groups were found during the phase of the late allergic reaction (4–24 h) in inflammatory cell influx, plasma protein leakage, ECP or MPO. Likewise, there were no differences in levels of chemotactic cytokines IL-5 and IL-8. In agreement with the results of nasal challenge, the late skin reaction after dermal challenge with a fixed allergen dose and after an allergen dose 10,000 times above the skin threshold for an early skin reaction did not differ between the groups. Conclusion: House dust mite-allergic patients with or without asthma have very similar late allergic inflammatory reactions in the skin and in the nose after allergen challenge. Hence, it is unlikely that the occurrence of pulmonary symptoms in asthma is explained by a general tendency of asthmatics to have an enhanced late allergic cellular inflammatory response. Nasal and dermal allergen provocations are adequate models to study allergen-induced inflammation but probably lack the pivotal link which is essential for the development of asthma.