Heterogeneity in allergic rhinitis: explained by inducible mechanistic traits?

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Modulating local airway immune responses to treat allergic asthma: lessons from experimental models and human studies

With asthma affecting over 300 million individuals world-wide and estimated to affect 400 million by 2025, developing effective, long-lasting therapeutics is essential. Allergic asthma, where Th2-type immunity plays a central role, represents 90% of child and 50% of adult asthma cases. Research based largely on animal models of allergic disease have led to the generation of a novel class of drugs, so-called biologicals, that target essential components of Th2-type inflammation. Although highly efficient in subclasses of patients, these biologicals and other existing medication only target the symptomatic stage of asthma and when therapy is ceased, a flare-up of the disease is often observed. Therefore, it is suggested to target earlier stages in the inflammatory cascade underlying allergic airway inflammation and to focus on changing and redirecting the initiation of type 2 inflammatory responses against allergens and certain viral agents. This focus on upstream aspects of innate immunity that drive development of Th2-type immunity is expected to have longer-lasting and disease-modifying effects, and may potentially lead to a cure for asthma. This review highlights the current understanding of the contribution of local innate immune elements in the development and maintenance of inflammatory airway responses and discusses available leads for successful targeting of those pathways for future therapeutics.Pathogenesis and treatment of chronic pulmonary disease

Allergenic food introduction and risk of childhood atopic diseases

Background: The role of timing and diversity of allergenic food introduction in the development of childhood allergic sensitization and atopic diseases is controversial. Objective: To examine whether timing and diversity of allergenic food introduction are associated with allergic sensitization, allergy and eczema in children until age 10 years. Materials and methods: This study among 5,202 children was performed in a population-based prospective cohort. Timing (age 6 months vs. >6 months) and diversity (0, 1, 2 and 3 foods) of allergenic food (cow’s milk, hen’s egg, peanut, tree nuts, soy and gluten) introduction were assessed by questionnaires at ages 6 and 12 months. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by questionnaire. Data on parental-reported physician-diagnosed eczema were obtained from birth until age 10 years. Results: Children introduced to gluten at age 6 months had a decreased risk of eczema (aOR (95% CI): 0.84 (0.72, 0.99)), compared with children introduced to gluten at age >6 months. However, timing of allergenic food introduction was not associated with allergic sensitization or physician-diagnosed allergy. Children introduced to 3 allergenic foods at age 6 months had a decreased risk of physician-diagnosed inhalant allergy (0.64 (0.42, 0.98)), compared with children not introduced to any allergenic food at age 6 months. However, diversity of allergenic food introduction was not associated with allergic sensitization, physician-diagnosed food allergy or eczema. Conclusion: Neither timing nor diversity of allergenic food introduction was consistently associate

Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome

Background: The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS. Methods: Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, αFH) and genetic profiles (CFH, CFI, CD46, CFB, C3) of the alternative complement pathway were prospectively determined in the acute and convalescent phase of disease in children newly diagnosed with STEC-HUS or aHUS. Serological profiles were compared with those of 90 age-matched controls. Results: Thirty-seven patients were studied (26 STEC-HUS, 11 aHUS). In 39 % of them, including 28 % of STEC-HUS patients, we identified a genetic and/or acquired complement abnormality. In all patient groups, the levels of investigated alternative pathway (AP) activation markers were elevated in the acute phase and normalized in remission. The levels were significantly higher in aHUS than in STEC-HUS patients. Conclusions: In both infection-induced HUS and aHUS patients, complement is activated in the acute phase of the disease but not during remission. The C3d/C3 ratio displayed the best discrepancy between acute and convalescent phase and between STEC-HUS and aHUS and might therefore be used as a biomarker in disease diagnosis and monitoring. The presence of aberrations in the alternative complement pathway in STEC-HUS patients was remarkable, as well

Measurement of the Atmospheric Muon Spectrum from 20 to 3000 GeV

The absolute muon flux between 20 GeV and 3000 GeV is measured with the L3 magnetic muon spectrometer for zenith angles ranging from 0 degree to 58 degree. Due to the large exposure of about 150 m2 sr d, and the excellent momentum resolution of the L3 muon chambers, a precision of 2.3 % at 150 GeV in the vertical direction is achieved. The ratio of positive to negative muons is studied between 20 GeV and 500 GeV, and the average vertical muon charge ratio is found to be 1.285 +- 0.003 (stat.) +- 0.019 (syst.).Comment: Total 32 pages, 9Figure

Quantile regression for the statistical analysis of immunological data with many non-detects

Background Immunological parameters are hard to measure. A well-known problem is the occurrence of values below the detection limit, the non-detects. Non-detects are a nuisance, because classical statistical analyses, like ANOVA and regression, cannot be applied. The more advanced statistical techniques currently available for the analysis of datasets with non-detects can only be used if a small percentage of the data are non-detects. Methods and results Quantile regression, a generalization of percentiles to regression models, models the median or higher percentiles and tolerates very high numbers of non-detects. We present a non-technical introduction and illustrate it with an implementation to real data from a clinical trial. We show that by using quantile regression, groups can be compared and that meaningful linear trends can be computed, even if more than half of the data consists of non-detects. Conclusion Quantile regression is a valuable addition to the statistical methods that can be used for the analysis of immunological datasets with non-detects

Allergic rhinitis in children in Dutch general practice in 1987 and 2001.

Introduction: Allergic rhinitis is a common chronic disorder in children, mostly diagnosed in primary health care. This study investigated the national incidence and treatment of allergic rhinitis among children aged 0-17 years in Dutch general practice in 1987 and 2001 to establich whether changes have occurred. Materials & methods: a comparison was made with data from the first (1987) and second (2001) Dutch National Surveys of General Practice on children aged 0-17 years. The management of the general practitioner was assessed regarding drug prescriptions and referrals to medical specialists, and compared with the clinical guideline issue in 1996. Results: the incidence rate of allergic rhinitis increased from 6.6 (1987) to 9.2 (2001) per 1000 person-years. We found a male predominance with a switch in adolescence to a female prodominance at both time points. Compared to 1987, there was a significant increase in incidence in the central part of the Netherlands in 2001. In 2001, children of natives and western immigrants visited the general practitioner more often with complaints of allergic rhinitis compared to 1987. In 1987 prescribed medication consisted mainly of nasal corticosterioids (36%) and in 2001 of oral antihistamines (45%). Overall, the treatment of allergic rhinits was in both years in accordance with te current clinical guideline, but with a stroger adherence in 2001. Conclusion: The results show an increased incidence in the past decades of allergic rhinits in children. The shift to a smaller spectrum of prescriptions in 2001 may be a result of the 1996 clinical guideline

Honeybee interference as a novel aid to reduce pollen exposure and nasal symptoms among greenhous workers allergic to sweet bell pepper (Capsicum annuum) pollen

Background: In 1999, an extensive study among bell pepper growers showed a prevalence of 53.8% work-related symptoms and 35.4% sensitisation to bell pepper pollen. Experiments with bees to remove pollen from bell pepper flowers have been done for a few years. Objectives: It was the aim of this study to investigate whether bees can reduce the pollen exposure in bell pepper greenhouses and whether this reduction results in a decrease in allergic complaints in the greenhouse workers. Methods: Eighteen greenhouses were selected for the study. In each greenhouse, pollen exposure was estimated. In 6 and 3 of the greenhouses, high, respectively low, numbers of honeybees were placed throughout the pollen season of the sweet bell pepper plant. Nine greenhouses without honeybees were used as control. At baseline, as well as after 4 and 8 months, nasal symptoms assessed with a visual analogue score and lung function parameters were used as outcome measure. Results: Forty-four of the 133 employees invited reported work-related symptoms. High numbers of bees reduced the pollen amount in a dose-dependent way to 18% of the baseline exposure. A significant trend relationship between the visual analogue scale in nasal symptoms and the number of colonies of bees was seen. Conclusions: The interference of bees in bell pepper greenhouses significantly reduces the pollen amount. This reduction is associated with less work-related rhinitis symptoms in allergic greenhouse workers. This intervention study supports the hypothesis that allergic work-related complaints of greenhouse workers, sensitised to bell pepper pollen, are caused by occupational exposure to this pollen in the greenhous

Differential effect of mattress covers on the level of Der p 1 and Der f 1 in dust

BACKGROUND: Exposure to house dust mite (HDM) allergens can lead to the development of allergic complaints. Mattress covers seem to be an obvious option for lowering allergen exposure in sensitized individuals. Previous studies have shown that Dermatophagoides pteronissinus was the most prevalent HDM species in the Netherlands. OBJECTIVE: In the present study, we investigated the effect of mattress covers on Der p 1 and Der f 1 concentrations in dust samples in three areas in the Netherlands; Groningen, Utrecht and Rotterdam. METHODS: Dust was obtained from mattresses of 277 patients at the beginning of the study and after 12 months of the placebo-controlled intervention. It was analysed for allergen content by immunoassay. The differential effect of the intervention on Der p 1 vs. Der f 1 was analysed in a subgroup with Der p 1+Der f 1>1 microg/g dust (N=161). It was tested whether the intervention caused a significant change in the Der f 1/Der p 1 ratio. RESULTS: At t=0 we found very similar levels of the group 1 allergens of both species. The relatively high prevalence of D. farinae in our study was geographically restricted: the median Der f 1/Der p 1 ratio was 11.1 in the Rotterdam area compared with 1.32 in the Utrecht area and 0.33 in the Groningen area. Analysis of our data showed that the favourable intervention effect found for the combined allergen data (reduction factor=2.9, P <0.001) is essentially due to a favourable effect of the intervention on the Der f 1 levels only (reduction factor=3.6, P <0.001). The effect on the Der p 1 level was remarkably small (reduction factor: 1.2, P=0.48). In the intervention group, the Der f 1/Der p 1 ratio decreased after 12 months by a factor 2.0, whereas in the placebo group it increased (probability of the intervention effect: P <0.005). CONCLUSION: Mite-impermeable covers are more effective in reducing the level of Der f 1 than that of Der p