Developments allergy in 2019 through the eyes of Clinical and Experimental Allergy, Part II clinical allergy.

In the second of two linked articles, we describe the development in clinical as described by Clinical & Experimental Allergy and other journals in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered. In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered.

Developments allergy in 2019 through the eyes of clinical and experimental allergy, part I mechanisms.

In the first of two linked articles, we describe the development in the mechanisms underlying allergy as described by Clinical & Experimental Allergy and other journals in 2019. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered.

Developments in the field of clinical allergy in 2018 through the eyes of Clinical and Experimental Allergy, Part II.

In this article, we describe developments in the field of clinical allergy as described by Clinical and Experimental Allergy in 2018; epidemiology, asthma and rhinitis, clinical allergy and allergens are all covered.

Developments in the field of allergy in 2017 through the eyes of Clinical and Experimental Allergy.

In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2017. Experimental models of allergic disease, basic mechanisms, clinical mechanisms, allergens, asthma and rhinitis and clinical allergy are all covered.

Developments in the field of allergy in 2016 through the eyes of Clinical and Experimental Allergy.

In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2016. Experimental models of allergic disease, basic mechanisms, clinical mechanisms, allergens, asthma and rhinitis, and clinical allergy are all covered.

Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection - a randomised controlled trial.

Ingestion of probiotics appears to have modest effects on the incidence of viral respiratory infection. The mechanism of these effects is not clear; however, there is evidence from animal models that the probiotic may have an effect on innate immune responses to pathogens. The purpose of this randomised, placebo-controlled study was to determine the effect of administration of Bifidobacterium animalis subspecies lactis Bl-04 on innate and adaptive host responses to experimental rhinovirus challenge. The effect on the response of chemokine (C-X-C motif) ligand 8 (CXCL8) to rhinovirus infection was defined as the primary endpoint for the study. 152 seronegative volunteers who had been supplemented for 28 days, 73 with probiotic and 79 with placebo, were challenged with RV-A39. Supplement or placebo administration was then continued for five days during collection of specimens for assessment of host response, infection, and symptoms. 58 probiotic and 57 placebo-supplemented volunteers met protocol-defined criteria for analysis. Probiotic resulted in higher nasal lavage CXCL8 on day 0 prior to virus challenge (90 vs 58 pg/ml, respectively, P=0.04, ANCOVA). The CXCL8 response to rhinovirus infection in nasal lavage was significantly reduced in the probiotic treated group (P=0.03, ANCOVA). Probiotic was also associated with a reduction in nasal lavage virus titre and the proportion of subjects shedding virus in nasal secretions (76% in the probiotic group, 91% in the placebo group, P=0.04, Fisher Exact test). The administration of probiotic did not influence lower respiratory inflammation (assessed by exhaled nitric oxide), subjective symptom scores, or infection rate. This study demonstrates that ingestion of Bl-04 may have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection. Clinicaltrials.gov registry number: NCT01669603.

Developments in the field of clinical allergy in 2015 through the eyes of Clinical and Experimental Allergy.

In the second of two papers, we describe developments in the field of clinical allergy as documented by Clinical and Experimental Allergy in 2015. Epidemiology, clinical allergy, asthma and rhinitis are all covered.

Developments in the field of allergy mechanisms in 2015 through the eyes of Clinical & Experimental Allergy.

In the first of two papers we described the development in the field of allergy mechanisms as described by Clinical and Experimental Allergy in 2015. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered. A second paper will cover clinical aspects.

Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy.

BACKGROUND: Only limited evidence is available regarding the cytokine repertoire of effector T cells associated with peanut allergy, and how these responses relate to IgE antibodies to peanut components. OBJECTIVE: To interrogate T cell effector cytokine populations induced by Ara h 1 and Ara h 2 among peanut allergic (PA) children in the context of IgE and to evaluate their modulation during oral immunotherapy (OIT). METHODS: Peanut-reactive effector T cells were analysed in conjunction with specific IgE profiles in PA children using intracellular staining and multiplex assay. Cytokine-expressing T cell subpopulations were visualized using SPICE. RESULTS: Ara h 2 dominated the antibody response to peanut as judged by prevalence and quantity among a cohort of children with IgE to peanut. High IgE (> 15 kU(A)/L) was almost exclusively associated with dual sensitization to Ara h 1 and Ara h 2 and was age independent. Among PA children, IL-4-biased responses to both major allergens were induced, regardless of whether IgE antibodies to Ara h 1 were present. Among subjects receiving OIT in whom high IgE was maintained, Th2 reactivity to peanut components persisted despite clinical desensitization and modulation of allergen-specific immune parameters including augmented specific IgG4 antibodies, Th1 skewing and enhanced IL-10. The complexity of cytokine-positive subpopulations within peanut-reactive IL-4(+) and IFN-γ(+) T cells was similar to that observed in those who received no OIT, but was modified with extended therapy. Nonetheless, high Foxp3 expression was a distinguishing feature of peanut-reactive IL-4(+) T cells irrespective of OIT, and a correlate of their ability to secrete type 2 cytokines. CONCLUSION: Although total numbers of peanut-reactive IL-4(+) and IFN-γ(+) T cells are modulated by OIT in highly allergic children, complex T cell populations with pathogenic potential persist in the presence of recognized immune markers of successful immunotherapy.

Infection with human rhinovirus 16 promotes enhanced IgE responsiveness in basophils of atopic asthmatics.

BACKGROUND: Rhinovirus and IgE act in concert to promote asthma exacerbations. While basophils are the principal cell type in the blood that is activated by IgE, their role in virus-induced asthma episodes remains elusive. OBJECTIVE: To monitor IgE responsiveness in circulating basophils of rhinovirus-infected atopic asthmatics during acute infection and convalescence. METHODS: The capacity for basophils to respond to IgE was assessed by testing the effects of allergen, or cross-linking anti-FcεRI and anti-IgE antibodies, on surface TSLP receptor in 24-hour PBMC cultures. Activation profiles of basophils from atopic asthmatics challenged intranasally with human rhinovirus 16 were monitored directly ex vivo or else in 24-hour cultures, at baseline (day 0), and then at days 4 and 21 post-challenge. RESULTS: Basophils in atopic asthmatics, but not in non-atopic controls, upregulated TSLP receptor upon IgE receptor ligation. The magnitude of this response was correlated with the proportion of serum total IgE that was allergen-specific (r = 0.615, P < 0.05). Following rhinovirus infection, all subjects developed nasal symptoms that peaked 3-5 days after viral challenge. Basophils displayed maximal IgE responsiveness 3 weeks post-challenge as judged by TSLP receptor levels in 24-hour cultures. No significant change in total IgE or specific IgE antibodies was detected during rhinovirus infection. By contrast, levels of IgE receptor-associated spleen tyrosine kinase, Syk, were increased on day 4 (P < 0.05), and elevated levels were also detected three weeks post-challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating basophils display increased IgE responsiveness 3 weeks after rhinovirus infection in atopic asthmatics. This observation, coupled with increased expression of Syk, implicates basophils in promoting, or else prolonging, rhinovirus-induced inflammation in atopic asthmatics.

Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is common in children; however, persistence of AD with or without asthma is less common. Longitudinal studies remain limited in their ability to characterize how IgE antibody responses evolve in AD, and their relationship with asthma. OBJECTIVE: To use a cross-sectional study design of children with active AD to analyse age-related differences in IgE antibodies and relation to wheeze. METHODS: IgE antibodies to food and inhalant allergens were measured in children with active AD (5 months to 15 years of age, n = 66), with and without history of wheeze. RESULTS: Whereas IgE antibodies to foods persisted at a similar prevalence and titre throughout childhood, IgE antibodies to all aeroallergens rose sharply into adolescence. From birth, the chance of sensitization for any aeroallergen increased for each 12-month increment in age (OR ≥ 1.21, P < 0.01), with the largest effect observed for dust mite (OR = 1.56, P < 0.001). A steeper age-related rise in IgE antibody titre to dust mite, but no other allergen was associated with more severe disease. Despite this, sensitization to cat was more strongly associated with wheeze (OR = 4.5, P < 0.01), and linked to Fel d 1 and Fel d 4, but not Fel d 2. Comparison of cat allergic children with AD to those without, revealed higher IgE levels to Fel d 2 and Fel d 4 (P < 0.05), but not Fel d 1. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in sensitization to cat and dust mite among young children with AD may aid in identifying those at increased risk for disease progression and development of asthma. Early sensitization to cat and risk for wheeze among children with AD may be linked to an increased risk for sensitization to a broader spectrum of allergen components from early life. Collectively, our findings argue for early intervention strategies designed to mitigate skin inflammation in children with AD.

Mechanisms of tolerance induction in allergic disease: integrating current and emerging concepts.

The prevalence of atopy and allergic disease continues to escalate worldwide. Defining immune mechanisms that suppress the underlying Th2-driven inflammatory process is critical for the rational design of new treatments to prevent or attenuate disease. Allergen immunotherapy has provided a useful framework for evaluating changes in the immune response that occur during the development of tolerance. Despite this, elucidating the phenotypic and functional properties of regulatory cells, has proven challenging in humans with allergic disease. This article provides an overview of our current understanding of the immune pathways that orchestrate allergen tolerance, with an emphasis on emerging concepts related to human disease. A variety of regulatory cell types, including IL-10-secreting T and B cells, play a pivotal role in suppressing allergic responses to inhaled, ingested and injected allergens. These cells may inhibit Th2 effectors directly, or else indirectly, through other cell types and mediators. Protective antibodies, including IgG4, Fc sialylated IgG, and IgA, have the capacity to modulate the response by preventing allergen binding to surface-bound IgE, or inhibiting dendritic cell maturation. Immune cell plasticity may augment suppression of Th2 cells by T regulatory cells, through mechanisms that involve T cell conversion, or else unconventional roles of classical effector cells. These actions depend upon external cues provided by the in vivo milieu. As such, specific anatomical sites may preferentially favour tolerance induction. Recent scientific advances now allow a global analysis of immune parameters that capture novel markers of tolerance induction in allergic patients. Such markers could provide new molecular targets for assessing tolerance, and for designing treatments that confer long-lasting protection in a safe and efficacious fashion.

Developments in the field of allergy in 2008 through the eyes of Clinical & Experimental Allergy.

In 2008, many thousands of articles were published on the subject of allergic disease with over 200 reviews, editorials and original papers in Clinical & Experimental Allergy alone. These represent a considerable amount of data and even the most avid reader could only hope to assimilate a small fraction of this knowledge. There is therefore a pressing need for the key messages that emerge from a journal such as Clinical & Experimental Allergy to be summarized by experts in the field in a form that highlights the significance of the developments and sets them in the context of important findings in the field published in other journals. This also has the advantage of making connections between new data in conditions such as asthma, where articles often appear in different sections of the journal. As can be seen from this review, the body of work is diverse both in terms of the disease of interest and the discipline that has been used to investigate it. However, taken as a whole, we hope that the reader will gain a flavour of where the field is mature, where there remain controversies and where the cutting edge is leading.

Biological potency of German cockroach allergen extracts determined in an inner city population.

BACKGROUND: Cockroach allergy is an important cause of inner city asthma. To perform valid studies on the diagnosis and treatment of cockroach allergy, biological potencies of test extracts need to be established, and a surrogate in vitro test for biological potency should be chosen. METHODS: Sixty-two cockroach-allergic adult subjects were recruited for quantitative skin testing with three commercial German cockroach extracts. The intradermal D50 values were determined using linear interpolation, and the biologic potencies were determined from D50 data. The extracts were also analysed for relative potency, using a competition ELISA, and for specific allergen content, using a two-site ELISA. RESULTS: Estimates of each extract's D50 were analysable in 48-55 subjects, with D50s between 10.3 and 11.8. All three extracts were bioequivalent using pre-set criteria. The biological potencies of the extracts were 1738-8570 bioequivalent allergy units (BAU)/mL (geometric mean=3300), and these relative potencies were similar to those estimated by competition ELISA and specific allergen content. IgE against cockroach allergens were detected in sera from 34 subjects with analysable D50s, and 17 subjects had IgE directed against specific cockroach allergens. Although the presence of anti-Bla g 5 correlated with the subjects' skin test responses for 2/3 extracts, no single allergen was immunodominant. Antibody responses among the subjects were heterogeneous. CONCLUSIONS: Although commercial cockroach extracts are relatively low in potency, immunotherapeutic doses should be achievable. Biological potency may be estimated using D50 testing, a combination of specific allergen determinations, or by an overall potency assay such as the competition ELISA. CAPSULE SUMMARY: The biological potency of three German cockroach allergen extracts, determined in an inner city population, was 1738-8570 BAU/mL. No one allergen was immunodominant, and surrogate in vitro testing methods were examined.

Cytokines as a therapeutic target for allergic diseases: a complex picture.

Production of IgE antibodies promotes the development of allergic disorders such as asthma, rhinitis and atopic eczema. Though Th2 cytokines play a pivotal role in the allergic inflammatory cascade, therapeutic strategies which target these factors have not been curative in clinical trials. In humans, the allergic phenotype encompasses a broad spectrum of diverse clinical entities, which are dictated by genetics as well as the nature of the allergen and the time in life at which allergen is encountered. The disparate findings in animal and human systems highlight the complexity of cytokine-mediated events in allergic responses in man. Different allergic phenotypes cannot be distinguished strictly on the basis of Th1 and Th2 cytokines. These observations coupled with an emerging role for regulatory T cells in modulation of the allergic response warrant re-examination of the cytokine network in allergic disease. This article highlights the challenges of dissecting the role of individual cytokines in the development of allergic responses and manifestation of allergic symptoms. Regulatory T cells have been implicated in modulation of the activity of allergen-specific Th1 and Th2 effector cells and immune outcome; however, the characteristics of these regulatory T cells remain largely undefined. The effects of existing and emerging therapies which target Th1, Th2 and regulatory cytokines on established allergic responses are examined in the context of this new paradigm. Taken together, existing data suggest that a multi-faceted approach, which is tailored to each patient, will be required in order to attain clinical benefit.

Asthma and indoor air: contrasts in the dose response to cat and dust-mite.

UNLABELLED: The role of the indoor environment in asthma is of major concern because (i) the disease has become more severe; (ii) we spend>or=90% of our lives indoors and (iii) a large proportion of asthmatic children and young adults are allergic to allergens found indoors. Recent evidence that children raised in a home with animals, i.e. indoor cat or dog, are less likely to become allergic has provided a great opportunity to understand the mechanisms controlling the prevalence of allergic disease. In addition the results pose a challenge to many of the hypotheses about reasons for the increase in asthma. The evidence that children or adults who make a modified TH2 response i.e. immunoglobulin (Ig)G and IgG4 ab without IgE, are not at increased risk of asthma strongly supports the role of IgE in asthma. Equally the results may give insight into a form of tolerance that could be a target for protecting patients against allergic disease. PRACTICAL IMPLICATIONS: Evidence for the immune response to cat allergen shows that the alternative response to an allergy, TH2 response, is a controlled or modified form of the response not a Th1 response. Furthermore, avoiding cats in the home in most communities would not decrease the prevalence of sensitization to cats because there is cat allergen distributed in schools, other public buildings, and homes without a cat.

Is the hygiene hypothesis still a viable explanation for the increased prevalence of asthma?

The hygiene hypothesis states that a reduced exposure to allergens in early life is solely implicated in the growing propensity for allergy sensitization. Important elements of the hypothesis include helminth infection, exposure to endotoxins, exposure to pets and growing up on a farm. However, the hygiene hypothesis alone does not provide an adequate explanation for the observed increase in allergic disease. For example, in North American inner cities, asthma is increasing among children who live in very poor housing, which might be assumed to be somewhat dirty. In order to explain the increase in asthma, we need to take a broader view and also consider alterations related to the adoption of a western lifestyle. It has been suggested that lifestyle changes related to obesity (e.g. a change in diet) are associated with asthma. Other changes include a progressive decrease in physical activity. This lifestyle factor seems to correlate best with the recent increase in asthma. Clearly, the link between physical activity and asthma needs to be investigated in more detail.

Quantitative measurement of airborne allergens from dust mites, dogs, and cats using an ion-charging device.

BACKGROUND: Increasing evidence suggests that children raised with an animal(s) in the house have a decreased risk of becoming sensitized. However, it is not clear whether this phenomenon is related to airborne exposure. OBJECTIVE: To estimate airborne exposure to animal dander and dust mite allergens using a device that can sample large volumes of air silently. METHODS: The device, which uses an ion-charging technique to move air and to collect particles, was run at 1.7 m3/min for 24 h in 44 homes with and without animals. The allergen collected was measured by ELISA for Fel d 1, Can f 1, Der p 1, and Der f 1. RESULTS: Airborne Fel d 1 was present in all homes with a cat (n=27). The quantities measured, i.e. 0.5-20 microg in 24 h, represent 0.01-0.3 microg Fel d 1 inhaled/day at normal breathing rates (20 L/h). Values for houses without a cat were 0.01-0.05 microg inhaled/day. Airborne Fel d 1 correlated significantly with floor Fel d 1 (r=0.58, P<0.001). Results for Can f 1 were similar in houses with a dog, but this allergen was only detected airborne in two houses without a dog. Neither Der p 1 nor Der f 1 (i.e. <0.01 microg) was detected, which represents < or =1 ng inhaled/day during normal domestic activity. During disturbance airborne mite was detected with both the ion-charging device and a filter run in parallel. For cat and mite allergens there was a close correlation between the two techniques (r=0.84, P<0.001). CONCLUSION: Exposure to cat or dog allergen airborne in homes with an animal can be up to 100 times higher than exposure to mite allergen. The results are in keeping with a model where immunological tolerance to animal dander allergens results from high exposure.