Mast cells are the major effector cells that mediate IgE-dependent allergic reactions. We sought to use integrated network analysis to identify genomic biomarkers associated with high response in IgE-mediated activation of primary human mast cells. Primary human mast cell cultures derived from 262 normal donors were categorized into High, Average and Low responder groups according to their activation response profiles. Transcriptome analysis was used to identify genes that were differentially expressed in different responder cultures in their baseline conditions, and the data were analyzed by constructing a personalized perturbed profile (PEEP). For upregulated genes, the construction of PEEP for each individual sample of all three responder groups revealed that High responders exhibited a higher percentage of “perturbed” samples whose PEEP values lay outside the normal range of expression. Moreover, the integration of PEEP of four selected upregulated genes into distinct sets of combinatorial profiles demonstrated that the specific pattern of upregulated expression of these four genes, in a tandem combination, was observed exclusively among the High responders. In conclusion, this combinatorial approach was useful in identifying a set of genomic biomarkers that are associated with high degranulation response in human mast cell cultures derived from the blood of a cohort of normal donors.

Peanut allergy is the commonest cause of food-induced anaphylaxis in the world, and it can be fatal. There have been many recent improvements to achieve safe methods of peanut desensitisation, one of which is to use a combination of anti-immunoglobulin E and oral immunotherapy. We have treated 27 patients with anti-immunoglobulin E and oral immunotherapy, and report on the outcomes and incidence of adverse reactions encountered during treatment. The dose of peanut protein tolerated increased from a median baseline of 5 to 2000 mg after desensitisation, which is substantially more than would be encountered through accidental ingestion. The incidence of adverse reactions during the escalation phase of oral immunotherapy was 1.8%, and that during the maintenance phase was 0.6%. Most adverse reactions were mild; three episodes were severe enough to warrant withdrawal from oral immunotherapy, but none required epinephrine injection. Preliminary data suggest that unresponsiveness is lost when daily ingestion of peanuts is stopped after the maintenance period.

INTRODUCTION:There is a high and rising prevalence of many allergic diseases in the Asia Pacific, including Hong Kong (HK), which is unmatched by a commensurate provision of clinical allergy services.METHOD:This review highlights progress and deficiencies in allergy service and training in HK. The allergy work force was estimated from the numbers of doctors practicing allergy registered with the HK Medical Council Specialist Register in Immunology and Allergy; Paediatric Immunology and Infectious Diseases (includes allergy); Paediatrics; and Immunology (as a discipline of Pathology). The numbers of trainees were estimated from the trainee lists of the Hong Kong Colleges of Physicians, Paediatrics and Pathology. The numbers of allergy clinics were estimated from existing services in Hospital Authority public hospitals in HK.RESULTS:In the last 3 years, two new drug allergy clinics have been established in public hospitals, and for the first time in 20 years, Hong Kong has a trainee in adult allergy. The current ratio of allergists per head of population has improved slightly from 1:1.46 million in 2014 to 1:1.17 million, but it is still low compared to many countries. There are 5-fold more paediatric allergists than adult allergists per head of population in HK.DISCUSSION:Hong Kong is not equipped to take advantage of major public health advances in allergy prevention. If the unbalance of adult to paediatric allergists remains uncorrected, continuing care for allergic children as they grow into adulthood will be an increasing problem.CONCLUSION:Hong Kong still has an unmet need for allergy specialists and is ill equipped to exploit recently discovered public health opportunities to prevent allergy. This review provides recommendations to improve allergy service provision and training, including the creation of Centres of Excellence in allergy to drive the growth of the specialty.

Global warming is a public health emergency. Substantial scientific evidence indicates an unequivocal rising trend in global surface temperature that has caused higher atmospheric levels of moisture retention leading to more frequent extreme weather conditions, shrinking ice volume, and gradually rising sea levels. The concomitant rise in the prevalence of allergic diseases is closely related to these environmental changes because warm and moist environments favour the proliferation of common allergens such as pollens, dust mites, molds, and fungi. Global warming also stresses ecosystems, further accelerating critical biodiversity loss. Excessive carbon dioxide, together with the warming of seawater, promotes ocean acidification and oxygen depletion. This results in a progressive decline of phytoplankton and fish growth that in turn promotes the formation of larger oceanic dead zones, disrupting the food chain and biodiversity. Poor environmental biodiversity and a reduction in the microbiome spectrum are risk factors for allergic diseases in human populations. While climate change and the existence of an allergy epidemic are closely linked according to robust international research, efforts to mitigate these have encountered strong resistance because of vested economic and political concerns in different countries. International collaboration to establish legally binding regulations should be mandatory for forest protection and energy saving. Lifestyle and behavioural changes should also be advocated at the individual level by focusing on low carbon living; avoiding food wastage; and implementing the 4Rs: reduce, reuse, recycle, and replace principles. These lifestyle measures are entirely consistent with the current recommendations for allergy prevention. Efforts to mitigate climate change, preserve biodiversity, and prevent chronic diseases are interdependent disciplines.

The treatment of asthma has improved greatly during the last two decades, and deaths from the disease have decreased.1 Despite these advances, many asthma patients fail to achieve optimal asthma control as defined by international guidelines.2,3 Severe asthma is associated with high risk of exacerbations and death.4 Definitions of severe asthma vary but, according to European Respiratory Society (ERS)/American Thoracic Society (ATS) and Global Initiative for Asthma (GINA) guidelines, severe asthma is asthma that requires treatment with high doses of inhaled corticosteroids plus a second controller, and/or systemic corticosteroids, to prevent it from becoming uncontrolled, or remains uncontrolled despite this therapy.2,5 In an expert interview, Professor Barnes discusses the latest advances in the management of both mild and severe asthma.

Vaccination of egg-allergic individuals has been a historical concern, particularly for influenza and measles-mumps-rubella-varicella vaccines that are developed in chicken egg embryos or chicken cell fibroblasts. The egg proteins in these vaccines were believed to trigger an immediate allergic reaction in egg-allergic individuals. However, recently published international guidelines have updated their recommendations and now state that these vaccines can be safely administered to egg-allergic individuals. This joint consensus statement by the Hong Kong Institute of Allergy and the Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases summarises the updates and provides recommendations for local general practitioners and paediatricians. Hong Kong Institute of Allergy and Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases joint consensus statement 2018 on vaccination in egg-allergic patients Background.

Allergic diseases are on the rise in many parts of the world, including the Asia–Pacific (APAC) region. Second-generation antihistamines are the first-line treatment option in the management of allergic rhinitis and urticaria. International guidelines describe the management of these conditions; however, clinicians perceive the additional need to tailor treatment according to patient profiles. This study serves as a consensus of experts from several countries in APAC (Hong Kong, Malaysia, the Philippines, Singapore, Thailand, Vietnam), which aims to describe the unmet needs, practical considerations, challenges, and key decision factors when determining optimal second-generation antihistamines for patients with allergic rhinitis and/or urticaria.

Major opportunities have been identified recently to prevent allergic disorders including the early introduction of allergenic foods to infants1-9 and immunotherapy.10,11 Breast feeding is still strongly encouraged, but new evidence suggests that the avoidance of allergenic foods in infancy to delay the onset of allergic diseases may have sustained rather than prevented food allergies and eczema. International guidelines on infant feeding are being revised.12-14 It is a moot point whether Hong Kong has the infrastructure required to exploit these transformative opportunities to improve public health in allergy.

Allergic diseases are a global problem. Mothers are advised to enjoy a healthy diet with no restrictions during pregnancy and lactation, as prophylactic dietary restriction is unlikely to reduce the development of atopic disease. Breastfeeding is recommended for the first 6 months of the newborn's life. Atopic eczema has been shown to be significantly reduced in high-risk infants fed a hydrolysed formula compared with standard cow's milk formula. Complementary food is also recommended for infants over 4 months if they are developmentally ready. Various environmental factors may influence the prevalence and course of allergic diseases. There is a strong epidemiological association between air pollution from traffic and allergies. Smoking is also a significant risk factor. Home dampness and visible mold are associated with recurrent wheeze and asthma. House dust mite is a possible cause of asthma. Lifestyle factors also play a role. Obesity shows a clear relationship with asthma and eczema. Stressful life events may increase the risk of atopic disease. Immunotherapy has been shown to be effective. It reduces new sensitisations and prevents progression of allergic rhinitis to asthma. Summary of the above recommendations are presented.

Exposure to urban particulate matter (UPM) exacerbates asthmatic lung inflammation. Lung dendritic cells (DCs) are critical for stimulating T cell immunity and in maintaining airway tolerance, but they also react to airway UPM. The adjuvant role of UPM in enhancing primary immune responses by naive cells to allergen has been reported, but the direct effects of UPM-activated DCs on the functionality of human memory CD4 T cells (Tms), which constitute the majority of T cells in the lung, has not been investigated. Blood CD1c(+) DCs were purified and activated with UPM in the presence or absence of house dust mite or tetanus toxoid control antigen. 5-(and -6)-Carboxyfluorescein diacetate succinimidyl ester-labeled blood Tms were cocultured with autologous DCs, T cell proliferation and effector function were assessed using flow cytometry, and secreted cytokines were measured by combined bead array. UPM-DCs elicited IFN-γ and IL-13 secretion and induced proliferation in Tms isolated from both allergic patients with asthma and healthy control subjects, whereas only IL-13 was produced by Tms from patients with atopic asthma stimulated by house dust mite-loaded DCs. UPM-DCs drove the expansion and differentiation of a mixed population of Th1, Th2, and Th17 cell effectors through a mechanism that was dependent on major histocompatibility class II but not on cytokine-driven expansion. The data suggest that UPM not only has adjuvant properties but is also a source of antigen that stimulates the generation of Th2, Th1, and Th17 effector phenotypes, which have been implicated in both exacerbations of asthma and chronic inflammatory diseases.

Introduction Transition of young adults (YA) from specialist paediatric to adult services is an active process that requires specific management and planning and does not merely represent the transfer of care as a single event. In other chronic diseases (e.g. Cystic Fibrosis; T1DM) it is well acknowledged that clinical outcomes improve when this process is well organised and where this is lacking the risk of non-adherence to treatment and loss of disease control increases. BTS guidelines1 clearly recommend a coordinated approach when transitioning YA in an asthma setting. Despite the importance of this process, little information is available on transition arrangements in asthma services. Methods An online survey was sent to 105 trusts with adult asthma services in all parts of the UK to establish their transition arrangements. Results Of the 43 responding centres (District General Hospital n = 20), only 60% had a designated lead (n = 26) and less than half made any form of specific arrangements for transition (n = 18). University Hospital trusts were more likely to have transitional care arrangements in place (n = 11/22) than District General Hospitals (n = 6/20). In those centres that did run joint clinics (n = 16), in the majority of cases this only involved adult team members attending paediatric clinics (n = 10). Most centres (n = 25) expected ≤5 patients to transition each year and over 90% (n = 37) did not initiate contact with YA until they were ≥15 yrs old. Only a third of centres delayed transition if YA were not perceived to be ready (n = 15) or remained in full time education (n = 15). Overall less than a third of respondents (n = 13) were satisfied with their transition arrangements. Conclusions Our survey reveals for the first time the wide variation in approaches to transition in asthma clinics across the UK. Our data suggests that currently most centres are not committing the recommended resources towards this process, no doubt hampered in part by the relatively small numbers of young adults with asthma transitioning each year. Reference British Thoracic Society. BTS/SIGN Asthma guideline. 2014. https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2014/ (accessed 28 June 2016).

Background Low Emission Zones are a novel public health intervention to address the adverse effects of traffic pollution on health. We investigated the association between traffic derived air pollutants and lung function in 8–9 year old children living in London’s Low Emission Zone. Methods Sequential yearly cross-sectional study of 2,297 children aged 8–9 years attending east London primary schools between 2009 and 2014, following the introduction of the Low Emission Zone. We examined the relationship between pollutant exposures (NOx, NO2, PM2.5 and PM10) and lung function. We assigned annual exposures by each child’s residential address. In addition, we used spatially resolved estimates of 12-hour, 24-hour, 7-day and annual exposures prior to each child’s assessment, allowing us to compare the relative effects of very short-, short-, medium- and long-term pollutant exposures. Primary outcome measure was post-bronchodilator FEV1. Findings We found inverse associations between exposures of PM10 and PM2.5 in the week prior to children’s assessment and FEV1 (P < 0.05); and inverse associations between annual exposures of PM10, NOx, and NO2, and FVC (p < 0.05); and exposures of PM10 and PM2.5 in the week prior to assessment, and FVC (p < 0.05). No associations were seen when shorter term exposure estimates were employed. We found no evidence of improvements in lung function over the duration of the Low Emission Zone. Interpretation Exposure of children to traffic pollution in central London is associated with decreased lung function and lung volumes. No detectable health benefit followed the introduction of the Low Emission Zone.

Peanut allergy is one of the commonest food hypersensitivities causing fatal or near-fatal reactions. There is, currently, no preventive treatment and the incidence of severe allergic reactions during peanut desensitisation has limited its clinical use. Anti-immunoglobulin E therapy has been shown to be effective in preventing peanut-induced reactions but it does not result in long-term tolerance. Two important advances have recently been reported. One involves gradual oral introduction of peanut protein to desensitise, whereas the other approach uses a combination of anti-immunoglobulin E and oral peanut immunotherapy. Both approaches could offer a way to desensitise with a far greater margin of safety than has, hitherto, been reported. This article provides an overview of the literature on peanut immunotherapy and describes the experience in a small group of children in Hong Kong who were treated successfully using anti-immunoglobulin E combined with oral peanut desensitisation.

Urban particulate matter (UPM) exacerbates asthmatic lung inflammation and depresses lung immunity. Lung dendritic cells (DCs) react to airway particulates, and have a critical role in linking innate and adaptive immunity, but the direct effects of UPM on DCs, that have been activated by granulocyte/macrophage colony-stimulating factor (GM-CSF), a product of stimulated normal human bronchial epithelial cells, has not been investigated. Human blood CD1c(+) DCs were purified and activated with UPM in the presence or absence of GM-CSF with and without LPS, and DC maturation was assessed by flow cytometry. DC stimulatory capacity and priming of 5-(and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled naive CD4 T cells was investigated using the allogeneic mixed lymphocyte reaction. T cell proliferation and effector function were assessed using flow cytometry and secreted cytokines were measured by combined bead array. UPM enhanced DC maturation in an LPS-independent manner. DCs activated by UPM plus GM-CSF (UPM + GM-CSF DCs) induced higher naive CD4 T cell proliferation in the allogeneic mixed lymphocyte reaction than DCs pretreated by GM-CSF alone (GM-CSF DCs), and elicited both substantially lower levels of IFN-γ, IL-13, and IL-5 secretion, and lower frequencies of alloantigen-specific T helper (Th) type 1 effector cells than naive CD4 T cells primed by GM-CSF DCs. UPM-stimulated DCs produced IL-6 and TNF-α. Neutralization of IL-6 decreased naive CD4 T cell proliferation stimulated by UPM + GM-CSF DCs, and significantly increased the frequency of alloantigen-specific Th1 effector cells, but did not reverse UPM-induced inhibition of IFN-γ secretion. We conclude that UPM enhances GM-CSF-induced DC maturation and stimulatory capacity, but inhibits the generation of Th1 cells. Thus, UPM exposure may impair Th1 responses to pulmonary pathogens.

BACKGROUND:Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug.METHODS:We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed.RESULTS:We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test.CONCLUSION:Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455).