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Nodulation regulation Legumes convert atmospheric nitrogen into biologically useful ammonium with the help of symbiotic bacteria housed in root nodules. Much of nodule development is controlled by the transcription factor NODULE INCEPTION (NIN). Feng et al . show that NIN is proteolytically processed to release a fragment that regulates the later stages of nodulation when the nodules acquire nitrogen-fixing capability. In related work, Jiang et al . identified members of the NIN-like protein (NLP) transcription factor family as being regulators of leghemoglobin expression acting through an unusual promotor motif shared across legumes. —PJH

Immunization of rats with a bystander antigen and the toxic lectin, ricin, results in a dramatically potentiated IgE response which was only seen when ricin was administered together with antigen, or 24 h later, suggesting that the toxin was acting on cells which were activated as the result of immunization. The identity of these activated cells was investigated in radioligand bindings studies with 125I ricin. No difference was seen in the number of ricin binding sites on splenic CD4+ and CD8+ T cells from untreated rats, but the number of ricin binding sites was 13-fold higher on CD8+ but not on CD4+ T cells from immunized rats. Adoptive transfer of 1 × 10899% pure CD8+ T cells from animals, immunized 3 days before with antigen alone, suppressed the IgE response to antigen plus alum by over 90%. The IgE suppressive effect of these CD8+ T cells was not antigen specific, and they had no effect on the IgG antibody response. CD4+ T cells from none of these animals had any effect on the subsequent IgE of IgG antibody response. The capacity of CD4+ and CD8+ T cells stimulated with PHA or PMA and ionomycin to secrete the cytokines IL-2 and IFN-γ or to make IL-4 mRNA was also compared. CD8+ T cells were the highest producers of IFN-γ and accounted for 65% oftotal splenic IFN-γ. Immunization with ricin plus antigen reduced the amount of IFN-γ secreted by CD4+ (OX22+/--) and CD8+ T cells 5- to 10-fold. Over 95% of the IL-2 produced was derived from OX22+CD4+ T cells, and this did not change. In spleen cells from unimmunized animals, the largest amounts of IL-4 mRNA were found in CD8+ T cells. Following immunization with antigen plus ricin, total splenic IL-4 mRNA production was increased 3- to 4-fold and following boosting with ricin plus antigen was increased a further 3 to 4-fold. These results show: (i) that approximately 50% of splenic CD8+T cells are activated within24h of immunization with antigen, (ii) that adoptive transfer of these cells suppresses IgE production, (iii) that co-administration of ricin and antigen selectively depletes them, (iv) that this is associated with a massive increase in serum IgE a decreased capacity of T cells to produce IFN-γ and an increased capacity to make IL-4. These data suggest that CD8+ T cells, activated early in the immune response, play an important part in regulating cytokine and IgE production.

There is increasing evidence implicating the central role of cells of monocyte/macrophage lineage in the pathogenesis of bronchial asthma. This evidence comes from studies on peripheral blood monocytes. BAL fluid and cells and, more recently, airway immunohistochemistry. Elucidation of the mechanisms of macrophage interactions may eventually lead to novel approaches in anti-asthma therapy.

Background: Mass coronavirus disease 2019 (COVID-19) vaccination to achieve herd immunity is an effective means to mitigate the current COVID-19 pandemic. Reports of COVID-19 vaccine-associated allergic reactions and lack of clear local guidance are contributing factors leading to a low vaccine acceptance rate in the community. A task force of experts from the Hong Kong Institute of Allergy (HKIA) has been formed to address current needs.Objective: To formulate a set of consensus statements (CS) on COVID-19 vaccine allergy safety (VAS) in Hong Kong.Methods: A nominated task force of experts managing patients with drug and vaccine allergies in Hong Kong formulated the CS by the Delphi method. An agreement was a priori defined as ≥80% consensus.Results: A total of 11 statements met the criteria for consensus with good overall agreement among task force members, including seven statements on pre-vaccination recommendations and four statements on vaccination and post-vaccination guidance. Individuals with a history of suspected allergic reaction to prior COVID-19 vaccination should not receive further COVID-19 vaccination, and other groups at risk of COVID-19 vaccine-associated allergic reactions have been identified. The importance of pre-vaccination and post-vaccination assessment by frontline healthcare workers and evaluation by allergists are highlighted.Conclusion: The CS provides pragmatic and timely guidance for local frontline healthcare providers on decisions regarding COVID-19 VAS.

Background Elucidation of the critical immune pathways involved in allergic inflammation has identified, apart from IgE, therapeutic targets in the cytokine network suitable for intervention by biological therapies. Objective The drugs that target the cytokine networks pertinent to asthma and allergic diseases are reviewed and some illustrative case histories presented. The overview proposes a framework to use when deciding which monoclonal antibody (mAb) to select for treatment of severe asthma based on total IgE concentration, peripheral blood eosinophil count, induced sputum analysis and measurement of fractional exhaled nitric oxide (FENO). Methods Internet-based literature search including PubMed for studies on biological therapies targeting IgE and the cytokine network in allergic inflammation focusing on asthma with and without rhinosinusitis and nasal polyposis, eczema, urticaria and food allergies. Lists of pivotal trials published in the peer reviewed literature and pertaining to their own mAb products were also provided by GSK, AstraZeneca and Sanofi. Therapeutic agents licensed or in advanced stages of development (Phase 2b and 3) were selected for discussion. Results The survey identifies a number of mAbs with substantial potential for the future targeted treatment of asthma with and without rhinosinusitis and nasal polyposis, eczema, urticaria and food allergies uncontrolled by existing therapies. A pragmatic framework is proposed for selecting the optimal mAb for initial use in individual patients with severe asthma. Conclusions Launch of these new biologicals may revolutionise the treatment of allergic diseases if employed in an endotype-specific fashion, heralding an unprecedented era of personalised medicine.

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.

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. Methods Specialists from allergology, dermatology, and otorhinolaryngology were surveyed on practical considerations and key decision points when treating patients with allergic rhinitis and/or urticaria. Results Clinicians felt the need for additional tools for diagnosis of these diseases and a single drug with all preferred features of an antihistamine. Challenges in treatment include lack of clinician and patient awareness and compliance, financial constraints, and treatment for special patient populations such as those with concomitant disease. Selection of optimal second-generation antihistamines depends on many factors, particularly drug safety and efficacy, impact on psychomotor abilities, and sedation. Country-specific considerations include drug availability and cost-effectiveness. Survey results reveal bilastine as a preferred choice due to its high efficacy and safety, suitability for special patient populations, and the lack of sedative effects. Conclusions Compliance to the international guidelines is present among allergists, dermatologists and otorhinolaryngologists; however, this is lower amongst general practitioners (GPs). To increase awareness, allergy education programs targeted at GPs and patients may be beneficial. Updates to the existing international guidelines are suggested in APAC to reflect appropriate management for different patient profiles and varying symptoms of allergic rhinitis and urticaria. Electronic supplementary material The online version of this article (doi:10.1186/s12948-017-0074-3) contains supplementary material, which is available to authorized users.

Aim: We investigated sublingual immunotherapy for mite-induced allergic rhinitis and its comorbid allergic conditions. Patients & methods: A prospective case-controlled study of 120 patients (case = 80, control = 40) over 12 months. Results: There was 53.6% reduction in total rhinitis symptom score (p

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.

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.

1. Specialist in Paediatrics, Clinical Assistant Professor (Hon.), University of Hong Kong 2. Senior Dietitian, Allergy Centre, Hong Kong Sanatorium & Hospital 3. Director, Allergy Centre, Hong Kong Sanatorium and Hospital, Clinical Professor (Hon.), University of Hong Kong 4. Professor and Chairman, Department of Paediatrics, The Chinese University of Hong Kong 5. Specialist in Paediatrics, Clinical Associate Professor (Hon.), University of Hong Kong

BackgroundLow emission zones (LEZ) are an increasingly common, but unevaluated, intervention aimed at improving urban air quality and public health. We investigated the impact of London's LEZ on air quality and children's respiratory health.MethodsWe did a sequential annual cross-sectional study of 2164 children aged 8–9 years attending primary schools between 2009–10 and 2013–14 in central London, UK, following the introduction of London's LEZ in February, 2008. We examined the association between modelled pollutant exposures of nitrogen oxides (including nitrogen dioxide [NO2]) and particulate matter with a diameter of less than 2·5 μm (PM2·5) and less than 10 μm (PM10) and lung function: postbronchodilator forced expiratory volume in 1 s (FEV1, primary outcome), forced vital capacity (FVC), and respiratory or allergic symptoms. We assigned annual exposures by each child's home and school address, as well as spatially resolved estimates for the 3 h (0600–0900 h), 24 h, and 7 days before each child's assessment, to isolate long-term from short-term effects.FindingsThe percentage of children living at addresses exceeding the EU limit value for annual NO2 (40 μg/m3) fell from 99% (444/450) in 2009 to 34% (150/441) in 2013. Over this period, we identified a reduction in NO2 at both roadside (median −1·35 μg/m3 per year; 95% CI −2·09 to −0·61; p=0·0004) and background locations (−0·97; −1·56 to −0·38; p=0·0013), but not for PM10. The effect on PM2·5 was equivocal. We found no association between postbronchodilator FEV1 and annual residential pollutant attributions. By contrast, FVC was inversely correlated with annual NO2 (−0·0023 L/μg per m3; −0·0044 to −0·0002; p=0·033) and PM10 (−0·0090 L/μg per m3; −0·0175 to −0·0005; p=0·038).InterpretationWithin London's LEZ, a smaller lung volume in children was associated with higher annual air pollutant exposures. We found no evidence of a reduction in the proportion of children with small lungs over this period, despite small improvements in air quality in highly polluted urban areas during the implementation of London's LEZ. Interventions that deliver larger reductions in emissions might yield improvements in children's health.FundingNational Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London, NHS Hackney, Lee Him donation, and Felicity Wilde Charitable Trust.

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.

Chronic mucus hypersecretion (CMH) contributes to the morbidity and mortality of asthma, and remains uncontrolled by current therapies in the subset of patients with severe, steroidresistant disease. Altered cross-talk between airway epithelium and airway smooth muscle cells (ASMCs), driven by pro-inflammatory cytokines such as interleukin (IL)-1 beta, provides a potential mechanism that influences CMH. This study investigated mechanisms underlying CMH by comparing IL-1 beta-induced gene expression profiles between asthma and control-derived ASMCs and the subsequent paracrine influence on airway epithelial mucus production in vitro.IL-1 beta-treated ASMCs from asthmatic patients and healthy donors were profiled using microarray analysis and ELISA. Air liquid interface (AM-cultured CALU-3 and primary airway epithelial cells were treated with identified candidates and mucus production assessed.The IL-1 beta-induced CCL20 expression and protein release was increased in ASMCs from moderate compared with mild asthmatic patients and healthy controls. 1L-10 induced lower MIR146A expression in asthma-derived ASMCs compared with controls. Decreased MIR146A expression was validated in vivo in bronchial biopsies from 16 asthmatic patients versus 39 healthy donors. miR-146a-5p overexpression abrogated CCL20 release in ASMCs. CCL20 treatment of ALI-cultured CALU-3 and primary airway epithelial cells induced mucus production, while CCL20 levels in sputum were associated with increased levels of CMH in asthmatic patients.Elevated CCL20 production by ASMCs, possibly resulting from dysregulated expression of the antiinflammatory miR-146a-5p, may contribute to enhanced mucus production in asthma.

2015 marked the 25th anniversary of the commercial use and availability of genetically modified crops. The area of planted biotech crops cultivated globally occupies a cumulative two billion hectares, equivalent to twice the land size of China or the United States. Foods derived from genetically modified plants are widely consumed in many countries and genetically modified soybean protein is extensively used in processed foods throughout the industrialised countries. Genetically modified food technology offers a possible solution to meet current and future challenges in food and medicine. Yet there is a strong undercurrent of anxiety that genetically modified foods are unsafe for human consumption, sometimes fuelled by criticisms based on little or no firm evidence. This has resulted in some countries turning away food destined for famine relief because of the perceived health risks of genetically modified foods. The major concerns include their possible allergenicity and toxicity despite the vigorous testing of genetically modified foods prior to marketing approval. It is imperative that scientists engage the public in a constructive evidence-based dialogue to address these concerns. At the same time, improved validated ways to test the safety of new foods should be developed. A post-launch strategy should be established routinely to allay concerns. Mandatory labelling of genetically modified ingredients should be adopted for the sake of transparency. Such ingredient listing and information facilitate tracing and recall if required.

Background It is important to study differential inflammatory cellular migration, particularly of eosinophils and neutrophils, in asthma and how this is influenced by environmental stimuli such as allergen exposure and the effects of anti asthma therapy. Methods We isolated blood neutrophils and eosinophils from 12 atopic asthmatic human volunteers (Group 1 — four Early Allergic Responders unchallenged (EAR); Group 2 — four Early and Late Allergic Responders (LAR) challenged; Group 3 — four EAR and LAR challenged and treated with systemic corticosteroids) using cGMP CD16 CliniMACS. Cells were isolated prior to allergen challenge where applicable, labelled with 99mTc-HMPAO and then re-infused intravenously. The kinetics of cellular influx/efflux into the lungs and other organs were imaged via scintigraphy over 4 h, starting at 5 to 6 h following allergen challenge where applicable. Results Neutrophils and eosinophils were isolated to a mean (SD) purity of 98.36% (1.09) and 96.31% (3.0), respectively. Asthmatic neutrophils were activated at baseline, mean (SD) CD11bHigh cells 46 (10.50) %. Isolation and radiolabelling significantly increased their activation to > 98%. Eosinophils were not activated at baseline, CD69+ cells 1.9 (0.6) %, increasing to 38 (3.46) % following isolation and labelling. Analysis of the kinetics of net eosinophil and neutrophil lung influx/efflux conformed to a net exponential clearance with respective mean half times of clearance 6.98 (2.18) and 14.01 (2.63) minutes for Group 1, 6.03 (0.72) and 16.04 (2.0) minutes for Group 2 and 5.63 (1.20) and 14.56 (3.36) minutes for Group 3. These did not significantly differ between the three asthma groups (p > 0.05). Conclusions Isolation and radiolabelling significantly increased activation of eosinophils (CD69) and completely activated neutrophils (CD11bHigh) in all asthma groups. Net lung neutrophil efflux was significantly slower than that of eosinophils in all asthma study groups. There was a trend for pre-treatment with systemic corticosteroids to reduce lung retention of eosinophils following allergen challenge., Highlights • Isolation and radiolabelling of eosinophils or neutrophils from asthmatics significantly activates them. • Corticosteroids alter eosinophil, but not neutrophil 99mTc-HMPAO radiolabelling efficiency. • Leukocyte activation as a result of manipulation ex vivo does not measurably alter lung sequestration. • Eosinophil migration through the lungs of asthmatic patients is slower than in healthy volunteers.

© 2017 Published by the BMJ Publishing Group Limited. Background Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. Objectives To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. Methods Human asthmatic and healthy ASMC grown in culture were run on Affymetrix-Hugene-1.0-ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. Results We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. Conclusions Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.

Overview Overview of the 5-Lipoxygenase Pathway, Jesper Z. Haeggstroem and Bengt Samuelsson Leukotriene Biochemistry 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein, Jilly F. Evans Leukotriene C4 Synthase: A Pivotal Enzyme in the Biosynthesis of Cysteinyl Leukotrienes, John F. Penrose and K. Frank Austen Leukotriene A4 Hydrolase, Jesper Z. Haeggstroem Leukotriene Export in Human Leukocytes, Bing K. Lam Cell Biology of the Leukotrienes Pathways of Leukotriene Metabolism in Isolated Cell Models and Human Subjects, Robert C. Murphy and Pat Wheelan Cell Biology of the 5-Lipoxygenase Pathway: Amplification and Generation of Leukotrienes and Lipoxins by Transcellular Biosynthesis, Timothy D. Bigby, Bruce D. Levy, and Charles N. Serhan Physiological Actions of the Leukotrienes Leukotriene Receptors: Incompletely Defined Targets for Treatment of Asthma and Inflammation, Sven-Erik Dahlen Physiological Effects of the Leukotrienes in Humans, Neil C. Barnes and Lewis J. Smith Recovery of Leukotrienes Analysis of Leukotrienes and Lipoxins, Graham W. Taylor Measurement of Leukotrienes from Human Biological Fluids, Jay Y. Westcott and Ian K. Taylor Leukotrienes in Asthma Cysteinyl-Leukotriene Receptor Antagonism and 5-Lipoxygenase Inhibition in Asthma, S. M. Shuaib Nasser and Tak H. Lee Leukotriene Receptor Antagonism and Synthesis in Chronic Stable Asthma, Elliot Israel and Jeffrey M. Drazen Specific Drug Products Montelukast-An Antileukotriene Treatment for Asthma: Changing the Asthma-Treatment Paradigm, Beth C. Seidenberg and Theodore F. Reiss Pranlukast-The First Orally Active Cysteinyl Leukotriene Receptor Antagonist Marketed for the Treatment of Asthma, Jeffrey W. Dubb and Anthony S. Rebuck Zafirlukast, Catherine M. Bonuccelli and Trevor J. C. Higgins Zileuton: The First Leukotriene Synthesis Inhibitor for Use in the Management of Chronic Asthma, Louise M. Dube, Linda J. Swanson, Walid Awni, Rachel F. Ochs, Randy L. Bell, and George W. Carter Antileukotrienes in the Management of Asthma, Paul M. O'Byrne

Leukotriene E4 (LTE4) the most stable of the cysteinyl leukotrienes (cysLTs) binds poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces potent responses in human airways in vivo, such as bronchoconstriction, airway hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel receptor that preferentially responds to LTE4. To identify such a receptor two human mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4 when analysed by intracellular signalling and gene expression. Comparative transcriptome analysis and recombinant gene overexpression experiments revealed CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not in LUVA cells, an observation confirmed further by gene knockdown and selective inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented intracellular calcium signalling induced by LTE4 but did not restore full agonist responses at the gene expression level. Our data support a model where both an increased expression of Gαq-coupled CysLT1, and sustained intracellular calcium mobilisation and extracellular signal-regulated kinase (Erk) activation, are required for LTE4-mediated regulation of gene expression in human cells. Our study shows for the first time that CysLT1 expression is critically important for responsiveness to LTE4 within a human cell system.

Leukotriene E4 (LTE4) the most stable of the cysteinyl leukotrienes (cysLTs) binds poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces potent responses in human airways in vivo, such as bronchoconstriction, airway hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel receptor that preferentially responds to LTE4. To identify such a receptor two human mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4 when analysed by intracellular signalling and gene expression. Comparative transcriptome analysis and recombinant gene overexpression experiments revealed CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not in LUVA cells, an observation confirmed further by gene knockdown and selective inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented intracellular calcium signalling induced by LTE4 but did not restore full agonist responses at the gene expression level. Our data support a model where both an increased expression of Gαq-coupled CysLT1, and sustained intracellular calcium mobilisation and extracellular signal-regulated kinase (Erk) activation, are required for LTE4-mediated regulation of gene expression in human cells. Our study shows for the first time that CysLT1 expression is critically important for responsiveness to LTE4 within a human cell system.

Many children in Hong Kong have allergic diseases and epidemiological data support a rising trend. Only a minority of children will grow out of their allergic diseases, so the heavy clinical burden will persist into adulthood. In an otherwise high-quality health care landscape in Hong Kong, allergy services and training are a seriously unmet need. There is one allergy specialist for 1.5 million people, which is low not only compared with international figures, but also compared with most other specialties in Hong Kong. The ratio of paediatric and adult allergists per person is around 1:460 000 and 1:2.8 million, respectively, so there is a severe lack of adult allergists, while the paediatric allergists only spend a fraction of their time working with allergy. There are no allergists and no dedicated allergy services in adult medicine in public hospitals. Laboratory support for allergy and immunology is not comprehensive and there is only one laboratory in the public sector supervised by accredited immunologists. These findings clearly have profound implications for the profession and the community of Hong Kong and should be remedied without delay. Key recommendations are proposed that could help bridge the gaps, including the creation of two new pilot allergy centres in a hub-and-spoke model in the public sector. This could require recruitment of specialists from overseas to develop the process if there are no accredited allergy specialists in Hong Kong who could fulfil this role.

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 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.

The adverse effects of traffic-related air pollution on children's respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8-9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00-1.02), NO2 (1.03, 1.00-1.06), PM10 (1.16, 1.04-1.28) and PM2.5 (1.38, 1.08-1.78), all per μg/m3 of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions.