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Background. Anaphylaxis is a severe and potentially life-threatening allergic reaction which has a detrimental impact on quality of life (QoL), however little is known about the impact of anaphylaxis, across the various causes, on adults. The aim of this study was to assess the impact of anaphylaxis on QoL and mental health in adults. Methods. Participants (n=142; 60% female) were recruited from a regional allergy centre (Birmingham, U.K) following systematic specialist evaluation. They completed measures of generic QoL (WHOQoL BREF), anaphylaxis specific QoL (A-QoL-Adults), anxiety and depression (HADS) and stress (PSS). Results. Anaphylaxis triggers were mainly to medication or during general anaesthesia (29.6%), food (29.6%), wasp or bee venom (16.2%), or were spontaneous (21.1%). Adults with anaphylaxis had significantly poorer general QoL and stress than published data from a healthy population. Females had significantly poorer anxiety and depression than norm data (all pConclusions. Anaphylaxis has an adverse impact on QoL and mental health of adults across different triggers. Anxiety, depression and number of reactions in particular seem to be important in explaining the impact on QoL and should be of particular note for clinicians managing adults with this condition, and when considering specialist psychological support.

Epidemiological studies have shown a rise in the prevalence of allergic diseases in India during the last two decades. However, recent evidence from the Global Asthma Network study has observed a decrease in allergic rhinitis, asthma and atopic dermatitis in children. Still, with a population over 1.3 billion, there is a huge burden of allergic rhinitis, asthma and atopic dermatitis, and this is compounded by an unmet demand for trained allergy specialists and poor health service framework. There is wide variation in the prevalence of allergic diseases between different geographical locations in India, and the reasons are unclear at present. This may at least in part be attributable to considerable heterogeneity in aero-biology, weather, air pollution levels, cultural and religious factors, diet, socioeconomic strata and literacy. At present, factors enhancing risks and those protecting from development of atopy and allergic diseases have not been well delineated, although there is some evidence for the influence of genetic factors alongside cultural and environmental variables such as diet, exposure to tobacco smoke and air pollution and residence in urban areas. This narrative review provides an overview of data from India regarding epidemiology, risk factors and genetics and highlights gaps in evidence as well as areas for future research.

Background: Global estimates suggest that tobacco will account for 8 million deaths per year by 2030. The Global Adult Tobacco Survey (2016-17) reported that more than half of men and one in ten women aged 15 years and above smoke in India. Introduction: Health science courses students (HCS), being the future of our health care system, are expected to be more knowledgeable regarding the hazards of tobacco and are considered less likely to use it compared to their peers (non-HCS) from other fields. The aim of the study is to determine the prevalence and determinants of tobacco use and levels of nicotine dependence amongst HCS and non-HCS students. Methods: Web-based survey (response rate of 72%) employing Global Youth Tobacco Survey (GYTS) and Fagerström standardized questionnaires (n = 4770 [21.5 (SD: ± 1.61) years: 62% male] was filled by HCS (43.5%) and non-HCS (56.3%) students from three universities. A descriptive, comparative and multivariate analysis was performed. Results: Half of non-HCS and a third of HCS used tobacco, with a higher proportion of male users in both groups. 70% of overall participants showed ‘low nicotine dependence’ with a higher proportion of ‘high dependence’ within the non-HCS group (13.89% vs. 9.2%). There were crucial differences in specific determinants and ages of initiation of tobacco use between the two groups. Conclusion: Tobacco use in HCS, apart from personal health risks, may potentially affect their future commitment to support patients in tobacco cessation programs. There is a need for further research into tobacco prevention and cessation programs tailored to the needs of student groups based on the determinants affecting them.

India is a Low-Middle Income Country (LMIC) with a population of ~1.3bn. It is the second most populous country comprising 20% of the global population. Whilst India has not faced an 'allergy epidemic' as in High Income Countries (HICs), there is some evidence that the burden of allergic diseases has gradually risen1, and is greatly magnified by the absolute numbers and is compounded by the unmet demand for allergy services2,3. Data regarding epidemiology, risk factors and natural course of allergic diseases in India are relatively sparse. By virtue of considerable diversity in culture, breast feeding, infections including parasitic, diet, environmental conditions such as weather, aero-allergens, and unacceptably high levels of particulate matter ≤2.5µm (PM2.5 ), India offers an invaluable platform to study immune-mediated diseases3,4 .

Allergen-specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long-term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side-effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4+ T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and a committee of experts and key stakeholders have developed this guideline for the evaluation and testing of patients with an unsubstantiated label of penicillin allergy. The guideline is intended for UK clinicians who are not trained in allergy or immunology, but who wish to develop a penicillin allergy de-labelling service for their patients. It is intended to supplement the BSACI 2015 guideline "Management of allergy to penicillin and other beta-lactams" and therefore does not detail the epidemiology or aetiology of penicillin allergy, as this is covered extensively in the 2015 guideline (1). The guideline is intended for use only in patients with a label of penicillin allergy and does not apply to other beta-lactam allergies. The recommendations include a checklist to identify patients at low risk of allergy and a framework for the conduct of drug provocation testing by non-allergists. There are separate sections for adults and paediatrics within the guideline, in recognition of the common differences in reported allergy history and likelihood of true allergy.

The burden of allergic diseases (ADs) such as asthma and rhinitis and autoimmune disorders (AIDs) such as rheumatoid arthritis (RA) are relatively low/moderate in low and low-middle income countries and there is some evidence regarding higher incidence rates of these conditions amongst immigrant population settled in high income countries . The burden of ADs are particularly high in high income countries such as UK, Republic of Ireland and New Zealand . Studies in immigrants have been limited by several factors including relatively small sample size, shorter duration, and methodological issues such as selection bias, survey or questionnaire-based data, focus on a single or limited number of ADs or AIDs, and some not accounting for important disease confounders such as smoking history.

Introduction India is low-middle-income country (LMIC) with a population of 1.3bn, comprising about 20% of the global population. While the high-income Western countries faced an "allergy epidemic" during the last three decades, there has been a gradual rise in prevalence of allergic diseases in India. Methods Narrative review. Results and discussion Allergic diseases occur as a consequence of a complex interplay between genetic and environmental factors. There are multiple contrasting determinants that are important to consider in India including high levels of air pollution, in particular PM2.5 due to burning of fossil fuels and biomass fuels, diverse aero-biology, tropical climate, cultural and social diversity, religious beliefs/myths, linguistic diversity, literacy level, breastfeeding and weaning, diet (large proportion vegetarian), and high incidence rates of TB, HIV, malaria, filariasis, parasitic infestations, and others, that not only shape the immune system early in life, but also impact on biomarkers relevant to allergic diseases. India has a relatively weak and heterogeneous healthcare framework, and allergology has not yet been recognized as an independent specialty. There are very few post-graduate training programs, and allergic diseases are managed by primary care physicians, organ-based specialists, and general pediatricians. Adrenaline auto-injectors are not available, there is patient unaffordability for inhalers, nasal sprays, and biologics, and this is compounded by poor compliance leading to 40%-50% of asthmatic children having uncontrolled disease and high rates of oral corticosteroid use. Standardized allergen extracts are not available for skin tests and desensitization. This article provides a critical analysis of pediatric allergic diseases in India.

Tuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low-Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)-TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti-TB drugs occur in over 60% and 3%-4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR-TB. HSRs to anti-TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T-cell mediated. Severe and systemic T-cell mediated HSRs and IgE mediated anaphylaxis to anti-TB drugs are relatively rare, but important to recognise and treat promptly. T-cell-mediated HSRs are more frequent amongst patients with co-existing HIV infection. Some patients develop multiple sensitisation to anti-TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti-TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource-dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low-income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti-TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re-challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real-time data on ADRs, HSRs, safety and clinical outcomes of these interventions.

The biological role of fungi in the pathophysiology of asthma has attracted renewed attention during the last decade. The term severe asthma with fungal sensitisation (SAFS) was first introduced in 2006 and has since been recognised as a distinct clinical phenotype in adult asthma.

Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as ‘empty mast cell (MC) syndrome’, is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis. Best practice guidelines regarding optimal timing for performing skin tests postanaphylaxis are largely based on expert opinion, and allergy work-up has been recommended after 4–6 weeks postanaphylaxis to avoid false-negative results.This article provides a review of clinical literature surrounding PAMA, critically evaluates intracellular events in MCs from in vitro data and hypothesises regarding plausible immune mechanisms. There are no published data to directly explain molecular mechanisms underlying this phenomenon. Although not evidence based, PAMA has been attributed to depletion of MC granules following anaphylaxis. It is also plausible that exposure to high allergen concentrations in anaphylaxis can induce a temporary shift in MCs towards dominance of inhibitory signalling pathways, thus contributing to a state of transient hyporesponsiveness observed in some patients. Other potential contributory factors for reduced MC reactivity include downregulation of FcεRI expression, cross-linking of FcεRI to the inhibitory, low-affinity IgG receptors and administration of pharmacotherapeutic agents for anaphylaxis treatment. It is likely that this interesting phenomenon can be explained by a combination of these proposed mechanisms in addition to other genetic/host factors that have not yet been identified.

Chronic spontaneous urticaria and angioedema (CSU/A) is a common condition with an estimated global point prevalence of 0.7% (95% C.I, 0.2‐1.4)(1), higher in non‐White populations. Symptoms present as an ‘allergy mimic’ but are underpinned by non‐specific, non‐IgE‐mediated mast cell histamine release. The combination of common population prevalence and likelihood of vaccines precipitating symptoms in those with CSU/A presents an immediate risk to the SARS‐COV‐2 global vaccine program.

Obtaining an accurate clinical history is fundamental to the holistic approach of modern day medicine. In allergology, the clinical examination is usually unremarkable. A detailed allergy history could provide a clear direction for specific IgE testing and avoid an unnecessary allergen challenge. IgE mediated reactions are caused by mast cell degranulation and occur soon after allergen exposure. The hallmark symptoms of IgE mediated reaction include sneezing, pruritus, urticaria, angioedema, bronchospasm, hypotension and tachycardia and rarely full blown anaphylaxis. Establishing a link between a potential trigger and the patient’s reactions is an essential part in the allergy history. The clinician should question whether the culprit could consistently reproduce the symptoms within a similar time frame. Although the mechanism is not clear, it is well known that co-factors such as the Non-Steroidal Anti-Inflammatory Drugs, exercise, alcohol, stress, and menstruation can potentially trigger or exacerbate symptoms of allergy.

Background The COVID-19 pandemic imposed multiple restrictions on healthcare services. Objective To investigate the impact of the pandemic on Allergy & Immunology (A&I) services in the UK. Methods National survey of all A&I services registered with the Royal College of Physicians and/or British Society for Allergy and Clinical Immunology. The survey covered staffing, facilities, personal protective equipment, appointments & patient review, investigations, treatments and research activity. Weeks commencing 03 Feb’20 (pre-COVID), 06 April’20 and 08’May’20 were used as reference points for the dataset. Results 99 services participated. There was a reduction in nursing, medical, administrative and allied health professional staff during pandemic; 86% and 92% of A&I services continued to accept non-urgent and urgent referrals respectively during the pandemic. There were changes in immunoglobulin (Ig) dose and infusion regimen in 67% and 14% of adult and pediatric services respectively; 30% discontinued immunoglobulin replacement in some patients. There was a significant (all variables, p≤0.0001) reduction in the following: face-to-face consultations (increase in telephone consultations), initiation of venom immunotherapy, sublingual and subcutaneous injection immunotherapy, anesthetic allergy testing and hospital procedures (food challenges, immunoglobulin and omalizumab, administration); and a significant increase (p≤0.0001) in home therapy for immunoglobulin and omalizumab. Adverse clinical outcomes were reported, but none were serious. Conclusion The pandemic had significant impact on A&I services leading to multiple unplanned pragmatic amendments in service delivery. There is an urgent need for prospective audits and strategic planning in the medium and long term to achieve equitable, safe and standardised healthcare., Highlights box: 1. What is already known about this topic? There are no published data regarding the impact of COVID-19 pandemic on Allergy & Immunology services in the UK National Health Service. 2. What does this article add to our knowledge? Data showed reduction in face-to-face consultations, increase in remote consultations, reduced access to allergy testing, and increase in self-administration of omalizumab and immunoglobulin replacement therapy. 3. How does this study impact current management guidelines? These findings will shape new guidelines regarding delivery of an equitable, safe and standardized Allergy & Immunology service and governance framework in the post-pandemic recovery phase.

India is the second most populous country in the world with a population of nearly 1.3 billion, comprising 20% of the global population. There are an estimated 37.5 million cases of asthma in India, and recent studies have reported a rise in prevalence of allergic rhinitis and asthma. Overall, 40–50% of paediatric asthma cases in India are uncontrolled or severe. Treatment of allergic rhinitis and asthma is sub-optimal in a significant proportion of cases due to multiple factors relating to unaffordability to buy medications, low national gross domestic product, religious beliefs, myths and stigma regarding chronic ailment, illiteracy, lack of allergy specialists, and lack of access to allergen-specific immunotherapy for allergic rhinitis and biologics for severe asthma. High quality allergen extracts for skin tests and adrenaline auto-injectors are currently not available in India. Higher postgraduate specialist training programmes in Allergy and Immunology are also not available. Another major challenge for the vast majority of the Indian population is an unacceptably high level of exposure to particulate matter (PM)2.5 generated from traffic pollution and use of fossil fuel and biomass fuel and burning of incense sticks and mosquito coils. This review provides an overview of the burden of allergic disorders in India. It appraises current evidence and justifies an urgent need for a strategic multipronged approach to enhance quality of care for allergic disorders. This may include creating an infrastructure for education and training of healthcare professionals and patients and involving regulatory authorities for making essential treatments accessible at subsidised prices. It calls for research into better phenotypic characterisation of allergic disorders, as evidence generated from high income western countries are not directly applicable to India, due to important confounders such as ethnicity, air pollution, high rates of parasitic infestation, and other infections.

Background A label of penicillin allergy is held by 6–10% of the general population and 15–20% of inpatients. > 90% of these labels are found to be spurious after formal allergy assessment. Carrying an unnecessary label of penicillin allergy is not benign. Such patients may receive second line, more expensive antibiotics, representing a significant impediment to antimicrobial stewardship. Aim of the review To (a) Explain the burden of spurious penicillin allergy, and evaluate the safety of direct oral penicillin challenge in ‘low risk’ patients (b) appraise the place for a clinical pharmacist-led penicillin allergy de-labelling programme. Method Narrative review. Search engines: PubMed, Google Scholar and Cochrane reviews. Search criteria: English language; search terms: penicillin allergy, antimicrobial stewardship, antimicrobial resistance, clostridium difficile, vancomycin resistant enterococci, risk stratification, clinical pharmacist and direct oral provocation test Results Penicillin allergy labels are associated with: longer hospital stay, higher readmission rates, enhanced risk of surgical site infections, risk of Clostridioides difficile infection and Methicillin resistant Staphylococcus aureus infection, a delay in the first dose of an antibiotic in sepsis and higher healthcare costs. A direct oral penicillin challenge in ‘low risk’ patients has proven to be safe. Discussion Recent studies including those led by a clinical pharmacist have demonstrated safety of a direct oral penicillin challenge in ‘low risk’ patients. This intervention needs validation within individual health services. Conclusion Direct oral penicillin challenge reduces the adverse impact of spurious penicillin allergy. A pharmacist-led penicillin allergy de-labelling program needs further validation in prospective multi-centre studies.

AimsAt a tissue level, matrix metalloproteinase-1 (MMP-1) and transforming growth factor-beta 1 (TGF-β1) contribute to allergic airway inflammation, tissue remodelling and disease severity in asthma via different pathways. Their peripheral blood levels and role in diagnosis and therapeutic monitoring has not been adequately explored. We investigated the association between MMP-1 and TGF-β in moderate and severe persistent asthma and evaluated their performance characteristics by constructing receiver operating characteristic curves.MethodsSerum MMP-1 and TGF-β1 were measured using ELISA in 75 adults; moderate persistent asthma (n=25), severe persistent asthma (n=25) and healthy community controls (n=25). Severity of asthma was determined as per Global Initiative for Asthma guidelines. Subjects were followed up for 3 months and treatment responsiveness was assessed by spirometry and symptom response.ResultsSerum MMP-1 and TGF-β1 were significantly elevated in asthmatics compared with controls (pConclusionThis pilot study showed that serum MMP-1 and TGF-β1 levels are elevated in chronic asthma and may serve as a useful adjunct in differentiating moderate from severe asthma. A large multicentre study in well characterised cohort of asthmatics is warranted to investigate their role in diagnosis and therapeutic monitoring.

Background: Knowledge of facilitators and barriers regarding the uptake of COVID-19 vaccination at a global population level is critical for combating the pandemic, saving lives, and protecting the economy. The aim of this work was to determine the proportion of people likely to accept or refuse to undergo COVID-19 vaccination. This study also investigated (a) time trends regarding the intention to undergo COVID-19 vaccination and (b) socio-demographic risk factors influencing vaccine refusal. Methods: Databases (01 March 2020-01 March 2021) searched included PubMed, MEDLINE, and Scopus. The sample size was n ≥1000 and selected studies were those that determined vaccine ‘acceptance’, ‘refusal’ and ‘hesitancy’. A random-effects model was employed to obtain the overall odds ratio (OR) and 95% confidence interval (CI) for socio-demographic predictors for vaccine refusal. Results: A total of 832 citations were screened and 35 studies from 21 countries (n=130,179) were analyzed. The pooled proportion of individuals reporting an intention to vaccinate was 0.70 (95% CI: 0.65 to 0.74; I2 = 99.68%). The proportion of people intending to vaccinate decreased (regression coefficient = -0.13; p Conclusions: A moderate proportion of people showed an intention to receive vaccination, although this declined during the study period. A global and national multi-pronged strategic and targeted approach is urgently needed to enhance vaccination uptake amongst females, those with a relatively lower educational and socioeconomic status, and those in rural areas.

AimTo record the level of allergy teaching occurring in UK medical schools. The UK has experienced an ‘allergy epidemic’ during the last 3–4 decades. Previous government reviews have emphasised the importance of allergy education and training, treating common allergies in primary care with referral pathways to a specialist and the creation of regional networks. It is acknowledged that the delivery of allergy teaching in UK medical schools is variable, despite the well-recognised need.MethodsAll consultant members of the British Society for Allergy and Clinical Immunology involved in teaching medical students were invited to partake in qualitative research, employing an online questionnaire for data collection. Participants were asked to comment on the format of the allergy teaching delivered, the student participation and the clinical opportunities provided. Students were recruited to complete a similar survey as supporting evidence.Results44 responses were collected, representing 64.7% of medical schools in the UK. Clinical allergy placements were compulsory in 31.8% of medical schools that responded. In 36.4%, it was reported that less than 10% of students had an opportunity to take an independent history from a patient with allergic disease, or practise using an epinephrine autoinjector. 90.9% responded that an allergy rotation was not offered to final year students.ConclusionsAllergy undergraduate teaching is suboptimal and heterogeneous in UK medical schools and there is a real need for standardisation as a means to enhance quality of care.

Allergen specific immunotherapy (SIT) alleviates symptoms, improves health-related quality of life and alters the natural course of the disease in patients suffering from allergic rhinitis. It is currently delivered in the UK National Health Service (NHS) via 2 modalities namely subcutaneous injection immunotherapy (SCIT) and sublingual immunotherapy (SLIT). The latter has a superior safety profile - anaphylaxis is a rare occurrence. Most vaccines currently employed for SIT in the UK NHS are unlicensed and available on a named-patient basis and prescribed in secondary care by a specialist. This article is protected by copyright. All rights reserved.

BackgroundMild oropharyngeal symptoms to peanut/hazelnut occur in ~30% of patients with pollen-food syndrome (PFS). Component tests are considered a useful adjunct to the diagnosis and may help differentiate PFS from those at a risk of anaphylaxis due to storage protein/lipid transfer protein (LTP) sensitisation.AimsTo assess concordance between component tests and clinical history in suspected PFS to peanut/hazelnut in a specialist clinic.MethodsAdult patients were classified into PFS (group 1, n=69) and PFS with mild systemic symptoms (group 2, n=45) based on clinical history. Specific IgE (sIgE) of ≥0.35 kUA/L was considered positive as per manufacturers’ recommendation. Kappa (κ) inter-rater agreement was calculated for concordance between clinical classification and test profiles.ResultsGroup 1 hazelnut: 85% monosensitised to Cor a1, 12% to storage protein/s or LTP and 3% negative to all components. Group 1 peanut: 41% monosensitised to Ara h8, 44% to storage protein/s or ±LTP and 15% negative to all components. Group 2 hazelnut: 67% monosensitised to Cor a1, 16% sensitised to storage protein/s and 17% negative to all components. Group 2 peanut: 19% monosensitised to Ara h8, 62% sensitised to storage protein/s and/or LTP and 19% negative to all components.SIgE to Ara h8 and Cor a1 were greater in group 1 versus group 2: (median (IQR) kUA/L; hazelnut: 12.1 (7.8-25.2) vs 2.4 (0.36-6.3), pConclusionConcordance between component tests and clinical history for adults with PFS was good for hazelnut (κ=0.63) but poor for peanut (κ=−0.12). Food challenges are warranted in discordant cases for an accurate diagnosis.

Background Bronchial airway inflammation is the hallmark of asthma, which may be driven by an imbalance between oxidative stress and antioxidant defenses. Antioxidants deficiency may play a role, but this has remained unconfirmed. Objective To evaluate the oxidative stress burden and antioxidants defenses in patients with increasing asthma severity. Methods This prospective case-control study compared fractional exhaled nitric oxide (FeNO), exhaled breath condensate nitrite/nitrate (EBC-NOx), spirometry, and serum vitamins and trace elements among patients with and without asthma. Results Sixty participants were recruited (30 with severe asthma number; 23 women [76.7%]; mean age, 41.4 years; mean forced expiratory volume in 1 second [FEV 1 ], 2.2 L [72.2% predicted]; mean inhaled corticosteroid dosage, 2,540 μg/d; 18/30 [60%] receiving maintenance oral corticosteroids; 15 with mild asthma; all corticosteroids naive; 9 women [60%]; mean age, 34.6 years; mean FEV 1 , 3.48 L [100.5% predicted]; 15 healthy controls; 12 women [80%]; mean age, 37.6 years; and mean FEV 1 , 3.53 L [111.7% predicted]). The mean FeNO levels increased significantly with increasing asthma severity ( P = .01), but the EBC-NOx levels did not change significantly ( P = .90). Paradoxically, vitamin A and vitamin E increased with increased disease severity, with vitamin E levels increasing significantly ( P = .07 and P P = .37), zinc ( P = .97), or selenium ( P = .90). Conclusion FeNO but not EBC-NOx is increased significantly with asthma severity with no evidence of vitamins or trace elements deficiency in severe asthma. Impaired oxidative stress defenses in severe asthma may be driven by factors other than vitamins or trace elements deficiency.

Many patients report allergies to penicillin, although in over 90% of these the label of penicillin allergy is shown to be incorrect following comprehensive testing. Inappropriate and inaccurate penicillin allergy labelling is a barrier to antimicrobial stewardship and can lead to patient harm. This review assesses an emergent evidence base and trend favouring delabelling using direct oral penicillin challenges following a stratified risk assessment of the likelihood and existence of true penicillin allergy, to identify and make recommendations for key components for implementation in standard practice. Research to date has focussed on the feasibility and clinical and financial outcomes of these direct delabelling strategies. There is a paucity of studies exploring the views and engagement of patients and healthcare professionals, and a gap in the evidence for prerequisites to safely deliver, sustain and spread the implementation of such services across health systems.

Spurious penicillin allergy (PenA) is a major public health problem. Up to 10% of the population and 20% of inpatients are labelled with PenA, but only

IntroductionThe association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns.MethodsThis was a retrospective cohort study (1990–2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters.Results782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old.ConclusionsThe long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.

BACKGROUND An increasing number of adults are being diagnosed with anaphylaxis, but its impact on health-related quality of life (HRQol) is not known. OBJECTIVE The aim of this study was to explore the impact of anaphylaxis on HRQoL of newly diagnosed adults. METHODS Interviews were conducted with 13 adults (aged 40-71; 5 males) with anaphylaxis (meeting WAO diagnostic criteria) to drugs, food, venom or spontaneous anaphylaxis, recruited using purposive sampling from allergy clinics in Birmingham, UK. Data was transcribed verbatim and analysed using thematic analysis. RESULTS Four themes were generated from the analysis: the journey from fear to frustration; the need to maintain a healthy identity; control over uncertainty; and the supportive role of others. Participants described their first experiences of anaphylaxis as frightening. Managing the condition was associated with frustration and anxiety, in part due to uncertainty regarding when anaphylaxis might occur. Participants did not consider their allergy as an illness and wanted to retain an identity as a healthy person. They felt a strong need to have control over their anaphylaxis so that it did not take over their lives. The support from others was extremely important, but a lack of understanding of anaphylaxis sometimes hindered that support. CONCLUSIONS AND CLINICAL RELEVANCE Anaphylaxis has an adverse impact on the HRQoL of adults irrespective of the cause. More information about anaphylaxis and its management from health care professionals may help patients gain a sense of control over their condition and reduce the worry and anxiety associated with it. This article is protected by copyright. All rights reserved.

A spurious label of penicillin allergy (Pen-A) negatively impacts on antibiotic stewardship and health care costs. Recent studies have proposed a guideline-steered direct penicillin challenge without undertaking allergy tests when "true allergy" is unlikely.To critically analyze Pen-A clinical presentation, perform risk stratification, and determine clinical predictors for "true allergy."Data were extracted retrospectively from clinical and electronic patient records.A total of 231 patients (M = 82; F =149; mean age 51.22 [standard deviation ± 18.07] years) were analyzed. Based on clinical history, patients were categorized as likely type I hypersensitivity reaction (HSR) (n = 27), likely type IV HSR (n = 65), indeterminate (n = 111), and HSR unlikely (n = 28). Based on an index reaction and comorbidities, patients were classified into "low risk" (n = 143) and "high risk" (n = 78). Pen-A was excluded in 74% of patients assessed having likely type I HSR, 91% with likely type IV HSR, 93% of indeterminate, and 100% of HSR unlikely patients. The negative predictive value for successful delabeling in the "low risk" group was 94% (odds ratio [OR] = 2.9; P = .02). Predictors for "true Pen-A" were history of anaphylaxis (OR = 30.6; P.001), hospitalization (OR = 7; P.001), ≤5 years since the index reaction (OR = 3; P = .04).Systematic clinical characterization and risk stratification has an important role in Pen-A delabeling. These data provide proof of concept for a guideline-based selection of patients labeled with Pen-A for a direct penicillin challenge. Patients in the "low risk" group seem suitable for this intervention, although a rigorous prospective evaluation is needed in a multicenter study.

Approximately 90-99% of patients with a label of penicillin allergy (PenA) are not allergic when comprehensively investigated. An inaccurate label of PenA has major public health implications-longer hospital stay, more frequent hospital admissions, greater use of fluoroquinolones, glycopeptides, cephalosporins and other expensive antibiotics resulting in significantly higher costs to the health service and predisposing to Clostridium difficile, methicillin-resistant Staphylococcus aureus infections and vancomycin-resistant enterococcus. We describe lessons learnt from recent studies regarding possible reasons contributing to an inaccurate label of PenA as well as propose a concerted multidisciplinary approach to address this important public health problem. Given the unmet need for allergy services in the UK and several other countries and knowledge gaps regarding PenA amongst healthcare professionals, we describe the potential role for a computerized clinical decision support system to enable non-specialists rapidly identify and de-label "low-risk" hospitalized patients with a label of PenA thereby obviating the need for allergy tests. This approach however needs rigorous evaluation for feasibility, safety, patient and physician acceptability, cost-effectiveness and its compatibility with information technology systems currently employed in the health service.

There is no standardized method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2× baseline tryptase+2 mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS). To validate consensus equation in a perioperative setting analyses of cases of suspected perioperative anaphylaxis during general anaesthesia (GA) were performed. Anaphylaxis was defined as per World Allergy Organisation (WAO) criteria. Timed serial MCT measurements were mapped against the consensus equation and receiver operating characteristic (ROC) curves produced. A total of 82 patients (60 females, mean age 56.5 years±SD17.2) underwent investigation. Sixty (73%) patients fulfilled WAO criteria for anaphylaxis, and 22 patients did not. Aetiology included 59% IgE-mediated anaphylaxis, 2% non-IgE-mediated anaphylaxis, 12% anaphylaxis of unknown cause and 27% deemed non-anaphylaxis. IgE-mediated anaphylaxis included the following: NMBA (35%), antibiotics (46%), chlorhexidine (8%), patent blue dye (8%) and others (8%). An acute MCT with a comparable baseline was available in 71 of 82 (87%) patients (60 anaphylaxis and 11 controls). The median interquartile range (IQR) time from reaction to peak MCT was 1.34 (0.82-2.51) hours. Analyses confirmed that a rise in acute MCT greater than that defined by the equation had a sensitivity, specificity, positive predictive value (PPV) and negative (N) PV of 78%, 91%, 98% and 44%, respectively. The magnitude of increase in acute MCT above the threshold predicted by consensus equation was higher in the anaphylaxis group compared to controls (P=.0001). This equation has a high specificity, PPV with a moderate NPV and sensitivity in perioperative anaphylaxis.