Allergy in the elderly: A case note review of referrals to an adult allergy clinic.

The UK population is ageing and we can expect more referrals to allergy clinics for this age group. 16% of patients to our clinic are aged >60. Compared to younger patients, 3 times as many referrals were for angioedema. Overall, allergy was excluded in 79% of cases. 15% were diagnosed with previously unrecognised allergies, while allergic disease was confirmed in 6%, enabling optimised management. While the differential diagnosis of allergic conditions is wider in older people, assessment in the allergy clinic is helpful and adds value.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

What proportion of adult allergy referrals to secondary care could be dealt with in primary care by a GP with special interest?

BACKGROUND: The concept of a General Practitioner with Special Interest (GPwSI) was first proposed in the 2000 National Health Service Plan, as a way of providing specialised treatment closer to the patient's home and reducing hospital waiting times. Given the patchy and inadequate provision of allergy services in the UK the introduction of GPwSIs might reduce the pressure on existing specialist services. OBJECTIVES: This study assessed what proportion of referrals to a specialist allergy clinic could be managed in a GPwSI allergy service with a predefined range of facilities and expertise (accurate diagnosis and management of allergy; skin prick testing; provision of advice on allergen avoidance; ability to assess suitability for desensitisation). METHODS: 100 consecutive GP referrals to a hospital allergy clinic were reviewed to determine whether patients could be seen in a community-based clinic led by a general practitioner with special interest (GPwSI) allergy. The documentation relating to each referral was independently assessed by three allergy specialists. The referrals were judged initially on the referral letter alone and then re-assessed with the benefit of information summarised in the clinic letter, to determine whether appropriate triage decisions could be made prospectively. The proportion of referrals suitable for a GPwSI was calculated and their referral characteristics identified. RESULTS: 29 % referrals were judged unanimously appropriate for management by a GPwSI and an additional 30 % by 2 of the 3 reviewers. 18 % referrals were unsuitable for a GPwSI service because of the complexity of the presenting problem, patient co-morbidity or the need for specialist knowledge or facilities. CONCLUSIONS AND CLINICAL RELEVANCE: At least a quarter, and possibly half, of allergy referrals to our hospital-based service could be dealt with in a GPwSI clinic, thereby diversifying the patient pathway, allowing specialist services to focus on more complex cases and reducing the waiting time for first appointments.

Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy.

BACKGROUND: Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. METHODS: In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated. RESULTS: A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12). CONCLUSIONS: Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation.

Immunotherapy for allergic rhinitis.

Allergic rhinitis (AR) affects more than 20% of the population in the United Kingdom and western Europe and represents a major cause of morbidity that includes interference with usual daily activities and impairment of sleep quality. This guidance prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) is for the management of AR in patients that have failed to achieve adequate relief of symptoms despite treatment with intranasal corticosteroids and/or antihistamines. The guideline is based on evidence and is for use by both adult physicians and paediatricians practising allergy. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are indications and contraindications for immunotherapy, criteria for patient selection, the evidence for short- and long-term efficacy of subcutaneous and sublingual immunotherapy, and discussion on safety and the different modes of immunotherapy including, pre-seasonal and co-seasonal treatments. There are sections on children, allergen standardization, vaccines used in the United Kingdom, oral allergy syndrome, cost effectiveness of immunotherapy and practical considerations of undertaking immunotherapy including recommendations on who should undertake immunotherapy and dosing schedules. Finally, there is discussion on potential biomarkers of response to immunotherapy, the use of component-resolved diagnostics, novel approaches, alternative routes and potential areas for future research.

Diagnosis and management of hymenoptera venom allergy: British Society for Allergy and Clinical Immunology (BSACI) guidelines.

This guidance for the management of patients with hymenoptera venom allergy has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and pediatricians practising allergy. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are epidemiology, risk factors, clinical features, diagnostic tests, natural history of hymenoptera venom allergy and guidance on undertaking venom immunotherapy (VIT). There are also separate sections on children, elevated baseline tryptase and mastocytosis and mechanisms underlying VIT. Finally, we have made recommendations for potential areas of future research.

Hundred years of allergen immunotherapy.

Allergic rhinitis was almost unknown until the early 19th century, but within 100 years it was described as a modern epidemic. Pollen was identified as the likely cause of hayfever and although the nature and mechanisms of the sensitivity remained obscure, it was speculated that hayfever might be caused by a toxin in pollen. Vaccination schedules were developed to treat this, but later it became clear that an antibody was responsible. The first clinical trials of specific immunotherapy (SIT) were published in 1911 and 1914 and were followed by several similar papers from the United States. The use of skin prick tests and new allergen extraction techniques accelerated the development of SIT, which became a widespread practice, especially in the United States. Formal controlled clinical trials were reported in 1953 (United Kingdom) and in 1965 (United States). Since then, many controlled clinical trials have confirmed the efficacy of SIT, and although some concerns have arisen around safety, SIT remains a valid option for treating allergic disease. Recent developments include the introduction of sublingual immunotherapy, and clinical trials of recombinant and peptide vaccines. Future developments should increase efficacy and safety, but the biggest challenge to the wider use of SIT is probably economic, as patients and healthcare providers become increasingly critical of all forms of allergy treatments.

Restaurant staff's knowledge of anaphylaxis and dietary care of people with allergies.

BACKGROUND: Deaths caused by food-induced anaphylactic reactions are increasing, with most caused by food purchased outside the home. Primary prevention by allergen avoidance is desirable, but is easier in the home than when eating out, where the responsibility is shared with restaurant staff. OBJECTIVE: To investigate restaurant staff's knowledge about food allergies. METHOD: A structured telephone questionnaire was administered to a member of staff at 90 table-service restaurants in Brighton. RESULTS: Fifty-six percent (90/162) restaurants that were contacted agreed to participate. Responders included seven owners, 48 managers, 20 waiters and 15 chefs. Ninety per cent (81/90) reported food hygiene training; 33% (30/90) reported specific food allergy training. Fifty-six percent (50/90) could name three or more food allergens. Eighty-one percent reported confidence (very or somewhat) in providing a safe meal to a food-allergic customer. Answers to true-false questions indicated some frequent misunderstandings: 38% believed an individual experiencing a reaction should drink water to dilute the allergen; 23% thought consuming a small amount of an allergen is safe; 21% reported allergen removal from a finished meal would render it safe; 16% agreed cooking food prevents it causing allergy and 12% were unaware allergy could cause death. Forty-eight percent expressed interest in further training on food allergy. CONCLUSIONS AND CLINICAL RELEVANCE: Despite a high confidence level, there are obvious gaps in restaurant staff's knowledge of allergy. Food-allergic patients need to be aware of this and adapt their behaviour accordingly. Our data challenge the impact of current food allergy training practice for restaurant staff, and support the need for more rigorous and accessible training.

What are the 'ideal' features of an adrenaline (epinephrine) auto-injector in the treatment of anaphylaxis?

Anaphylaxis is a systemic allergic reaction that often involves respiratory symptoms and cardiovascular collapse, which are potentially life-threatening if not treated promptly with intramuscular adrenaline. Owing to the unpredictable nature of anaphylaxis and accidental exposure to allergens (such as peanuts and shellfish), patients should be prescribed intramuscular adrenaline auto-injectors and carry these with them at all times. Patients also need to be able to use their auto-injectors correctly while under high stress, when an anaphylactic attack occurs. Despite this, an alarming number of patients fail to carry their auto-injectors and many patients, carers of children with known anaphylaxis and healthcare professionals do not know how to use the device correctly, despite having had training. Currently available auto-injector devices have various limitations that may impede their use in the management of anaphylaxis. There is also a lack of validated assessment criteria and regulatory requirements for new devices. This review describes the different delivery systems used in currently available auto-injectors and discusses the key barriers to the use of adrenaline auto-injectors, with the goal of identifying the 'ideal' features/characteristics of such devices in the emergency treatment of anaphylaxis that will ensure ease of use, portability and accurate delivery of a life-saving drug.

Measuring asthma-specific quality of life: structured review.

Measuring quality of life (QoL) has become an increasingly important dimension of assessing patient well-being and drug efficacy. As there are now several asthma QoL questionnaires to choose from, it is important to appreciate their strengths and weaknesses. To assist in this choice, we have reviewed the existing questionnaires in a structured way. Information relating to the conceptual and measurement model, reliability, validity, interpretability, burden, administration format and translations was extracted from the published literature. The instruments differ in almost all criteria considered, and therefore it cannot be assumed that they measure the same thing. We recommend the selection of questionnaires that are designed only for asthma and that do not assess symptoms as part of QoL. Only two of the questionnaires reviewed fulfill these requirements: the Sydney Asthma QoL Questionnaire (AQLQ-S) and the Living with Asthma Questionnaire (LWAQ). However, for multinational studies, it may be convenient or practical to use questionnaires that have been linguistically validated in many languages (AQLQ-J, SGRQ). It remains unclear which of these questionnaires best reflects patient perceptions of QoL. Our review did not involve patients, so for the time being choosing from existing questionnaires requires a compromise based on the rigor of the development process and the target patient group.

Ozone exposure enhances mast-cell inflammation in asthmatic airways despite inhaled corticosteroid therapy.

Asthmatics are recognised to be more susceptible than healthy individuals to adverse health effects caused by exposure to the common air pollutant ozone. Ozone has been reported to induce airway neutrophilia in mild asthmatics, but little is known about how it affects the airways of asthmatic subjects on inhaled corticosteroids. We hypothesised that ozone exposure would exacerbate the pre-existent asthmatic airway inflammation despite regular inhaled corticosteroid treatment. Therefore, we exposed subjects with persistent asthma on inhaled corticosteroid therapy to 0.2 ppm ozone or filtered air for 2 h, on 2 separate occasions. Lung function was evaluated before and immediately after exposure, while bronchoscopy was performed 18 h post exposure. Compared to filtered air, ozone exposure increased airway resistance. Ozone significantly enhanced neutrophil numbers and myeloperoxidase levels in airway lavages, and induced a fourfold increase in bronchial mucosal mast cell numbers. The present findings indicate that ozone worsened asthmatic airway inflammation and offer a possible biological explanation for the epidemiological findings of increased need for rescue medication and hospitalisation in asthmatic people following exposure to ambient ozone.

Practice of venom immunotherapy in the United Kingdom: a national audit and review of literature.

BACKGROUND: Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, controversies exist relating to diagnosis, indications for treatment and treatment schedules. We audited current practice of VIT in the United Kingdom to evaluate adherence to international guidelines. METHODS: An online questionnaire was sent to all clinicians practising immunotherapy identified on the British Society of Allergy and Clinical Immunology website. Eighty-six questionnaires were sent and 53 responses (61.6%) were received. Of these, 48 (85%) carried out VIT at their centre. RESULTS: Skin prick tests (SPT) and serum venom-specific IgE (SSIgE) were equally preferred as first-line investigation. Fifty percent of the respondents perform intradermal tests if both SPT and SSIgE are negative. While 8% of respondents commence VIT in patients with negative SSIgE and a history of severe reaction, 57% prefer to repeat the tests in 6-12 months if serum tryptase is elevated. If the insect responsible is uncertain and SSIgE is detected against bee and wasp venoms, 22% of the respondents will desensitize to both while 32% initiate treatment against the venom with the higher SSIgE. A protocol of weekly up-dosing for 12 weeks is preferred for induction and only 25% of respondents have ever used rush or ultra-rush protocols. Three years is thought to be optimum duration of VIT by most (56%). Eleven percent perform sting challenges at the end of treatment. Although 47% measure SSIgE at the end of treatment, only 3% use these results as a basis for discontinuing VIT. CONCLUSION: Currently there is considerable variation in the diagnosis and management of hymenoptera venom allergy in the United Kingdom. This audit has demonstrated that the current international guidelines for the diagnosis and management of hymenoptera venom allergy are not being followed by UK allergy practitioners.

Practical allergy (PRACTALL) report: risk assessment in anaphylaxis.

Effector mechanisms in anaphylaxis were reviewed. Current approaches to confirmation of the clinical diagnosis were discussed. Improved methods for distinguishing between allergen sensitization (which is common in the general population) and clinical risk of anaphylaxis (which is uncommon) were deliberated. Innovative techniques that will improve risk assessment in anaphylaxis in the future were described.

Effect of grass pollen immunotherapy with Alutard SQ on quality of life in seasonal allergic rhinoconjunctivitis.

BACKGROUND: Treatment of allergic rhinitis with subcutaneous allergen immunotherapy is effective in terms of reductions in symptoms and seasonal use of reliever medication. Its effect on quality of life (QoL), reflecting the impact of symptoms on work/school performance and leisure activities is, however, important and often overlooked. AIMS OF THE STUDY: To assess effect on QoL of specific immunotherapy with two doses of Alutard SQ Phleum pratense in patients with moderately to severe seasonal allergic rhinoconjunctivitis inadequately controlled by standard drug therapy. METHODS: Double-blind, randomized, placebo-controlled study of 410 patients with seasonal allergic rhinoconjunctivitis. Participants were randomized (2 : 1 : 1) to receive Alutard SQ P. pratense (ALK-Abelló) at maintenance doses of 100,000 SQ-U (203 subjects), 10,000 SQ-U (104 subjects) or placebo (103 subjects) given by subcutaneous injections. The groups were well matched for demographics and baseline symptoms. Quality of life was assessed using the Rhinoconjunctivitis Quality of Life Questionnaire which covers seven domains of health before and in the peak of the pollen season. RESULTS: While all domain scores were significantly improved when comparing 100,000 SQ-U with placebo, two domain scores were significantly improved when comparing 10,000 SQ-U with placebo. When comparing 100,000 SQ-U with 10,000 SQ-U, four domain scores were significantly improved. CONCLUSION: Treatment with Alutard SQ significantly improved the seasonal QoL of patients suffering from allergic rhinoconjunctivitis. The improvement was more pronounced and wider ranging in patients who received the higher 100,000 SQ-U maintenance dose.

Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma.

Histone deacetylase inhibitors (HDACi) can elicit a range of biological responses that affect tumor growth and survival, including inhibition of cell cycle progression, induction of tumor cell-selective apoptosis, suppression of angiogenesis, and modulation of immune responses, and show promising activity against hematological malignancies in clinical trials. Using the Emu-myc model of B cell lymphoma, we screened tumors with defined genetic alterations in apoptotic pathways for therapeutic responsiveness to the HDACi vorinostat. We demonstrated a direct correlation between induction of tumor cell apoptosis in vivo and therapeutic efficacy. Vorinostat did not require p53 activity or a functional death receptor pathway to kill Emu-myc lymphomas and mediate a therapeutic response but depended on activation of the intrinsic apoptotic pathway with the proapoptotic BH3-only proteins Bid and Bim playing an important role. Our studies provide important information regarding the mechanisms of action of HDACi that have broad implications regarding stratification of patients receiving HDACi therapy alone or in combination with other anticancer agents.

Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls.

BACKGROUND: Allergic rhinitis (AR) and asthma represent a continuum of atopic disease. AR is believed to pre-dispose an individual to asthma. Compared with asthmatics and normal controls, the inflammatory response in the lower airways of rhinitics is not fully elucidated. To test the hypothesis that the inflammatory response in the airways of subjects with AR is at a level intermediate between that in normal controls and asthmatics, we have characterized bronchial inflammation and cytokine mRNA levels in non-asthmatic allergic rhinitics and compared it with subjects with allergic asthma and with normal controls. METHODS: Endobronchial mucosal biopsies were obtained at bronchoscopy from 14 allergic rhinitics, 16 asthmatics and 21 normal controls. Biopsies were embedded into glycol methacrylate resin for immunohistochemical analysis of cellular inflammation and snap frozen for semi-quantitative PCR analysis of cytokine mRNA levels. RESULTS: Airway inflammation in rhinitic subjects was characterized by an increase in submucosal eosinophils, mast cells and the mRNA expression of TNF-alpha, at an intermediate level between healthy and asthmatics. In addition, CD3(+) and CD8(+) lymphocytes in the epithelium, the endothelial expression of vascular adhesion molecule-1 and IL-1 beta mRNA were higher in the allergic rhinitics compared with both normal controls and asthmatics, whereas growth-related oncogene alpha-mRNA was decreased in AR compared with both healthy and asthmatics. Airway inflammation in the asthmatic group was characterized by higher numbers of eosinophils and mast cells, together with an increase in TNF-alpha-mRNA compared with both healthy and rhinitics. IFN-gamma mRNA was the highest in normal controls and lowest in the asthmatics. CONCLUSIONS: In individuals with AR the present data suggest an intermediate state of airway inflammation between that observed in normal individuals and subjects with clinical asthma. It is also indicated that IFN-gamma production by CD8(+) T lymphocytes could be protective against the development of airway hyperresponsiveness. Further work is needed to evaluate this hypothesis.

Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.

Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.