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Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug‐induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work‐up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section. [ABSTRACT FROM AUTHOR]

The article presents information on Rhinosinusitis. Rhinosinusitis is a significant health problem which seems to mirror the increasing frequency of allergic rhinitis and which results in a large financial burden on society. The last decade has seen the development of a number of guidelines, consensus documents and position papers on the epidemiology, diagnosis and treatment of rhinosinusitis and nasal polyposis. The diagnosis of rhinosinusitis is made by a wide variety of practitioners, including allergologists, otolaryngologists, pulmonologists, primary care physicians and many others.

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients’ inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis. [ABSTRACT FROM AUTHOR]

Immunotherapy has been used extensively for 80 years as a specific treatment of allergy. In the last decade, the clinical practice of immunotherapy has changed markedly in certain parts of Europe. In southern Europe immunotherapy still represents the cornerstone of allergy treatment, while in Scandinavia and Great Britain a large number of allergic patients receive immunotherapy. In spite of the fact that a large number of recently published, wee-performed clinical trials have documented the evidently beneficial effect of immunotherapy, the decrease is probably caused by a combination of some degree of uncertainty as to the clinical efficacy, the risk of side effects, and the introduction of potent new drugs for prophylactic treatment of allergic diseases. With the overall aim of improving the safety of immunotherapy and making it more convenient to patients, routes other than the subcutaneous administration of allergens have been investigated.

To evaluate difference in clinical efficacy, side effects, in vivo and in vitro parameters, 25 patients allergic to Yellow Jacket were treated with clustered immunotherapy using either 7 or 14 days interval between dusters. Twenty-one patients completed the 6 months' treatment period and four were withdrawn due to adverse reactions (2 cases of anaphylactic shock). Sixteen patients were challenged by in-hospital sting and the clinical efficacy was complete. Local side effects were observed in the majority of patients, but only rarely limited the course of immunotherapy. Skin sensitivity estimated as the venom concentration eliciting a wheal equal to histamine HCl 0.1 mg/ml using intradermal test was significantly reduced after 6 months of treatment. Specific IgE showed an initial increase, thereafter declining to pretreatment levels. IgG subclasses were determined by a triple antibody assay. Only subclasses 1 and 4 showed response. Subclass 4 showed a steady increase contrary to subclass 1 which decreased after reaching maintenance dose. No unambiguous relation between either the absolute value or the change of IgG1 and IgG4 at the time of challenge was observed in the patients who tolerated a sting. Furthermore, the IgG response was not correlated to the cumulative dose of venom administered. No simple regulatory function of IgG subclasses in the skin and IgE response was found, and the occurrence of local side effects did not seem to be determined by IgG antibodies. We conclude that clustered immunotherapy with Yellow Jacket venom is highly effective and that the frequency of side effects is acceptable. Neither the IgE nor the IgG response is significantly different with a 7- and 14-day interval between dusters, indicating that a protective dose of venom might be reached within 1 month. [ABSTRACT FROM AUTHOR]

Thirty-two patients with previous systemic allergic reaction to yellow jacket stings were randomly allocated to three groups receiving immunotherapy with different preparations of yellow jacket venom: 1) extract adsorbed to aluminium hydroxide (Alutard®-SQ), 2) Pharmalgen® extract or 3) non-adsorbed extract from Allergologisk Laboratorium (ALK aq.). Regular examinations showed a decrease in skin prick test size in nearly all patients. Specific IgE-antibody (RAST and CRIE scores) showed a similar, but not significant tendency to decrease in all three groups. Specific IgG-antibody increased considerably in the Alutard group only; after 2 years, however, no difference could be detected between the three groups. During dose increase, patients treated with ALK aq. generally had smaller local reactions to injections than those treated with Pharmalgen. Few systemic reactions occurred in all three groups. Nineteen patients treated for 2½-3½ years were challenged in-hospital with stings from yellow jackets. No systemic and only minor local reactions occurred. Consequently, with the dose regimens applied all three extracts seem effective even though no common changes in either specific IgE or IgG could be demonstrated. [ABSTRACT FROM AUTHOR]

Abstract: While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2‐biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines. [ABSTRACT FROM AUTHOR]

Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses. [ABSTRACT FROM AUTHOR]

Methodology for Disease Specific Programme (DSP©) surveys designed by Adelphi Group Products is used each year to survey patients and physicians on their perceptions of treatment effectiveness, symptoms and impact of diseases. These point-in-time surveys, conducted in the USA and Europe (France, Germany, Italy, Spain and UK), provide useful information on the real-world management and treatment of diseases. This paper describes the methodology for the DSP survey in allergic rhinitis, detailing the preparation of materials, recruitment of physicians, data collection and data management. [ABSTRACT FROM AUTHOR]

Oral glucocorticoids are used for immunosuppressive or anti-inflammatory treatment of a wide range of diseases, including rheumatoid arthritis, polymyalgia rheumatica, temporal arteritis, inflammatory bowel diseases, transplant surgery, systemic sclerosis, and asthma. Systemic glucocorticoid therapy affects immune system function essentially by depressing cell-mediated immunity. Corticosteroids also induce suppression of neutrophil granulocyte aggregation to inflammatory sites and impairment of phagocytosis, as well as decrease in peripheral blood eosinophils.

Background: Guideline-based treatment approaches for managing anaphylaxis are widely believed to result in good outcomes, but the strength of evidence underpinning the recommendations made therein is unclear. Objective: To identify and compare national guidelines for the emergency medical management of anaphylaxis and to describe the extent to which the evidence base in support of key recommendations is made clear. Methods: We systematically searched key medical databases and contacted the World Allergy Organization and anaphylaxis charities in several countries to identify national guidelines. Full text copies of relevant papers were obtained and, where necessary, translated. Data were abstracted onto a customized data extraction sheet; this process was independently checked by a second reviewer. Results: Guidelines originating from Australia, Canada, Russia, UK, Ukraine and the USA were identified. While these were in agreement on the broad principles of management, there were important variations in relation to the treatments to be used and the dose and route of administration of these preparations. Most guidelines failed to make clear the strength of evidence underpinning the recommendations being made. Conclusions: There are important international differences in the recommended emergency management of anaphylaxis. It is important that an agreed core evidence-based guideline for the management of anaphylaxis is now developed, which can then be adapted for national/local use. Clinicians need to be aware of the limitations of existing guidelines. [ABSTRACT FROM AUTHOR]

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy (FA) and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of FA is evolving toward less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, coadministration of biologicals, adjuvants, and tolerance‐inducing formulations. The ultimate goal is to improve immunotherapy and develop precision‐based medicine via risk phenotyping allowing optimal treatment for each food‐allergic patient. [ABSTRACT FROM AUTHOR]

Acupuncture, homoeopathy, mind-body therapies, and nutritional, herbal, and environmental medicine have all been used in the management of patients with asthma. This paper reviews the evidence base for the use of these unconventional or complementary therapies. Although there is a paucity of large randomized, controlled trials in this area, there is sufficient evidence to suggest that many of these therapies can produce objective and subjective benefit in selected groups of patients. In view of the increasing popularity of complementary medicine among patients and general practitioners, there is now an urgent need for high-quality research to determine how, or whether, these therapies may be interwoven with the more orthodox treatments currently available. [ABSTRACT FROM AUTHOR]

Treatment of allergic and nonallergic rhinitis may consist of allergen avoidance, pharmacotherapy, immunotherapy, and surgery. The introduction, in 1973, of potent glucocorticosteroids (GCSs) which can be given locally in the nose without significant risk of systemic adverse effects was a major therapeutic advance, and it has strengthened the pharmacologic approach to rhinitis therapy. This paper reviews the literature, and presents 20 years' clinical experience of topical GCS treatment for rhinitis, In addition, it describes the pathophysiology of the disease and the putative modes of action of GCSs in the nose.

Most extracts used in hyposensitization (immunotherapy) are complex and ill- defined mixtures of a large number of' non-antigenic and antigenic components, only a few of the latter being of significance for allergy and allergen specific immunotherapy. A new purified and well-characterized allergen preparation from timothy pollen is now available, and it has been shown to be superior to the cor- responding crude aqueous extract in the diagnosis of IgE-mediated human allergy to timothy pollen. This paper describes the results of hyposensitization for 2 years, with the purified preparation and the crude extract compared. The changes in in vivo and in vitro tests following this treatment in 40 patients with allergic rhinitis due to grass pollen are reported. Both patient groups showed a significant decrease in clinical symptom scores when compared with a control group during the grass pollen season. For all groups the symptom scores correlated well with atmospheric pollen counts. Nasal challenge tests showed a significant increase in nasal tolerance to timothy pollen after 2 years of treat- merit, but nasal tolerance was unchanged in the control group. Nasal function as a criterion for evaluating the effect of specific hyposensitization is discussed. Serum concentrations of timothy pollen-specific IgE antibodies showed a significant decrease for the group treated with the purified preparation and a slighter and non-significant reduction for the other treated group. There was no significant change in total serum IgE levels. The results indicate that the purified preparation is preferable to the crude aqueous extract in hyposensitization. [ABSTRACT FROM AUTHOR]

Yang and colleagues expounded two possible pathways contributing to pollen's effect on COVID-19 infection using a multiple-adjusted generalized additive (GAM) model.[12] Besides further recognizing the features of allergy,[13] knowing the allergen-encoding genes and their isoforms at the chromosomal level may also help us to detect novel allergens.[14] Zhao and colleagues have identified three well-recognized mango fruit allergen molecules by using combined omics tools and immunological methods. It has now been over 3 years since the coronavirus disease 2019 (COVID-19) was declared a global pandemic, and its end now appears to be in sight. The latest progress and contributions of these scholars in understanding the "epithelial barrier theory" as the gateway to allergic diseases, allergen recognition, and promising treatments are highlighted in this special "China Issue" of I Allergy i (Figure 1). [Extracted from the article]

Background: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. Methods: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best‐Worst Scaling of 32 food reactions was calculated. Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC‐AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC‐AUC showed negligible biases (1.0 × 10−6–1.23 × 10−3). In external validation, nFASS performed best with higher ROC‐AUC. nFASS was strongly correlated (R 0.89) to best‐worst scoring of 334 expert clinicians. Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings. [ABSTRACT FROM AUTHOR]

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell–driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert‐guided and evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria. [ABSTRACT FROM AUTHOR]

Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil‐reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin‐5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add‐on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real‐world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI‐A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases. [ABSTRACT FROM AUTHOR]

Background: Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen‐specific immunotherapy (AIT), although mechanistic side‐by‐side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high‐dose HDM extract and low‐dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy. Methods: Cellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant‐free intranasal sensitization followed by subcutaneous AIT. Results: While low‐dose allergoid and high‐dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2‐type cytokine secretion of lung‐resident lymphocytes and draining lymph node cells, low‐dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low‐dose allergoid AIT with MCT or MCT and dose‐adjusted MPL promoted Th1‐inducing mechanisms and robust B‐cell activation counterbalancing the allergic Th2 immune response. Conclusion: Low allergen doses induce cellular and humoral mechanisms counteracting Th2‐driven inflammation by using allergoids and dose‐adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low‐dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses. [ABSTRACT FROM AUTHOR]

The aim of this survey was to explore the specific educational needs of a cohort of European GPs with regards to allergy training so that future educational initiatives may better support the delivery of allergy services in primary care. Method: This study took the form of a cross‐sectional observational study in which a structured electronic questionnaire was distributed to primary care providers, in eight languages, across 8 European countries between September 2019 and November 2019. Data associated with demographic parameters, professional qualifications, type of employment, level of confidence regarding competencies for diagnosis and treatment of allergic diseases, referral of patients to allergist and preferred method of learning and assessment were collected. A 5‐point Likert scale was used to assess level of confidence. Exploratory analysis was carried out. Results: A total of 687 responses were available for analysis, with 99.3% of responders working within Europe. 70.1% of participants were female; and 48.0% and 48.0% of participants respectively had received some undergraduate and/or postgraduate allergy education. Confidence in dealing with different aspect of allergy management differed between countries. The main reason for specialist referral was a perceived need for tertiary assessment (54.3%), and the main barrier for referral was the consideration that the patient's condition could be appropriately diagnosed and treated in a primary care facility. Up to 44.7% and 55.3% of participants reported that they preferred e‐Learning over traditional learning. Conclusions: This study identified the specific areas of skills training and educational needs of GPs in managing allergic conditions in primary care, and provided insights into possible strategies for more feasible and cost‐effective approaches. [ABSTRACT FROM AUTHOR]

Hypersensitivity pneumonitis is an immune‐mediated interstitial lung disease caused by an aberrant response to an inhaled exposure, which results in mostly T cell–mediated inflammation, granuloma formation, and fibrosis in some cases. HP is diagnosed by exposure identification, HRCT findings of ground‐glass opacities, centrilobular nodules, and mosaic attenuation, with traction bronchiectasis and honeycombing in fibrotic cases. Additional testing including serum IgG testing for the presence of antigen exposure, bronchoalveolar lavage lymphocytosis, and lung biopsy demonstrating granulomas, inflammation, and fibrosis, increases the diagnostic confidence. Treatment for HP includes avoidance of the implicated exposure, immunosuppression, and anti‐fibrotic therapy in select cases. This narrative review presents the recent literature in the understanding of the immunopathological mechanisms, diagnosis, and treatment of HP. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H1R‐antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home‐based) and its cost‐effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed. [ABSTRACT FROM AUTHOR]

Atopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological and environmental factors. One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. Extrinsic factors seem to play a major role in the development of AE. As AE is a first step in the atopic march, its prevention and appropriate treatment are essential. Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. However, thorough endotyping of the individual patients is still required for ideal precision medicine approaches in future. Therefore, novel microbial and immunological biomarkers were described recently for the prediction of disease development and treatment response. This review summarizes the current state of the art in AE research. [ABSTRACT FROM AUTHOR]

Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain‐dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker‐guided therapy, discerning those patients that might benefit from antibiotic therapy. [ABSTRACT FROM AUTHOR]

Mepolizumab for chronic rhinosinusitis with nasal polyps: treatment efficacy by comorbidity and blood eosinophil count. Knowledge gaps in using type 2 biologics for real-world treatment of chronic rhinosinusitis with nasal polyps By translating scientific results into an integrated care strategy, biologics targeting T2 inflammation have achieved major progress in treating severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) during the last decade. In RCTs, discontinuation of biologics caused a slow bounce of nasal polyp scores and nasal symptoms, indicating that continued treatment is necessary to sustain positive outcomes. [Extracted from the article]

A computer program for the analysis of differences or changes in skin sensitivity has been developed. It is based on parallel line assays and its main features are its ability to conduct a validation process which ensures that the data from skin tests conform to the conditions imposed by the analysis which is carried out (regression, parallelism, etc.), the estimation of the difference or change iii skin sensitivity, and the determination of the 95% and 99% confidence intervals of this estimation. This program is capable of managing data from independent groups, as well as paired data, and it may be applied to the comparison of allergen extracts, with the aim of determining their biologic activity, as well as to the analysis of changes in skin sensitivity appearing as a consequence of treatment such as immunotherapy. [ABSTRACT FROM AUTHOR]

This article presents information on the evaluation of changes in skin sensitivity by means of skin tests. Skin sensitivity to allergens and histamine can vary spontaneously, or as a consequence or specific immunotherapy, the use of antihistamines or other drugs, and other circumstances. The principle of standardization by skin tests is based on the dose-response relationship of allergen, derived by melting the wheal size produced by different concentrations of the allergen. Most authors evaluating changes in skin sensitivity reactivity.

The article presents information on treatment of patients allergic to house dust mites. In the treatment of patients allergic to house dust mites two different principles can be applied; symptomatic or specific treatment. The symptomatic treatment includes medicamental treatment and the elimination of now specific irritants, while specific treatment includes elimination of allergens and immunotherapy. In case of bronchial asthma, the purpose of therapy is to keep patients free of symptoms and provide normal lung functioning. It is important neither to undertreat nor overtreat and this means variable and individual pharmacotherapy.

The article focuses on the standardization of biological methods in clinical work in allergy. For several allergens in the IgE-dependent systems, biological and laboratory methods are available which correlate fairly well with each other when adequately performed and which are suggested should be used together to express the total diagnostic potency of allergen extracts. The specificity of the skin test for quantitation of the total allergenic activity of extracts for diagnosis appears to be accepted. Similar standardization of allergen preparations meant for immunotherapy is, however, likely to raise a quite lively debate.

The article discusses the use of medical algorithms for managing chronic rhinosinusitis (CRS) in tandem with the availability of endotypes and trials for analysis as of 2019. Topics covered include the prediction of treatment efficacy from pathophysiology, and the effectiveness of surgery in the CRS phenotypes with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). Also noted is the option of combining endoscopy and eosinophils in analyzing patients with CRS.

The specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules. This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring of allergic diseases, asthma, allergic and nonallergic rhinitis, and new approaches to the diagnosis and treatment of drug hypersensitivity reactions are discussed in further detail. In the third section, unmet needs and future research areas for the treatment of allergic diseases are highlighted with topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease. Unknowns and future research needs are discussed at the end of each subsection. [ABSTRACT FROM AUTHOR]

Allergic reaction to stinging insects is one of the more dramatic allergic diseases. The combination of sudden pain, acute onset of reactions, and knowledge of sting-induced fatalities will often make the victim seek medical advice. Judged from the rather low mortality rate reported, emergency treatment is often sufficient to manage such cases. `the effect has uniformly been confirmed, and during the period when the need for immunotherapy in general was debated and safety regulations in some countries led to a reduction in the use of this kind of treatment, the need for venom immunotherapy was not questioned among specialists.

The article focuses on the analysis and standardization of allergen extracts intended for therapeutic use. Over the past decade, many papers and international meetings have been devoted to establishing methods and requirements for analysis and standardization of allergen extracts. In fact, manufacturers and control authorities are in demand to produce procedures enabling precise and viable quantitation of allergenic activity as well as analysis of extracts. Such an approach would allow physicians to prescribe uniformly labeled extracts of known quality and guarantee therapeutic procedures.

Chronic rhinosinusitis (CRS) is a disease affecting more than 10% of the European population, causing symptoms and impacting quality of life. CRSsNP mostly is characterized by non-type 2 inflammatory disease, may express IL-17 or related cytokines in some patients, and has low asthma comorbidity. The majority of CRSwNP in Europe is characterized by moderate type 2 inflammation, but also may be severely inflamed (with cytokine concentrations significantly higher than mild-moderate type 2 disease) and high late-onset asthma comorbidity (up to 70%). [Extracted from the article]

Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data‐driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three‐grade‐based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice. [ABSTRACT FROM AUTHOR]

Abstract: Background: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect “real‐world” everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real‐life treatment of allergic rhinitis (AR) using mobile technology. Methods: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. Results: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1‐antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses. [ABSTRACT FROM AUTHOR]

Abstract: Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE‐mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost‐effectiveness of AIT for these conditions. Methods: We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. Results: Twenty‐three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost‐effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost‐effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost‐effectiveness threshold of £20 000/quality‐adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost‐effective with an incremental cost‐effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost‐effective for very high‐risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost‐effectiveness of AIT for food allergy. Conclusions: Overall, the evidence to support the cost‐effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost‐effective for people with allergic rhinitis with or without asthma and in high‐risk subgroups for venom allergy. We were unable to draw any conclusions on the cost‐effectiveness of AIT for food allergy. [ABSTRACT FROM AUTHOR]

Background Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second ( FEV1) of omalizumab responders and nonresponders at 6 months. Methods A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity ( FVC), pre- and postbronchodilator FEV1, residual volume ( RV), and total lung capacity ( TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. Results Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and −0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/ FVC remained unchanged over time, but the proportion of patients with an FEV1/ FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months ( P<.05). Residual volume/total lung capacity ( RV/ TLC) ratio decreased at 6 months and remained unchanged at 24 months. Conclusion After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/ TLC improved at 6 months. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that the airway microbiota plays an important role in viral bronchiolitis pathobiology. However, little is known about the combined role of airway microbiota and CCL5 in infants with bronchiolitis. In this multicenter prospective cohort study of 1005 infants (age <1 year) hospitalized for bronchiolitis during 2011-2014, we observed statistically significant interactions between nasopharyngeal airway CCL5 levels and microbiota profiles with regard to the risk of both intensive care use ( Pinteraction=.02) and hospital length-of-stay ≥3 days ( Pinteraction=.03). Among infants with lower CCL5 levels, the Haemophilus-dominant microbiota profile was associated with a higher risk of intensive care use ( OR, 3.20; 95% CI, 1.18-8.68; P=.02) and hospital length-of-stay ≥3 days ( OR, 4.14; 95% CI, 2.08-8.24; P<.001) compared to the Moraxella-dominant profile. Conversely, among those with higher CCL5 levels, there were no significant associations between the microbiota profiles and these severity outcomes (all P≥.10). [ABSTRACT FROM AUTHOR]

A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in A. fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis. [ABSTRACT FROM AUTHOR]

Background The European Academy of Allergy and Clinical Immunology ( EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy ( AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. Methods We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. Results Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy ( VIT) could substantially reduce the risk of subsequent severe systemic sting reactions ( OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. Conclusions The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established. [ABSTRACT FROM AUTHOR]

International guidelines provide conflicting recommendations on how to use bronchodilators to manage childhood acute wheezing conditions in the emergency department ( ED), and there is variation within and among countries in how these conditions are managed. This may be reflective of uncertainty about the evidence. This overview of systematic reviews ( SRs) aimed to synthesize, appraise, and present all SR evidence on the efficacy and safety of inhaled short-acting bronchodilators to treat asthma and wheeze exacerbations in children 0-18 years presenting to the ED. Searching, review selection, data extraction and analysis, and quality assessments were conducted using methods recommended by The Cochrane Collaboration. Thirteen SRs containing 56 relevant trials and 5526 patients were included. Results demonstrate the efficacy of short-acting beta-agonist ( SABA) delivered by metered-dose inhaler as first-line therapy for younger and older children (hospital admission decreased by 44% in younger children, and ED length of stay decreased by 33 min in older children). Short-acting anticholinergic ( SAAC) should be added to SABA for older children in severe cases (hospital admission decreased by 27% and 74% when compared to SABA and SAAC alone, respectively). Continuous nebulization, addition of magnesium sulfate to SABA, and levosalbutamol compared to salbutamol cannot be recommended in routine practice. [ABSTRACT FROM AUTHOR]

In the past years, several investigators have demonstrated the existence of local nasal responses in some patients with typical allergic rhinitis symptoms but without atopy and have defined a new phenotype called local allergic rhinitis ( LAR) or 'entopy'. In a percentage of LAR subjects, the upper airway disease is also associated with lower airway symptoms. After the description of this phenotype, the differential diagnosis between LAR and nonallergic rhinitis ( NAR) has become a challenge for the clinician. To correctly identify LAR patients is of high importance for treatment and management of these patients, and for an appropriate inclusion of patients in clinical trials and genetics studies. The treatment of LAR patients, in contrast with NAR, is oriented to allergen avoidance and specific treatment. Allergen immunotherapy, the aetiological treatment for allergic respiratory diseases, has demonstrated to be an effective and safe treatment in LAR, increasing immunological tolerance, and reducing the clinical symptoms and the use of medication. In this article, the important and novel aspects of LAR in terms of mechanisms, diagnosis and treatment will be discussed. Also, the involvement of the lower airway and the potential role of IgE in the bronchial disease will be also reviewed. [ABSTRACT FROM AUTHOR]

Background Genomewide association studies ( GWASs) of asthma have identified single-nucleotide polymorphisms ( SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness ( BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis- eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR. Methods A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis- eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. Results A total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3 BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. Conclusions Combining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma. [ABSTRACT FROM AUTHOR]

Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunicable diseases and are driven by chronic inflammatory reactions. They have a strong impact on the quality of life and represent a substantial and growing socio-economic burden. Interestingly, there is an increasing interest in the development of new therapeutic options with a number of biologics and small molecules targeting potential key mechanisms in atopic conditions. However, besides the safety issue, most of the new active substances are still evaluated according to the traditional efficacy paradigm focusing on the success in treating exacerbations and flares. Instead, the future approaches in drug development and assessment should rather concentrate on the long-term control of these diseases and consider their potential as disease-modifying strategies in the era of precision medicine. To reach this goal, a number of unsolved issues have to be addressed and consensually accepted by the stakeholders in this field. Thus, a successful and rapid development of new treatments requests a paradigm shift and a new way of thinking in the mind of physicians, pharmaceutical industry, regulators, and HTAs. This seems mandatory in order to optimize drug development and to facilitate the accessibility of new therapies to the growing population of patients suffering from atopic conditions on a global level. [ABSTRACT FROM AUTHOR]

Background A major drawback of oral immunotherapy for food allergy is the possibility of severe side-effects. We assessed both safety and efficacy of a low allergenic hydrolysed egg (HydE) preparation used in a double-blind placebo-controlled randomized study in egg allergic children. Methods In a pilot multicentre study, 29 egg allergic patients (aged 1-5.5 years) were administered daily for 6 months 9 g HydE or placebo in a blinded, randomized manner. Safety was verified by oral food challenge to assess tolerance towards HydE at the start and efficacy by an open oral food challenge ( OFC, primary outcome) at the end. Additionally, changes in basophil activation and specific IgE and IgG4 were assessed. Results All egg allergic patients randomized to HydE ( n = 15) tolerated the full dose at day 1 and received the maintenance dose from the start at home. No statistically significant difference was observed on the final OFC (36% and 21% had a negative OFC in the treatment and placebo groups, respectively). Specific IgG4 levels increased, while both CD203c+ and CD63+ basophils decreased significantly more over time in the treatment than in the placebo group. Conclusions HydE can be regarded as a safe, low allergenic product to use in children allergic to egg. Although not significant, HydE given for 6 months increased numerically the proportion of patients becoming tolerant to egg. HydE induced a modulation of the immune response towards better tolerance. A longer treatment period and/or a higher dose may improve the clinical outcome and should be evaluated. [ABSTRACT FROM AUTHOR]

Background Chronic spontaneous urticaria ( CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. Objective The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life ( CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. Methods X- ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Results Of the 91 patients randomized to omalizumab ( n = 44) or placebo ( n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 ( P < 0.001). There was a threefold improvement in angioedema-burdened days/week with omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and <5 days with placebo. Omalizumab significantly improved angioedema-specific QoL ( P < 0.001). The adverse events reported are in line with the established safety profile of omalizumab. Conclusion Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment. [ABSTRACT FROM AUTHOR]

Background The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy ( SCIT) product was previously established. The aim of this study (EudraCT number: 2011-000393-61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite ( HDM)-induced allergic rhinoconjunctivitis ( ARC) using a titrated nasal provocation test ( TNPT). Methods In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AUeq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments. Results After 12 months, a dose-response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of ≥20 000 AUeq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG4 levels were dose dependently increased. In the highest dose group, more treatment-emergent adverse events were observed compared with the lower dose groups. Conclusion In this mite allergoid SCIT dose finding study in HDM-induced ARC, concentrations of ≥20 000 AUeq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk-benefit ratio favours 20 000 AUeq/ml and 50 000 AUeq/ml strengths for further clinical development. [ABSTRACT FROM AUTHOR]

Background Although ibuprofen and other arylpropionic acid derivatives ( APs) are the most common medicines involved in hypersensitivity drug reactions ( HDRs) to NSAIDs, no patient series studies have been performed regarding immediate selective reactions ( SRs) to these drugs. Objective To characterize patients with immediate selective HDRs to ibuprofen and other APs through clinical history and challenge. Methods Subjects who developed an HDR to APs less than 1 h after drug intake were included. Tolerance to aspirin was assessed and challenge was performed with ibuprofen in all cases, and additionally with the culprit drug (if different) in those patients that tolerated ibuprofen. Serum tryptase levels and tryptase immunohistochemical staining in skin biopsies were also assessed in some patients with a positive DPT to ibuprofen. Results From a total of 245 patients with a confirmed history of HDRs to APs, 17% were classified as selective immediate hypersensitivity reactors by both clinical history and challenge. A selective response to naproxen and dexketoprofen with tolerance to ibuprofen was found in 16 of 20 cases. Significant differences in serum tryptase levels were observed between 2 and 24 h in the 11 cases that were studied further. Conclusions Within the group of patients with HDRs to NSAIDs, APs can induce immediate SRs. Within this group, selective responses to a single drug or responders to several APs may exist, suggesting potential immunological cross-reactivity. [ABSTRACT FROM AUTHOR]