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Abstract: In the European Union (EU), the regulatory framework regarding diagnostic allergen extracts is currently in the process of being implemented at the national level. Due to these regulations, the initial and periodic renewal expenses for the registration of diagnostic allergen extracts may render extract production unprofitable. Consequently, many extracts may be at risk of removal from the market. The current survey, which was conducted by a task force of the European Academy of Allergy and Clinical Immunology, aimed to assess the current practice of allergy diagnosis in Europe. This survey revealed that skin tests continue to be the main diagnostic procedure and are used as the first option in almost two‐third of all types of allergic diseases and in 90% of individuals suffering from respiratory allergies. Therefore, there is a need to ensure the availability of high‐quality allergen extracts to maintain the common diagnostic procedures used by EU professionals. To reach this goal, it is necessary to align efforts and establish active partnerships between manufacturers, relevant scientific societies, consumer organizations and authorities to maintain the availability of these diagnostic tools. [ABSTRACT FROM AUTHOR]

Background Perennial allergic rhinitis ( PAR) represents a global and public health problem, due to its prevalence, morbidity, and impact on the quality of life. PAR is frequently associated with allergic asthma ( AA). Costs of PAR with or without AA are poorly documented. Objective Our study aimed to detail medical resource utilization ( MRU) and related direct cost for PAR, with or without concomitant AA, in France. Methods Using Electronic Health Records ( EHRs), we identified in 2010 two cohorts of PAR patients, based on General Practitioners' diagnoses and prescribing data, with and without concomitant AA. For each patient, the EHRs were linked to corresponding claims data with MRU and costs during years 2011 to 2013. Predefined subgroup analyses were performed according to severity of PAR and level of AA control. Results The median annual cost reimbursed by social security system for a patient with PAR, and no AA was 159€ in 2013. This varied from 111€ to 188€ depending on PAR severity. For patients with PAR and concomitant AA, the median annual cost varied between 266€ and 375€, and drug treatment accounted for 42-55% of the costs, depending on asthma control. Conclusion This study linking diagnoses from EHRs to claims data collected valid information on PAR management, with or without concomitant AA, and on related costs. There was a clear increase in costs with severity of PAR and control of AA. [ABSTRACT FROM AUTHOR]

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing. [ABSTRACT FROM AUTHOR]

Clinical indications for allergen immunotherapy ( AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as 'absolute' or 'relative'. EAACI Task Force on 'Contraindications to AIT' was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β-blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT-related side-effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient. [ABSTRACT FROM AUTHOR]

Treatment with SQ (standardised quality) house dust mite sublingual tablet for 1 year resulted in a decreased probability of having an allergic rhinitis (AR) exacerbation day (from 11% [placebo] to 5% [ SQ house dust mite sublingual tablet]) and an increased probability of having a mild AR day (from 16% [placebo] to 34% [ SQ house dust mite sublingual tablet]). [ABSTRACT FROM AUTHOR]

Background Allergen immunotherapy ( AIT) has been thoroughly documented in randomized controlled trials ( RCTs). It is the only immune-modifying and causal treatment available for patients suffering from Ig E-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy ( SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. Methods As elaborated by a Task Force ( TF) of the European Academy of Allergy and Clinical Immunology ( EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis. Results Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score ( CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. Conclusion A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis. [ABSTRACT FROM AUTHOR]

Hypersensitivity diseases are not adequately coded in the International Coding of Diseases ( ICD)-10 resulting in misclassification, leading to low visibility of these conditions and general accuracy of official statistics. To call attention to the inadequacy of the ICD-10 in relation to allergic and hypersensitivity diseases and to contribute to improvements to be made in the forthcoming revision of ICD, a web-based global survey of healthcare professionals' attitudes toward allergic disorders classification was proposed to the members of European Academy of Allergy and Clinical Immunology ( EAACI) (individuals) and World Allergy Organization ( WAO) (representative responding on behalf of the national society), launched via internet and circulated for 6 week. As a result, we had 612 members of 144 countries from all six World Health Organization ( WHO) global regions who answered the survey. ICD-10 is the most used classification worldwide, but it was not considered appropriate in clinical practice by the majority of participants. The majority indicated the EAACI- WAO classification as being easier and more accurate in the daily practice. They saw the need for a diagnostic system useful for nonallergists and endorsed the possibility of a global, cross-culturally applicable classification system of allergic disorders. This first and most broadly international survey ever conducted of health professionals' attitudes toward allergic disorders classification supports the need to update the current classifications of allergic diseases and can be useful to the WHO in improving the clinical utility of the classification and its global acceptability for the revised ICD-11. [ABSTRACT FROM AUTHOR]

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions ( DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (i CAALL), formed by the European Academy of Allergy and Clinical Immunology ( EAACI), the American Academy of Allergy, Asthma and Immunology ( AAAAI), the American College of Allergy, Asthma and Immunology ( ACAAI), and the World Allergy Organization ( WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs. [ABSTRACT FROM AUTHOR]

The number of patients with allergic diseases in Europe, and thus relevant demand for health care, is continuously increasing. In this EAACI- UEMS position paper, a rationale is given for the medical specialty of allergology. General practitioners and general paediatricians usually cannot elucidate and address all causative factors. Throughout Europe, therefore, the expertise of allergologists (allergists) is required. In collaboration with other medical professionals, they take care of allergic patients, in private practices or in specialized public centres. A well-structured collaboration between allergists and allergy centres offers the possibility of rapid signalling of new trends developing in the population of allergic patients (e.g. in food and drug allergy). Allergy centres also can perform clinical (and basic) research, teach medical students, future allergists and provide postgraduate training. To prevent that the quality of care in one or several countries within Europe lags behind developments in other countries, the UEMS Section and Board on Allergology together with the European Academy of Allergy and Clinical Immunology advocates the status of a full specialty of allergology in each European country, with a further intention to align their activities (blueprint, curriculum and centre visitation) with the UEMS Section of Paediatrics. [ABSTRACT FROM AUTHOR]

Background Allergic rhinitis ( AR) severity is evaluated using scores such as Rhinoconjunctivitis Quality-of-Life Questionnaire ( RQLQ) and total symptom score ( TSS). However, a simple assessment is needed to enable physicians to evaluate the severity of the AR and the efficacy of the treatment. Objective The main objective was to validate visual analogue scale ( VAS) as a simple quantitative tool to assess the burden of AR in primary care. Methods The study was multi-centre prospective observational conducted in patients consulting general practitioners for symptomatic rhinitis. VAS, RQLQ and TSS6 were assessed at the consultation day and 14 days later, and changes were analysed using paired test. Correlations between VAS, RQLQ and TSS6 were assessed. Cut-off levels for VAS, which discriminate significant from insignificant changes, were established using Receiver Operating Characteristic curves. Results A total of 990 patients were included in the study. According to allergic rhinitis and its impact on asthma classification, mild intermittent rhinitis was diagnosed in 20% patients, mild persistent in 17%, moderate/severe intermittent in 15% and moderate/severe persistent in 48%, at the consultation day. At day-14, rhinitis symptoms and QoL improved significantly in almost all patients. Impairment incurred by AR and assessed with VAS improved also. The established cut-off variation of 23 mm for VAS was associated with a cut-off variation of 0.5 for RQLQ. Sensitivity analysis with RQLQ and TSS6 scales confirmed the aptitude of the cut-off value (23 mm) to discriminate changes in symptoms and QoL. Conclusion and Clinical Relevance The VAS can detect with high sensitivity the variations of symptoms and QoL in patients with AR. [ABSTRACT FROM AUTHOR]

Background Allergic rhinitis affects the lives of patients for whom discomfort is, in most cases, significantly improved by pharmacological treatment. Objective To develop and validate a self-assessment global score for allergic rhinitis control (five items scored from 1 to 5 assessing the rhinitis over the 2 previous weeks). Methods Study of acceptability, reliability, validity and sensitivity to change during a prospective observational study in 902 patients selected by 411 general practitioners or allergists. Results The score correlated significantly to the clinical picture and to the impact of the rhinitis on social and sports activities at inclusion (Po0.0001). A significant improvement in the score was observed after 15 days of treatment: 14.9±4.0 at inclusion and 21.5±2.9 at reevaluation after 15 days of treatment (Po0.0001). Using receiver operating characteristics curve, a score of 20 was the cut-off for poor vs. well-controlled rhinitis; a score strictly higher than 20 (best being 25) had a sensitivity of 67%, a specificity of 82%, a negative predictive value of 32% and a positive predictive value of 95%. Conclusion and Clinical Relevance The self-assessment score for allergic rhinitis control appeared to be sensitive to change and correlated to the clinical expression of rhinitis and also to its involvement with treatment. These results suggest that this self-completion questionnaire could be used in daily practice at each consultation to determine, in a standardized manner, the level of control of the allergic rhinitis of an individual patient. [ABSTRACT FROM AUTHOR]

To cite this article: Demoly P, Romano A, Botelho C, Bousquet-Rouanet L, Gaeta F, Silva R, Rumi G, Rodrigues Cernadas J, Bousquet PJ. Determining the negative predictive value of provocation tests with beta-lactams. Allergy 2010; 65: 327–332. Background: The beta-lactam allergic work-up is mostly standardized. However, the negative predictive value of drug provocation tests is not yet well established. Method: A historical-prospective multicentre cohort study was conducted in four centres (one in France, one in Portugal, two in Italy) to assess the negative predictive value of provocation tests with beta-lactams in patients initially tested for a suspicion of drug allergy/hypersensitivity. Patients were contacted at least 6 months after the work-up, between 2003 and 2007. A new allergic work-up was proposed to reacting patients. Results: Among the 457 patients included, 365 (79.9%) were followed up (159 [79.1%] from France, 153 [82.7%] from Italy and 53 [74.6%] from Portugal). Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8–98.3) (111 out of 118 patients). Conclusion: Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one regarding a proposal for an update in the diagnosis of β-lactam allergy from the European Network for Drug Allergy, one regarding a review on the diagnosis and management of HIV drug hypersensitivity, and another one regarding a systematic review on the treatment of anaphylaxis using the Cochrane system.

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA2LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD®) has been established under FileMaker® Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA2LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA2LEN–ENDA–DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to determine the spreading level of the WHO-ARIA (World Health Organization's Allergic Rhinitis and its Impact on Asthma) guidelines among the medical community and their influence on medical practices. Methods A cross-sectional study based on a questionnaire was performed between April and July 2005 on randomly chosen general practitioners (GPs) (943) and ear, nose and throat (ENT) physicians (277). Results About 54.4% of the physicians claimed to know the WHO-ARIA guidelines and 49.7% said they followed them. These results vary significantly, mainly according to medical specialty (ENT vs. GP). In comparison to those who did not know the guidelines, their patients benefited more frequently ( P<0.0001) from allergen search (42.2% vs. 31.7%), a nasal endoscopy (38.3% vs. 26.0%), a follow-up consultation (64.9% vs. 52.6%) and written information on rhinitis (30.7% vs. 14.1%). Paradoxically, they do not search more frequently for asthma and do not provide different first-line treatment strategy and duration. [ABSTRACT FROM AUTHOR]

Background: Specific immunotherapy (SIT) is the only aetiological treatment used in allergic rhinitis (AR). A telephone survey of patients and physicians in France was carried out to understand better the real and perceived advantages and inconveniences of this therapeutic approach. Methods: A cohort of 453 individuals with AR was selected using the Score For Allergic Rhinitis questionnaire. The survey evaluated the level of understanding of allergic rhinitis and its management, including both pharmacotherapy and SIT. A parallel survey was conducted with 400 general practitioners, allergists and nonallergist specialists. Results: Approximately 50% of patients had heard about SIT as a therapeutic option. Of these, 56% had a positive view of SIT and 14% a negative image. A majority of patients and physicians with a positive opinion associated SIT with improved well-being and quality of life, while those with a negative opinion considered it to be a long and inconvenient treatment, with uncertain results. Over 50% of patients who had been offered SIT had accepted it and approximately 60% of these were satisfied with it. The future availability of SIT as sublingual tablets was perceived positively by both patients and physicians. Conclusions: Many patients with AR are unaware of their pathology and few seek help from health professionals. When patients take medication, they are generally satisfied with their treatment, even if it is only symptomatic. Patients and physicians see the notion of definitive recovery as the main benefit of SIT, whereas the main disadvantage is the duration of treatment. [ABSTRACT FROM AUTHOR]

The article presents detailed information on drug hypersensitivity reactions (DHRs). More than 7% of the general population is affected by DHRs and therefore, it represents a significant public health problem. The diagnosis of DHRs relies on clinical histories, skin tests and a few validations in vitro tests. It is stated that during the different drug development phases, DHRs are barely predictable.

The article presents information on the links between allergic rhinitis and asthma. It has been consistently shown by epidemiologic studies that asthma and rhinitis often co-exist in the same patients in every region of the world. It is stated that several patients with allergic rhinitis have an increased bronchial reactivity to methacholine or histamine, particularly during and some time after the pollen season.

Abstract: The diagnosis of drug allergy is important because most suspected cases are not confirmed. Diagnosis is based on immediate or delayed skin test reactions, done in the absence of contraindications. In vitro laboratory tests have not yet replaced skin testing. Skin tests are not without risk, which accentuates the very important place of the clinical history, and also the need for precaution in skin testing, but in the large majority of cases they are the only means of confirming or rejecting the diagnosis of drug allergy. [Copyright &y& Elsevier]

Abstract: To assess the influence of international guidelines on the management of intermittent allergic rhinitis in France, a sample of 226 randomly chosen general practitioners were surveyed by questionnaire. The objectives were to evaluate their approach to nasal steroid prescription and their assessment of this treatment. Only 28% of these doctors claimed to systematically attempt to diagnose allergy, and only 17% systematically performed an endonasal examination. The survey also showed that 97% relied on evaluation of seasonal symptoms to define the intermittent aspect of their patients’ allergic rhinitis. They used the degree of nasal obstruction to define the severity of the rhinitis. Nasal steroids (59%) and H1 antihistamines (45%) were the principal drugs prescribed. They determined the duration of nasal steroid treatment according to the severity of the symptoms. These physicians had a very positive opinion on the usefulness of nasal steroid therapy. This type of survey is useful in assessing the impact of guidelines on the management of allergic rhinitis in general practice in France. [Copyright &y& Elsevier]

Abstract: Introduction: The WHO–ARIA allergic rhinitis recommendations are evidence-based. Objectives: To determine the percentage of doctors who know and follow the WHO-ARIA guidelines and to evaluate their influence on medical practices. Methods: A cross sectional analysis based on a questionnaire was performed between April and July 2005 on randomly chosen general practitioners (943) and ENT doctors (277). Results: 54.4% of the doctors claimed to know the WHO-ARIA guidelines. 4.7% knew but did not follow them. Patients whom doctors knew the guidelines benefitted more frequently (p<0.0001) from an allergen search (42.2 vs 31.7%), a nasal endoscopy (38.3 vs 26.0%), a follow-up consultation (64.9 vs 52.6%) and written informations on rhinitis (30.7 vs 14.1%). There was no difference in terms of asthma search, first line treatment and duration of treatment. Conclusions: When the WHO–ARIA guidelines are known by doctors (half), they seem to be followed. They favor: allergy testing, nose examination, repeat visit, written information but paradoxically do not influence search for asthma and first line treatment strategy and duration. [Copyright &y& Elsevier]

A preface to articles on immunotherapy published in this periodical is presented.

Abstract: Dendritic cells are professional antigen presenting cells, counceling innate and adaptative immune responses. They express all types of membrane histamine receptors, differencially according to their maturation state. Immature dendritic cells express H1R and H3R receptors. Their stimulation activates cell migration and costimulatory molecule expression. Mature dendritic cells express H2R, H3R and H4R, and their stimulation by histamine, decreases IL-12 secretion and is responsible for Th2 cytokine expression. Anti-histamines are H1R inverse agonists. In vitro and animal models suggest that these drugs may well act on the immune response. The presence of histamine receptors on dendritic cells and the better understanding of their roles may lead to new therapeutic perspectives of these drugs. [Copyright &y& Elsevier]

Background: All recent guidelines recommend a search for asthma utilizing both specific interrogation and pulmonary function tests in patients suffering from allergic rhinitis. Although the mandatory place of spirometry has not been confirmed, a self-questionnaire containing nine specific questions on asthma symptoms in different daily life situations was found to be capable of discriminating asthmatics from nonasthmatics in a rhinitic population. Objective: We addressed the questions of prevalence of asthma using a validated self-questionnaire and what might be the risk factors of being asthmatic according to that specific self-questionnaire. Methods: Between April 2003 and September 2004, nearly 12 000 rhinitis patients were enrolled by more than 2300 physicians (78% general practitioners, 22% ear nose and throat specialists). Patients were consulting for an exacerbation of chronic rhinitis and did not have a previous diagnosis of asthma. Both doctors and patients filled out a specific questionnaire on rhinitis and asthma. Results: Almost 30% of the patients had at least three positive answers to the self-questionnaire and could possibly be considered as asthmatics. We found five independent clinical risk factors for having ≥3 positive answers to the self-questionnaire. Severity of rhinitis (moderate-severe vs mild, OR = 1.84; 95% CI = 1.68–2.00), diagnosis of allergy (yes vs no) (OR = 1.86; 95% CI = 1.68–2.00), body mass index (≤18.5 vs >30) (OR = 0.51; 95% CI = 0.39–0.66), type of rhinitis (persistent vs intermittent) (OR = 1.25; 95% CI = 1.15–1.37), and patient age (≤25 vs >47) (OR = 0.73; 95% CI = 0.65–0.80). Conclusion: Asthma symptoms are frequent in rhinitics without a prior history of asthma. Several variables were shown to be predictive of asthma in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Hypersensitivity drug reactions, including immediate allergic reactions, are one of many types of adverse drug reactions. While urticaria is one of the most frequent clinical forms of drug allergy, other manifestations may also occur. To determine that the cause of an urticarial reaction is drug-induced is important, although in most cases this diagnosis is not established. Diagnosis is based on immediate skin test reactions and drug provocation testing. These tests are not without danger, which is why a complete clinical history and the patient''s responses to the ENDA (European Network for Drug Allergy) questionnaire, as well as careful attention to necessary precautions, are important. The Drug Allergy and Hypersensitivity Database (DAHD) includes 1,267 reports of urticaria possibly due to drugs; β-lactams were the most frequently involved (35.6%). However, a drug allergy work-up demonstrated that only 15.4% of these reactions were actually due to a drug; 44.6% were diagnosed by means of skin tests, the rest by provocation tests. Of the positive tests, 41.2% were positive within the first hour and 16.6% only after 24 hours. Urticaria may be induced by drugs, especially antibiotics, but drugs are not the main cause of urticaria. The diagnosis of drug allergy requires confirmation by relevant tests. [Copyright &y& Elsevier]

Abstract: Hypersensitivity reactions are but one of many different types of adverse drug reactions. Reactions of this type may be potentially lifethreatening, induce and prolong hospitalization, affect physicians'' drug prescribing patterns and result in considerable socioeconomic costs. Welldesigned epidemiological studies limited to allergic drug reactions are lacking; most of the studies related to this problem have included all types of adverse drug reactions. The results of such studies should help us to identify patients at risk, particularly those at risk for severe reactions, and allow us to implement preventive measures. This review will summarize current knowledge on the incidence, prevalence, mortality and risk factors for hypersensitivity drug reactions. [Copyright &y& Elsevier]

Abstract: Asthma morbidity and mortality have increased over the last ten years in most countries. In some countries now, it apears that asthma prevalence has reached a plateau. The increased prevalence, especially in children, should be explained by environnemental factors, since obviously our genes have not changed. In this paper, we will review the recent data concerning asthma prevalence, mortality, socio-economic impact and both environnemental and genetic risk factors. [Copyright &y& Elsevier]

Abstract: The notion of conjunctival hyperreactivity (CHR) is not used much at present. However, its existence is supported by the results of a number of investigations. Here we will review a number of the publications on this subject. The results of conjunctival provocation tests (CPT) with different non-specific irritants have been reported. In patients with allergic conjunctivitis, a positive CPT is evidence of the coexistence of non-specific bronchial hyperreactivity, which often exists along with allergen-induced bronchial hyperreactivity. Non-specific CHR can also be a sign of persistent minimal inflammation, as observed in patients suffering from allergy to mites. These findings allow us to describe a clinical picture of CHR, with the result that treatment can be started sooner in patients with this condition. Finally, minimal non-specific CHR is often seen in patients between periods of allergen-induced CHR. [Copyright &y& Elsevier]

Abstract: Ten-to-twenty percent of hospitalised patients experience secondary drug reactions, and a third of these reactions may be allergic in nature. Multiple immune mechanisms may be at the base of these reactions. Antibiotics (especially β-lactams) are the principle type of drugs concerned, and they most often induce IgE-mediated allergic reactions. Information on the risk factors for drug allergies is limited, and few studies on genetic polymorphisms have been reported, except those involving certain enzymes that participate in drug metabolism or those concerning certain HLA haplotypes. Data coming from immunogenetic investigations should result in new diagnostic tools and, certainly, in better prediction of these events. Nevertheless, the results of such studies will vary depending on the population involved. Identification of genetic markers that are sufficiently predictive in clinical practice is going to require screening of hundreds of single nucleotide polymorphisms in the genome to be able to identify the subpopulation of patients that are at risk for each class of drugs. [Copyright &y& Elsevier]

Abstract: Any asthmatic woman in the childbearing age may become pregnant. Generally, asthma is not a contraindication for pregnancy, and drug treatment of pregnant asthmatic women is indicated. Neither mother nor child are particularly at risk for complications, as demonstrated in recently published long-term studies. Pharmacologic data are reassuring, especially those concerning inhaled corticosteroids. Nevertheless, regular follow-up of asthmatic pregnant patients is necessary to assure good control of the patient''s asthma. [Copyright &y& Elsevier]

The diagnosis of drug allergy is difficult and is usually based on clinical history, skin tests (for some drugs) and, in a few specialised allergy centers, provocation tests. Currently available laboratory tests are of limited interest: they sometimes provide information on the severity of certain clinical conditions, they may suggest an immunopathological mechanism in cases of intra-operative anaphylaxis and, more rarely, they can lead to the identification of the responsible drug. The few available tests, in particular, measurement of specific IgE antibody, in vitro leukocyte histamine and leukotrienes release, have not been sufficiently validated, lacking data on reproducibility and predictive values. The use of flow cytometry for that purpose appears to be a promising technique. [Copyright &y& Elsevier]

Asthma control and prevention of exacerbations are primary objectives for asthma care. However there is a lack of universal definition of these notions which may therefore have a different meaning according to the physician's practice. In the present survey, 1805 general practitioners, 551 pulmonologists, 176 allergologists and 470 resuscitation/emergency care physicians were randomly selected in fall 2001 and asked to answer one question on asthma control and three questions on asthma exacerbation. Regarding asthma control, the presence of minimum symptoms was the primary criterion for asthma specialists (pulmonologists and allergologists), while a normal respiratory function was first considered by nonspecialist physicians (general practitioners and emergency care physicians). The first criterion of mild exacerbation for asthma specialists was the occurrence during at least 2 days of an increase in the frequency of dyspnoea and/or the use of short-acting bronchodilators. For nonspecialist physicians, dyspnoea affecting daily activities and/or sleeping was the preferred notion. Hospitalization was unanimously recognized as the first criterion for severe exacerbations. A decrease in peak expiratory flow of more than 30% below the baseline value on two consecutive days and an episode requiring systemic corticosteroids were the next criteria. This survey emphasizes the complexity of the notions of asthma control and exacerbation and provides novel informations to orient continuing education programmes. [ABSTRACT FROM AUTHOR]

Allergic drug reactions are a frequent problem and can be difficult to manage. Once the diagnosis has been established, strict avoidance of the drug and all others that are structurally similar is then necessary. Nevertheless, re-introduction of the drug, leading to tolerance can be considered. Although the mechanisms of drug tolerance are not well known, induction of tolerance is usually possible in most patients. While the induction of tolerance is not standardized and the protocols used vary in duration from several hours to a few days, two guiding principals must be kept in mind: 1) the drug must be necessary, with no satisfactory alternative and 2) much precaution must be taken when tolerance induction is undertaken. In this review, after summarizing the guidelines for the diagnosis of drug allergy (allergic or not), we will discuss in detail some published examples and comment on how induction of tolerance to the drugs was carried out. [Copyright &y& Elsevier]

The diagnosis of allergic reactions in clinical practice is based on both clinical history and the determination of specific immunoglobulin E (IgE), either in the serum or on skin mast cells. However, for various reasons, identification of the causative factors is not possible in all the cases. Moreover, not all allergies are IgE-dependent. In an attempt to find sensitive, specific and cost-effective methods to investigate hypersensitivity reactions, in vitro tests were developed at a very early stage. Allergen-induced mediator release assays analyze the mediator released from effector cells, mainly peripheral blood cells, when stimulated in vitro with serial dilutions of the putative allergens. Described initially as research tools, they could well become diagnostic tests. However, relatively few high quality reports have been published so far. In this review, we will detail allergen-dependent histamine, tryptase, arachidonic acid metabolite, e.g. cysteinyl leukotrienes and 15-hydroxyeicosatetraenoic mediator release tests. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis is commonly divided into seasonal and perennial rhinitis. The recent Allergic Rhinitis and its Impact on Asthma (ARIA) workshop proposes to replace these terms by intermittent vs persistent rhinitis. Methods: In order to test the new ARIA classification against the classical one used in medical practice in France, we designed two cross-sectional surveys: (i) a spring survey, where 1321 general practitioners enrolled 3026 patients consulting for seasonal allergic rhinitis and (ii) an autumn–winter survey, where 1346 doctors enrolled 3507 patients for perennial allergic rhinitis. Both doctors and patients filled out a specific questionnaire on allergic rhinitis. Results: Focusing on the number of days per week and consecutive weeks per year, the patients described the duration of their symptoms (based on an auto-questionnaire). About 43.7% of the patients, classified by their doctor as seasonal, did in fact have persistent rhinitis, whereas 44.6% classified as perennial had intermittent rhinitis. Conclusions: The proposal of the ARIA expert panel defining the chronology of allergic rhinitis as number of days per week and consecutive weeks per year is likely to change daily physician practice. [ABSTRACT FROM AUTHOR]

Background: Epidemiological and pathophysiologic studies have shown that allergic rhinitis and asthma often occur in combination. The internationally developed ARIA position paper (Allergic Rhinitis and its Impact on Asthma) recently offered recommendations on allergic rhinitis. As part of this new report and prior to its diffusion, we investigated the management of rhinopathies in asthma patients by pulmonologists in their everyday practice. Methods: From March to June 2000, 477 (48%) French pulmonologists in office-based practice participated in the survey. They were asked to include their first five asthmatic adult patients. In addition to descriptive statistics, univariate and multivariate analyzes were performed. Results: We studied 1623 patients with varying severity of asthma (sex ratio 0.9; median age 35 years). The pulmonologists reported rhinopathy in 76.6% of these, with a chronic course in 91%. Among the patients, 67.1% reported rhinopathy. The diagnosis was allergic rhinitis in 66.2% of participants and nasal polyposis in 10.1%. Examination of the nasal cavities was performed by the pulmonologists themselves in 56.2% of patients. Imaging of the sinuses was performed radiographically in 55.3% of enrolled patients and/or by computed tomography in 17.2%. Referral to an ENT specialist occurred for 21.6% of patients, being more common for patients with rhinitis that failed to respond to medical therapy (although some pulmonologists referred their patients routinely). Conclusions: The high prevalence of rhinopathies in asthma patients requires that these conditions are recognized and managed by pulmonologists. Thus, our findings support one of the central messages contained in the new ARIA guidelines—asthma patients should be investigated routinely for rhinitis and other rhinopathies. [ABSTRACT FROM AUTHOR]

H1–antihistamines are antagonist drugs that block histamine at the H1 receptor level. Some also possess anti-allergic effects, but the clinical relevance of such effects is still questionable. During the past 20 years, pharmacological research has produced compounds with higher potency, longer duration of action, faster onset of action and minimal sedative effect and impairment - the so-called second generation H1–antihistamines (as opposed to the first generation H1–antihistamines). In this document, we will review the requirements for new H1–antihistamines. [Copyright &y& Elsevier]

Past as well as recent studies, both retrospective and prospective, have shown that specific immunotherapy may prevent the onset of newly acquired sensitization in young children who have a limited number of specific sensitizations. Moreover, pollen immunotherapy may prevent the development of asthma in children with allergic rhinitis. Thus, in contrast to pharmacotherapy, specific immunotherapy appears to be the only treatment capable of changing the natural course of allergic diseases. [Copyright &y& Elsevier]

Drug hypersensitivity reactions are a daily worry for clinicians. The tools allowing a definitive diagnosis are few and poorly validated. They include a thorough clinical history, standardized skin tests, reliable biological test, and sometimes drug provocation tests. These tools are currently being evaluated by the European Network of Drug Allergy, under the aegis of the EAACI drug hpersensitivity group of interest. [ABSTRACT FROM AUTHOR]

Background: The actual management of intermittent allergic rhinitis is still little known about, despite the disease being very prevalent. We used a cross-sectional survey to address this issue in everyday general medical practice in France. Methods A total of 1321 general practitioners enrolled 3026 patients consulting for a spring exacerbation of allergic rhinitis. Both doctors and patients filled out a specific questionnaire on allergic rhinitis. Results These patients consulted their doctor two-and-a-half weeks, on average, after the onset of their symptoms. They were bothered for an average of six days per week (5.9 ± 1.7 days) and for two months per year (8.7 ± 7.7 weeks) by symptoms which largely exceed the ENT (ear, nose and throat) field, with ocular symptoms (51.7%), pharyngeal irritation (39.0%), cough (30.8%), or respiratory discomfort (17.9%). Of these patients 79.2% had some impairment of their professional life and 91.8% of their daily life. Fifty percent of patients knew to what allergens they were allergic; only 11.1% had additional laboratory tests and 10.3% had subsequent specialist consultation (for most this was with an allergologist). Prescribed drugs were oral antihistamines (92.4%) and nasal glucocorticosteroids (45.2%). Prescriptions were written for a duration of six weeks on average. Seventy-nine percent of patients considered that the information they had received was adequate and easy to understand, but 58.2% of patients would have liked more advice. Furthermore, only 54.7% followed their doctor's prescription scrupulously, and 44% used frequent self-medication. Conclusions Intermittent allergic rhinitis is a real health problem because of its increasing prevalence, the induction of impaired quality of life and loss of performance, especially at work. General practitioners play a major role in this disorder; they make the diagnosis, start the treatment, give the relevant information, and monitor most of the patients. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of immediate allergic reactions to drugs is difficult, requiring in vitro test development. Basophils are likely to be involved in these reactions, and to evaluate the sensitivity, the specificity, and the predictive values of the histamine‐release test, we performed a prospective study in 68 patients tested for suspected drug allergy. Methods: Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Histamine release in the presence of the drug was assessed on heparinized whole blood by enzyme immunoassay (Immunotech, France), and the cutoff value was set at 5% of total histamine content. Spontaneous and anti‐IgE‐induced histamine release was also studied in all subjects. Results: All patients presented to our clinic with reactions ranging from maculopapular exanthema to anaphylactic shock. Thirty‐five patients had proven drug allergy; 33 were not allergic to drugs and served as a control group together with 40 other subjects with no history of drug allergy. Net histamine release was positive in 18/35 allergics and 27/73 nonallergics, giving poor sensitivity (51.4%), specificity (63.0%), and positive predictive value (29.3%), but valuable negative predictive value (81.1%). Conclusions: The usefulness of the in vitro histamine‐release test for the diagnosis of drug allergy appears to be insufficient. [ABSTRACT FROM AUTHOR]

Asthma is a disease which is increasing in frequency and severity despite the incontestable advances in the understanding of its physiology and treatment. New therapeutic strategies are therefore required and at the time when a new treatment, that of gene therapy, is giving hope for the treatment of so far incurable illnesses, it would seem to us to be useful to discuss the possible use of this treatment in severe asthma and in particular in the case of the most severe asthmatic patients requiring continuous oral steroid treatment (referred to as steroid-dependent). These patients are those who require particular medical attention, they often need to be admitted to hospital and they represent over 50% of the total costs associated with asthma. No satisfactory alternative therapy is currently available. In this regard, a variety of gene-based strategies have recently been proposed for inflammatory and immunologic disorders. It is thus the purpose of this review to consider its application to asthma therapy, although there are very few published works that directly bear on gene therapy linked to asthma. After a brief outline of the epidemiology of asthma, its genetics and the available animal models, we will focus on its immunopathology slanting the discussion towards the possibility of a gene-based treatment. [ABSTRACT FROM AUTHOR]

Assesses intercellular cell adhesion molecule-1 (ICAM-1) expression in the upper respiratory mucosa. ICAM-1 immunoreactivity; Comparison of ICAM-1 expression with both eosinophil and neutrophil infiltrates; ICAM-1 distribution within the epithelium; Role of ICAM-1 in nuetrophil and eosinophil recruitment according to the allergic status.

We have recently phenotyped inflammation in non-infectious allergic and non-allergic chronic maxillary sinusitis using sinus biopsies and lavage fluids. In this first paper, we have concentrated our work on the eosinophil, T cell, mast cell and macrophage infiltrates. However, many unresolved questions remain and particularly the role of neutrophils needed to be addressed. In the present study, we focused on the neutrophilic inflammation: myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured by immunoassays and neutrophils were enumerated by conventional staining in the sinus lavage fluids of 16 patient with chronic sinusitis and six control subjects. Both MPO and IL-8 levels were significantly higher in patients than in controls (P<0.01) and 0.005, respectively). There was a significant correlation between MPO levels and neutrophil numbers, and between MPO and IL-8 levels in the sinus lavage fluid (P<0.0001, Spearman rank correlation). The presence of high levels of IL-8 in the lavage fluids of patients suffering from chronic sinusitis, levels which correlate with those of MPO, suggests that this cytokine may activate neutrophils in this chronic disease. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy is used to treat allergic rhinoconjuctivitis and asthma worldwide. The clinical efficacy of the most common routes, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, is documented for respiratory allergy by double-blind, placebo-controlled, randomised clinical trials (DB PC RCT). However, dose–effect relationships are not available for all extracts. The 1998 WHO Consensus Report on Allergen Immunotherapy found SCIT ineffective at low doses, with high doses more likely to result in an unacceptably high level of systemic reactions. Recent large well-designed DB PC RCTs using SLIT grass pollen tablets have undergone phase II–III studies in adults with allergic rhinitis, yielding proper dose– response studies. These were analysed by the European Academy of Allergy and Clinical Immunology Immunotherapy Interest Group task force on dose effect. In general, low doses (5–7 lg of allergen Phl p 5 per day) are ineffective. Daily doses of 15–25 lg of the major allergen protein are required for significant clinical improvement measured by symptom scores. A higher dose (33–40 lg of Phl p 5 per day) was not more effective than 15–25 lg. Optimization of the allergen/adjuvant ratio may allow for lower allergen doses, increase the safety/efficacy profile and allow for shorter updosing. However, our analysis of the available studies concluded that every product requires its own dose–response relationship study. [ABSTRACT FROM AUTHOR]

The article focuses on the proposed modification of the severity classification of Allergic Rhinitis and its Impact on Asthma (ARIA). It says that H. Van Hoecke and colleagues tried to simplify the severity classification by asking two questions among Belgian subjects. It mentions that the classification by Van Hoecke and colleagues, when applied in French population, seemed to be less relevant than to ARIA's proposal and does not simplify the correlation between symptoms severity and treatment.

The authors reflects on the use of new diagnostic tool called basophil activation test (BAT) for drug allergy. They state that the routine use of the tool could increase the sensitivity of diagnostic work-ups, therefore, it reduces the need for drug provocation tests. They stress that there is an evidence that the BAT can contribute to the diagnosis of anaphylactic reactions due to several drugs.

Abstract: Hypersensitivity reactions to radiocontrast media are associated with 3.8–12.7% of injections. They are generally mild to moderate but can occasionally be severe. Immediate reactions are less frequent with noniodinated products: the frequency of severe immediate reactions is 0.1–0.4% with iodinated products and 0.02–0.04% with noniodinated products. An allergic sensitivity should be investigated systematically when reactions are produced by noniodinated products, as published reports have shown. The frequency of delayed skin reactions varies from 1–3%, and analysis of these reports emphasizes the usefulness of testing for allergic sensitivity. [Copyright &y& Elsevier]