Showing papers in "Allergy in 2003"

Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations.

Abstract: A drug provocation test (DPT) is the controlled administration of a drug in order to diagnose drug hypersensitivity reactions. DPTs are performed under medical surveillance, whether this drug is an alternative compound, or structurally/pharmacologically related, or the suspected drug itself. DPT is sometimes termed controlled challenge or reexposure (1), drug challenge (2), graded (2) or incremental challenge (3), test dosing (2), W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez, K. Brockow, W. J. Pichler, P. Demoly for ENDA, and the EAACI interest group on drug hypersensitivity Department of Environmental Dermatology, University of Graz, Graz, Austria; Department of Dermatology, Basle, Switzerland; Allergy Service, Catholic University of Rome, Italy; Allergy Service, University La Paz, Madrid, Spain; Clinic for Allergy and Immunology, Florence, Italy; Allergy Section, Dept. Clin. Med., UMH, Elche, Spain; Klinik und Poliklinik f1r Dermatologie und Allergologie, Muenchen, Germany; Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, Bern, Switzerland; Maladies Respiratoires-INSERM U454, H7pital Arnaud de Villeneuve, Montpellier, France

Diagnosis of immediate allergic reactions to beta‐lactam antibiotics

Abstract: Allergic reactions to betalactams are the most common cause of adverse drug reactions mediated by specific immunological mechanisms. Reactions may be induced by all betalactams currently available, ranging from benzylpenicillin (BP) to other more recently introduced betalactams, such as aztreonam or the related betalactamase-inhibitor clavulanic acid (Fig. 1) (1–5). Although the production process of betalactams has improved over the years, the number of reactions has not decreased, M. J. Torres, M. Blanca, J. Fernandez, A. Romano, A. de Weck, W. Aberer, K. Brockow, W. J. Pichler, P. Demoly for ENDA, and the EAACI interest group on drug hypersensitivity Allergy Service, Carlos Haya Hospital, Malaga, Spain; Allergy Service, University La Paz, Madrid, Spain; Allergy Section, Dept. Clin. Med., UMH, Elche, Spain; Allergy Service, Catholic University of Rome, Italy; Fondation Gerimmun, Beaumont 18, CH1700, Fribourg, Switzerland; Department of Environmental Dermatology, Graz, Austria; Klinik und Poliklinik f5r Dermatologie und Allergologie, Muenchen, Germany; Clinic for Rheumatology and Clinical Immunology/Allergy, Inselspital, Bern, Switzerland; Maladies Respiratoires-INSERM U454, Hopital Arnaud de Villeneuve, Montpellier, France

Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966–2001) on the mode of early feeding in infancy and its impact on later atopic manifestations

Abstract: Background: Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers. Methods: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group. Results: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design. Conclusions: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.

Links between rhinitis and asthma.

Abstract: There is compelling evidence of a close relationship between the upper and lower airways in asthma and rhinitis. Rhinitis is present in the majority of patients with asthma, and a significant minority of patients with rhinitis have concomitant asthma. Similarities between the two conditions occur in the nature of the inflammation present in the target tissues. A common initiating step in the inflammatory process of allergic airways disease is the presence of immunoglobulin E providing an adaptor molecule between the offending allergen and inflammatory cell activation and mediator release. Differences in the two conditions arise largely from the structural differences between the nose and the lungs. In an asthmatic, concomitant allergic rhinitis increases healthcare costs and further impairs quality of life. The presence of rhinitis should always be investigated in children and young adults with asthma. Subjects with allergic rhinitis have an increased risk of developing asthma and may form a suitable population for secondary intervention to interrupt the 'allergic march'.

Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in Münster, Germany.

Abstract: Objective: To assess time trends in symptoms of asthma, allergic rhinitis, and atopic eczema among children in Munster, Germany. Methods: Two cross-sectional surveys 5-years apart (1994/1995, 1999/2000) using ISAAC core written and video questionnaires and applying the ISAAC protocol. Two main age groups (6–7 and 13–14 year olds) were designated with information collected by parental and self-report for both age groups, respectively. A school-based sample of 7744 participants in the 1994/1995 survey and 7962 participants in the 1999/2000 survey was recruited. In the first and second surveys, response rates for the 6–7 year olds were 81 and 82%, respectively, while for the 13–14 year olds response rates were 94% in both. Analyses focus on the change in 12-month prevalence of symptoms of asthma, rhinitis, and eczema. Results: There is a tendency towards an increase in current symptoms for all three conditions and in both age groups, but more so among girls. Indices of diagnosis either remained the same or increased in parallel to the increase in symptoms. Indices of severity also showed a homogenous increase in the 5-year study period. Conclusions: Our study shows that symptoms of asthma, rhinitis, and eczema are increasing, reflecting a change in the morbidity of these conditions in our population.

Side-effects of complementary and alternative medicine

Abstract: Complementary and alternative medicine are increasingly used to diagnose or treat allergic diseases, and numerous studies have reported benefits of this type of medicine. This article presents a review of the literature on risks of these methods. The potential sensitizing capacity of numerous herbal remedies may lead to allergic contact dermatitis and more rarely to IgE-mediated clinical symptoms. Mechanical injuries may be observed following acupuncture leading to pneumothorax, cardiac tamponade or spinal injury. Infectious complications after acupuncture include hepatitis and bacterial endocariditis. Organ toxicity has been observed associated with various herbal preparations involving the liver, kidneys, and the heart. Some herbs may have cancerogenic properties. Severe nutritional deficiencies can occur in infants and small children given strict alternative diets, resembling 'kwashiorkor'. Finally, among other miscellaneous adverse effects, adulteration with steroids, and herbal and drug interactions are discussed. The pattern of side-effects is similar to that observed by the use of conventional medicine. Therefore, caution may be justified using both conventional and unconventional methods. Only if the benefit is proven and the side-effects are established, should a given method be chosen.

Maternal smoking in pregnancy alters neonatal cytokine responses.

Abstract: Background: Maternal cigarette smoking in pregnancy is an important, common and avoidable exposure that has been linked with elevated cord blood (CB) immunoglobulin E levels and subsequent asthma and allergic disease in childhood. Despite this, there is still very little information about the immunological effects of maternal smoking on the fetus. Methods: This aim of this study was to compare cord blood mononuclear cell (CBMC) cytokine responses to allergens [ovalbumin (OVA) or house dust mite (HDM)] and mitogens [concanavalin A (ConA) or phytohemaglutinen (PHA)] in neonates whose mothers smoked throughout pregnancy (n = 17) with responses of neonates whose mothers never smoked (n = 40). Cell cultures were stimulated for 24 h and supernatants collected for cytokine detection by enzyme-linked immunosorbent assay [interleukin (IL)-13, IL-6, interferon (IFN)γ and IL-10]. Cell pellets were also collected for cytokine mRNA detection (IL-5, IL-9, IFNγ). Results: Maternal smoking in pregnancy was associated with significantly higher neonatal T helper type 2 (IL-13 protein) responses to both HDM (P = 0.01) and OVA (P = 0.035). These effects remained statistically significant after allowing for confounding factors, including the effects of maternal atopy. Similar trends were also seen for IL-9mRNA, IL-5mRNA and IL-6 responses, although these were not statistically significant. Although IFNγ mRNA responses to PHA (P = 0.015) and ConA (P = 0.025) were lower if mothers smoked in pregnancy, there were no differences in neonatal (Th1) IFNγ protein responses to allergens or mitogens. Conclusions: These findings indicate that maternal cigarette smoking can modify aspects of fetal immune function and highlight the need for further studies in this area.

Allergy testing in children: why, who, when and how?

Abstract: The aim of this paper is to establish evidence-based recommendations on allergy testing in children. Besides sound scientifically based recommendations for allergy testing, a well-organised cooperation between primary care physicians for children and specialists in allergy is crucial in order to ensure a high quality and effectiveness of allergy diagnosis and treatment to the benefit of the individual patient. It is our intention that these recommendations on allergy testing in children will be adopted by the European Society and implemented in all European countries according to local needs and possibilities. During the last decade, a new system for classification of levels of evidence and grading recommendations in evidence-based medicine has been developed. Originally, evidence classification was created for causal and intervention/treatment studies (1, 2). Based on a classification of studies in four categories of statements of evidence (I (highest)-II-III-IV) guidelines for treatment/intervention graded A (highest)-B-C-D have been developed. Typically, randomized placebo-controlled trials and meta-analyses of such trials got the highest statement of evidence (I) and accordingly the highest grade of recommendations (A). However, in many cases randomization is not possible and recommendations must be based on lower levels of evidence. Thus, for some areas of practice such as diagnostic tests, recommendations higher than grade B are unlikely because of the type of study that can feasibly be conducted in those areas (2). Recently two well-established systems for grading of evidence for diagnostic tests have been developed (3, 4). The prevalence of allergic diseases in childhood (atopic dermatitis, asthma, and allergic rhinitis and conjunctivitis) has increased considerably in developed countries (5, 6) in the last 20–30 years, and accordingly the need of allergy testing has increased (Table 1). In population-based studies a cumulative prevalence of allergic diseases in childhood around 25–30% has been reported, atopic dermatitis in 15–20%, asthma in 7–10%, and allergic rhinitis and conjunctivitis in 15–20% (5–11). In infancy the main symptoms of possible allergic nature are atopic dermatitis, gastrointestinal symptoms, recurrent wheezing, whereas bronchial asthma and allergic rhinitis and conjunctivitis are the main problems later in childhood (12, 13). Adverse reactions to foods, mainly cow’s milk protein and hen’s egg are most common in the first years of life, whereas allergy to inhalant allergens mostly occurs later (12, 14). Correspondingly, specific immunoglobulin E (IgE) antibodies against milk and egg are most frequent during the first 2–3 years of life, whereas IgE against inhalant allergens is predominant later in childhood (13, 15). Interestingly, IgE antibodies to allergens (hen’s egg white, cow’s milk) in infants A. Host, S. Andrae, S. Charkin, C. Diaz-V zquez, S. Dreborg, P. A. Eigenmann, F. Friedrichs, P. Grinsted, G. Lack, G. Meylan, P. Miglioranzi, A. Muraro, A. Nieto, B. Niggemann, C. Pascual, M-G. Pouech, F. Ranc*, E. Rietschel, M. Wickman Statement of The Section on Pediatrics, European Academy of Allergy and Clinical Immunology

Quality of life and patients' satisfaction in chronic urticaria and respiratory allergy

Abstract: Background: Few articles are available about chronic urticaria (CU) impact on patients’ quality of life (QoL). The aim of our study was to evaluate QoL in CU patients both focusing on health status and subjective satisfaction. We adopted two generic tools: SF-36 (an health status questionnaire) and SAT-P (a satisfaction profile). Methods: Twenty-one untreated patients (five males, 16 females; aged 46.3 ± 12.4) affected by CU, were enrolled. SF-36 and SAT-P scores of CU patients were compared with scores of a group of 27 patients with respiratory allergy. Published reference values of 608 and 241 Italian healthy subjects were used as controls, respectively, for SF-36 and SAT-P. Results: Patients with CU compared with allergic patients referred significantly lower scores in physical functioning (P = 0.046), role physical (P = 0.01), bodily pain (P = 0.0001), general health (P = 0.0043) and role emotional (P = 0.04), and compared with reference sample reported lower scores in all SF-36 domains (P < 0.0001). SAT-P scores of CU patients compared with patients with respiratory allergy and with reference sample were significantly lower in many aspects of daily life. Conclusions: These results show a significant impact on health status and on subjective satisfaction in patients with CU: the symptoms affect everyday life, limiting and impairing physical and emotional functioning, and acts as an indirect burden on life satisfaction.

Dustborne and airborne fungal propagules represent a different spectrum of fungi with differing relations to home characteristics

Abstract: Background: Exposure to fungi is often assessed by culturing floor dust or air samples. Our objective was to evaluate the relationships between dustborne and airborne fungi and to identify factors that modify these relationships. Methods: From November 1994 to September 1996 sequential duplicate 45-l air samples were collected in bedrooms of 496 homes in the Boston area, using a Burkard culture plate sampler. After air sampling, bedroom floors were sampled with a vacuum cleaner that was modified to collect dust in a cellulose extraction thimble. Dust was sieved, and the fine dust was dilution-plated onto DG-18 media. Results: Concentrations of total culturable fungi per gram of bedroom-floor dust were correlated weakly, but significantly, with those of indoor air (r = 0.13, P < 0.05). Concentrations of some individual taxa in the dust and indoor air were also weakly associated. Adjusting for the concentrations of fungi in outdoor air, dustborne fungal concentrations were positively associated with those in indoor air for the taxa Cladosporium and Penicillium, but not for total fungi. The indoor air fungal levels were often predicted by different covariates to those predicting fungal levels in dust. The type of housing (house or apartment) and the presence of carpeting were often predictive factors for dust fungi. In contrast, outdoor fungal levels were often predictive of the indoor air fungal levels. Conclusions: Because our data do not indicate a strong overall relationship between culturable fungi in dust and indoor air, the results from these two methods (dust and air sampling) likely represent different types of potential fungal exposures to residents. It may be essential to collect both air and dust samples, as well as information on housing characteristics, as indicators for fungal exposure.

Validation of the classification of ARIA (allergic rhinitis and its impact on asthma).

Abstract: 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.

Roasted hazelnuts – allergenic activity evaluated by double‐blind, placebo‐controlled food challenge

Abstract: Background: Allergy to hazelnuts is a common example of birch pollen related food allergy. Symptoms upon ingestion are often confined to the mouth and throat, but severe systemic reactions have been described in some patients. The aim of the study was to evaluate the reduction in allergenicity by roasting of the nuts. Methods: Double-blind, placebo-controlled food challenges (DBPCFC) with roasted hazelnuts (140°C, 40 min) were performed in 17 birch pollen allergic patients with DBPCFC-confirmed food allergy to raw hazelnuts. The effect of roasting was further evaluated by skin prick test (SPT), histamine release (HR), measurement of specific IgE, and IgE-inhibition experiments. Results: In 5/17 patients the DBPCFC with the roasted nuts were positive. The symptoms were generally mild and included OAS (oral allergy syndrome) in all patients. Roasting of the nuts significantly reduced the allergenic activity evaluated by SPT, HR, specific IgE, and IgE-inhibition. Immunoblotting experiments with recombinant hazelnut allergens showed sensitization against Cor a 1.04 in 16/17 patients and against Cor a 2 in 7/17 patients. None of the patients were sensitized to Cor a 8. Challenge-positive patients did not differ from the rest in IgE-binding pattern. Conclusions: All the applied methods indicated that roasting of hazelnuts reduces the allergenicity, but since 5/17 birch pollen allergic patients were DBPCFC-positive to the roasted nuts, ingestion of roasted hazelnuts or products containing roasted hazelnuts can not be considered safe for a number of hazelnut allergic consumers. For patients with a history of severe allergic symptoms upon ingestion of hazelnuts, thorough and conscientious food labelling of hazelnuts and hazelnut residues is essential.

Peanut allergen Ara h 3: isolation from peanuts and biochemical characterization.

Abstract: Background: Peanut allergen Ara h 3 has been the subject of investigation for the last few years. The reported data strongly depend on recombinant Ara h 3, since a purification protocol for Ara h 3 from peanuts was not available. Methods: Peanut allergen Ara h 3 (glycinin), was purified and its posttranslational processing was investigated. Its allergenic properties were determined by studying IgE binding characteristics of the purified protein. Results: Ara h 3 consists of a series of polypeptides ranging from approximately 14 to 45 kDa that can be classified as acidic and basic subunits, similar to the subunit organization of soy glycinin. N-terminal sequences of the individual polypeptides were determined, and using the cDNA deduced amino-acid sequence, the organization into subunits was explained by revealing posttranslational processing of the different polypeptides. IgE-binding properties of Ara h 3 were investigated using direct elisa and Western blotting with sera from peanut-allergic individuals. The basic subunits, and to a lesser extent the acidic subunits, bind IgE and may act as allergenic peptides. Conclusions: We conclude that peanut-derived Ara h 3, in contrast to earlier reported recombinant Ara h 3, resembles, to a large extent, the molecular organization typical for proteins from the glycinin family. Furthermore, posttranslational processing of Ara h 3 affects the IgE-binding properties and is therefore an essential subject of study for research on the allergenicity of Ara h 3.

Implementation of guidelines for seasonal allergic rhinitis: a randomized controlled trial

Abstract: Background: Allergic rhinitis is a common disease altering quality of life. Its treatment is well established and guidelines have been proposed. However, their efficacy has never been tested. The aim of the study was to validate the guidelines of the International Consensus on Rhinitis in the treatment of seasonal allergic rhinitis. Methods: A multicenter, multinational, open label, parallel, randomized study compared two therapeutic strategies in seasonal allergic rhinitis during a 3-week treatment. General practitioners were randomized into two groups. In the first group of 224 patients, doctors followed guidelines from the International Consensus on Rhinitis. Depending on the severity of nasal and ocular symptoms defined using visual analogue scales, patients received ebastine (an oral antihistamine), triamcinolone acetonide (a topical corticosteroid) and/or ophthalmic nedocromil sodium (a topical ocular cromone). In the second group of 241 patients, general practitioners had a free choice of treatment. The primary efficacy end points were quality of life measured using the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ) and the symptom-medication scores assessed daily with an electronic dairy system. Results: Adjusted mean total symptom scores over 21 days were 4.93 in the guidelines strategy group compared with 7.48 in the free-choice treatment group (P = 0.0001). Mean total scores in the RQLQ decreased by 2.19 in the guidelines group compared with a decrease of 1.79 in the free-choice treatment group (P = 0.0001). At 21 days, the least square mean difference in improvement in overall scores for RQLQ in the guidelines group compared with the free-choice treatment group was 0.53, which was greater than the minimal important difference. Conclusions: Patients with seasonal allergic rhinitis often present severe symptoms which are not well recognized or controlled by physicians using their own criteria of severity and treatment. Using a simple method for the evaluation of the severity and a simple therapeutic scheme based on International Guidelines, patients with seasonal allergic rhinitis presented a significant improvement by comparison with those receiving a non-standardized treatment.

An update on the diagnosis and treatment of sinusitis and nasal polyposis

Abstract: IntroductionTerminologySinusitis (more properly known as rhinosinusitis due tothe regular involvement of the nasal cavity) is a conditionwith a high and clearly increasing prevalence. According1to figures from IMS Health,acute sinusitis was diagnosed6.3 million times and chronic sinusitis 2.6 million times ina country like Germany over the course of one year (July2000–June 2001),resulting in 8.5 million and 3.4 millionprescriptions,respectively. The number of diagnoses of‘‘nasal polyposis’’ was approximately 221 000 (accordingto IMS Health 2001). Even though no reliable epidemi-ological studies of the incidence of sinusitis exist,thesefigures do indicate that sinusitis represents a considerablesocioeconomic problem. Alongside allergic and viralconditions of the upper airways,sinusitis thereforeconstitutes one of the most common respiratory tractconditions in humans.Similar data are reported from the USA: in 1997,sinusitis was prevalent in approximately 15% of thepopulation. In the last decade,the frequency of diagnosisin the USA rose by around 18%. The economicsignificance of sinusitis is huge: for 1992,the total cost,including costs resulting from loss of work,was estima-ted at over 6 billion dollars for the USA. In the periodfrom 1985 to 1992,the number of antibiotic prescrip-tions for sinusitis rose from 7.2 million to 13 million(1,2).Sinusitis is an inflammatory process involving themucous membranes of one or more sinuses. Generallyspeaking,the mucous lining of the nose is also involved.Even in the presence of a viral cold,a CT scan will revealthe involvement of the paranasal sinuses in 87% of cases,which is why we speak of rhinosinusitis (3). Bacterialrhinosinusitis (acute sinusitis) is generally preceded by avirus-induced inflammation of the sinuses; approximately5–10% of childhood upper airway infections develop intoacute sinusitis (4). The swelling and ‘‘immunologicalweakness’’ of the mucous membrane and the blockageof the ostia by the viral infection are today believed tocause bacterial infection of the intrinsically sterile para-nasal sinuses by local microorganisms. This gives rise toacute sinusitis,with severe inflammatory infiltration ofC.Bachert

A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae.

Abstract: Background: We cultured Dermatophagoides farinae (Df), one of the most common mites in house dust and the most important allergen among natural allergens. With this material, we attempted to produce an animal model of the atopic eczema/dermatitis syndrome (AEDS). Methods: We cultured Df mites in high density and prepared a crude extract of Df (DfE) together with the culture medium. We applied the extract to the back skin of NC/Nga and BALB/c mice three times per week for 8 weeks. Results: In the NC/Nga group, dryness or scaling appeared on the skin, and scratching behavior increased at the second week in the DfE-treated group. Skin erosion and hemorrhage occurred at the fourth week. The epidermis thickened and deepened into the upper dermis, in which mast cells were highly accumulated, corresponding with the skin lesion of AEDS patients. Specific IgE and IgG to DfE and total IgE were elevated in the sera. Mice treated with an extract of mite culture medium did not develop skin lesions. In the BALB/c group, mice developed specific IgE and IgG to DfE, however, no typical skin lesions appeared. Mast cells in the upper dermis did not increase. Conclusions: Repeated painting of Dermatophagoides extract produced IgE-associated AEDS-like lesions on the skin of NC mice.

Rhinasthma: a new specific QoL questionnaire for patients with rhinitis and asthma

Abstract: Introduction: To date we have available specific instruments assessing health-related quality of life (HRQL) in rhinoconjunctivitis or in asthma, but not instruments evaluating rhinitis and asthma together, although they often coexist. The aim of our study was to develop and validate a specific quality of life (QoL) questionnaire for adult patients with rhinoconjunctivitis, asthma or both. Materials and methods: A pool of 42 items covering the main symptoms and problems related to respiratory allergy, was generated based on literature review and clinical experience. The items were randomly listed and presented to 148 consecutive outpatients 46 suffering from asthma (age 32.9 ± 14.3 years), 53 suffering from rhinoconjunctivitis (age 32.6 ± 11.5 years) and 49 from asthma and rhinoconjunctivitis (age 35.6 ± 12.2 years). The patients were asked to indicate which item they had directly experienced and for each of them, its importance on a four-point scale (1 = not important; 4 = very important). Twelve items were cancelled from the list, because of low importance or redundance. In the instrument validation phase, 104 patients (42 with rhinoconjunctivitis alone and 62 with asthma and rhinoconjunctivitis) were evaluated with the generic instrument SF-36 and the new questionnaire (RHINASTHMA). Results: RHINASTHMA was able to differentiate patients with rhinitis from those with both rhinitis and asthma. In stable condition, RHINASTHMA showed good reliability. The factor analysis extracted three factors with a good reliability (0.93, 0.87, 0.76). Discussion: RHINASTHMA is the first tool aimed at evaluating HRQL impairment in patients with rhinitis and/or asthma. It provides a short and simple assessment, and has overall psychometric properties. This is of relevance because of the frequent asthma–rhinitis comorbidity.

Requirements for medications commonly used in the treatment of allergic rhinitis: European Academy of Allergy and Clinical Immunology (EAACI) Allergic Rhinitis and its Impact on Asthma (ARIA)

Abstract: It has been shown that several medications are effective in the treatment of allergic rhinitis (1–3). Among them, oral H1-antihistamines and intra-nasal corticosteroids are the most widely used. A large number of studies have been carried out with these drugs but they use various end points which make these studies difficult to be compared. Moreover, the pharmacological properties of these drugs are well known but recently, new data have focussed on the mechanisms of action of H1-antihistamines and their so-called antiallergic properties. Guidelines for the development of drugs used in allergic rhinitis are pending. It seemed therefore important before proposing recommendations for such guidelines to define the properties of oral H1-antihistamines, anti-allergic effects of H1-antihistamines and intra-nasal corticosteroids. There is therefore an urgent need to make internationally valid definitions. These will be of importance for physicians and scientists but also for drug companies developing new drugs and registration authorities.

Montelukast improves symptoms of seasonal allergic rhinitis over a 4‐week treatment period

Abstract: Background: Proinflammatory mediators such as the cysteinyl leukotrienes are important in the pathophysiology of allergic rhinitis. This study evaluated the efficacy and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, given once daily in the morning for treatment of seasonal (fall) allergic rhinitis for 4 weeks. Methods: This was a randomized, double-blind trial with a placebo run-in and a 4-week treatment period. Patients (n = 1079) with a history of allergic rhinitis and a positive skin test to seasonal pollen allergens were assigned to placebo, montelukast 10 mg, or loratadine 10 mg. Symptoms were assessed with a daily diary. Results: Montelukast was more effective than placebo in improving scores for the primary endpoint of daytime nasal symptoms (P = 0.003) and the secondary endpoints of night-time, composite, and daytime eye symptoms, patient's and physician's global evaluations of allergic rhinitis, and rhinoconjunctivitis quality-of-life (P ≤ 0.006). The positive control loratadine also improved scores for the primary endpoint (P ≤ 0.001) and the majority of the secondary endpoints (P < 0.03). When analyzed by week, the treatment effect of montelukast was more persistent than loratadine over all 4 weeks of treatment. Conclusion: Montelukast provided effective relief of seasonal allergic rhinitis symptoms when given once daily in the morning, showed significant and sustained improvement in symptoms of allergic rhinitis over 4 weeks of treatment, and was well-tolerated.

Human beta-defensins and toll-like receptors in the upper airway.

Abstract: Background: Measurement of innate markers in nasal mucosa, tonsils and adenoids might lead to new views about the role of innate immunity in the upper airway In this study, the expression of human β-defensins (HBD) 2 and 3 and toll-like receptors (TLR) 2 and 4 in various upper airway diseases was investigated Methods: Surgical samples from patients with tonsillar disease (n = 18), hypertrophic adenoids (n = 10) and sinonasal disease (n = 30) (chronic sinusitis, nasal polyps, turbinate mucosa as controls) were investigated by immunohistochemistry Quantification of HBD-2 and 3 mRNA, TLR-2 and 4 mRNA expression was performed by real-time polymerase chain reaction (PCR) Results: Immunohistochemistry revealed a strong expression of HBD-2 in tonsillar tissue Quantification of HBD-2 and HBD-3 mRNA showed a more than tenfold higher expression in tonsillar tissue than in adenoids, whereas in nasal biopsies, only negligible defensin expression could be measured No significant differences were found for TLR-4 between the various tissues, whereas TLR-2 expression in adenoids was significantly lower compared with other tissues Conclusion: These results demonstrate a strong defensin expression in tonsillar tissue compared with nasal and paranasal mucosa and adenoids Toll-like receptor expression in all these tissues illustrates a possibly important immunological sentinel function of upper airway mucosa

Microbial products in allergy prevention and therapy.

Abstract: Epidemiological and experimental studies have led to the hypothesis that stimulation of the immune system by certain microbial products may prevent or treat allergic diseases (1–5). There are also bacterial products on the market which have been proposed for treatment of allergic diseases but their clinical efficacy is not well documented, however. The European Academy of Allergology and Clinical Immunology (EAACI) appointed a Task Force to critically evaluate available information on the potential use of microbial products in allergy prevention and therapy and to discuss guidelines for future research. This first position paper is separately assessing the effects of bacterial extracts, probiotics, mycobacteria, oligodesoxynucleotides (ISS-ODN), and lipopolysaccharide derived molecules in allergic diseases. The section for each of the listed products is structured to present the alleged rationale that would justify their use against allergy and experimental data supporting it. Then, the outcome of representative clinical trials are summarized with regard to efficacy and safety (Table 1). Finally, conclusions are made regarding their potential role in allergic diseases and the eventual need for further research. As this is a very dynamically evolving field, the EAACITask Force will keep monitoring the new developments and will upgrade this position paper at regular intervals. Bacterial extracts

Prevalence of asthma with aspirin hypersensitivity in the adult population of Poland

Abstract: Background: Acetylsalicylic acid (ASA) and other nonsteroid anti-inflammatory drugs (NSAIDs) are reported to account for 21–25% of all adverse drug reactions. Some asthmatics may react to ASA and other NSAIDs with acute bronchoconstriction, profuse rhinorrhea and skin flushing. This is a distinct clinical syndrome called aspirin-induced asthma (AIA). The prevalence of AIA among asthmatic patients in Poland has not been previously assessed. Methods: A questionnaire survey of 12 970 adults of both sexes, randomly selected from the population of Poland. Results: The prevalence of AIA in the general population of Poland was estimated as 0.6%. Thirty patients (4.3%; 95% CI: 2.8–5.8) of 703 asthmatics (5.4% of general population) reported symptoms attesting to hypersensitivity to aspirin. In 27% of them the reactions were precipitated by aspirin, whereas in the remaining subjects by other NSAIDs. Conclusions: The prevalence of AIA in Poland is 4.3%, being somewhat lower than in Finland and Australia, where it was recently reported to account for 8.8 and 10.9% of the adult asthmatics, respectively. These figures indicate that aspirin hypersensitivity might be a significant community problem.

IVIG--mechanisms of action.

Abstract: Intravenous immunoglobulin (IVIG) preparations are fractionated from a plasma pool of several thousand donors. IVIG contain immune antibodies and physiologic autoantibodies. Immune antibodies reflect the immunologic experience of the donor population. This fraction of IVIG preparations is useful for replacement therapy and passive immunisation. Natural autoantibodies are able to react with the immune system of the recipient of IVIG and are suggested to help to correct immune deregulation. Immunomodulatory and anti-inflammatory properties are based on multiple mechanisms of action which are described. These mechanisms are effective concomitantly and synergistically at every occasion of use of IVIG in inflammatory and autoimmune disorders.

Use of CD63 expression as a marker of in vitro basophil activation and leukotriene determination in metamizol allergic patients.

Abstract: Background: We assessed the reliability of basophil activation test (FAST) and sulphidoleukotriene production (CAST) in the in vitro diagnosis of allergy to metamizol, evaluating its sensitivity and specificity. Methods: Twenty-six patients allergic to metamizol and 30 control individuals were studied. Skin tests with metamizol, FAST, and CAST were performed. Results: FAST sensitivity was 42.3% and specificity 100%. The PPV of FAST is 100% and the NPV 99.4%. The likelihood ratio for a positive value cannot be calculated because the specificity is 100% and the likelihood ratio for a negative value is 0.58. CAST sensitivity was 52%, and specificity 90%. The PPV of the test is 5% and the NPV 99.5%. The likelihood ratio for a positive result was 5.2 and that for a negative result 0.53. FAST detects a larger number of cases when patients are studied within the first 6 months after the clinical reaction (χ = 4.2, P = 0.04) than later. Together with skin tests, FAST allowed detection of 69.2% patients allergic to metamizol, the same as CAST 76%. The joint use of the three techniques allowed identification of 76.9% of cases. Conclusions: FAST and CAST are useful for the diagnosis of allergy to pyrazolones. Its usefulness clearly increases when recent reactions are studied.

Efficacy of the topical nasal steroid budesonide on improving sleep and daytime somnolence in patients with perennial allergic rhinitis.

Abstract: Background: Improving quality of life is considered to be a major endpoint and motivation for clinical intervention in patients with perennial allergic rhinitis (PAR). In addition to classical symptoms of congestion, pruritus, and rhinorrhea, patients will often complain of not being able to sleep well at night and of feeling fatigued during the day. Like sleep apnea, PAR has also been shown to cause sleep disturbance and consequently worsen daytime fatigue and somnolence. Hypothesis: It is proposed that by decreasing nasal obstruction due to allergic rhinitis by treating with the topical steroid budesonide, symptoms of daytime fatigue and somnolence can be improved. Methods: Twenty-two subjects were enrolled in a double-blind, placebo-controlled, crossover study using Baalam's design. Patients were treated with either budesonide 128 μg/day or placebo. Subjective data include the Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Rhino-conjunctivitis Quality of Life Questionnaire, and a daily diary recording nasal symptoms, sleep problems, and daytime fatigue. Results: The results illustrated that the topical nasal corticosteroid significantly improved daytime fatigue (P = 0.03), somnolence (P = 0.02), and quality of sleep (P = 0.05) compared to placebo in patients suffering from PAR. Summary: Budesonide is able to improve congestion, sleep, and daytime somnolence.

Clinical and immunological effects of low-dose IFN-α treatment in patients with corticosteroid-resistant asthma

Abstract: Background: Interferon (IFN)-α is a cytokine that possesses potent anti-viral and immunoregulatory activities. We aimed to assess clinical and immunological effects of low-dose IFN-α in patients with severe corticosteroid-resistant asthma with and without Churg–Strauss syndrome. There is currently no efficient pharmacological treatment available for this group of patients. Methods: We studied 10 patients with corticosteroid-resistant asthma, in which 3×106 IU/day IFN-α were administrated in addition to the prednisone dose given already before introduction of the cytokine therapy. The prednisone dose was gradually reduced dependent on the clinical situation and used as a clinical readout to evaluate the efficacy of the cytokine therapy. To distinguish between IFN-α- and prednisone-mediated immunological changes, the corticosteroid dose was kept constant for at least 2 weeks upon introduction of the cytokine therapy in seven patients. The effects of treatment on clinical and immunological parameters were measured at 2–4 weeks and 5–10 months depending on the availability of the patient. Results: Interferon-α treatment rapidly improved the clinical situation as assessed by lung function parameters and required prednisone dose. Important immunological changes included: decreased leukocyte numbers, increased relative numbers of CD4+ T cells, increased differentiation of T helper (Th)1 cells, and increased expression of interleukin (IL)-10 in peripheral blood mononuclear cells. Conclusion: Interferon-α treatment was associated with dramatic improvements in the condition of patients with corticosteroid-resistant asthma with and without Churg–Strauss syndrome. Potential mechanisms of action include the establishment of a correct Th1/Th2 balance and the induction of the anti-inflammatory IL-10 gene.

T cell activation, from atopy to asthma: more a paradox than a paradigm

Abstract: During the last 15 years, it was largely shown that allergic inflammation was orchestrated by activated Th2 lymphocytes, leading to IgE production and eosinophil activation. Indeed, Th2 activation was shown to be necessary to induce allergic sensitization in animal models. In humans, a Th2 skewing was shown in atopic children soon after birth. In asthma, descriptive studies showed that Th2 cells were more numerous in patients than in controls. In addition, during specific allergen stimulation, an increase of Th2 cells was described in most cases. According to this Th2 paradigm, it was proposed that early avoidance of microbial exposure could explain the increase of atopic diseases seen in the last 20 years in developed countries, as the "hygiene hypothesis". Recently, it was proposed that early exposure to lipopolysaccharide (LPS) could be protective against atopic diseases. However, it is well established that exposure to LPS can induce asthma symptoms, both in animals and humans, although it induces a Th1 inflammatory response. In addition, most infections induce asthma exacerbations and Th1 responses. Recently, some studies have showed that some Th1 cells were present in asthmatic patients, which could be related to bronchial hyperreactivity. There is therefore an "infectious paradox" in asthma, which contributes to show that the Th2 paradigm is insufficient to explain the whole inflammatory reaction of this disease. We propose that the Th2paradigm is relevant to atopy and inception of asthma albeit a Th1 activation would account at least in part for bronchial hyperreactivity and asthma symptoms.

Food allergy in adulthood.

Abstract: In the last decades, the results of studies involving controlled food challenges have provided a reliable scientific basis on the role of foods as a cause of hypersensitivity reactions. Most of these investigations have been focused on paediatric populations, highlighting the role of food allergy in the pathogenesis of atopic dermatitis, identifying foods that most commonly cause allergic reactions, and calling attention to the limited value of skin tests and in vitro assays in the diagnosis of clinical allergy (1). However, less evidence for specific features of adverse reactions to foods in adults has been available. Loveless (2) and Graham et al. (3) verified the association between the ingestion of food and development of symptoms in adults in the 1950s. Further, the remarkable studies conducted by Bernstein et al. (4) and Atkins et al. (5, 6) in the early and mid 1980s, definitely confirmed the role of foods as a cause of IgE-mediated allergic reactions in adults and evaluated the relationship between diagnostic procedures and reactivity to food on oral challenge. In 1987, Amlot et al. (7) coined the term, oral allergy syndrome (OAS) to describe the symptoms experienced by a subgroup of patients with positive skin tests to food, typically oral symptoms such as oral irritation and throat tightness, followed in a proportion of patients with systemic symptoms. The OAS was a new term to describe an old featured clinical condition, the association between local oropharyngeal signs and symptoms with the ingestion of foods such as hazelnuts, apples, pears, carrots, celery, and potatoes with allergy to pollen, particularly birch. At that time, Ortolani et al. (8) published a large case series of adult patients who had oral symptoms after ingestion of fresh fruits and vegetables under the title The oral allergy syndrome . From then on, this term has rapidly gained acceptance, although its exact meaning has not been kept out of some controversy (9, 10). For some years, however, most studies of food allergy in adults were anecdotal reports of anaphylactic reactions after ingestion of a specific food or based mainly on the clinical history supported by positive allergy skin testing and in vitro studies. In the last few years, a number of studies have evaluated adverse reactions to plant-derived foods in adults using DBPCFC models (11–17). Further, by identifying well-characterized clinically allergic patients, these studies have been the basis for detailed immunochemical analysis of allergenic components. The objective of the present review is to provide an overview of the complex nature of the relationship of foods and IgE-mediated allergic reactions in adults, focusing on distinctive features. Following the recommendations of the EAACI Nomenclature Task Force (18), the term food hypersensitivity (FH) will be used to designate an adverse reaction to food, food allergy (FA), when immunological mechanisms have been demonstrated, and IgE-mediated food allergy, if the role of IgE is highlighted.

Nasal involvement in allergic asthma

Abstract: Even since the late 19th century, a relationship has been suspected between upper airway disease and the subsequent development or aggravation of asthma symptoms. To date, it has been generally accepted that pathologic conditions of the upper airways, e.g. allergic rhinitis, chronic sinusitis and nasal polyposis, may influence the lower airways. However, the mechanisms underlying this relationship were, for a long time, poorly understood. Recently, evidence has been accumulating which indicates a systemic connection as one of the responsible mechanisms in nasobronchial crosstalk. In this review, the pathophysiologic and immunologic aspects of the interaction between upper and lower airways will be discussed.

Pet-keeping in early childhood and airway, nose and skin symptoms later in life.

Abstract: Background: It is discussed whether exposure to pets during childhood is a risk or a protective factor for sensitization and allergic symptoms. The aim of this study was to investigate the association between pet-keeping at time of birth and allergic symptoms in airways, nose and skin among young children in Sweden. Method: A questionnaire was sent to the parents of 14 077 children (1–6 years), the focus being on allergic symptoms, home environment and other background factors including pet-keeping and avoidance behaviour. The response rate was 79%. Results: Almost one-tenth of the population had got rid of pets because of allergy in the family, and 27.3% reported ‘avoidance’ behaviour towards pets. In a cross-sectional analysis current pet-keeping was ‘protective’, but this may be due to the fact that people avoid exposing their child to something that they believe is a risk factor for allergies. Pet-keeping at the time of birth was associated with ‘wheezing’, ‘asthma’ and ‘rhinitis on pet-exposure’ later in life for children from families with an ‘avoidance’ behaviour, and was not ‘protective’ for other children. There was also an indication of a dose–response relationship between the number of types of furred pets at time of birth and later symptoms in analyses adjusted for avoidance behaviour or current pet-keeping. Conclusion: The distribution of pet-keeping in the population is largely explained by avoidance behaviour, meaning that those who have pets mainly are those who can stand them, indicating a ‘healthy pet-keeping effect’.