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BACKGROUND Sensitization to house dust mite (HDM) is a leading cause of allergic rhinitis and asthma. Despite more than 30 HDM-derived allergens having been identified to date, specific therapeutic approaches do not yet take into account the local sensitization profiles of patients. This study aimed to identify patterns of HDM sensitization in HDM-allergic adults living in distinct geographic areas, to inform the development of targeted diagnostic and therapeutic tools. METHODS Serum samples from 685 HDM-allergic subjects from Canada, Europe, South Africa, and the USA were tested for levels of IgE specific for 17 micro-arrayed HDM allergens by ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) technology. RESULTS The results confirmed significant geographical variability in sensitization patterns and levels of IgE. In all areas, the major sensitizers were the group 1 and group 2 allergens and Der p 23. Der p 23 was a frequent sensitizer: 64% of the subjects had IgE specific for Der p 23, and 2.3% were monosensitized to it. In South Africa, Der p 23 was the dominant HDM allergen (86% prevalence) and Der p 7 achieved major allergen status (56%). IgE sensitization to HDM was influenced by asthmatic status, levels of allergen exposure, age, race-ethnicity and smoking status, but not by BMI. CONCLUSION Sensitization profiles to HDM allergens differ considerably among distinct geographic areas, with Der p 7 and Der p 23 being major sensitizers in South Africa. Such heterogeneity should be taken into account in the diagnosis and treatment of HDM-allergic patients.

Allergen immunotherapy (AIT) is a safe, effective treatment for allergic rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still contested-primarily due to heterogeneity in clinical trial designs, study populations, therapeutic formulations, and efficacy criteria. After discussing current concepts and unmet needs, an international panel of experts made several recommendations: (i) explore and validate definitions for (clinical) responders in AIT trials; (ii) use of well-documented, standardized provocation tests prior to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring neo-sensitizations and occurrence of new allergy in extended AIT trials, and exclusion of polyallergic participants; (iv) validation of allergen exposure chambers with regard to natural exposure; (v) in studies of seasonal allergies, focus on peak exposure but also consider organizing two parallel, geographically distinct but otherwise identical trials; (vi) discuss adaptive trial designs with the regulatory authorities; (vii) use e-health and m-health technologies to capture more information on individual exposure to allergens; (viii) initiate research on potential psychological, biochemical, immune, neural, and even genomic markers of the placebo response; (ix) identify trial designs and primary endpoints that will give children with allergies easier, faster access to AIT formulations; and (x) promote and apply standardized methods for reporting systemic and local adverse events. The latest technologies and trial designs may provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical trials. There is scope for physicians, patient organizations, companies, and regulators to improve clinical trials in AIT and, ultimately, to provide patients with better treatments.

Anaphylaxis is a systemic allergic reaction, potentially life-threatening that can be due to nonoccupational or, less commonly, to occupational triggers. Occupational anaphylaxis (OcAn) could be defined as anaphylaxis arising out of triggers and conditions attributable to a particular work environment. Hymenoptera stings and natural rubber latex are the commonest triggers of OcAn. Other triggers include food, medications, insect/mammal/snake bites, and chemicals. The underlying mechanisms of anaphylactic reactions due to occupational exposure are usually IgE-mediated and less frequently non-IgE-mediated allergy or nonallergic. Some aspects of work-related allergen exposure, such as route and frequency of exposure, type of allergens, and cofactors may explain the variability of symptoms in contrast to the nonoccupational setting. When assessing OcAn, both confirmation of the diagnosis of anaphylactic reaction and identification of the trigger are required. Prevention of further episodes is important and is based on removal from further exposure. Workers with a history of OcAn should immediately be provided with a written emergency management plan and an adrenaline auto-injector and educated to its use. Immunotherapy is recommended only for OcAn due to Hymenoptera stings.

BACKGROUND Early-life sensitization to indoor allergens predicts asthma development. The aim of this study was to compare allergen concentrations in day-care centers (DCC) with those in private homes. METHODS Settled airborne dust was collected 4 times a year from 20 German DCC (620 samples) and from the homes of children and day-care workers (602 samples) using electrostatic dust collectors (EDC). The samples were analyzed with fluorescence enzyme immunoassays recognizing domestic mite allergens (DM), Fel d 1, Can f 1, and Mus m 1. Pet allergen thresholds that discriminate samples from homes with cats or dogs from those without were calculated using receiver-operating characteristics. Influences on allergen levels were analyzed using multilevel models. RESULTS Allergen loads were on average higher in DCC than in homes. In DCC, 96% of the samples were positive for DM, 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m 1. In homes, 84% contained DM, 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The threshold level for homes with dogs was 75 ng/m² Can f 1 (96.8% sensitivity, 96% specificity), and the threshold level for homes with cats was 46 ng/m² Fel d 1 (92% sensitivity, 94.9% specificity). In DCC, Can f 1 and Fel d 1 loads were higher than these thresholds in 37% and 54% of the samples, respectively. Allergen levels were significantly influenced by the season and room type; however, carpets on floors had no influence. CONCLUSIONS Mite, mouse, cat, and dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat allergens in DCC often reached levels of households with pets.

Pollen is routinely monitored, but it is unknown whether pollen counts represent allergen exposure. We therefore simultaneously determined olive pollen and Ole e 1 in ambient air in Córdoba, Spain, and Évora, Portugal, using Hirst-type traps for pollen and high-volume cascade impactors for allergen. Pollen from different days released 12-fold different amounts of Ole e 1 per pollen (both locations P40% of Ole e 1 exposure in Évora was explained by high-potency pollen originating from the south of Spain. Thus, olive pollen can vary substantially in allergen release, even though they are morphologically identical.

The clinical development of allergen immunotherapy for allergic rhinoconjunctivitis because of pollen is complicated by seasonal, geographical and subject-related variability in allergen exposure. Using an allergen challenge chamber (ACC), a room that enables reproducible challenges with controlled levels of inhalant allergens for several hours, these factors can be controlled. The ACC has often been used to evaluate symptomatic medications but is underexploited in the field of allergen immunotherapy. When used in conjunction with a programme of natural-exposure trials, the ACC enables researchers to (i) facilitate the allergen immunotherapy dose-finding process, (ii) accelerate the transition from Phase I/II to Phase III trials, (iii) characterize the onset and maintenance of action, (iv) avoid the confounding effects of rescue medication, (v) better characterize the baseline or pretreatment characteristics of trial subjects, (vi) perform better-standardized physical and laboratory measurements during an acute challenge, (vii) simplify trial logistics and use smaller numbers of subjects than would be required in equivalent natural-exposure studies and (viii) support (but not replace) Phase III natural-exposure trials for the investigation into long-term and disease-modifying effects. ACC studies can further increase levels of evidence for allergen immunotherapy--the only current therapy potentially capable of modifying the underlying allergic disease.

Identification and characterization of risk and protective factors for allergy is important for developing strategies for prevention or treatment. The prevalence of allergy is clearly higher in affluent countries than in developing countries like, e.g. Africa. Especially in urban areas of developing countries, allergy is however on the increase. In Africa, we have the unique opportunity to investigate risk and protective factors and the influence of urbanization and westernization, i.e. almost to take a look at Europe, Australia or the USA as they were before their allergy epidemics. Moreover, migrants from developing to affluent countries experiencing an increased burden of allergy provide new insights into risk and protective factors. Allergen exposure, diet and infections are the major exogenous influences playing a role as risk and protective factors. Depending on the nature, timing, chronicity and level of exposure, each of them can promote or inhibit allergy. Perhaps with the exception of infections, availability of data from Africa on their role in the development of allergy is limited. Detailed epidemiological studies in rural and urban Africa combined with basic immunological research are needed to unravel mechanisms of increase in allergy and of protection. The maturation of the immune system at young age under influence of exogenous factors results in differences in T-cell-skewing (Th1/Th2/Treg) and humoral responses. It is essential to perform studies from a ‘non-Eurocentric’ angle (e.g. local allergens, locally validated questionnaires and diagnostic procedures). Such studies will provide the affluent countries with new leads to combat the allergy epidemic and more importantly help prevent it in Africa.

It is estimated that pollen allergies affect approximately 40% of allergic individuals. In general, tree pollen allergies are mainly elicited by allergenic trees belonging to the orders Fagales, Lamiales, Proteales, and Pinales. Over 25 years ago, the gene encoding the major birch pollen allergen Bet v 1 was the first such gene to be cloned and its product characterized. Since that time, 53 tree pollen allergens have been identified and acknowledged by the WHO/IUIS allergen nomenclature subcommittee. Molecule‐based profiling of allergic sensitization has helped to elucidate the immunological connections of allergen cross‐reactivity, whereas advances in biochemistry have revealed structural and functional aspects of allergenic proteins. In this review, we provide a comprehensive overview of the present knowledge of the molecular aspects of tree pollen allergens. We analyze the geographic distribution of allergenic trees, discuss factors pivotal for allergic sensitization, and describe the role of tree pollen panallergens. Novel allergenic tree species as well as tree pollen allergens are continually being identified, making research in this field highly competitive and instrumental for clinical applications.

Studies have demonstrated that families of children with food allergy have significant deficiencies in their knowledge of how to avoid allergen exposure and how to manage allergic reactions. This study aims to assess the impact of a multidisciplinary paediatric allergy clinic consultation on parental knowledge of food allergy and to determine the rate of subsequent allergic reactions.Sixty-two subjects (17 years) referred with food allergy were prospectively enrolled. Parental knowledge was assessed by questionnaire and EpiPen trainer. Families saw a paediatric allergist, clinical nurse specialist and dietician. Knowledge was reassessed after 3 months and rate of allergic reactions after 1 year.After one visit to the paediatric allergy clinic, there was a significant improvement in parental knowledge of allergen avoidance (26.9%, P0.001), managing allergic reactions (185.4%, P0.0001) and EpiPen usage (83.3%, P0.001). Additionally, there was a significant reduction in allergic reactions (P0.001). Children with egg, milk or multiple food allergies were more likely to suffer subsequent reactions.A single visit to a multidisciplinary allergy clinic considerably improves families' abilities to manage allergic reactions to foods with an accompanying reduction in allergic reactions. Young children with egg, milk or multiple food allergies were at greatest risk of further reactions.

The predominant sensitizing allergens in Swedish asthmatic children are furred pet animals. Poor ventilation and increased indoor humidity cause accumulation of pet allergens indoors. Indirect contacts with cats also increase pet allergen exposure. We investigated whether the concentration and the total amount of cat (Fel d I) and dog (Can f I) allergen in dust from various surfaces in a day-care center were influenced by extensive renovation, installation of a new ventilation system, ventilation of floors, and avoidance by families and personnel of direct and indirect contacts with pets. The cleaning routine in the day-care center was changed extensively after renovation. Old mattresses, pillowcases, curtains, sofas, and soft toys were removed, and new material were purchased. Dust was collected from various surfaces before and after renovation from table and chair surfaces, floors, curtains, mattresses, pillows, cushion-like toys, and sofas on five occasions during a 12-month period. Fel d I and Can f I allergen levels were determined by sandwich ELISA. The reduction in the total amount of both Fel d I and Can f I/sampling area was more pronounced than the reduction in the concentration of allergen/g of dust. After renovation, the mean cat and dog allergen concentration was decreased by six and 10 times, respectively. After 1 year, the total amount of cat allergen was lower in all areas (from 24 ng to < 1 ng/sampling area, P < 0.05). Already at the first sampling after renovation, the total amount of dog allergen had decreased more than 10 times. In a previous study, we found the median concentration of cat and dog allergen to be 10-30 times higher in ordinary day-care centers. Our present study demonstrates that children changing from a normal center to the renovated center would be exposed to much lower levels of cat and dog allergen. Combined measures such as installation of mechanical ventilation, ventilated floors, regular extensive cleaning, and, probably most important, avoidance of direct and indirect contacts with pets, should decrease cat and dog allergen exposure in day-care centers.

The amounts of dust, protein, and allergens in vacuumed floor covering samples taken from both schools and homes in Norway have been investigated. Classrooms contained significantly more crude dust per unit area than homes, while the mean protein content per unit area was somewhat higher in homes. The main allergen exposure problem in classrooms was that of pet allergens; the contents of dog allergens and the major cat (Felis domesticus) allergen Fel d I per unit area were significantly higher in school classrooms than in homes of families who do not keep pets. The mite and food allergens, on the contrary, were more prevalent in homes. Carpeted floors in schools and homes contained significantly more dust, proteins, and allergens than smooth floors (P < 0.05). Fel d I was detected in the vacuum cleaners' filter system in concentrations from < 1 ng to 1080 ng, confirming that this allergen can pass through the dust bag during vacuuming.

Forty-three patients allergic to mites and suffering mainly from asthma were recruited: 25 were mite-monosensitive and 18 were polysensitive, as determined by skin tests and specific serum IgE determinations with various allergens. In vitro spontaneous histamine release (SHR) by washed blood basophils was measured once or several times for each patient. Throughout this study, the mean periods of high and low mite-allergen exposure were defined on the basis of relative indoor humidity and temperature data. For the mite-monosensitive patients, there was a significant increase in mean SHR during the season of high mite-allergen exposure as compared to the months of lower mite-allergen presence (P < 0.002). No significant difference between mean SHR values was observed when comparing the monosensitive group during the season of high mite-allergen exposure with polysensitive patients (allergic to mite and pollen) during the period of exposure to both allergens. Differences in mean SHR reported here emphasize the positive relationship between intense allergen exposure and the in vitro SHR increase in blood basophils of mite-allergic patients.

Background: T helper (Th)-17 cells are a subset of T helper lymphocytes that exert regulatory activities. Recently, it has been reported that serum interleukin (IL)-17 levels are high in the most severe cases of birch allergy studied outside the pollen season. Objective: The aim of this study was to investigate a possible relationship between serum IL-17 levels and clinical parameters in patients with allergic rhinitis studied during the pollen season. Methods: In all, 56 patients with persistent pollen-induced allergic rhinitis were evaluated during the pollen season. Serum IL-17 levels were evaluated by enzyme-linked immunosorbent assay. Symptoms were assessed by visual analogue scale, drug use was monitored and peripheral eosinophils were counted. Results: Serum IL-17 levels were significantly related to clinical symptoms, drug use and peripheral eosinophil counts (P = 0.0001 for all). Conclusion: This study provides evidence that serum IL-17 level assessment might be considered to classify allergy severity.

Allergen exposure in sensitized individuals is one of the numerous factors which have been related to the worsening of asthma and rhinitis (1–3). If allergen exposure contributes to the severity of symptoms, then one would expect that reducing exposure should improve the symptom control. However, the evidence is equivocal as to whether measures to change the indoor environment are effective in the treatment of allergic airway diseases. In this document we focussed on studies of the effectiveness of environmental control measures aimed at reducing allergen exposure to house dust mites and domestic pets in the management of allergic rhinitis and asthma published between January 2000 and September 2004 (i.e. primary prevention by allergen avoidance and measures to reduce outdoor allergen exposure are not included in this review).

Background: Simple, inexpensive methods of sampling from allergen reservoirs are necessary for large-scale studies or low-cost householder-operated allergen measurement. Methods: We tested two commercial devices: the Indoor Biotechnologies Mitest Dust Collector and the Drager Bio-Check Allergen Control; two devices of our own design: the Electrostatic Cloth Sampler (ECS) and the Press Tape Sampler (PTS); and a Vacuum Sampler as used in many allergen studies (our Reference Method). Devices were used to collect dust mite allergen samples from 16 domestic carpets. Results were examined for correlations between the sampling methods. Results: With mite allergen concentration expressed as μg/g, the Mitest, the ECS and the PTS correlated with the Reference Method but not with each other. When mite allergen concentration was expressed as μg/m2 the Mitest and the ECS correlated with the Reference Method but the PTS did not. In the high allergen conditions of this study, the Drager Bio-Check did not relate to any methods. Conclusions: The Mitest Dust Collector, the ECS and the PTS show performance consistent with the Reference Method. Many techniques can be used to collect dust mite allergen samples. More investigation is needed to prove any method as superior for estimating allergen exposure.

We have investigated the levels of cat (Fel d I), dog (Can f I), and cockroach (Per a I) allergens in dust from bedrooms, living rooms, kitchens, and bathrooms from 123 homes of asthmatic children in three zones of Sweden with varying climates. Absolute indoor humidity (AIH), relative humidity (RH), rate of ventilation in air changes per hour (ach), and number of airborne particles were also measured. Fel d I, Can f I, and Per a I allergen contents were determined by mab ELISA, and the levels were related to various environmental factors. The major cat allergen. Fel d I, was detected in all homes, and the concentrations varied between 16 ng and 28000 ng/g fine dust. The dog allergen, Can f I, was detected in 85% of the homes, and the levels varied from 60 ng to 866000 ng/g dust. Cockroach allergen was detected in only one home (40 ng/g). Fel d I and Can f I allergens were equally distributed geographically. Dust from living rooms contained significantly higher (P < 0.05) concentrations of both Fel d I and Can f I allergens than dust from bedrooms, kitchens, and bathrooms. The levels tended to be higher in homes with poor ventilation (

The recently published paper in your jour-nal by Gotzsche and Johansen (1) hascaught our attention. We would like to addsome comments.In this newly updated meta-analysis onhouse dust mite control measures forasthma, 44 trials with a total of 3302subjects were included. When comparedwith the last meta-analysis published by thesame authors in 2004 (2), the newly addedstudies were seen to be based on reductionmethods concentrated only on mattressesand bed covers. It has been demonstratedby Frederick in 1997 (3) and more recentlyby Woodcook et al. (4) that house dustmite reduction measures performed only onthe beddings were not able to decrease themite-allergen exposure. Consequently, it isdifficult to state that mite-allergen reduc-tion is not clinically efficient and should notbe recommended as it has been showed thatthese methods are not able to decreasesignificantly the mite-allergen exposure.It is surprising, that the two multifacetedallergen-reduction studies (5, 6) have notbeen taken into consideration for thismeta-analysis as the conclusion of theprevious meta-analysis suggested thatglobal allergen reduction had to be per-formed (2). These two studies, which gath-ered 937 children for the first one (5) and274 for the second one (6), demonstratedthe efficacy of global allergen reduction onallergen exposure and on clinical outcomesin moderate to severe asthma. In the firststudy published by Morgan et al. in 2004(5), the reduction of allergen exposure wasobtained 1 and 2 years after the interven-tion for Dermatophagoides farinae (Der f 1)in the bed and on the bedroom floor andfor Dermatophagoides pteronyssinus (Der p1) and cockroach on the floor. A significantreduction of days with symptoms was alsoobtained when compared with the controlgroup and the reduction of dust mite (Derf 1) and cockroach allergen levels on thebedroom floor was significantly correlatedwith reduced complications of asthma. Inthe second multifaceted study published in2005 by Krieger et al. (6), it was alsodemonstrated that global reduction mea-sures were clinically more efficient thansingle reduction measures.Moreover, these two studies (5, 6)clearly demonstrated the role of indoortechnicians, performing home visits toachieve a global allergen reduction, andconfirmed the results of the French study(7). Brandt et al. (8) underlined also veryrecently the role of indoor techniciansand recommended that public healthprograms should consider the use oftrained field workers such as medicalindoor environment counselors to preventthe progression of allergic asthma andrhinitis.In conclusion, this last meta-analysis byGotzsche and Johansen on house dust mitecontrol measures for asthma clearly dem-onstrated that specific house dust mitecontrol measures for asthma only concen-trated on the bedding were not efficient onallergen exposure and clinical symptoms.So, we think that it is not yet useful toperform every 4 years a new meta-analysisbased on single mite-allergen reductionmeasures for asthma and suggest for thenext meta-analysis to include multi-facetedstudies.F. De Blay, C. Barnig, M. OttDivision of Asthma and Allergy –Department of Chest Diseases UniversityHospital Strasbourg, Strasbourg, France

To assess allergen-reducing effect of dust collection from mattresses, patients were asked to vacuum clean the entire surface of their mattresses for 5 min with their household cleaners at specified intervals ranging from 1-21 days. Ten patients performed four collections, nine patients only two. Amounts of dust, concentrations and amounts of major allergens from Dermatophagoides pteronyssinus (Dp42), Dermatophagoides microceras (Dm6), and Dermatophagoides farinae (Df6) were determined. The first sampling caused a statistically significant reduction in the absolute amounts of allergens in a following sample. The same tendency was seen in dust weight but not in concentrations of allergens. At intervals of 1 or 3 weeks no consistent changes could be registered. Differences were small and good reproducibility of the sampling and analysing procedure could be assumed. Since the self-administered procedure is much cheaper and easier to handle than sampling done by technicians with special equipment, it can be recommended for sequential analysis of allergen exposure.