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Background: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. Objectives: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. Methods: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. Results: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of ­78% and ­57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 ( P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. Conclusions: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma (ClinicalTrials.gov Identifier: NCT00842270). [ABSTRACT FROM AUTHOR]

Abstract: In spite of numerous publications on occupational lung diseases, latex allergy, and the relationship of nose-to-bronchi, the particularities of the clinical, epidemiological and therapeutic aspects of latex allergic rhinitis (LAR) are very little considered in the literature. Based on our own experience and on a review of the literature, we will examine the environmental context of LAR and try to define its most important diagnostic and therapeutic criteria. An early diagnosis of LAR and reduction of exposure to latex allergens before its evolution to asthma, can limit the socioeconomic impact of this condition. [Copyright &y& Elsevier]

Abstract: Primary and tertiary prevention of childhood allergies and asthma has progressed. It appears ever more certain that avoidance, whether primary or tertiary, should be global to be effective in the prevention of asthma. That is why it seems useful that medical home environment councilors (CMEI) who have the necessary time should audit the quality of the indoor air and give advice on the widest possible avoidance measures (including other household pollutants that may aggravate allergic asthma). With an environmental disease such as asthma, control of the environment is a therapeutic approach that should be offered to children with allergic asthma. [Copyright &y& Elsevier]

Abstract: This review presents recent data on new therapeutic agents for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Type 4-phosphodiesterase inhibitors, in particular roflumilast, seem to have an effect on the immediate and delayed bronchial response and on FEV1 in asthmatics. Ciclesonide is a novel inhaled corticosteroid that appears interesting because of its long lasting effect and its better local and systemic safety profile. Tiotropium bromide is a new long-acting inhaled anti-cholinergic bronchodilator approved for once-daily, long-term treatment in COPD; it is of has a particular interest because of its effect on FEV1. Generally, these three new therapeutic agents are meant to be used in the treatment of asthma and COPD in combination with other drugs. [Copyright &y& Elsevier]

Background Stem cell factor (SCF) is a major mast cell growth factor promoting differentiation, chemotaxis as well as inhibition of apoptosis of mast cells. Regulation of SCF expression by glucocorticoids has not yet been reported in human asthmatic bronchi. Objective To evaluate SCF mRNA and protein expression in biopsy specimen and bronchoalveolar lavage fluid, respectively, and to determine the mast cell numbers in biopsy sections from control and asthmatic subjects treated or not with glucocorticoids. Methods Volunteers were recruited out of pollen season. Asthmatic patients were allergic to common allergen extracts including grass and tree pollen, cat, dog or mite; three volunteers had non-allergic asthma. Mast cell numbers were counted after anti-human tryptase immunolabelling. SCF mRNA was quantified by real-time fluorescent PCR (LightCycler™) after reverse transcription, and SCF protein was measured by ELISA. Results Asthmatic patients not treated with glucocorticoids showed a 5.8-, 1.8- and 3.1-fold significant increase in SCF mRNA, protein levels and mast cell numbers, respectively, compared with healthy volunteers of the control group (7.8 and 1.3 pg/μg SCF mRNA/GAPDH; 99.8±11.5 and 56.0±11.0 pg/mL SCF protein; 103±21 and 33±8 mast cells/mm2, respectively; P<0.05). In asthmatic patients treated with glucocorticoids, a significant decrease of SCF mRNA, protein levels and mast cell numbers was observed as compared with untreated asthmatic patients (1.1 pg/μg mRNA; 62.0±10.3 pg/mL SCF protein and 39±13 mast cells/mm2; P<0.05), reaching levels comparable to those of the control group. Conclusion Our study shows that SCF is expressed in the bronchus in humans in vivo. This expression is increased in asthma, and is parallel to the increased mast cell numbers in the airways. Both increases were normalized in glucocorticoid-treated patients, strongly suggesting an involvement of SCF in the mast cell-associated asthmatic disease. [ABSTRACT FROM AUTHOR]

Abstract: In the thirty years after the first studies on avoidance of aeroallergens, important progress has been made. If avoidance strategies are more and more evident, the point in time for them to be applied remains controversial. Indeed, the efficacy of primary prevention remains to be demonstrated and it cannot be recommended in light of results of recent studies. Concerning secondary prevention, its interest has been demonstrated in one very large study in allergic asthmatic infants for whom the concept of global avoidance has been confirmed. Thanks to methods for measuring allergens such as airborne dust, it is now possible to give lists of products for which efficacy has been demonstrated both in vitro as well as under natural conditions. Moreover, determination of the level of exposure to aeroallergens allows us to recommend avoidance only for those places that are infected. For this reason, home visits by an Interior Environment Medical Advisor who has the time to measure, counsel and control compliance appears necessary, and it is likely that their field of action will be extended in the future to include non-allergenic pollutants that are responsible for other respiratory diseases. Nevertheless, it must be remembered that for an environmental disease such as respiratory allergy, control of the environment is the first therapeutic measure to recommend for allergic children. [Copyright &y& Elsevier]

Background: Levels of endotoxins greatly differ according to environmental settings. Objective To study the effect of lipopolysaccharide (LPS) at increasing doses (0.1-1000 ng) on allergen sensitization and challenge in the mouse. Methods: Mice were sensitized systemically and challenged locally with ovalbumin (OVA) in the presence or absence of LPS. Inflammation was assessed by determining total and differential cell counts and T-helper type 2 (Th)2 cytokine (IL-4 and IL-5) levels in bronchoalveolar lavage fluid (BALF). Total and OVA-specific IgE levels were quantified in serum. Airway hyper-responsiveness (AHR) was assessed by whole-body barometric plethysmography. Results: Administered prior to sensitization, LPS at 100 or 1000 ng dose-dependently decreased allergen- induced total and OVA-specific IgE, airway eosinophilia and Th2 cytokines in BALF, without changing AHR. Administered during OVA challenge, LPS at 1 ng (an infra-clinical dose) or 100 ng (a dose triggering neutrophilia) enhanced airway eosinophilia, without affecting IgE levels or AHR. Conclusion: Our data clearly demonstrate that exposure to LPS influences allergen-induced IgE production and airway eosinophilia in a time and dose-dependent manner, preventing IgE production and development of eosinophilia when administered during allergen sensitization at high doses, and inducing exacerbation of eosinophilia when administered upon allergen challenge at low doses, including infra-clinical doses. [ABSTRACT FROM AUTHOR]

Background: In order to improve patient compliance in allergen avoidance, a new occupational activity was created: Medical Indoor Environment Counselor (MIEC). The aim of this study was to assess the impact of an MIEC on compliance with advice for mite allergen reduction in patients sensitized and exposed to mite allergens, and on mite allergen levels. Methods: The study included 378 patients from four centers (Marseilles, Montpellier, Paris, Strasbourg) in a randomized prospective study. Patients in group A received advice from doctors only, and those in group B from doctors and MIEC. Mite allergen levels were measured on mattresses, mattress bases, and floors. Compliance and mite allergen levels were assessed 5 months later. Results: Compliance for changing the mattress bases, removing or treating the carpets, washing duvets, pillows and stuffed animals were significantly higher in group B than in group A. A significant decrease in mite allergen was obtained for group B in mattress bases (83.8–22.9 µg/g) and in carpets (15.8–6.3 µg/g), but not in group A. Conclusion: Our results suggest that the home visit by the MIEC 1) increased the compliance to mite reduction methods advised; 2) induced a significant difference in mite reduction levels on mattress bases and on carpets; 3) avoided nonestablished avoidance advice. [ABSTRACT FROM AUTHOR]

Data on the protective effect of early exposure to cat and dog allergens on the onset and subsequent development of atopic sensitisation and asthma are scant and frequently contradictory. Indeed, the studies that appear to demonstrate a protective effect are mostly retrospective and those that are prospective usually contradict them. If early exposure to large quantities of Fel d 1 or Can f 1 have a protective effect on the development of sensitisation to cat or dog allergens, it is not known how long such protection will last. Concerning the potential protective effect of IgG4, while an elevation of IgG anti-Fel d 1 can be found in individuals exposed to large amounts of cat allergen, a causal relationship between these immunoglobulins and the absence of asthma has not yet been demonstrated. Therefore, before giving one’s approval for the acquisition of a cat or a dog to a pregnant atopic woman, she should be informed that, even if a protective effect does exist, no one knows for how long such an effect will last.  Knowing that these animals can live for more than 10 years, the mother’s child could also become sensitised to cat or dog allergens. Then, since it appears to have been demonstrated in epidemiological studies and in daily clinical practice that individuals sensitised and exposed to an allergen increase their chances of developing allergic asthma, it seems reasonable to advise the pregnant atopic patient against acquiring a cat or a dog. [Copyright &y& Elsevier]

The role of architecture in the reduction of allergen exposure has not been extensively studied. For mites, several publications described the role of ventilation in mite allergen exposure and demonstrated that tight houses had high levels of mite allergen. For molds, the results seem to be similar but the data are less convincing. For cats, decreasing air change per hour and covering floors with carpets induced an increase in airborne cat allergen Fel d 1. We performed a study with 120 architects in the Bas-Rhin and demonstrated that 80% of them wanted to collaborate with medical doctors. In the future, allergists will have to answer more frequently to patients and to building professionals on the relation between allergy and housing and methods of improvement of indoor air quality. [Copyright &y& Elsevier]

BackgroundRepeated inhalation of allergen at low-dose induces an increase in bronchial hyper-responsiveness, without any associated symptom. The concomitant events in the bronchus have not been described. ObjectiveWe have studied the dynamic number of mast cells in the airways of patients with mild asthma before and after repeated inhalation of allergen at low-dose and the expression of nerve growth factor (NGF), which is reported to promote growth and survival of mast cells. MethodsTwelve patients with mild asthma to cat allergen were enrolled at random in a blind placebo-controlled study, and submitted to repeated low-dose allergen exposure (1/5 of the provocative dose). Mast cells were immunolocalized using an antibody against mast cell tryptase. NGF and its high affinity receptor, TrkA, were immunolocalized using anti-NGF and anti-TrkA antibodies, respectively. NGF mRNA was quantified by competitive polymerase chain reaction (PCR) after reverse transcription of total RNA extracted from bronchial biopsy. NGF protein levels were measured by ELISA in bronchoalveolar lavage (BAL) fluid. ResultsBronchial mast cell number was increased significantly after allergen exposure as compared with before. NGF expression in the bronchus was immunolocalized mainly to epithelial cells, but also to fibroblasts, blood vessels, and a few infiltrated cells. NGF mRNA levels in bronchial biopsies were increased significantly after allergen exposure. The high affinity receptor for NGF, TrkA, was immunolocalized to the infiltrated mast cell membrane. ConclusionOur study shows that the increase in the number of mast cells and in the expression of NGF induced by allergen exposure in the bronchus of asthmatic patients is occurring before the onset of symptoms. In addition, our finding of the presence of the TrkA receptor on the membrane of the infiltrated mast cell in situ brings evidence of the mast cell as a target cell for the growth factor activity of NGF in the airways in asthma. [ABSTRACT FROM AUTHOR]

Provocation and challenge tests have been used to understand the pathobiology of asthma, to facilitate diagnosis and to assess therapeutic efficacy and dosage. Current challenge tests expose the patient to 'natural conditions', for example, in an allergen chamber. For determining drug efficacy in asthma, allergen challenge has a moderate positive predictive value and an excellent negative predictive value. The best challenge tests are standardized, and the best bronchial challenge tests use a large allergen particle size. Allergen provocation tests are safe when performed by experienced investigators. [ABSTRACT FROM AUTHOR]

Abstract: Assessment of the indoor allergen load encountered by patients with respiratory allergy symptoms is essential in order to obtain objective evidence of the allergens present in the indoor environment. It is equally essential to justify application of efforts to eliminate the responsible allergen sources (mites, domestic animals, molds, etc.). The methods used to measure indoor allergens can be grouped into (1) quantitative immunoassays (ELISA using monoclonal antibodies specific for purified native allergens or recombinant allergens) and (2) home-based tests. The latter include the Acarex test (semiquantitative assay for guanine in mite feces) and semiquantitative immunoassays. Quantitative tests are used mainly for epidemiologic studies whereas the results of home-based tests are considered in the management of allergic patients. [Copyright &y& Elsevier]

Abstract: Exposure of atopic children and adults to molds appears to be a risk factor for asthma. However, the fact that many studies have not been able to confirm this association points to the extreme difficulty of correctly assessing exposure to molds and, a fortiori, their allergens. In effect, the impossibility of demonstrating in the home environment the presence of mold allergens without germination of spores justifies the necessity of developing methods that will allow these allergens to be appraised in that environment. Furthermore, if atopic individuals are at greater risk for asthma, then the onset of cough and wheezing in atopic children and adults when exposed to molds might not only be the consequence of an allergic reaction but it could also be related to an inflammatory phenomenon due to the inhalation of mycotoxins and volatile organic substances liberated by the molds. [Copyright &y& Elsevier]

Abstract: The development of methods to measure pollutants and the creation of a new set of professionals have provided better means of controlling diseases associated with the indoor environment. These profesionnals come to patients'' homes, at the request of a physician, to measure exposure to suspected pollutants and to recommend measures to be taken by the patient to avoid exposure. A large multicentric study which involved 378 patients in France demonstrated the value of these advisors in terms of reduction of allergen exposure and better control of the environment by the patient. Another study, carried out in the USA and reported in 2004, demonstrated the clinical benefit of such home visits. The proposed training programs (diplôme inter-universitaire; licence professionnelle) should lead to the development of this profession. [Copyright &y& Elsevier]

Background: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. Methods: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. Results: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73–0.74). Pru p 3 tended to be a risk factor in South Europe only. Conclusions: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article by P. C. Gotzsche and H. K. Johansen on the house dust mite control measures for asthma in the previous issue.

A letter to the editor is presented in response to the article "House dust mite control measures for asthma: systematic review" by P. C. Gotzsche and H. K. Johansen, which appeared in volume 63 of the journal.

Bovine serum albumin (BSA) is often present in the dilution fluid added to semen for artificial insemination. A case of serum sickness due to BSA after a first in vitro fertilization has been reported, in addition to an IgE-mediated reaction to BSA in a case of anaphylaxis due to infusion of autologous bone marrow. A 36-year-old nonatopic female developed generalized urticaria and angioedema 30 minutes after her 1st course of artificial insemination. The fluid inseminated contained her husbands semen diluted in a solution of antibiotics and BSA.

To cite this article: Quirce S, Lemière C, de Blay F, del Pozo V, Gerth Van Wijk R, Maestrelli P, Pauli G, Pignatti P, Raulf-Heimsoth M, Sastre J, Storaas T, Moscato G. Noninvasive methods for assessment of airway inflammation in occupational settings. Allergy 2010; 65: 445–458. The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of ‘united airway disease’ in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued. [ABSTRACT FROM AUTHOR]

Abstract: Allergen extracts used in diagnosis by clinicians are manufactured from crude source materials. These extracts contain a number of allergenic proteins and their composition can vary. The employment of molecular biological methods in the field of allergy has led to the production of recombinant allergens from a variety of sources. Their use has allowed us to improve our understanding of allergenic proteins, to define families of allergens, to explain allergenic cross-reactions, and to show that pollen sensitivity profiles vary as a function of the geographic region in which individuals live. As a result, in the 21st century reasoning on the molecular scale should be included in patient management. In 2005, the clinician has at his disposal the level of specific IgE with 27 recombinant allergens from 7 different allergenic sources. The use of these materials can, in certain cases, allow us to have a more precise diagnosis and to orient the therapeutic decision more accurately. Three observations made in our consultation service are described to illustrate the contribution of these new diagnostic methods. [Copyright &y& Elsevier]

Le syndrome œuf-oiseau est l''induction d''une allergie alimentaire à l''œuf par sensibilisation respiratoire aux protéines aviaires. Ce syndrome, décrit pour la première fois en 1985, a fait l''objet de nombreuses publications. Le cas clinique rapporté a pour originalité : l''absence de traduction clinique respiratoire de la sensibilisation aux protéines aviaires, la gravité des manifestations cliniques révélant l''allergie à l''œuf, la tolérance partielle à l''œuf cuit. Dans le cas décrit, des tests de provocation orale au blanc puis au jaune d''œuf cuit ont été réalisés en se référant aux données de la littérature qui font état d''une thermolabilité partielle de l''alpha livétine, protéine allergénique croisante impliquée dans le syndrome œuf-oiseau. [Copyright 2004 Elsevier]

Abstract: The role of allergens as a trigger for bronchial symptoms has always appeared to be deeply linked to their ability to get into the respiratory tract. Interest in large diameter particles has focussed essentially on their capacity to reach the lower airways. The recent demonstration of the effect of aerosols of allergen-loaded pollen particles of a respirable size supports this hypothesis. Nevertheless, the exact site of allergen deposition leading to asthma symptoms is still not known. Studies carried out with allergen bronchial challenge tests using particles of different sizes have lead to a better understanding of the associated pathophysiological phenomena. Thus, the role of large-diameter particles could be more important than previously thought. Indeed, the results obtained provide support for the importance of these particles and their proximal deposition in the immediate bronchial response. [Copyright &y& Elsevier]

Abstract: Multiple chemical sensitivity (MCS) is a widely discussed entity that appears to be increasing. A number of pathophysiological mechanisms, including immunological, toxicological and neurological ones, and, in addition, psychological and sociological factors, have been proposed. The most plausible data, although still debated, concern the neurotoxic hypothesis. Clinically, objective criteria for diagnosis are lacking and the diagnosis of MCS is made on the basis of the patient''s history. In 1999, a consensus established six major criteria defining this condition. No laboratory investigations have been validated for the diagnosis. Despite the uncertainties of certain experts on the origin and even on the existence of MCS, nevertheless, most of them accept the reality of the distress of the affected individuals. [Copyright &y& Elsevier]

We report two cases of cutaneous mastocytosis associated with anaphylactic reactions after hymenoptera stings. An IgE-mediated mechanism was confirmed in one case by cutaneous tests and radioimmunoassay (CAP RAST). Specific immunotherapy was successful in one case but was interrupted in the second case because of generalized secondary reactions. These rare cases are concordant with those reported in the literature, and confirm the severity of symptoms and the heterogeneity of the results of allergological investigations. [Copyright &y& Elsevier]

Farmers constitute a large professional group worldwide. In developed countries farms tend to become larger, with a concentration of farm operations. Animal farming has been associated with negative respiratory effects such as work-related asthma and rhinitis. However, being born and raised or working on a farm reduces the risk of atopic asthma and rhinitis later in life. A risk of chronic bronchitis and bronchial obstruction/COPD has been reported in confinement buildings and livestock farmers. This position paper reviews the literature linking exposure information to intensive animal farming and the risk of work-related respiratory diseases and focuses on prevention. Animal farming is associated with exposure to organic dust containing allergens and microbial matter including alive microorganisms and viruses, endotoxins and other factors like irritant gases such as ammonia and disinfectants. These exposures have been identified as specific agents/risk factors of asthma, rhinitis, chronic bronchitis, COPD and reduced FEV1. Published studies on dust and endotoxin exposure in livestock farmers do not show a downward trend in exposure over the last 30 years, suggesting that the workforce in these industries is still overexposed and at risk of developing respiratory disease. In cases of occupational asthma and rhinitis, avoidance of further exposure to causal agents is recommended, but it may not be obtainable in agriculture, mainly due to socio-economic considerations. Hence, there is an urgent need for focus on farming exposure in order to protect farmers and others at work in these and related industries from developing respiratory diseases and allergy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Component‐resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. Aim: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. Methods: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double‐blind placebo‐controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD‐ and extract‐based). Odds ratios (ORs) and areas under receiver‐operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. Results: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70‐073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. Conclusion: A model combining CRD with clinical background and extract‐based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions. [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]

Background: Sensitization to hazelnut allergens vary depending on the geographic origin and age of the patients. The objective of this study was to further investigate the allergenic activity of hazelnut allergens using sera from patients recruited in various European regions and presenting different sensitization patterns to hazelnut proteins. Methods: Natural Cor a 11 and Cor a 9 were purified from hazelnut whereas Cor a 1 and Cor a 8 were produced as recombinant proteins (rCor a 1.04 and rCor a 8). Sera from hazelnut allergic patients were collected in France (n = 5), Switzerland (n = 2), Greece (n = 11) and Spain (n = 3), within the Europrevall project. Total and allergen-specific IgE were quantified by enzyme allergosorbent test and IgE immunoblot were performed using pooled sera from birch-pollen endemic region or from Greece. Histamine Release (HR) assays were performed with stripped basophils passively sensitized with individual sera and challenged by a hazelnut extract or the different hazelnut allergens. Results: As previously described, hazelnut allergic patients from Mediterranean countries are mainly sensitized to the nsLTP Cor a 8 whereas patients from France and Switzerland are sensitized to pollen-related allergens. Interestingly, an intermediate profile was evidenced in patients from Madrid. Hazelnut 7S globulin (Cor a 11) and 11S globulin (Cor a 9) were found to be minor allergens, recognized only by patients from Mediterranean countries. The biologic activity of the 4 tested allergens, analysed by HR assay, further confirmed the sensitization patterns, but also demonstrated the very high elicitation potency of Cor a 8. Conclusions: This work, extending previously published researches, represents a step towards the better understanding of the complexity of hazelnut allergy and provides new data on the biological activity of hazelnut allergens and extracts. [ABSTRACT FROM AUTHOR]

Background: Relationships between indoor air quality (IAQ) found in schools and the allergic and respiratory health of schoolchildren have been insufficiently explored. A survey was conducted in a large sample of classrooms of primary schools in France to provide objective assessments of IAQ to which young schoolchildren are exposed in classrooms, and to relate exposure to major air pollutants found in classrooms to asthma and allergies of schoolchildren.Methods: Concentrations of fine particles with aerodynamic diameter ≤2.5 μm (PM(2.5)), nitrogen dioxide (NO(2)) and three aldehydes were objectively assessed in 401 randomly chosen classrooms in 108 primary schools attended by 6590 children (mean age 10.4 years, SD ±0.7) in the French 6 Cities Study. The survey incorporated a medical visit including skin prick testing (SPT) for common allergens, a test for screening exercise-induced asthma (EIA) and a standardised health questionnaire completed by parents.Results: Children were differently exposed to poor air quality in classrooms, with almost 30% being highly exposed according to available standards. After adjusting for confounders, past year rhinoconjunctivitis was significantly associated with high levels of formaldehyde in classrooms (OR 1.19; 95% CI 1.04 to 1.36). Additionally, an increased prevalence of past year asthma was found in the classrooms with high levels of PM(2.5) (OR 1.21; 95% CI 1.05 to 1.39), acrolein (OR 1.22; 95% CI 1.09 to 1.38) and NO(2) (OR 1.16; 95% CI 0.95 to 1.41) compared with others. The relationship was observed mostly for allergic asthma as defined using SPT. A significant positive correlation was found between EIA and the levels of PM(2.5) and acrolein in the same week.Conclusions: In this random sample, air quality in classrooms was poor, varied significantly among schools and cities, and was related to an increased prevalence of clinical manifestations of asthma and rhinitis in schoolchildren. Children with a background of allergies seemed at increased risk. [ABSTRACT FROM AUTHOR]

Abstract: This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient. [Copyright &y& Elsevier]

To cite this article: Randriamanantany ZA, Annesi-Maesano I, Moreau D, Raherison C, Charpin D, Kopferschmitt C, Lavaud F, Taytard A, De Blay F, Caillaud D. Alternaria sensitization and allergic rhinitis with or without asthma in the French Six Cities study. Allergy 2010; 65: 368–375. Background: Allergic sensitization to Alternaria has been related to asthma in various studies, but its association with allergic rhinitis is still controversial. Objectives: The aim of this study was to assess at the population level the relationships in childhood between Alternaria sensitization and ‘past-year rhinoconjunctivitis’ (PYRC), ‘ever hay fever’ (EHF) and ‘ever allergic rhinitis caused by allergens other than pollens’ (EAR) according to the presence or the absence of asthma. Methods: This study is part of the Six Cities Study, the French contribution to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II. Children underwent skin prick test (SPT) to Alternaria and parents filled a standardized medical questionnaire. Results: Some 6726 children with a mean age of 10 years were examined. The overall prevalence of Alternaria sensitization was 2.8%, 0.8% for monosensitization. Prevalences of symptoms in sensitized children were 27.7% for PYRC, 27.0% for EHF and 30.4% for EAR. Adjusted Odds Ratios (OR) between Alternaria sensitization and allergic rhinitis phenotypes were 2.34 (95% confidence interval: 1.51–3.63) for PYRC, 2.40 (1.65–3.50) for EHF and 2.95 (2.05–4.23) for EAR. The relationship still remained in the case of monosensitization to Alternaria for both PYRC and EAR when excluding the asthmatic children [OR = 3.87 (1.54–9.78) and 2.88 (1.10–7.55) respectively]. Conclusion: In our population-based sample of children, we found a link between Alternaria sensitization and allergic rhinitis, independently of asthma, which is compatible with the mechanisms of deposition of Alternaria in the upper airways. [ABSTRACT FROM AUTHOR]

Background: Animal-derived proteins are implicated in primary food allergies, but also in inhalant allergies with secondary food allergy symptoms. The objective of this study was to define the allergen(s) implicated in a case of food allergy to chicken meat, which developed in a person previously sensitized to pork after occupational exposure. Methods: A 42-year-old female with a history of occupational inhalant allergy to pork reported rhinitis, asthma, dysphonia and conjunctivitis 30 min after ingestion of chicken. Skin tests were positive to chicken meat. Protein extracts were prepared from chicken meat. Allergens were characterized by IgE immunoblotting, N-terminal sequencing and ELISA. Results: The patient showed specific IgE binding to chicken meat proteins at 12, 14, 26, 55 and 65 kDa. N-terminal amino acid sequencing identified the 12- and 14-kDa proteins as the α- and β-chain of hemoglobin. ELISA and immunoblot showed specific IgE binding to hemoglobin purified from chicken blood. IgE antibodies to chicken serum albumin were detected by ELISA. Inhibition studies with chicken and porcine hemoglobin as well as with serum albumins demonstrated cross-reactive IgE antibodies. Conclusions: We report a case of confirmed occupational inhalant allergy due to pork followed by food allergy to pork and 3 years later by food allergy to chicken. Porcine and chicken hemoglobin were found to be cross-reactive allergens. Cross-reactivity between porcine and chicken serum albumin was possibly linked to a prior sensitization to cat serum albumin. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aldehydes concentrations were measured in 162 homes in the Strasbourg area (East of France) in the context of a case/control study pairing asthmatic and non-asthmatic people. The surveyed people have completed a questionnaire aiming to characterize the indoor homes and the people life practices. Gaseous aldehyde levels were quantified by a conventional DNHP-derivatization method followed by HPLC/UV. Formaldehyde, acetaldehyde and hexanal were the main encountered aldehydes with mean concentrations of 32.2±14.6, 14.3±9.7 and 8.6±8.1μgm−3, respectively, while propionaldehyde and benzaldehyde concentrations were usually <3μgm−3. The aldehydes concentrations simultaneously measured in both bedroom and living room were not significantly different except for formaldehyde and were correlated between them meaning that indoor air was quite homogenous in homes. Combination of information collected in our questionnaires and statistical analysis was used to investigate indoor aldehydes determinants. Even if formaldehyde sources are theoretically well identified, they are multiple so that it was difficult to determine the main parameters influencing its concentrations in domestic environment. Higher hexanal concentrations were related to new coatings such as painting, wallpapers and laminate floorings. Hexanal concentration decreased with both coating and furniture ages so that this compound may be considered as a tracer of these emissions. [Copyright &y& Elsevier]

Abstract: Purpose of the study: From the data of the microbiology environment laboratory, we wanted to describe the fungic flora isolated from the residence of people presenting clinical symptoms which could be associated to the presence of moulds. Material and methods: From the data of the laboratory we propose a retrospective and descriptive study of the residence fungic contamination. Several techniques were used to highlight the moulds of the environment: cleaning surfaces, gelose print, direct taking away with an adhesive tape, house dust collecting. We listed the moulds most frequently met and studied the output of the technique to characterize the mycoflore dwellings: direct observation (adhesive tape) or culture techniques. Results: Three hundred and thirty-eight samples carried out in 61 houses between 1996 and 2006 were studied. A total of 38 fungic species were identified, that means an average ratio of 9.2 different kinds per dwelling. The most often identified species were Cladosporium sp. (present in 88% of the studied residences), Aspergillus sp. (82%) and Penicillium sp. (78%). We show that the techniques used are complementary and the association of several collecting sites of dust, ground or surface increases the number of different fungic species isolated in each house. Conclusion: A lot of dust collect samples associated with several techniques on several sites have to be used to characterize the whole mycoflore of a residence. [Copyright &y& Elsevier]

Abstract: The French society of allergology (SFAIC) is editing recommendations concerning the practice of allergic challenge tests. The different challenges are listed (food, drugs, respiratory allergens, rush immunotherapy), together with their indications and procedures. It is recommended that the above allergic challenge tests should be performed in hospital settings with a trained staff with sufficient knowledge in allergology to confirm diagnosis, follow the tests and be able to promptly and adequately treat severe reactions; this unit should be close enough to an ICU for adults and children. [Copyright &y& Elsevier]

Abstract: The indentification of allergic fungal sinusitis (AFS) is still controversial and much more recent than that of allergic bronchopulmonary aspergillosis (ABPA). These two fungal respiratory diseases can be isolated or associated in a sinobronchial allergic mycosis. A retrospective study of a series of 15 cases of AFS fulfilling all the diagnostic criteria reported in the literature (eight isolated AFS and seven AFS associated with ABPA) and the review of the literature highlight the similarities between AFS and ABPA independently of the signs linked to the organs involved (sinuses, bronchi): pathophysiological mechanisms, immunoallergological, biological and mycological features, diagnostic procedure, treatment and follow-up. Therefore, AFS appears to be a sinonasal ABPA-like syndrome. [Copyright &y& Elsevier]

Abstract: Formaldehyde is a chemical pollutant that is ubiquitous in indoor environments. Exposure to high concentrations in occupational environments has revealed its irritant and allergenic character. However, low levels of exposure in households can likewise have an effect on respiratory health in a non-specific manner, as is equally the case with other pollutants. Augmentation of the response to allergen by formaldehyde has been demonstrated in animals and in children. An effect has also been observed on respiratory symptoms, with the risk of asthma being increased by 39% with domestic exposure to more than 60μgm−3. We have recently been able to show in a study involving mite-sensitized asthmatics that bronchial provocation tests with an allergen are augmented after exposure to 100μgm−3 of formaldehyde for 30min. All data show that exposure in households to a low concentration of formaldehyde is sufficient to induce sensitization but it can also aggravate symptoms of patients with allergic asthma. Considering the published evidence, it is agreed that the concentrations of formaldehyde in products used in households should be known in order to allow improvement in the quality of indoor air. [Copyright &y& Elsevier]

Background: Formaldehyde, an indoor air pollutant, is known to be an irritant and an etiologic factor in occupational asthma. An epidemiologic study suggests that it may also increase the risk of childhood asthma for concentrations above 60 μg/m3. Aim: To evaluate the influence of pre-exposure to low-dose formaldehyde (100 μg/m3 in 30 min according to the World Health Organization's recommended maximum value for indoor environments) on bronchial response to Dermatophagoides pteronyssinus. Method: Nineteen asthmatic subjects were included. Each subject underwent a mite allergen bronchial challenge test immediately after a standardized exposure in a chamber to formaldehyde or air (random order). Induced sputum were collected 24 h before and after mite challenge. Results: After formaldehyde inhalation, patients developed an immediate bronchial response at a significantly lower dose of mite allergen than after air exposure (the geometric mean PD20 for Der p 1 was 34.3 ng after formaldehyde and 45.4 ng after placebo, P = 0.05). The late-phase reaction, expressed as the maximum fall in forced expiratory volume in 1 s (FEV1) from baseline, was significantly higher after formaldehyde (15% vs 11%, P = 0.046). Conclusion: Our study demonstrated that exposure to low levels of formaldehyde significantly enhanced bronchial responsiveness to mite allergen in mite-sensitized subjects with asthma. [ABSTRACT FROM AUTHOR]

Background Endotoxin was proposed to increase the severity of asthma. Endotoxin levels greatly differ according to settings. In domestic environments, airborne concentrations may be dramatically low compared with levels reported in occupational settings. Objective Our first objective was therefore to assess the effect of inhalation of low-level lipopolysaccharide (LPS) on the immediate and late-phase asthmatic bronchial response. Our second objective was to evaluate the effect of exposure to LPS on the local and systemic inflammatory response. Methods Nineteen asthmatics sensitized to cat underwent on two separate occasions a bronchial challenge test to cat allergen (cat BCT) preceded randomly by a pre-exposure to either saline or LPS (2 μg). Methacholine challenge test was performed 24 h before exposure to LPS or saline. The Borg scale for dyspnoea and lung function were recorded before and after exposure to LPS or saline, and before and after cat BCT. Induced sputum and blood samples were collected before and after cat BCT, and analysed for cell counts and eosinophil cationic protein (ECP) levels. Results Inhalation of 2 μg LPS did not induce any changes in forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), FEF 25–75 and Borg scale of dyspnoea. It neither modified Fel d 1 PD20 (45.03 ng as compared with 87.03; P=0.42). As well, there was no significant difference in late-phase reaction. Pre-exposure to LPS did not influence eosinophil counts or ECP levels in blood and sputum. Conclusion Our study demonstrated that pre-exposure to LPS at low levels, which may be encountered in domestic environment, had no significant effect on the immediate and late-phase bronchial response to cat allergen. It neither modified local and systemic eosinophilic inflammation. [ABSTRACT FROM AUTHOR]

Abstract: We report the case of a 39 years old female industrial pork butcher who developed urticaria, rhinitis and asthma in contact with pig gut and pig-gut soaking water (LR). In addition, she developed an asthma attack after ingestion of pork meat. She was atopic, allergic to cats and dogs, and lived with a cat. Skin prick tests were positive with commercial dog and cat dander extracts, pig albumin, cat and pig gamma globulin, and LR. She was found to have high serum levels of IgE specific for cat, pig and beef albumin, for beef, sheep and pork meat, and for pig gut and LR. A bronchial challenge test with LR induced an immediate bronchial response, with a 23% drop in FEV1. SDS-PAGE electrophoresis with pork meat and LR revealed albumin (mw 67 kDa) in these samples. Immunoblots and immunoblot-inhibition assays with the patient''s serum revealed evidence of IgE specific for pig albumin and gamma globulin; an allergen band with mw 26 kDa, not previously reported, was also seen. Cross-reactions between pig and cat albumin and between pig and cat gamma globulin was demonstrated by RAST inhibition. This patient represents a case of cutaneous and respiratory occupational allergy caused by pig albumin and gamma globulin, in this case acting as aeroallergens. For this patient, who has what we might call the pig-cat syndrome, we recommended that she avoid occupational exposure to pork, avoid eating pork products, and also avoid exposure to cats. [Copyright &y& Elsevier]

Abstract: We evaluated the value of recombinant Bet v 1 (rBet v 1)-specific IgE as a new diagnostic tool in the evaluation of spring pollinosis. Methods. – Based on the results of rBet v 1-specific IgE assays, 117 patients with a variety of symptoms who had been referred to our clinic were included. The diagnosis of birch pollinosis was based on a positive clinical history with positive skin test to birch pollen extract. One hundred and five patients were asked if they had had oral allergy symptoms. Associated asthma was considered an aggravating factor. Assays for rBet v 2-specific IgE and birch pollen-specific IgE (t3) were then done in 82 and 28 of these patients, respectively. Results. – In the studied population, the sensitivity, specificity, PPV and NPV of the rBet v 1 specific-IgE assay were excellent (91%, 82%, 92% and 93%, respectively). In patients with positive t3-specific IgEs, the sensitivity and the specificity of the rBet v 1 specific-IgE assay were higher than those of the t3-specific IgE assay. Assays for rBet v 2-specific IgE carried out concomitantly were positive in 19.5% of the cases, with a median level of 2.46 KU/l. Oral allergy syndromes were more frequently found in patients with levels of rBet v 1 specific IgEs superior to 50 KU/l. On the other hand, the level of rBet v 1-specific IgE was not predictive of pollinosis-associated asthma. Conclusion. – Measurement of rBet v 1-specific IgE allows one to define the sensitization profiles of pollen-sensitive patients and may be useful as a guide for specific immunotherapy. [Copyright &y& Elsevier]

Since the first bronchial provocation tests (BPT) done by Pepys in 1975 for the diagnosis of occupational asthma, BPTs with allergen have continued to undergo standardization. It is nevertheless important that these tests remain realistic. We will examine a certain number of important points that must be taken into account in order to obtain a realistic BPT: the quality of the allergen extracts and also any recombinant allergens used; the method used in the allergen challenge; the size of the allergen-bearing particles; and the concomitant exposure to other environmental pollutants to which the patient is exposed naturally. [Copyright &y& Elsevier]

We report the case of a 37 years-old nonatopic woman who experienced several anaphylactic reactions after ingesting low doses of the methylmorphine derivatives codeine and codethyline. The IgE mediated mechanism was confirmed by the detection of morphine-specific IgE antibody, determined by radioimmunoassay (RAST). Cross reactivity with codeine was shown by inhibition of the morphine RAST. The gravity of the clinical state not permitting an oral provocation test, we were able to confirm an IgE-mediated mechanism by demonstrating that the anti-morphine IgE did not recognize the quarternary ammonium group. [Copyright &y& Elsevier]

Few teams have studied the effects of particle size on the bronchial response to inhaled allergen. Nonetheless, the aerodynamic characteristics of the particles carrying allergens may explain some of the differences observed between bronchial responses to different allergens, between responses during bronchial provocation tests (BPT) and to responses under realistic conditions. We have shown that the dose of allergen inducing symptoms in BPT is 20 times smaller when cat allergen is carried by particles measuring 10.3 μm in aerodynamic diameter than when carried by particles measuring only 1.4 μm. Accordingly, the immediate bronchial response to cat allergen appears to be localized in the proximal airways and should be studied in BPT with particles of 10 μm diameter. [Copyright &y& Elsevier]

Allergy to penicillin is reported to occur in up to 8% of the patients who receive this class of drugs. 80 to 85% of the patients with a positive clinical history to penicillin will nevertheless tolerate penicillin with no adverse effect. Of the remaining 15 to 20%, only a few will develop a severe adverse reaction, and these patients can be identified by skin tests with derivatives of penicillin used at optimal concentrations according to a protocol that is effective and safe. Skin tests to penicillin are positive in 25% of patients with a history of an immediate reaction to penicillin; they are more frequently positive in those who have had a severe reaction. In addition to being able to identify patients who are at risk for a severe reaction when they take penicillin, skin tests can also provide immunological evidence of the origin of delayed clinical reactions such as maculopapular rashes. Such rashes, a frequent and benign manifestation of penicillin allergy, are usually caused by the widely used aminopenicillins. Intradermal skin tests (IDR) and late phase (patch) tests can demonstrate allergy to betalactamines in 5 to 45% of patients with negative skin tests to major and minor determinants of penicillin. When skin tests are positive, provocation tests are not recommended. On the other hand, when the skin tests are negative, an oral provocation test should be done, but such tests can result in an immediate clinical reaction, which may be severe in 3 to 10% of cases. [Copyright &y& Elsevier]