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Work-related asthma (WRA) is a relevant problem in several countries, is cause of disability and socioeconomic consequences for both the patient and the society and is probably still underdiagnosed. A correct diagnosis is extremely important to reduce or limit the consequences of the disease. This consensus document was prepared by a EAACI Task Force consisting of an expert panel of allergologists, pneumologists and occupational physicians from different European countries. This document is not intended to address in detail the full diagnostic work-up of WRA, nor to be a formal evidence-based guideline. It is written to provide an operative protocol to allergologists and physicians dealing with asthma useful for identifying the subjects suspected of having WRA to address them to in-depth investigations in a specialized centre. No evidence-based system could be used because of the low grade of evidence of published studies in this area, and instead, 'key messages' or 'suggestions' are provided based on consensus of the expert panel members., (© 2012 John Wiley & Sons A/S.)

Background: Cow's milk is one of the most common causes of food allergy. In two-thirds of patients, adverse symptoms following milk ingestion are caused by IgE-mediated allergic reactions, whereas for one-third, the mechanisms are unknown. Aim of this study was to investigate whether patients suffering from non-IgE-mediated cow's milk protein intolerance can be distinguished from persons without cow's milk protein intolerance based on serological measurement of IgG and IgA specific for purified cow's milk antigens., Methods: We determined IgG(1-4) subclass and IgA antibody levels to purified recombinant αS1-casein, αS2-casein, β-casein, κ-casein, α-lactalbumin, and β-lactoglobulin in four patient groups by ELISA: Patients with IgE-mediated cow's milk allergy (CMA, n=25), patients with non-IgE-mediated cow's milk protein intolerance (CMPI, n=19), patients with gastrointestinal symptoms not associated with cow's milk ingestion (GI, n=15) and control persons without gastrointestinal problems (C, n=26). Cow's milk-specific IgE levels were determined by ImmunoCAP., Results: Only CMA patients had IgE antibodies to cow's milk. Cow's milk allergic patients mounted the highest IgG(1) and IgG(4) antibody levels to αS1-casein, αS2-casein, β-casein, κ-casein, and α-lactalbumin. No elevated levels of IgG(4) , IgA, and complement-binding IgG subclasses (IgG(1) , IgG(2) , IgG(3) ) to purified cow's milk allergens were found within the CMPI patients compared to persons without cow's milk protein intolerance (GI and C groups)., Conclusion: Cow's milk protein intolerant patients cannot be distinguished from persons without cow's milk protein intolerance on the basis of IgG subclass or IgA reactivity to cow's milk allergens., (© 2011 John Wiley & Sons A/S.)

Background: In Europe, sensitization to ash pollen induces pollinosis with cross-reactivities with other pollen sources. The aim of the study was to identify the repertoire of ash pollen allergens and evaluate the extent of the diversity of the IgE response in ash allergic patients., Methods: The IgE reactivities of 114 ash pollen- and eight grass pollen-sensitized patients were screened by 1D immunoblot (SDS-PAGE) against ash pollen extract. The IgE reactivities of 13 ash pollen- and two grass pollen-sensitized patients were then evaluated in 2D immunoblots. Some IgE- and non-IgE-reactive proteins were identified by mass spectrometry., Results: In 1D analysis, 86% of sera showed binding to Fra e 1 (18-20 kDa), 23% to Fra e 2 (14 kDa), 3% to Fra e 3 (10 kDa) and 57% to High Molecular Weight allergens (HMW, >30 kDa). Individual analysis of 2D immunoblots showed several IgE-binding protein areas among which three were more often recognized: (i) Fra e 1 comprising, at least, 15 isoforms, (ii) a series of acidic spots (45 kDa), and (iii) Fra e 2, the ash profilin. HMW allergens could be resolved in four areas; two unidentified, one homologous to beta-galactosidase and the other to sugar transport proteins. A malate deshydrogenase and calmodulin were shown to be IgE-binding proteins and 10 non-IgE reactive proteins were identified., Conclusions: No direct correlation was evidenced between IgE profile and the degree of sensitization even though 2 spectrotypes could be distinguished. Our data contribute to a better delineation of ash pollen allergens and patterns of sensitization.

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.

Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.

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 micro g/g) and in carpets (15.8-6.3 micro g/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.

A double-blind, placebo-controlled study was carried out in 85 patients with a well-documented history of perennial asthma caused by house-dust mites. Patients received either placebo or sublingual immunotherapy (SLIT) with a standardized Dermatophagoides pteronyssinus (DP)-D. farinae (DF) 50/50 extract. After a run-in period, patients received increasing doses up to 300 IR every day for 4 weeks and then three times a week for the following 24 months. The cumulative dose was about 104000 IR, equivalent to 4.2 mg Der p 1 and 7.3 mg Der f 1. Symptom and medication scores and respiratory function were assessed throughout the trial. Serum specific IgE and IgG4 were determined before SLIT (t0) and after 6 (t1), 11 (t2), 17 (t3), and 25 months (t4) of SLIT. Mite exposure was evaluated at t0, t2, and t4 by semiquantitative guanine determinations. Patients aged 15 years and older were asked to assess their quality of life (QoL) by completing the SF20 (Short Form Health Status Survey) plus two items at t0, t2, and t4. Use of inhaled corticosteroids and beta2-agonists was significantly decreased after 25 months of treatment in both groups (P<0.03). SLIT patients showed significant improvements in respiratory function at t4 (% predicted FEV1 (P = 0.01), VC (P = 0.002), morning (P = 0.01) and evening (P = 0.03) PEFR), and reduction in daytime asthma score (P = 0.02). In the SLIT group, the post-treatment PD20 was 1.75 times higher than the baseline value. There was no change in PD20 in the placebo group. Compared to the placebo group, the SLIT group showed a significant increase in specific IgE DP(P = 0.05), IgE DF(P = 0.02), IgG4 DP(P = 0.001), and IgG4 DF (P = 0.001) levels after SLIT. QoL scores were similar in both groups at t0 and t2. At t4, all scores were better in the SLIT group than in the placebo group, with the differences being most marked for the general perception of health (P = 0.01) and physical pain (P = 0.02). Adverse events were similar in the two groups. This study shows that SLIT in house-dust-mite-related asthma has a good safety profile and improves respiratory function, bronchial hyperreactivity, and QoL.

Background: It has been shown that a vacuum cleaner (VC) can increase airborne cat allergen levels. This study aimed to compare the degree of leakage of airborne Fel d 1 levels among five different VCs, both under laboratory conditions and in an apartment with cats., Methods: Three of the VCs were marketed as antiallergic: a HEPA filter VC (VC A), a water impingement and HEPA filter VC (VC B), and a foam fabric filter VC (VC C). The other two were standard VCs: VC D and VC E. VCs were tested in a 20 m3, airtight, experimental room and in a 53 m3 living room in an apartment with three cats. Air was sampled with a glass-fiber filter and an impinger at 20 l/min for 30 min before, during, and after vacuuming. Airborne Fel d 1 was measured with a two-site monoclonal ELISA assay., Results: In the experimental room, no airborne Fel d 1 level was measured before using the VCs. After introducing a dust sample containing Fel d 1 in the VCs, we found that VCs A, B, and E did not provoke any increase in airborne Fel d 1. In contrast, VCs C and D significantly increased airborne Fel d 1 levels (GM: 4.9 and 5.3 ng/m3, respectively). In the apartment, all VCs induced an increase in airborne Fel d 1, which was carried by particles greater than 5 microm. However, VCs C and D provoked significantly greater increases in airborne Fel d 1 than VCs A, B, and E (P=0.0001)., Conclusions: Our results suggest that: 1) The two VCs with leakage in the experimental room had greater leakages in the apartment. 2) In the apartment with cats, all VCs provoked increases in airborne Fel d 1, primarily carried by large particles. 3) Given the increased marketing of "antiallergic" VCs, further studies are needed to standardize methods for testing airborne allergen leakage by VCs.

Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH2O.l-1.s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine (P < 0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine (P < 0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.

We report an anaphylactic reaction which occurred very shortly after ingestion of a fresh fig. The IgE-dependent mechanism was demonstrated on the basis of positivity of the prick test performed with fresh fig (Ficus carica) extract. In addition, we were able to detect specific IgE to the same extract in the serum. The patient did not demonstrate sensitization to other common allergens involved in respiratory and food allergies. However, detection of specific IgE to F. benjamina indicated a sensitization to weeping fig. The CAP F. benjamina was partially inhibited by preincubation of the serum with fig extract, suggesting that these two species of Ficus share some common allergens. In this context, the assumption can be made that weeping fig was responsible for the initial sensitization in this patient.

We studied the sensitivity and specificity of guanine environmental tests in the evaluation of the two mite allergen levels, i.e. 2 micrograms/g and 10 micrograms/g of Der p I and Der f I, considered to be risk factors for sensitization or for the development of acute asthma. We examined 239 house-dust samples for Der p I and Der f I levels (ELISA) and guanine contents (semiquantitative guanine test and quantitative assays). All house-dust samples with class 2 or 3 guanine tests contained more than 2 micrograms/g of Der p I and Der f I. The probability that house-dust samples of class 2 contained more than 10 micrograms/g of mite allergens was 88%; it was 100% for house-dust samples of class 3. The probability that a house-dust sample of class 0 contained less than 2 micrograms/g of mite allergen was 87%. For each level of mite allergen, a ROC curve was constructed with the true positive rates and the false positive rates calculated by different cutoffs of guanine concentration. The cutoff point which gave the best compromise between sensitivity (76%) and specificity (89%) was 2100 micrograms/g for the threshold of 2 micrograms/g of Der p I and Der f I. For detection of a mite allergen > 10 micrograms, a guanine content of 3000 micrograms/g gave the best compromise between sensitivity (86%) and specificity (93%). In conclusion, the guanine test represents a satisfactory environmental test, inexpensive and simple, for predicting mite allergen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

The present work reports the results of a double-blind clinical trial, comparing the effects of hyposensitization treatment versus placebo in 33 patients with allergic rhinitis, sensitive to a crude extract of the pollen of four different grasses (Dactylis glomerata, Lolium perenne, Secale cereale, and Phleum pratense). The distribution of these patients in the two groups was done randomly and gave two comparable groups, as far as clinical and biological features are concerned. The treatment course included five low doses of the aqueous extract followed by 12 injections of Al(OH)3-adsorbed aliquots of the same extract. Evaluation of the clinical scores was based on diary cards on which symptoms and medications were recorded. A reevaluation of the significance of the symptom and medication scores is presented and the link between both scores is studied. Particular attention is given to the methodological and statistical problems raised during this study. The non-parametric tests reveal a significant difference (P less or equal to than 0.03) in the total clinical score between the treated and the placebo groups for the second half of the observation period, when the pathology was most intense.

The month of birth distribution for 1301 French patients born between 1953 and 1975 with at least one positive skin test was compared to that of the whole population. A chi-square test was performed, and the expected birth month distribution of the groups calculated from the INSEE* data for 1953-1975. All patients underwent skin testing with house dust, Dermatophagoides pternyssinus (Dpt), cat and dog allergens, grass, tree and weed pollens, and moulds. The only study criterion was a positive skin test unrelated to any specific disorder. A significant difference in month of birth distribution was observed 1) for patients with positive skin test to grass pollen, with a high rate of births from January to May, and 2) for patients with mould sensitization, with a low rate of births in April, May and December. Tree and weed pollens, house dust and Dpt showed no significant relation with month of birth. For cat and dog allergens, the observed and expected distributions of birth month were similar. For the whole sensitized population the birth rate tended to be low in December except for the cat and dog sensitized. Our study confirms the well-known seasonal peak of births in the first 5 months of the year for grass pollen sensitized patients. No consistent monthly or seasonal tendency could be statistically demonstrated for other allergens except moulds.

The present study was undertaken to verify that mites are not the only allergens in house dust extracts and that other allergens such as cat epithelia can also be responsible for house dust hypersensitivities detected both by house dust skin tests and house dust RAST studies. In order to determine whether mite or epithelia fixed on a solid phase could remove not only the IgE antibodies reactive with the homologous allergens, but also the IgE antibodies reactive with house dust allergens, the authors have absorbed 10 sera of house dust allergic patients with solid phase mite or epithelia. The absorption procedure removed a large part of the IgE antibodies reactive with specific immunosorbent (Dermatophagoides pteronyssinus or cat epithelia) and in the same way the IgE antibodies reactive with house dust immunosorbent. The percentage of RAST inhibition varied from 65% to 92% for Dermatophagoides pteronyssinus and from 65% to 94% for house dust in patients allergic to house dust and mite; the percentage of RAST inhibition varied from 67% to 92% for cat epithelia and from 73% to 90% for house dust in patients allergic to house dust and cat epithelia. This is in accordance with the hypothesis that house dust is not an allergen per se, but rather a complex mosaic of several allergens including mite, animal epithelia, etc.