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Exposure to biocontaminants, such as dust mites, animal dander, bacteria, and mold, is associated with a range of health effects. This study identified household characteristics associated with indoor biocontaminant loadings in four Canadian cities. Floor dust was collected in 290 Canadian homes in Edmonton, Halifax, Montreal, and Windsor. The dust samples were analyzed for house dust mite allergens (Der f 1 and Der p 1), cat allergen (Fel d 1), cockroach allergen (Bla g 1), beta‐(1,3)‐D‐glucan, and endotoxin. Household information was obtained through questionnaires and home inspections. We performed univariate and multivariate analyses to identify household determinants of biocontaminant loadings and mold odor presence. We observed large regional variations for all biocontaminants, except for cockroach allergen. The ranges of the contaminants measured in loadings and concentrations were similar to that of previous Canadian studies. Household characteristics including presence of carpeting, low floor cleaning frequency, older home age, presence of pets, and indoor relative humidity above 45% were positively associated with the presence of multiple indoor biocontaminants. High floor cleaning frequency and use of dehumidifiers were negatively associated with the presence of multiple indoor biocontaminants. Mold odor was positively associated with older home age, past water damage, and visible mold growth. [ABSTRACT FROM AUTHOR]

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) technology offers the unique potential for unequivocally deleting allergen genes at the source. Compared to prior gene editing approaches, CRISPR boasts substantial improvements in editing efficiency, throughput, and precision. CRISPR has demonstrated success in several clinical applications such as sickle cell disease and β-thalassemia, and preliminary knockout studies of allergenic proteins using CRISPR editing show promise. Given the advantages of CRISPR, as well as specific DNA targets in the allergen genes, CRISPR gene editing is a viable approach for tackling allergy, which may lead to significant disease improvement. This review will highlight recent applications of CRISPR editing of allergens, particularly cat allergen Fel d 1, and will discuss the advantages and limitations of this approach compared to existing treatment options.

Summary: Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals".

Purpose of Review: The goal of this review is to compress all important information and results of the research in reducing cat allergen exposure using air filtration. Fel d 1 is the major allergen responsible for IgE responses in 90 to 95% of patients with cat allergy. Recent Findings: Reduction of cat allergen in indoor air with different air filtration systems and portable devices has been demonstrated in the majority of the studies. Recently, early and late asthmatic responses were significantly reduced using portable HEPA air cleaners in an environmental exposure chamber. Summary: This review provides a comprehensive overview of the current state of airborne Fel d 1 air filtration targeting the most efficient devices in cat allergen reduction. Novel emerging HEPA filters are targeting reduction of cat indoor asthma trigger so patient can might benefit from efficient solution. [ABSTRACT FROM AUTHOR]

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa. [ABSTRACT FROM AUTHOR]

Background: Environmental control to reduce the amount of allergens in a living place is thought to be important to avoid sensitization to airborne allergens. However, efficacy of environmental control on inactivation of airborne allergens is not fully investigated. We have previously reported that positively- and negatively-charged plasma cluster ions (PC-ions) reduce the IgE-binding capacity of crude allergens from Japanese cedar pollen as important seasonal airborne allergens. Cat (Felis domesticus) and fungus (Aspergillus fumigatus) are also important sources of common airborne allergens in living spaces throughout the year, and early sensitization with those allergens is considered to be a risk factor for future development of allergic rhinitis, pollinosis and asthma. The aim of this study is to examine whether the PC-ions reduce the IgE-binding capacity of a cat major allergen (Fel d 1) and fungal allergens in an experimental condition. Methods: Fel d 1, crude fungal extract, or a fungal major allergen Asp f 1, was treated with PC-ions for 6 h in an experimental cylindrical apparatus. Sham-treated allergens were prepared in the same experimental apparatus without generation of PC-ions. The degradation of the PC-ions-treated Fel d 1 was analyzed by SDS-PAGE, and the IgE-binding capacity of the PC-ions-treated allergens was analyzed by ELISA inhibition assay. Discussion: Our data suggest that treatment with PC-ions not only reduce indoor cat and fungal allergens, but also impair their allergenicity. Conclusion: These results suggest that environmental control with PC-ions is useful for inactivation of indoor cat and fungal allergens. [ABSTRACT FROM AUTHOR]

Information on the antigenic repertoire, especially the IgE-binding epitopes of an allergen is important for understanding the allergen induced immune response and cross-reactivity, as well as for generating the hypoallergenic variants for specific component resolved immunotherapy/diagnosis (CRIT and CRD). Data on the IgE-binding epitopes of cat allergens are scarce. In this study, a novel IgE-binding epitope of the cat major allergen, Fel d 1, was identified. Mouse monoclonal antibody (MAb) specific to the Fel d 1 was produced. Computerized intermolecular docking was used for determining the residues of the Fel d 1 bound by the specific MAb. The presumptive surface exposed residues of the Fel d 1 intrigued by the MAb are located on the chain 1. They are: L34 and T37 (helix 1); T39 (between helices 1 and 2); P40, E42 and E45 (helix 2); R61, K64, N65 and D68 (helix 3); and E73 and K76 (helix 4). The MAb competed efficiently with the cat allergic patients' serum IgE for Fel d 1 binding in the competitive IgE binding assay, indicating allergenicity of the MAb epitope. The newly identified allergenic epitope of the Fel d 1 is useful in a design of the CRIT and CRD for cat allergy. [ABSTRACT FROM AUTHOR]

Background: Recently, a series of assays has been conducted in which sublingual immunotherapy (SLIT) maintenance extracts of European manufacturers were compared with U.S. concentrated extracts by using U.S. Food and Drug Administration recommended in vitro testing. These test results have been published. We herein performed further data analysis to facilitate interpretation of SLIT dosing by U.S. physicians. Objective: To express the allergen quantity of maintenance SLIT as recommended by European manufacturers relative to U.S. subcutaneous immunotherapy (SCIT) maintenance dosing. Methods: We analyzed the maintenance SLIT solutions of Dermatophagoides pteronyssinus, timothy grass pollen, cat, and ragweed pollen from four European manufacturers and concentrated extracts from three U.S. manufacturers and from the U.S. Food and Drug Administration. Here, we expressed the potency of these European SLIT solutions in U.S. terms and from there calculated the monthly maintenance dose relative to the recommended monthly SCIT doses per allergen. Results: Over the whole range of allergen extracts analyzed here, one of the manufacturers consistently dosed low ('EUR1,' monthly SLIT dose 1-5 times the SCIT dose) and one of the manufacturers dosed high ('EUR4,' monthly SLIT dose 16-237 times the SCIT dose). Discussion: For more than half of the products, SLIT was not 'high dose' as has originally been recommended. When reviewing the low- and high-dose products with respect to efficacy in clinical trials included in a meta-analysis on SLIT, some low-dose extracts showed efficacy. Thus, apart from the allergen dose, it might very well be possible that other factors also play an important role in determining clinical efficacy in SLIT. [ABSTRACT FROM AUTHOR]

Temperature-controlled laminar airflow improves symptoms in atopic asthmatics, but its effects on personal allergen exposure are unknown. We aimed to evaluate its effects on personal cat allergen and particulate exposures in a simulated bedroom environment. Five healthy volunteers lay under an active and an inactive temperature-controlled laminar airflow device for 175 min, in a simulated bedroom containing bedding from a cat owner. Total airborne particles (≥0.5 - ≥10 μm diameter) were quantified with a laser particle counter. Airborne allergen was sampled with Institute of Occupational Medicine filters. Inhaled exposure was sampled with nasal air samplers. Allergen-containing particles were quantified by immunoassay. Treatment reduced total airborne particles (>0.5 μm diameter) by >99% ( P < 0.001) and reduced airborne allergen concentration within the breathing zone (ratio of median counts = 30, P = 0.043). Treatment reduced inhaled allergen (ratio of median counts = 7, P = 0.043). Treatment was not associated with a change in airborne allergen concentration outside of the breathing zone ( P = 0.160). Temperature-controlled laminar airflow treatment of individuals in an allergen-rich experimental environment results in significant reductions in breathing zone allergenic and non-allergenic particle exposure, and in inhaled cat allergen exposure. These findings may explain the clinical benefits of temperature-controlled laminar airflow. [ABSTRACT FROM AUTHOR]

Background: Allergic asthma is a chronic inflammatory airway disease caused by exposure to airborne allergens. In order to develop novel therapies for allergic asthma, models that are relevant to human disease are needed. Methods: Female BALB/c mice were presensitised subcutaneously with alum-adsorbed recombinant cat allergen Fel d 1, followed by intranasal challenges with cat dander extract spiked with recombinant Fel d 1 for 7 weeks. For reference, mice were presensitised and challenged with ovalbumin following the same protocol. Airway hyperresponsiveness, serum antibodies, airway inflammation and cell infiltration, and cytokines in lung tissue and bronchoalveolar lavage were measured. Results: Mice presensitised with recombinant Fel d 1 and challenged with cat dander extract or presensitised and challenged with ovalbumin showed airway hyperresponsiveness in response to metacholine. Mice of the cat allergen model showed influx of neutrophils, eosinophils and lymphocytes in bronchoalveolar lavage, combined with increased levels of IL-17a and increased IL-4 mRNA expression in lung tissue. In contrast, mice sensitised and challenged with ovalbumin showed a predominant influx of eosinophils in bronchoalveolar lavage and had an increased expression of IL-5 in lung tissue. Both protocols induced features of lung tissue remodelling and allergen-specific antibody responses. Conclusions: The presented mouse model for cat allergen-induced asthma exhibits hallmarks of chronic allergic asthma, like airway hyperresponsiveness, a mixed neutrophilic/eosinophilic infiltration in bronchoalveolar lavage, expression of IL-17a and signs of remodelling in lung tissue. The model will provide a relevant platform for the development of novel treatment strategies. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to demonstrate the potential of real-time monitoring of airborne cat allergen powder using quartz crystal microbalance (QCM) technology. Monoclonal antibodies of cat allergen (Fel d 1) were immobilized onto a gold-coated quartz crystal using a cysteamine self-assembled monolayer (SAM). The QCM responses exhibited negative frequency shifts characteristic of mass uptake onto the sensor surface when exposed to airborne cat allergen powder. The cat allergen powder was 0.01wt% Fel d 1; therefore, antigen–antibody binding occurred despite potential interference from dust particles. The absolute frequency shift increased linearly (log–log, R 2 =0.968) over the immunosensor working range, from 5.2ng/L to 1.6×105 ng/L. Selectivity of the immunosensor between the cat allergen and a test dust was confirmed using SEM images and antibody affinity was confirmed by challenging an Escherichia coli antibody-coated crystal with airborne cat allergen. Positive frequency shifts were observed with the QCM for both negative controls. The research demonstrates that immunosensors based on QCM technology may become a viable alternative to conventional methods of real-time monitoring of bioaerosols. [Copyright &y& Elsevier]

Allergic disorders are the most common childhood-related chronic diseases in developed countries. It is essential to assess the exposure, especially in schools, where children spend a large portion of their time. We aimed to investigate allergen and endotoxin levels in the air of schools and to observe seasonal variations of these factors. We evaluated airborne concentrations of house dust mites allergens (Der p 1, Der f 1), cat allergen (Fel d 1), and endotoxin in PM10in 14 classrooms during the school days in the region of Munich, each over 20 consecutive days and in 1 classroom over the course of a year (at 83 days); we also tested outdoor air close to the schools. Endotoxin levels were quantified using two different analytical methods. In addition, indoor air climate parameters were measured. The median daily indoor CO2and PM10concentrations in the classrooms ranged from 423 to 3,135 ppm (median: 1,211 ppm) and 9 to 390 μg/m3(median: 127 μg/m3), respectively. Fel d 1 in the PM10samples was the most frequently detected allergen, with levels from 0.02 to 1.15 ng/m3in a total of 301 samples (median: 0.19 ng/m3, 95th percentile: 0.57 ng/m3). Der p 1 and Der f 1 were detected in only 51% and 19% of the samples, with 95th percentiles at 0.5 and 0.3 ng/m3. Endotoxin levels in the PM10and inhalable dust samples ranged from 0.5 to 84.1 EU/m3(median: 15.3 EU/m3; 95th percentile: 58.2 EU/m3) and from 0.03 to 115 EU/m3(median: 8.4 EU/m3; 95th percentile: 27.9 EU/m3). Fel d 1 and endotoxin were found in higher levels in the winter months. The results of the two different indoor sampling techniques for endotoxin were statistically significantly correlated. The results of airborne allergens indicate a generally low exposure level in classrooms. With regard to endotoxin, our study showed higher levels in schools compared with residences. [ABSTRACT FROM PUBLISHER]

Background: Cat exposure during childhood has been shown to increase the risk of developing cat sensitization, while the effect of cat exposure in adulthood has not yet been established. Objective: To evaluate new-onset sensitization to cat in adulthood in relation to changes in cat keeping. Methods: A total of 6292 European Community Respiratory Health Survey I (ECRHS I) participants aged 20 to 44 years from 28 European centers, who were not sensitized to cat, were reevaluated 9 years later in ECRHS II. Present and past cat ownership and total and specific IgE levels were assessed in both surveys. Allergen-specific sensitization was defined as a specific serum IgE level of 0.35 kU/L or more. Results: A total of 4468 subjects did not have a cat in ECRHS I or ECRHS II, 473 had a cat only at baseline, 651 acquired a cat during the follow-up, and 700 had a cat at both evaluations. Two hundred thirty-one subjects (3.7%) became sensitized to cat. In a 2-level multivariable Poisson regression model, cat acquisition during follow-up was significantly associated with new-onset cat sensitization (relative risk = 1.85, 95% CI 1.23-2.78) when compared with those without a cat at both surveys. Preexisting sensitization to other allergens, a history of asthma, nasal allergies and eczema, and high total IgE level were also significant risk factors for developing cat sensitization, while cat ownership in childhood was a significant protective factor. Conclusion: Our data support that acquiring a cat in adulthood nearly doubles the risk of developing cat sensitization. Hence, cat avoidance should be considered in adults, especially in those sensitized to other allergens and reporting a history of allergic diseases. [ABSTRACT FROM AUTHOR]

Basophil histamine release (BHR) to allergen has been used as a confirmatory test to support the clinical diagnosis of allergic disease. Among subjects reporting respiratory cat allergy, we hypothesized that cat-induced BHR in vitro would predict nasal allergen challenge (NAC) response in that same individual. We therefore compared the magnitude of cat allergen-induced BHR to NAC outcome and serological measures of cat-specific IgE and the ratio of cat-specific IgE to total IgE. Forty-two subjects with a history of cat allergy, positive cat puncture skin test (PST) and detectable cat-specific IgE (>0.1 kAU/L, ImmunoCap) participated with consent. Subjects were grouped as positive or negative cat allergen-induced BHR, with a positive result defined as the release of 20% of the total cellular histamine content. The majority of subjects also underwent a NAC with a positive result defined as 5 total sneezes. Subjects with a positive compared with a negative cat allergen BHR had higher cat-specific IgE levels at 5.40±1.24 kAU/L ( n=25) vs. 1.55±0.73 kAU/L ( n=17, P=0.01) as well as a higher cat-specific IgE/total IgE ratio [6.1±1.4% ( n=25) vs. 1.6±0.9% ( n=17, P=0.01)]. Of the 31 subjects who underwent a NAC, a positive NAC was observed in 78% (18/23) with a positive cat allergen BHR compared with 37% (3/8) with a negative cat allergen BHR, giving a positive predictive value of 78% and a negative predictive value of 63%. The diagnostic sensitivity and specificity of a positive BHR to predict a positive NAC was 86% and 50%, respectively. A positive cat allergen-induced BHR is associated with higher cat-specific IgE levels, a higher cat-specific to total IgE ratio and is predictive of a positive cat-induced NAC [ClinicalTrials.gov NCT00604786]. Cite this as: M. Paterniti, D. C. Kelly, J. A. Eckman, P. M. Sterba, R. G. Hamilton, B. S. Bochner, D. W. MacGlashan Jr. and S. S. Saini, Clinical & Experimental Allergy, 2011 (41) 963-969. [ABSTRACT FROM AUTHOR]

Sensitization to cat is a common cause of allergic disease all over the world. Symptoms range from mild rhinoconjunctivitis to potentially life-threatening asthmatic exacerbations. In vivo and in vitro diagnostics of cat allergy is currently based on cat dander extract. As allergen extracts from natural sources are heterogeneous in composition, the allergen content may vary. With the introduction of allergens produced by recombinant techniques, a large panel of recombinant allergenic molecules including the major cat allergen, recombinant Fel d 1, has become available for immunological investigations, diagnosis and treatment. Studies have shown that this single allergen, which belongs to the uteroglobin protein family, is at least as good as cat dander extract in identifying cat-allergic patients. The introduction of recombinant Fel d 1-based tests into clinical practice will increase our knowledge of this single allergen molecule as a diagnostic tool and improve the selection for therapy of cat allergy. Several different modes for allergen-specific immunotherapy of cat allergy based on Fel d 1 have been developed. These include Fel d 1 hypoallergens and allergen constructs where Fel d 1 is coupled to immunomodulatory proteins or carriers. The approaches have been evaluated in experimental in vitro and in vivo model systems with promising results. In addition, immunotherapy with Fel d 1 peptides containing T-cell epitopes has been tested in clinical trials. After initial problems with adverse reactions, more recent data show that peptide immunotherapy modulates the immune response to Fel d 1 and reduces early- and late-phase effector reactions in cat-allergic patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: IgE-mediated allergy can be treated by subcutaneous allergen-specific immunotherapy (SIT). However, the percentage of allergic patients undergoing SIT is low, mainly due to the long duration of the therapy and the risk of severe systemic allergic reactions associated with the allergen administration. To improve the safety and attractiveness of SIT for patients, alternative routes of allergen administration are being explored, such as sub-lingual or oral administration. Methods: The present study evaluated direct intralymphatic allergen administration as a means to enhance SIT with bee venom and cat fur allergens in mice. Allergen-specific antibody and T-cell responses were analysed by ELISA and flow cytometry. The therapeutic potential of intralymphatic immunisation in sensitised mice was analysed using an anaphylaxis model. Results: Direct injection of the major bee venom allergen phospholipase A2 or the major cat fur allergen Fel d 1 into inguinal lymph nodes enhanced allergen-specific IgG and T-cell responses when compared with subcutaneous injections. Moreover, only intralymphatic immunisation stimulated the production of the Th1-dependent subclass IgG2a, which is associated with improved protection against allergen-induced anaphylaxis. Biodistribution studies showed that injection into the lymph node delivered antigen more efficiently to subcutaneous lymph nodes than subcutaneous injection. Conclusions: As intralymphatic immunisation induced more than 10-fold higher IgG2a responses with 100-fold lower allergen doses than subcutaneous immunisation, this approach should allow to reduce both the number of allergen injections as well as the allergen dose, improving both efficacy and safety of SIT. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cat allergen (Fel d 1) is a pervasive and common trigger of exacerbations in sensitized patients with IgE-mediated asthma. This study was designed to evaluate the effect on asthma-related outcome measures of adding omalizumab to current treatment in patients with moderate-to-severe persistent asthma and cat allergen sensitivity. A pooled analysis was conducted of two double-blind, placebo-controlled, 28-week pivotal U.S. registration trials. In all patients, asthma was inadequately controlled with moderate-high dose inhaled corticosteroids. Patients were randomized to receive subcutaneous omalizumab (minimum, 0.016 mg/kg per IgE IU/mL every 4 weeks) or matched placebo. The effects of omalizumab on asthma-related outcomes were assessed for patients with cat allergen sensitivity (n = 811), identified by positive skin-prick test. The mean number of asthma exacerbations requiring treatment with systemic steroid bursts in cat allergen-sensitive patients was lower in those receiving omalizumab versus placebo (0.6 versus 1.3, respectively; relative risk = 0.50, p < 0.001). Compared with placebo, omalizumab treatment led to significantly lower asthma symptom scores (least squares means (LSMs) treatment difference [95% confidence interval {CI}]: -0.57 [-0.77, -0.37]; p < 0.001), less rescue medication use (LSMs treatment difference [95% CI]: -0.75 puffs of rescue beta-agonist per day [-1.04, -0.46]; p < 0.001), and improvement in forced expiratory volume in 1 second (LSMs treatment difference [95% CI]: 100.84 mL [51.86, 149.81]; p < 0.001). Patient and investigator global evaluations of treatment effectiveness paralleled these outcomes. Omalizumab improved asthma control by reducing exacerbations and decreasing symptoms in cat-allergic patients with moderate-to-severe persistent IgE-mediated asthma. [ABSTRACT FROM AUTHOR]

Background: Exposure and sensitization to pet allergens are associated with allergic asthma in children. Conflicting data have emerged regarding the potential benefit of air cleaners with respect to a reduction of indoor pet allergens and bronchial hyperresponsiveness (BHR). Methods: In a randomized controlled trial 36 asthmatic children with sensitization to cat and/or dog and significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g of carpet dust) were included in order to study the effect of high-efficiency particulate arresting (HEPA) air cleaners placed in the living room and bedroom compared with the effect of sham air cleaners. Patients were allocated to two groups: group 1 exposed to active filters and group 2 exposed to sham filters. At month 0, after 6 months and after 12 months, pulmonary function testing and cold air challenge were performed, serum eosinophil cationic protein (ECP) and specific IgE to seven aeroallergens were determined, and carpet dust samples and filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were determined in filters and bulk dust samples. Results: Thirty patients completed the study. After 6 and 12 months, there was no significant change in delta FEV1 after cold air challenge, or in the use of medication and serum ECP levels. However, there was a trend in the active group towards an improvement of bronchial hyperresponsiveness, whereas the sham filter group showed a deterioration of BHR. Conclusion: Although HEPA air cleaners retained airborne pet allergens, no effect on disease activity or allergen concentrations in bulk dust samples was observed in this study. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Studies have presented conflicting associations between cat allergen exposure and sensitisation and atopic disease. We therefore investigated the association between the observed domestic cat allergen level and cat sensitisation in young children in four study populations from three European countries. We recruited children from a nested case–control study, which is composed of four ongoing birth cohorts conducted in three European countries. Children at 2–4 years of age in the four cohorts who were sensitised to cat allergens (n=106) were compared with 554 non-sensitised children (controls). House dust samples were collected when the children were 5 to 7 years old, and cat allergen levels were measured in ng/g dust and ng/m2 surface area. In the German study population we found a positive association between domestic cat allergen in house dust and cat sensitisation (OR (CI)=3.01 (1.16, 7.99)) while in the Swedish study population, we found a negative association (OR (CI)=0.41 (0.16, 0.98)). No association was found in the Dutch study population (OR (CI)=0.83 (0.22, 2.93)). Looking into the family history of cat keeping, we found the lowest prevalence of cat sensitisation in children who were cat owners at the age of blood sampling (11%) and the highest prevalence was found in those who have had a cat but not anymore, at the age of blood sampling (41%). The mixed results may be explained by differences in age and avoidance patterns. [Copyright &y& Elsevier]

Background: Endotoxins, comprised of bacterial cell wall lipopolysaccharides (LPS), have been reported to have both protective and exacerbating effects on the development and maintenance of allergic disease in humans and on markers of allergic inflammation in animal models of allergy. In this study, we investigated the effect of low concentrations of LPS on human peripheral blood mononuclear cells (PBMC) stimulated with the major cat allergen Fel d 1. Methods: Extensive purification of recombinant (r) Fel d 1 yielded essentially endotoxin-free rFel d 1 (0.2 ng LPS /mg protein). PBMCs prepared from 15 subjects having IgE to cat (>0.7 kUA/l) and 8 subjects IgE negative to cat were stimulated with 2, 10 or 25 μg/ml of rFel d 1 in the presence or absence of 50 pg/ml LPS. Proliferation was measured after 7 days of culture and supernatants were analyzed for IFNγ, IL-5 and IL-10. Results: LPS (50 pg/ml) increased rFel d 1-stimulated proliferation of PBMCs both from subjects IgE-positive and subjects negative to cat allergens. PBMCs from 13 of the subjects did not proliferate in response to stimulation with 2 and 10 μg/ml rFel d 1 alone but did so in the presence of LPS. Moreover, LPS increased the levels of rFel d 1-stimulated IFNγ in cultures from cat-negative subjects, IL-5 from cat-positive subjects and IL-10 from both groups. Conclusion: Very low doses of LPS enhance proliferation and decrease the apparent threshold level for cell activation, prompting careful evaluation of allergen stimulated T cell activation in vitro. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This guidance for the management of patients with allergic and non-allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co-morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research. [ABSTRACT FROM AUTHOR]

Indoor environment has been associated with allergic disease. Further, it has been observed that the prevalences of allergic sensitization are different in different social groups. We therefore investigated the association between socioeconomic status (SES) and indoor bio-contaminants. House dust samples were collected from parents’ and infants’ mattress from 2166 families in Munich (62.2%) and Leipzig (37.8%), Germany. Major mite allergen Der p 1 and Der f 1, cat allergen Fel d 1, and endotoxin were extracted and quantified. Parental educational level and family equivalent income were used independently as socioeconomic indicators. Indoor endotoxin, mite allergen Der p 1, and the amount of sampled dust were not associated with the social factors. Mite allergen Der f 1 was slightly associated by family SES but without a consistent pattern. In families who are not cat owners, however, a negative association between the amount of cat allergen and family SES were observed. The observed negative association between cat allergen loads and concentrations in mattress and family SES in non-cat owners’ homes indicated that community is an important source of cat allergen exposure. Practical Implications The study indicated that community is a major source of cat allergen exposure especially in communities of low SES. [ABSTRACT FROM AUTHOR]

Abstract: Felis domesticus allergen 1(Fel d 1) is a 35 kDa tetrameric glycoprotein formed by two heterodimers which elicits IgE responses in 95% of patients with allergy to cat. We have previously established in vitro conditions for the appropriate folding of recombinant Fel d 1 using a direct linkage of chain 1 to chain 2 (construct Fel d 1 (1+2)) and chain 2 to chain 1 (construct Fel d 1 (2+1)). Although the crystal structure of Fel d 1 (2+1) revealed a striking structural similarity to that of uteroglobin, a steroid-inducible cytokine-like molecule with anti-inflammatory and immunomodulatory properties, no functional tetrameric form of Fel d 1 could be identified. Here we present the crystal structure of the Fel d 1 (1+2) tetramer at 1.6 Å resolution. Interestingly, the crystal structure of tetrameric Fel d 1 reveals two different calcium-binding sites. Symmetrically positioned on each side of the Fel d 1 tetramer, the external Ca2+-binding sites correspond to a putative Ca2+-binding site previously suggested for uteroglobin. The second Ca2+-binding site lies within the dimerization interface, stabilizing the formation of the Fel d 1 tetramer, and inducing important local conformational changes that directly govern the shape of two water-filled cavities. The crystal structure suggests a potential portal for an unknown ligand. Alternatively, the two cavities could be used by the allergen as a conditional inner space allowing for the spatial rearrangement of centrally localized side-chains, such as Asp130, without altering the overall fold of the molecule. The striking structural similarity of the major cat allergen to uteroglobin, coupled to the identification in the present study of a common Ca2+-binding site, let us speculate that Fel d 1 could provoke an allergic response through the modulation of phospholipase A2, by sequestering Ca ions in a similar manner as previously suggested for uteroglobin. [Copyright &y& Elsevier]

Background The relationship between exposure to indoor aeroallergens in early life and subsequent eczema is unclear. We have previously failed to show any significant associations between early life exposure to house dust mite and cat fur allergens and either sensitization to these allergens or wheeze. We have also previously reported a lower prevalence of parent-reported, doctor-diagnosed eczema by age 2 years for children exposed to higher concentrations of house dust mite, but no other associations with other definitions of eczema or for exposure to cat allergen. Objectives To extend the exposure–response analysis of allergen exposure and eczema outcomes measured up to age 8 years, and to investigate the role of other genetic and environmental determinants. Methods A total of 593 children (92·4% of those eligible) born to all newly pregnant women attending one of three general practitioner surgeries in Ashford, Kent, were followed from birth to age 8 years. Concentrations of house dust mite and cat allergen were measured in dust samples collected from the home at 8 weeks after birth. The risk of subsequent eczema as defined by the U.K. diagnostic criteria was determined according to different levels (quintiles) of allergen exposure at birth. Results By age 8 years, 150 (25·3%) children had met the diagnostic criteria for eczema at least once. Visible flexural dermatitis was recorded at least once for 129 (28·0%). As in other studies, parental allergic history was positively associated with most eczema outcomes, as were higher maternal education and less crowded homes. No clear linear associations between early exposure to house dust mite or cat allergen were found, regardless of the definition of eczema used. The risk of eczema appeared to increase for the three lowest quintiles of house dust mite allergen exposure (odds ratio, OR 1·37 for third quintile compared with first), and then to fall for the two highest quintiles (OR 0·66 and 0·71) even after controlling for confounding factors. Conclusions The lack of any clear exposure–disease relationship between allergens in early life and subsequent eczema argues against allergen exposure being a major factor causing eczema. If the lower levels of eczema at higher levels of house dust mite are confirmed, then interventions aimed at reducing house dust mite in early infancy could paradoxically increase the risk of subsequent eczema. [ABSTRACT FROM AUTHOR]

Background: Allergens from cat are among the most potent elicitors of allergic disease. Four cat allergens have been identified; however, evidence indicates the existence of additional allergens. Objective: In this study, we evaluated IgE sensitization to IgA from cat. Methods: Sera from cat-sensitized patients (n = 81) were analyzed for IgE antibodies to purified cat IgA in the Pharmacia CAP System. Indirect ELISA was performed with cat IgA, cat IgM, and deglycosylated cat IgA. Competitive inhibition ELISA was performed with cat IgA, cat IgM, calf intestine alkaline phosphatase (CIP), and cat serum albumin on solid phase bound cat IgA. IgE reactivity was also evaluated on membrane blotted cat IgA. Results: Thirty-eight percent (31/81) of the cat-sensitized sera were ImmunoCAP-positive to cat IgA. Indirect ELISA demonstrated a high correlation between IgE reactivity to cat IgA and cat IgM (r = 0.94; P < .001). Very low responses were observed to deglycosylated IgA. Strong inhibition of cat IgA was observed in all sera after preincubation with cat IgA and cat IgM. Inhibition was also observed in most sera after preincubation with CIP. Immunoblotting demonstrated that the IgE reactivity was mainly directed to the heavy chain of IgA. Conclusion: This study has revealed a new allergen, cat IgA, containing a novel group of cross-reactive epitopes depending on carbohydrates also present on IgM and partially on CIP. Clinical implications: This new group of cross-reactive carbohydrate IgE epitopes should be taken into consideration when diagnosing patients with suspected animal allergy. [Copyright &y& Elsevier]

Background Studies of the association between indoor allergen exposure and the development of allergic diseases have often measured allergen exposure at one point in time. Objective We investigated the variability of house dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years. Methods Data were obtained in the Dutch PIAMA birth cohort study. Dust from the child's mattress, the parents' mattress and the living room floor was collected at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno assay. Results Mite allergen concentrations for the child's mattress, the parents' mattress and the living room floor were moderately correlated between time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on the child's mattress, the within-home variance was close to or smaller than the between-home variance in most cases. For Fel d 1, the within-home variance was almost always smaller than the between-home variance. Results were similar for allergen levels expressed per gram of dust and allergen levels expressed per square metre of the sampled surface. Variance ratios were smaller when samples were taken at shorter time intervals than at longer time intervals. Conclusion Over a period of 4 years, mite and cat allergens measured in house dust are sufficiently stable to use single measurements with confidence in epidemiological studies. The within-home variance was larger when samples were taken 8 years apart so that over such long periods, repetition of sampling is recommended. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Cat allergen is a major cause of morbidity among sensitised asthma patients, but little is known about distribution of cat allergen exposure and its determinants in homes. Methods: We measured cat allergen and potential determinants of cat allergen levels in more than 1000 homes. House dust was collected from children''s mattresses and living room floors in approximately 360 homes in The Netherlands, Sweden and Germany and analysed for Fel d 1 in one central laboratory. Exposure was expressed both in concentration (ng/g) and in loads (ng/m2). Results: Levels on mattresses were similar in Sweden and Germany but higher on Dutch mattresses. Dutch floors had higher concentrations than Swedish floors, which had higher concentrations than German floors. The differences in load were less clear. Cat allergen on mattress and floor were moderately to highly correlated. The most important variable quantifying cat allergen variation was the presence of a cat. Floor cover type and last time that floor was vacuumed were important in all three countries. The ratio of cat allergen loads between mattresses from homes with and without cats was higher for Sweden and Germany than for The Netherlands. This is likely related to higher prevalence of cat ownership in The Netherlands which leads to more contamination of homes in which cats were never held. Dust samples from 27–35% of mattresses from homes without cats contained more than 1000 ng/g cat allergen. Conclusion: With the exception of cat ownership and floor cover, questionnaire data on housing characteristics did not accurately predict cat allergen in the home. [Copyright &y& Elsevier]

Background: Cat allergen level in settled house dust and its determinants in Europe are unknown. Objective: The aim of this study is to quantify the level of cat allergens in mattress dust, to study its determinants, and to analyze the relationship with cat specific IgE on community level across European centers. Methods: Trained field workers collected dust from approximately 3000 mattresses during home visits in 22 European Community Respiratory Health Survey II centers. Sieved dust extracts were assayed for cat allergen using a mAb ELISA assay. Results: The overall geometric mean cat allergen was 0.94 μg/g, ranging from 0.12 μg/g in Huelva, Spain, to 3.76 μg/g in Antwerp, Belgium. Current cat owners'' homes showed substantially higher levels than past cat owners'' and never cat owners'' homes (geometric mean and 95% CI, 61.4 μg/g [48.4-77.9] vs 1.37 μg/g [0.97-1.9] vs 0.29 μg/g [0.27-0.31]). Community prevalence of cat ownership was moderately correlated with cat allergen levels in noncat owners (r s = 0.50), but not for past or current cat owners. The multilevel model identified community prevalence of cat keeping as the only statistically significant determinant of mattress cat allergen levels for noncat owners. However, averaged cat allergen levels per center were not related to community prevalence of detectable specific IgE to cat. Conclusion: Not having a cat in the home is associated with substantially lower Fel d 1 concentration, but does not protect against high Fel d 1 exposure in communities where cat ownership is common. Clinical implications: People (including patients with cat allergy) who do not own cats may be exposed to high levels of cat allergen in their home, particularly if they live in communities with high levels of cat ownership. [Copyright &y& Elsevier]

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]

Summary: It is widely acknowledged that avoidance of allergens such as those derived from foods, drugs, latex and stinging insects results in a complete disappearance of symptoms. By contrast, although it has been clearly shown that allergens are an important risk factor for the development of respiratory symptoms and that several avoidance measures reduce allergen levels, whether this gives clinical improvement in symptoms is debatable. Many reasons could be invoked to justify this evident discrepancy. Apart from the intrinsic methodological aspects (e.g. single or combined interventions measure, population studied, severity of respiratory symptoms, outcomes, evaluated parameters, etc.), it is important to outline that a successful approach requires that the avoided allergen is the only and real factor responsible for symptoms, the patient''s education and the use of a comprehensive protocol to reduce allergen exposure. Other important factors include the involvement of the patient, the relevance of other allergens/non-specific agents, and exposure to sensitizing agents also outside patient''s home. It is likely that the clinical phase of allergic airway disease and the degree of bronchial (and also nasal) remodelling, in each individual, represent relevant factors for the clinical outcome of allergen avoidance procedures. Since the management of respiratory allergy is a complex strategy (including drugs, allergen avoidance, immunological and educational interventions), it is difficult in real life to distinguish the efficacy of a single intervention in comparison to the others. A combined strategy is likely to produce better clinical results. [Copyright &y& Elsevier]

The upper airway mucosa of healthy humans contains a dense network of cells with dendritic morphology of which the majority express a macrophage-like phenotype (CD14+CD64+CD68+), whereas the smaller population are immature dendritic cells (DC; CD11c+CD14−). Our aim was to study the proinflammatory response of human monocytes and in vitro-generated macrophages and DC after contact with cat allergens. Monocyte-derived DC and monocyte-derived macrophages were exposed to cat allergen extract or Escherichia coli. Purified monocytes were stimulated with allergen extracts from cat or house dust mite (HDM) or the major allergenic protein Fel d 1 and induction of proinflammatory cytokines by monocytes was analyzed before and after blocking CD14. We show that cat allergen extract induced tumor necrosis factor (TNF) and interleukin (IL)-6 production by CD14-positive macrophages but not by CD14-negative DC. Moreover, monocytes produced significantly higher levels of TNF in response to cat allergens than in response to HDM allergens. We observed no differences in levels of TNF and IL-6 from either macrophages or monocytes after exposure to cat allergen when comparing healthy and cat-allergic individuals. Finally, the proinflammatory cytokine production from monocytes in response to cat allergen extract but not to HDM allergen was significantly reduced by blocking CD14. These results indicate that closely related innate immune cells from the myeloid lineage respond differentially to cat allergen extract and that the pattern-recognition receptor CD14 might be one of the mediators involved in the inflammatory responses to inhalant allergens. [ABSTRACT FROM AUTHOR]

We have previously shown that airborne cat allergen levels are significantly lower in school classes using special school clothing or in classes with no pet owners. However, cat allergen is present and the levels are in fact two- to threefold higher on cat owners’ than noncat owners’ school clothing which is used, washed and stored at school only. This suggests that allergen is transferred to schools by routes other than clothing.To analyse levels of cat allergen (Fel d 1) in hair from cat owners and noncat owners among children and adults.Samples of unwashed hair (≥1 day prior to sampling) from adults and children with (n = 22) or without (n = 22) cats at home were collected at a hairdresser. In addition, samples of newly washed hair (adults only,n = 11) were collected. The hair sample was extracted and analysed for Fel d 1 content with ELISA.The geometric mean levels were more than two orders of magnitude higher in unwashed hair from cat owners, compared with noncat owners (P < 0.0001) and more than 10-fold higher in newly washed hair from adults. The allergen contamination of unwashed hair among noncat owners appeared higher in children than in adults (P = 0.045).Hair may be an important source for transfer and deposition of cat allergen in schools and may explain why cat allergen is found in environments with strict allergen avoidance measures. Although it may be unrealistic to apply allergen avoidance strategies against this allergen source, it is important to be aware of it. [ABSTRACT FROM AUTHOR]

Background: With 63% of US children under 5 years of age in regular child care, day-care facilities could be an important source of exposure to indoor allergens. Objective: This study examined levels of 7 indoor allergens in 89 day-care facilities in 2 North Carolina counties. Methods: At each facility, a questionnaire was administered, observations were made, and vacuumed dust samples were collected from carpeted and noncarpeted areas of one room. Allergen concentrations were measured with antibody-based ELISAs. Results: Each allergen was detected in a majority of facilities (52% to 100%). Geometric mean concentrations were 5.19 μg/g for Alternaria alternata, 2.06 μg/g for Can f 1, 1.43 μg/g for Fel d 1, 0.21 U/g for Bla g 1, 0.20 μg/g for Der p 1, 0.10 μg/g for Der f 1, and 0.01 μg/g for Mus m 1. Concentrations for 5 of the 7 allergens were not statistically different from concentrations found in southern US homes sampled in the National Survey of Lead and Allergens in Housing. In rooms with carpet and hard-surfaced flooring, levels of A alternata, Can f 1, Der f 1, Der p 1, and Fel d 1 were statistically higher on carpet. Conclusions: In this survey of day-care facilities in North Carolina, detectable levels of indoor allergens were commonly found. For many young children and day-care staff, day-care facilities might be a source of clinically relevant exposures to indoor allergens. [Copyright &y& Elsevier]

Background: Cat allergens are ubiquitous because the clothing of cat owners constitutes an important source of distribution of Fel d 1 in cat-free environments. Since Fel d 1 can adhere to a variety of surfaces, we sought to verify if human hair belonging to individuals with or without a cat at home might represent a reservoir and be a possible carrier of cat allergens. Methods: Seventy-three women (25 with a non-neutered male cat and 25 with a dog at home, and 23 controls without any direct contact with these animals) were recruited. The collection of material from hair was carried out using a modified version of a battery-powdered portable sampler. Particulate material was harvested onto glass fiber filters (25 mm in diameter, with a pore size of 2 μm; AP 20 Millipore, Milan Italy), extracted in phosphate buffer with BSA and then assayed for the evaluation of cat allergen using an ELISA based on anti-Fel d 1 monoclonal antibody. Results: Detectable levels of cat allergen were found in 2 controls, in 2 women with a dog at home and in 13 women with a cat at home, respectively. Conclusions: In some women with a cat at home, hair constitutes a significant reservoir of Fel d 1. It is likely that these amounts of cat allergen might contribute to allergic sensitization when released in cat-free environments. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The concentrations of cat (Fel d1) and dust-mite (Der f1 andDer p1) allergens were measured in 92 large office buildings in the US Environmental Protection Agency's Building Assessment Survey and Evaluation (BASE) Study (251 dust samples; one to four samples per building).Fel d1 was detected in almost all buildings and samples (91 buildings, 99%; 235 samples, 94%; range:<0.01–19 μg/g; median: 0.3 μg/g). Cat allergen exceeded 1 μg/g (a lower symptom threshold) in 56 samples (22%) from 45 buildings, but exceeded 8 μg/g (a sensitization threshold) in only two samples (1%) from two buildings.Der f1 orDer p1 was found in approximately half of all buildings and samples (63 and 70% of buildings; 45 and 51% of samples; range:<0.01–53 μg/g and<0.01–25 μg/g; median:<0.02 and 0.03 μg/g, respectively). Mite allergen exceeded 2 μg/g (a sensitization threshold) in seven samples (3%) from five buildings and exceeded 10 μg/g (a symptom threshold) in three samples (1%) from three buildings.Fel d1 concentration was significantly higher in samples collected in summer (June to September, 48 buildings), but cat allergen was not correlated with either mite allergen.Der f1, but notDer p1, concentration tended to be higher in samples collected in winter (December to April, 44 buildings), and the two mite allergens were significantly correlated only in winter. Cat and mite allergens were detected in 78% of representative US office buildings, but the concentrations seldom exceeded levels associated with sensitization or symptom provocation. The information on the concentrations of cat and dust-mite allergens in representative large US offices has expanded the baseline data available for interpretation of measurements from other building investigations. With suggested refinements, the BASE protocol for measurement of allergen concentrations in dust samples may serve as a guide to future studies of building characteristics, bioaerosol concentrations, and occupant perceptions of the indoor environment. [ABSTRACT FROM AUTHOR]

An environmental survey was conducted in two hospital buildings in Montana, one of which had historical water incursion on the top floors and higher prevalence of reported respiratory symptoms that improved when the occupants were away from work. We measured culturable fungi and bacteria, fungal spores, endotoxin, and sub-micron particles in air; and culturable fungi and bacteria, endotoxin, markers of fungi (extra-cellular polysaccharides specific forPenicillium/Aspergillus, ergosterol, andβ(1→3) glucans) and cat allergen in chair and floor dusts. For the analytes measured in air, the correlation coefficients ranged from 0.43 to 0.78 (P < 0.05). In chair dust,β(1→3) glucan concentrations correlated with culturable fungi and ergosterol concentrations. We found that sub-micron particles and markers of microbiological agents, but not culturable microbiological agents, were significantly positively associated with the building that had both historical water damage and higher prevalence of reported respiratory symptoms. Chair dust measurements tended to be higher in the non-complaint building. These results suggest that air and floor dust measurements of marker compounds may be better indicators of current health risk in a water-damaged environment than chair dust measurements or measurements of culturable fungi or bacteria in air or settled dust. Detection and quantification of nonculture-based microbiological markers and/or agents of disease may be useful methods to assess microbial contamination and to more accurately evaluate microbial exposures in the indoor environment for exposure-response studies. [ABSTRACT FROM AUTHOR]

Abstract: Concurrent size-resolved measurements of airborne cat allergen (Fel d 1) and total particulate matter (PM) were collected in an experimental chamber for the first 5min following a typical dust-generating household activity (vacuuming a carpet). Three different heights representative of typical elevations for human exposure were measured to assess vertical variations. Experiments showed that only a limited amount of deposited house dust is available for resuspension; the reservoir of dust in the carpet appears to become substantially depleted after about 3 iterations of a resuspension activity, and vertical variations in large PM (aerodynamic diameters ) become less pronounced. Measured removal rates of PM suggested that the average density of house dust may be substantially less than 1.0g/cm3. The allergenic content of the resuspended house dust was found to range between 0.03–0.10%, with a preliminary suggestion of somewhat higher Fel d 1 levels in the submicron size range particles. [Copyright &y& Elsevier]

Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy.The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen.The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay.Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400–900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1.By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients. [ABSTRACT FROM AUTHOR]

Summary: Background: The relationship between pet ownership and the risk of developing respiratory allergic sensitization to pet allergens is still controversial. Objective: To determine the degree of cutaneous immediate hypersensitivity and the levels of specific IgE and IgG4 antibodies to cat allergen in cat sensitized patients directly or indirectly exposed to this animal. Methods: We studied 112 adolescents and adults sensitized to cat allergens (43 with and 69 without a cat at home). There were also 52 control subjects, 27 atopic non-sensitized to cat and 25 non-atopic. The degree of immediate hypersensitivity was assessed by using, in duplicate, skin prick test with four five-fold dilutions of cat hair allergen extract with the content of its major allergen Fel d 1 quantified in micrograms plus positive (10mg/ml histamine chlorhydrate) and negative (saline solution) controls. The resulting wheal areas were analysed by means of Parallel Line Assay. A blood sample was collected from every patient and control subjects for the evaluation of serological cat specific IgE and IgG4 antibodies. Results: Patients with cat at home had a lower cutaneous response than patients without this pet. The difference in the skin sensitivity was estimated in 3.4 times . There was no statistical difference between the levels of cat specific IgE antibodies in the two groups of patients . The levels of Fel d 1 specific IgG4 antibodies showed a statistically significant association with the presence of cat at home, with higher levels in patients owing cat at home than in patients without this pet . Conclusion: The results of this study demonstrate that direct cat exposure in adolescents and adults with respiratory allergy is associated with a lower cutaneous response to cat allergenic extract, assessed by SPT and compared with indirect exposure. In patients with cat at home mean levels of specific IgE are statistically comparable whereas the levels of IgG4 are higher in comparison with subjects not exposed to cats. The role of indirect exposure to cat allergens in airways sensitization also in adults is emphasized. Moreover, patients with cat at home show a cutaneous and serological sensitization to cat allergen not higher in comparison with subjects not exposed to cats. [Copyright &y& Elsevier]

Reports of decreased sensitization to cat allergen (Fel d 1) among individuals living with a cat or subjects exposed to high-dose cat allergen may be explained by the development of a form of high-dose tolerance resulting from natural exposure to an inhalant allergen. Although the epidemiological data regarding the relationship between exposure and sensitization to Fel d 1 are conflicting, the ability for high-dose Fel d 1 to induce a characteristic nonallergic immune response with a distinctive serum antibody profile has been established. Definition of this modified T-helper (Th)2 response to cat allergen, coupled with the renewed interest in regulatory T cells within the immunology field, has provided an avenue for exploring the mechanism by which IgE antibody-mediated responses are controlled. There is mounting evidence to suggest that the modified Th2 response is a variation of the allergic response and that the modified Th2-allergic axis is influenced by allergen dose and genetics. This article discusses putative immune mechanisms of tolerance within the context of an allergen-specific system. The relevance of high-dose allergen exposure and alternate factors such as endotoxin to the development of tolerance is considered. Fel d 1 exhibits unique molecular and immunological characteristics that may contribute to its tolerogenic properties. Major T-cell epitopes of Fel d 1 that preferentially induce regulatory factors have been defined. Furthermore, hightiter IgE antibody responses associated with atopic dermatitis are characterized by a defect in the T-cell repertoire that is specific to these epitopes. Identification of Fel d 1 epitopes that induce interleukin-10 may provide new targets for treatment. [ABSTRACT FROM AUTHOR]