Environmental Allergens and Asthma Morbidity in Low-Income Children

Asthma morbidity is high in inner-city children in the United States, which may be related in part to increased allergens in poorly maintained housing. This study examined asthma morbidity in relation to mold, cockroach, dust mite, and cat allergens in the homes of 61 low-income Chicago children with asthma. Children exposed to higher levels of Penicillium in the bedroom had more frequent asthma symptoms, whereas those exposed to higher levels of cockroach allergen in the bedroom had a higher number of asthma symptoms. Respiratory infections confounded the association of cockroach allergen with number of asthma symptoms.     

Environmental Allergens and Asthma Morbidity in Low-Income Children

Asthma morbidity is high in inner-city children in the United States, which may be related in part to increased allergens in poorly maintained housing. This study examined asthma morbidity in relation to mold, cockroach, dust mite, and cat allergens in the homes of 61 low-income Chicago children with asthma. Children exposed to higher levels of Penicillium in the bedroom had more frequent asthma symptoms, whereas those exposed to higher levels of cockroach allergen in the bedroom had a higher number of asthma symptoms. Respiratory infections confounded the association of cockroach allergen with number of asthma symptoms.     

The Role of Inhalant Food Allergens in Occupational Asthma

Workers handling food products and derivatives are at increased risk of developing occupational asthma. Exposure to food allergens occurs primarily through inhalation of dust, steam, vapors, and aerosolized proteins generated during cutting, scrubbing or cleaning, cooking or boiling, and drying activities. Suspicion of the diagnosis of occupational asthma should lead to proper investigation to confirm the diagnosis objectively. Most inhaled food allergy is IgE mediated, and skin prick tests or specific IgE tests are useful tools to support the diagnosis, but objective evidence of asthma by monitoring of peak expiratory flows at and off work or specific inhalation challenges offers a better diagnostic value. This article provides a list of the various foods, food additives, and contaminants that have been associated with occupational asthma.     

Matrix Metalloproteinases in the Pathogenesis of Asthma and COPD

While asthma is an inflammatory disorder of the airways involving mediators released from mast cells and eosinophils, inflammation alone is insufficient to explain the chronic nature of the disease. Recent progress in the understanding of disease pathogenesis has revealed that airway remodeling, which is at least in part due to an excess of extracellular matrix (ECM) deposition in the airway wall, plays a significant role in airflow obstruction. Matrix metalloproteinases (MMPs) have been suggested to be the major proteolytic enzymes to induce airway remodeling in asthma and COPD. It has been widely accepted that different inflammatory processes are involved in asthma and COPD with different inflammatory cells, mediators, and responses to treatments. Despite these different processes, airflow obstruction and airway remodeling characterize these two diseases. MMP-2 and -9 have been reported to be involved in the pathogenesis of airway remodeling in both diseases and MMP-12, in addition to these MMPs, in the pathogenesis of COPD. In this review, we discuss the current views on the role of MMPs in the pathogenesis of bronchial asthma and COPD. Anti-MMP therapy could theoretically be useful to prevent airway remodeling in asthma and COPD. However, to date no clinical data are available regarding the efficacy of anti-MMP therapies in the treatment of patients with asthma and COPD.     

Role of Animal Danders as Inhalant Allergens in Bronchial Asthma in India

The etiological significance of animal danders in Indian patients with nasobronchial disorders has not yet been investigated. In the present study, the role of animal danders in the etiology of bronchial asthma was studied. Extracts of danders from 6 animals along with guinea pig whole pelt were prepared. Intradermal and bronchial provocation tests with these extracts were performed on (i) 68 asthmatics and (ii) 20 nonallergic healthy volunteers. In patients, significant positive skin reactions (2+ to 4+) ranged from 1.4% each with guinea pig whole pelt and ox dander to 8.8% with dog dander extracts. None of the healthy volunteers elicited such a response. On bronchial provocation, 20% and 53.8% of the tests were positive in asthmatics showing 1 +and 2+skin reactivity, respectively. All the patients as well as controls eliciting negative intradermal responses demonstrated uniformly negative bronchial provocation tests to different dander extracts. Analysis of various clinical features of asthmatics with respect to skin positivity to dander/pelt extract was also carried out. Radioallergosorbent tests (RASTs) were performed to estimate dander-specific IgE levels in the sera of patients showing different grades of skin response to dander extracts of dog, horse, and goat. Sixty percent of sera from the patients showing 2+ to 4+ skin reactivity to various animal dander extracts showed positive RASTs. RAST positivity as well as RAST ratio increased with increase in the intensity of skin response. All the patients with positive cutaneous as well as positive bronchial responses also showed positive RASTs. Similarly, all the patients with positive skin and positive RASTs showed positive bronchoprovocation tests. These results suggested that animal danders play an important role in the etiology of bronchial asthma. Some of the clinical characteristics of asthmatics, such as (i) early age at onset of asthma, (ii) positive family history, and (iii) asthma with associated allergies, have significant bearing on the cutaneous response to various dander extracts.     

Pathogenesis and Management of Aspirin-Intolerant Asthma

In 2-23% of adults with asthma, and rarely in children with asthma, aspirin (acetylsalicylic acid) and non-steroidal anti-inflammatory drugs (NSAIDs) cause asthma exacerbations. Within 3 hours of ingestion of aspirin/NSAIDs, individuals with aspirin-intolerant asthma (AIA) develop bronchoconstriction, often accompanied by rhinorrhea, conjunctival irritation, and scarlet flush. In severe cases, a single therapeutic dose of aspirin/NSAIDs can provoke violent bronchospasm, loss of consciousness, and respiratory arrest. In order to diagnose AIA, oral, inhaled, nasal or intravenous aspirin challenge tests are performed in facilities where experienced physicians are present and emergency treatment is available. The exact differences in the pathogenesis of AIA and other types of asthma are not fully understood. The interference of aspirin/NSAIDs with arachidonic acid metabolism in the lungs plays an important role in the mechanism of AIA; inhibition of cyclo-oxygenase is accompanied by overproduction of cysteinyl leukotrienes (cys-LTs). It has been proposed that overproduction of cys-LTs, together with removal by aspirin/NSAIDs of the 'brake' imposed by the bronchodilator prostaglandin E2, may cause an asthma attack in patients with AIA. Development of a suitable animal model to investigate the pathogenesis of AIA would help to clarify this question. Although it is still controversial whether leukotriene modifiers are more effective in patients with AIA compared with other types of asthma, because LT plays an important role in the pathogenesis of AIA, leukotriene modifiers are the preferred medication for the long-term control of AIA. Add-on efficacy of leukotriene modifiers has been confirmed in patients with AIA already treated with inhaled corticosteroids. However, this does not mean that aspirin/NSAIDs can be safely taken by aspirin-sensitive patients treated with leukotriene modifiers. To prevent attacks of AIA, sensitive patients should avoid the use of aspirin/NSAIDs or use selective cyclo-oxygenase 2 inhibitors when required. When patients with AIA need aspirin for specific situations they should receive aspirin desensitization therapy or treatment with selective cyclo-oxygenase 2 inhibitors.     

Airborne Seafood Allergens as a Cause of Occupational Allergy and Asthma

Occupational allergy and asthma is a serious adverse health outcome affecting seafood-processing workers. Allergic reactions are directed to two major seafood groups: fish and shellfish, with the latter group comprising crustaceans and molluscs. Several allergenic proteins have been identified in these different groups, but few have been characterised on a molecular level. Parvalbumin appears to be the major fish allergen, while tropomyosin the major crustacean allergen. Other IgE-binding proteins have also been identified in molluscs and other seafood-associated agents (e.g. Anisakis sp), although their molecular nature has not been characterised. Aerosolised allergens can be identified and quantified using immunological and chemical approaches, detecting levels as low as 10 ng/m³. This contemporary review discusses interesting and recent findings in the area of occupational seafood allergy including high-risk occupations, environmental risk factors for airborne exposures, major and minor allergens implicated and innovative approaches in diagnosing and managing occupational allergy and asthma associated with seafood processing.     

Effect of Exposure and Sensitization to Indoor Allergens on Asthma Control Level

BackgroundReducing risk factors, such as exposure to allergens, and stepwise pharmacotherapy to achieve and maintain control of asthma are the mainstay of asthma care. The purpose of this study was to clarify the effect of exposure and sensitization to indoor allergens, including house dust mites, cats, and dogs, on the asthma control level.MethodsDust samples were collected from the mattresses of 101 adult asthma patient homes and the Dermatophagoides mite group 1 (Der 1), Fel d 1, and Can f 1 concentrations were measured using ELISA. Sensitization was determined by positive specific IgE antibodies. The Asthma Control Test (ACT), lowest peak expiratory flow (PEF) during 1 week expressed as a percentage of the highest PEF (Min%Max PEF), and spirometry were measured for the assessment of asthma control. Univariate and multivariate regression analyses were used to assess the relationships.ResultsSixty-nine patients were exposed to high levels (> 10 μg/g dust for Der 1 and Can f 1 and > 8 μg/g dust for Fel d 1) of 1 or more allergens and 39 patients were sensitized to at least one allergen. Multivariate logistic regression analyses revealed that the FEV₁ (% of predicted value) was associated with low ACT scores (< 19) and that the number of highly exposed allergens and inhaled corticosteroid dose were associated with a low level of Min%Max PEF (< 80%).ConclusionsThe level of exposure to multiple indoor allergens, but not sensitization, is associated with the asthma control level determined by PEF variation.     

Asthma Symptoms and Bronchial Reactivity in School Children Sensitized to Food Allergens in Infancy

Food allergy in infancy usually disappears but is followed primarily by respiratory allergy. We hypothesized that children allergic to common food allergens in infancy are at increased risk of wheezing illness and bronchial hyperresponsiveness during school age. In a case-control study 69 children 7.2 to 13.3 years of age allergic to egg (N = 60) and/or fish (N = 29) in early life (first 3 years) who attended our allergy outpatient clinic were recruited. They received follow-up for 1 year and were evaluated by parental questionnaire, skin prick testing, spirometry, and metacholine bronchial challenge. Another 154 children (70 sensitized to inhaled allergens) recruited selectively from a general population sample with no history of food allergy during their first 3 years served as control subjects. Twenty-three children (38.3%) maintained their sensitization to egg and 19 (65.5%) to fish; the prevalence of sensitization to ≥ 1 inhaled allergen(s) increased from 59.4% to 71% during childhood. Current asthma symptoms were reported more frequently in the study group than in either control groups, sensitized to inhaled allergens and non-sensitized. Children of the study group showed a significantly increased frequency of positive response to metacholine bronchial challenge compared to the control group as a whole; the difference was statistically indicative when study groups separately were compared to the sensitized control subjects. Multivariate logistic regression analysis showed that bronchial hyperresponsiveness, as well as reported current asthma symptoms were associated with early wheezing and early sensitization to inhaled allergens but not with atopic dermatitis in infancy or persistence of egg or fish allergy. Children allergic to egg or fish in infancy are at increased risk for wheezing illness and hyperactive airways in school age; asthma and bronchial hyperresponsiveness development is mostly determined by wheezing and senzitization to inhaled allergens in early life regardless of atopic dermatitis in infancy or retention of food allergy.     

Inhalant Allergens as Risk Factors for the Development and Severity of Mild-to-Moderate Asthma in Hong Kong Chinese Children

Sensitization to aeroallergens has been found to be a dominant risk factor for asthma in population-based studies. Similar results in asthmatic children being managed in hospital-affiliated outpatient clinic have not been established. We therefore conducted a case-control study on asthmatic children attending a university hospital-based outpatient clinic to investigate the pattern of aeroallergen sensitization, and to assess the correlation between asthma control and the presence of allergen-specific IgEs. Asthmatic patients underwent a questionnaire assessment of their asthma control, skin prick tests (SPT) for allergen sensitization, and spirometric evaluation. Peripheral blood was collected from all subjects for in vitro serum specific IgE assay (RAST) to common aeroallergens. One hundred and seventy asthmatics (aged 9.8 ± 3.7 years) and 57 age-matched control subjects were enrolled. Our patients had a median of two asthmatic attacks within 6 months prior to evaluation, and their median Disease Severity Score was 13. The median FEV₁ in our asthmatic children was 98%, whereas serum logarithmic total IgE concentrations in patients and controls were 2.57 and 2.09, respectively (p<0.0001). More than 85 % of our asthmatic children were sensitized to house-dust mite (HDM), and sensitization to HDM and cat, as well as elevated serum total IgE concentration, was a significant risk factor for the development of asthma in this cohort. Several objective measures of asthma severity, as well as FEV₁, correlated significantly with sensitization to HDM, pets, and cockroaches. In conclusion, indoor aeroallergens are one of the risk factors for the development and severity of mild-to-moderate asthma in Chinese children in Hong Kong.     

Sensitization to Common Food Allergens Is a Risk Factor for Asthma in Young Chinese Children in Hong Kong

Sensitization to aeroallergens is a major risk factor for asthma. Although patients frequently consider food ingestion as an asthma trigger, the relationship between serum food-specific IgE antibodies and childhood asthma in China remains unclear. We therefore conducted a case–control study on asthmatic children attending a university hospital-based outpatient clinic to investigate their pattern of food sensitization. Asthmatic patients underwent spirometric assessment, and peripheral blood was collected for serum-specific IgE antibodies to common food and inhalant allergens. Two hundred and thirty-one asthmatics (aged 9.3±4.3 years) and 79 age- and sex-matched controls were enrolled. The serum logarithmic total IgE concentrations in patients and controls were 2.49 and 1.92, respectively (p<0.0001). Subjects with increased serum total IgE level were significantly more likely to have food sensitization than those with normal values (33% vs. 16%; p = 0.001). Twenty-nine (52%) of 56 asthmatics younger than 6 years old and seven (27%) of 26 age-matched controls had food-specific IgE in their sera (p = 0.035). Asthmatics with food-specific IgE also used more doses of as-needed bronchodilator weekly (p = 0.005). Nonetheless, no association was found between asthma diagnosis and sensitization to individual food allergens. Significant food sensitization, with food-specific IgE level above 95% predictive values for clinical food allergy as proposed by Sampson, was only found in two patients for peanut and three subjects for egg white. In conclusion, a significant association was found between asthma and the presence of food-specific IgE antibodies in young Chinese children. Significant sensitization to common foods is rare in this cohort.     

难治性哮喘发病机制及治疗进展

难治性哮喘是对目前常规治疗反应不理想的哮喘,是临床的难点问题,本文就其定义、发病机制、危险因素、药物治疗及支气管热成型术治疗等方面进行阐述。     

Allergens in Household Dust and Serological Indicators of Atopy and Sensitization in Detroit Children with History-Based Evidence of Asthma

Background. Home exposure to allergens is an important factor in the development of sensitization and subsequent exacerbations of allergic asthma. We investigated linkages among allergen exposure, immunological measurements, and asthma by examining (1) reservoir dust allergen levels in homes, (2) associations between presence of allergens in homes and sensitization status of resident children, and (3) associations between asthma status and total IgE, atopy (by Phadiatop), and positive allergen-specific tests. Methods. The study protocol was approved by Institutional Review Boards (IRBs) of the University of North Carolina Chapel Hill; Westat, Inc.; and the US Environmental Protection Agency Human Research Protocol Office. Data were collected from questionnaires, serum analyses, and household vacuum dust. Children (n = 205) were predominately African American (AA) (85.4%) and 51.6% were asthmatic. Sera from 185 children and home dust samples (n = 141) were analyzed for total and specific IgE antibodies to allergens from cat and dog dander, cockroach, dust mites, mice, rats, and molds. Results. Sixty percent of the homes had detectable levels of three or more dust allergens. The proportions of children with positive allergen-specific IgE tests were dust mite (32%), dog (28%), cat (23%), cockroach (18%), mouse (5%), rat (4%), and molds (24–36%). Children testing positive to a single allergen also had positive responses to other allergens. Those children with positive serum tests for cat, dog, and dust mite lived in homes with detectable levels of cat (51%), dog (90%), and dust mite (Der f 1) (92%) allergens. Correlations between children’s specific IgE levels and dust levels were linearly related for dog (p < .04), but not for cat (p = .12) or dust mite (Der f 1) (p = .21). Odds ratios (95% CI) for the associations between asthma and serum-specific IgE were over 1.0 for cat, dog, dust mite (Der f 1), cockroach, and four types of molds. House dust allergen exposure levels, however, exhibited no differences between asthmatic and non-asthmatic homes. Conclusions. Both the co-occurrence of multiple allergens in dust and the high frequency of multiple allergen sensitizations indicate that a broad-based intervention aimed at reducing multiple allergens (pets, pests, and molds) would be more successful than any approach that aimed at reducing one type of allergen.     

Dangerous Allergens: Why Some Allergens are Bad Actors

Immune responses can be compartmentalized into innate versus adaptive components. This relatively recent dichotomy positioned the innate immune system at the interface between the host and the external environment and provided a new conceptual framework with which to view allergic diseases, including asthma. Airway epithelial cells and dendritic cells are key components of the innate immune system in the nose and lung and are now known to be intimately involved in allergen recognition and in modulating allergic immune responses. Here we review current thinking about how these two key cell types sense and respond to inhaled allergens, and emphasize how an understanding of “allergic innate immunity” can translate into new thinking about mechanisms of allergen sensitization and potentially lead to new therapeutic targets.     

Animal Lipocalin Allergens

Lipocalins represent the most important group of inhalant animal allergens. For some of them, three-dimensional protein structures have been resolved, but their functions are still elusive. Lipocalins generally display a low sequence identity between family members. The characterization of new lipocalin allergens has revealed however that some of them display a high sequence identity to lipocalins from another species. They constitute a new group of potentially cross-reactive molecules which, in addition to serum albumins, may contribute to allergic cross-reactions between animal dander of different species. However, the clinical relevance of cross-reactivity needs to be assessed. Further studies are needed to understand which of these animal lipocalins are the primary allergens and which are cross-reacting molecules. The use of single, well characterized allergens for diagnosis will allow the identification of the sensitizing animal, which is a prerequisite for specific immunotherapy.     

Cross-Reactivity of Peanut Allergens

Peanut seeds are currently widely used as source of human food ingredients in the United States of America and in European countries due to their high quality protein and oil content. This article describes the classification and molecular biology of peanut seed allergens with particular reference to their cross-reactivities. Currently, the IUIS allergen nomenclature subcommittee accepts 12 peanut allergens. Two allergens belong to the cupin and four to the prolamin superfamily, and six are distributed among profilins, Bet v 1-like proteins, oleosins, and defensins. Clinical observations frequently report an association of peanut allergy with allergies to legumes, tree nuts, seeds, fruits and pollen. Molecular cross-reactivity has been described between members of the Bet v 1-like proteins, the non-specific lipid transfer proteins, and the profilins. This review also addresses the less well-studied cross-reactivity between cupin and prolamin allergens of peanuts and of other plant food sources and the recently discovered cross-reactivity between peanut allergens of unrelated protein families.