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Cytokine fingerprinting and hazard assessment of chemical respiratory allergy.

Allergic sensitization of the respiratory tract resulting in occupational asthma and other symptoms can be caused by a variety of chemicals and represents an important occupational health problem. Although there is a need to identify and characterize those chemicals that are able to cause respiratory allergy, there are currently no well validated or widely accepted predictive test methods. Some progress has been made with guinea pig assays, but our attention in this laboratory has focused instead on the development of novel approaches based on an understanding of the nature of immune responses induced in mice by chemical allergens. We have shown that whereas contact allergens provoke in mice selective type 1 immune responses, characterized by the secretion by draining lymph node cells (LNC) of high levels of the cytokine interferon gamma (IFN-gamma), chemical respiratory allergens stimulate instead preferential type 2 responses associated with comparatively high levels of interleukins 4 and 10 (IL-4 and IL-10). The divergent immune responses provoked by different classes of chemical allergens, and the phenotypes of selective cytokine secretion that characterize such responses, form the basis of a novel method-cytokine fingerprinting--that permits chemicals that have the potential to cause respiratory allergy to be identified and distinguished from those that are associated primarily with contact sensitization. In this article the immunobiological basis for cytokine fingerprinting is considered and the development, evaluation and practical application of the assay are reviewed.

Allergens↗

Contact allergy from Frullania and respiratory allergy from Thuja.

Occupational allergic contact dermatitis in 52 forest-workers was caused by sesquiterpene lactones from liverworts (Frullania) and by usnic acid from lichens which grow on various trees including cedar (Thuja). Occupational asthma and rhinitis in 35 wood-workers was caused by wood dust of western red cedar (Thuja plicata). Characteristically, the respiratory symptoms occurred in the evening and at night and not during working hours; inhalation challenge with plicatic acid from the wood provoked immediate, late or dual (combined immediate and late) asthmatic reactions. Another class of compounds, tropolones, derived from Thuja plicata wood, was responsible for dermatitis in a wood-worker. These distinct industrial hazards in two groups of workers at the tree-felling and wood-working levels in the forest-products industry can be identified by clinical history and examination supplemented by specific cutaneous or respiratory clinical investigation.

Alcohols↗

Allergenicity of common foods restricted in respiratory allergy.

Although hypersensitivity to foods is often linked to exacerbations of symptoms of respiratory allergy, no such information is available regarding the foods traditionally considered to play a probable etiological role in respiratory allergy in India, which are in fact quite different from the ones implicated in the West. The present study was undertaken to investigate whether the practice of withholding certain common foods by parents and practitioners of indigenous systems of medicine (i.e. Ayurvedic and Unani systems of medicine) in children suffering from respiratory allergy had any scientific basis or explanation as judged by modern techniques of investigation. Skin prick tests were performed on 64 children with symptoms pertaining to respiratory allergy (32 each in study and control group) using crude antigenic food extracts. Oral food challenges were administered to children to confirm or rule out allergenicity of food (s) incriminated on the basis of the clinical history and/or a positive skin test. Parental history of food restriction alone, in absence of positive skin prick test was of little value in predicting a positive response to the food challenges (1 challenge positive out of 77 based on food restriction: 1.29%). Only 27.02% and 18.75% of positive skin tests were found to be clinically significant in study and control groups respectively. Traditionally, food beliefs were upheld in only 12.5% children for immediate onset clinical reactions (with 5.31% of the foods restricted in their diet) and 9.37% children for delayed onset clinical reactions (with 3.19% of the foods restricted in their diet). The present study shows that even though food restriction is a common practice in patients with respiratory allergy in India, objective documentation of Type I reactions due to these foods cannot be obtained in a majority of such children.

Adolescent↗

Respiratory allergy.

Allergic rhinitis (AR) and asthma are common respiratory allergic disorders which are increasing globally more in developed countries. Although much has been written about childhood asthma and guidelines published by various international and national fora, not much information is available on AR. This is most common in children, is a significant risk factor for developing asthma, is a common comorbidity with asthma and affects quality of life. This paper highlights the risk factors for developing respiratory allergy asthma and AR, linkages between them and the management issues, particularly in relation to the allergic or allergological aspects as they have important bearing on management of children suffering from respiratory allergy. Specific immunotherapy (SIT) is re-emerging as useful therapy which alone has the potential to modify the natural history of disease and prevent the 'allergic march'. Timely diagnosis, correct management including timely referrals can ensure good quality life for those suffering from respiratory allergies.

Child↗

Pharmacology of upper respiratory allergy.

Patients with upper respiratory allergy may benefit from the use of many pharmacologic products. Using the simplest form of therapy that will relieve the problem is usually both clinically efficacious and cost efficient. Understanding the indications, benefits, and potential adverse effects of each group of drugs, particularly the classic and new antihistamines, decongestants, intranasal and systemic corticosteroids, and mast cell stabilizers (such as cromolyn) will provide direction for the best total patient care.

Adrenal Cortex Hormones↗

Respiratory allergy: hazard identification and risk assessment.

Various chemicals and proteins of industrial importance are known to cause respiratory allergy, with occupational asthma being the most important manifestation of the disease. This paper describes clinical syndromes, mechanisms associated with occupational respiratory hypersensitivity, and methods available currently for the prospective identification of potential respiratory allergens. Certain classes of chemicals are commonly associated with occupational respiratory allergy. There is insufficient information, however, to predict respiratory sensitization potential from analysis of structure alone, although reactivity with proteins is likely to be relevant. As yet there exist no fully validated or widely applied predictive methods or internationally harmonized guidelines. The most promising predictive animal methods are the mouse IgE test and guinea pig models. Work in mice has focused upon events occurring during the induction phase of sensitization following primary encounter with the test chemical. In contrast, guinea pig models have been used primarily to identify respiratory allergens (chemicals or proteins) as a function of elicitation reactions induced in previously sensitized animals. Given the possible serious health manifestations of respiratory allergy, early identification of respiratory sensitizers is urgently required. The two methods should, as a priority, be developed further and the production of a detailed protocol for these methods be undertaken to facilitate further validation. Together, this information will allow for two types of risk assessment associated with respiratory allergy: the risk that exposure to a material will (1) induce sensitization in an individual and (2) elicit allergic reactions in a previously sensitized individual.

Allergens↗

Evidence for major genetic control of wheeze in relation to history of respiratory allergy: Humboldt family study.

We report the results of segregation analyses for wheeze before and after a history of respiratory allergy was taken into consideration. The analyses were based on data from 309 nuclear families with 1,053 individuals living in the town of Humboldt, Saskatchewan in 1993, and were performed by using the REGD program of the SAGE package. For adults, information on wheeze and history of respiratory allergy was provided by themselves, and for children, by their parents. Segregation analyses were first conducted before adjustment for history of respiratory allergy. Other covariates were adjusted including sex, current smoking, household exposure to tobacco smoke, and type of house. A single locus model with residual familial effects fit the data well, but none of the Mendelian models (recessive, dominant, and codominant) could be distinguished. The no-parent-offspring-transmission hypothesis was rejected. However, when the variable of respiratory allergy was included in the models as a covariate, both Mendelian and environmental hypotheses were rejected. The Mendelian model had a relatively lower value of Akaike's Information Criterion than did the environmental model (1095.56 versus 1111.24). The data suggest that a single locus gene explains a portion of wheeze that is related to respiratory allergy, and that common environmental factors and/or polygenes also account for a certain familial aggregation of wheeze.

Adolescent↗

Basidiomycete mycelia and spore-allergen extracts: skin test reactivity in adults with symptoms of respiratory allergy.

One hundred fifty adults, with respiratory-allergic disease, and 14 control subjects, without symptoms of respiratory allergy, were skin prick tested with 16 common inhalant allergens, 12 extracts of mycelia from Basidiomycetes grown in vitro, and/or 10 to 15 basidiospore extracts. Eighty-three subjects (58%) had positive skin tests to two or more of the common inhalant allergens. Twenty-seven percent of the study subjects had positive skin reactions to one or more of the Basidiomycete mycelia extracts, and 32% demonstrated positive skin reactions to one or more basidiospore extracts. None of the 14 control subjects had positive skin reactivity to basidiospore extracts. Skin prick reactivity of study subjects to 15 different basidiospore extracts ranged from 5% for Cantharellus cibarius to 17% for Scleroderma sp. The prevalence of skin test reactivity to basidiospores did not differ significantly from the reactivity to commercial mold extracts of several common species of the Fungi Imperfecti (6% for Cladosporium herbarum or Penicillium notatum to 13% for Alternaria tenuis). These results demonstrate that a significant number of individuals reporting symptoms of respiratory allergy have skin test reactivity to basidiospores and suggest that these spores are important fungal aeroallergens in the New Orleans environment.

Adult↗

The microbiology of chronic sinus disease in children with respiratory allergy.

Chronic maxillary sinusitis is common in children with respiratory allergy and is associated with increased morbidity. The bacteriology of chronic sinus disease in these children has not been adequately evaluated. Between May 1987 and January 1988, 12 children (aged 3 to 9 years), all with documented respiratory allergy and chronic respiratory symptoms consistent with chronic sinusitis (greater than 30 days), were fully evaluated. History, physical examination, complete blood count, nasal smear, and Waters x-ray were done. All patients had opacification of one or both maxillary sinuses, failed to respond to multiple courses of antibiotics, and subsequently underwent maxillary sinus aspiration and irrigation. Specimens were cultured for aerobic and anaerobic organisms with standard technique, and sensitivities were obtained. Culture results revealed a single organism (Moraxella [Branhamella] catarrhalis) in five patients, one patient yielded M. catarrhalis plus Streptococcus species, three were negative, and three patients grew multiple organisms (two with multiple aerobic streptococcal species and one patient with aerobic streptococci and Peptostreptococcus). All children received appropriate culture-directed antimicrobial therapy. Sequential biweekly follow-up revealed progressive radiographic clearing and significant symptomatic improvement. M. catarrhalis is a common pathogen, whereas anaerobic organisms are unusual as a cause of chronic maxillary sinusitis in allergic children. Some children, despite negative cultures, may benefit from maxillary sinus irrigation.

Child↗

Prevalence of sensitization to aeroallergens in California patients with respiratory allergy. Allergy Skin Test Project Team.

BACKGROUND: The number of allergy skin tests required to evaluate patients with respiratory allergy has recently been challenged by the managed care community. OBJECTIVES: The purpose of this study was to determine which aeroallergens are prevalent in patients with respiratory allergy (allergic rhinitis and bronchial asthma) in California. METHODS: Utilizing aeroallergens thought to be relevant from recent aerobiologic and botanic data, 141 allergic and 17 asymptomatic control subjects were tested for the prevalence of 103 allergens. A standardized prick puncture technique and standardized interpretation of wheal/flare responses were utilized using the same lot of allergen for 13 allergy practices distributed throughout California. Frequency curves based on prevalence were established to determine the number of tests required to give up to 90% of positive responses for tree, weed and grass pollen, mold spores, and miscellaneous allergens which included house dust mite, cat, dog, and cockroach allergens. RESULTS: Positive responses in allergic subjects for grasses ranged from 46% to 54%, for weeds 19% to 37%, and for trees 10% to 42%. For molds the range was from 11% to 22%. The response rate for Dermatophagoides pteronyssinus was 53%, for Dermatophagoides farinae 42%, for cat pelt 39% and cat hair 37%, for cockroach 23% and dog dander 19%. Asymptomatic control subjects responded to only 4% of all allergens tested. Ninety percent of all positive tests required three miscellaneous allergens (house dust mite, cat, and cockroach), 9 molds, 2 grasses, 16 weeds, and 27 trees for a total of 57 allergens (56% of total tested). There was no clear relationship between locale and specific allergen response, probably related to the limited number of subjects tested and variability within the same geographic region. Several seldom tested tree and weed allergens showed a higher prevalence rate than several commonly tested for allergens. CONCLUSIONS: This preliminary study suggests that approximately 57 aeroalleroens might be adequate to detect 90% of all positive responses in patients with respiratory allergy in California. This study was limited by subject number and variability between study sites. It is hoped a standardized model can be developed from this pilot study to definitively determine which aeroallergens are relevant in the United States.

Adult↗

The type of sensitizing allergen can affect the evolution of respiratory allergy.

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. METHODS: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. CONCLUSION: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.

Adolescent↗

Addressing the prevalence of respiratory allergy in the home environment.

Respiratory allergy prevalence has always depended both on genetic predisposition and specific environmental allergenic stimulation that leads to sensitization and eventual symptomatic disease. Changes brought about by modern technology that have afforded a higher quality of life have also accidentally increased the levels of many respirable and ingestible allergens in the environment. In many cases these higher levels of exposure have exceeded individual thresholds, resulting in the phenotypic expression of allergy in many individuals who were previously asymptomatic even though they were genotypically predisposed to developing allergies. Prevalence can be decreased only if susceptible populations are identified as early as possible through careful family history taking and appropriate testing for sensitivity and if exposure to selected allergens is controlled.

Air Pollution, Indoor↗

Dose-response relationships and threshold levels in skin and respiratory allergy.

A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well as for intradermal and topical elicitation of allergenic responses in epidemiological, clinical, and animal studies. Skin damage or irritation may result in a significant reduction of the no-effect level for a specific compound. With respect to the respiratory tract, dose-response relationships and no-effect levels for induction were found in several human as well as animal studies. Although dose-response relationships for elicitation were found in some epidemiological studies, concentration-response relationships were present only in a limited number of animal studies. Reported results suggest that especially relatively high peak concentrations can induce sensitization, and that prevention of such concentrations will prevent workers from developing respiratory allergy. Moreover, induction of skin sensitization may result in subsequent heightened respiratory responsiveness following inhalation exposure. The threshold concentration for the elicitation of allergic airway reactions in sensitized subjects is generally lower than the threshold to induce sensitization. Therefore, it is important to consider the low threshold levels for elicitation for recommendation of health-based occupational exposure limits, and to avoid high peak concentrations. Notwithstanding the observation of dose-response relationships and no-effect levels, due to a number of uncertainties, no definite conclusions can be drawn about absolute threshold values for allergens with respect to sensitization of and elicitation reactions in the skin and respiratory tract. Most predictive tests are generally meant to detect the potential of a chemical to induce skin and/or respiratory allergy at relatively high doses. Consequently, these tests do not provide information of dose-response relationships at lower doses such as found in, for example, occupational situations. In addition, the observed dose-response relationships and threshold values have been obtained by a wide variety of test methods using different techniques, such as intradermal exposure versus topical or inhalation exposure at the workplace, or using different endpoints, which all appear important for the outcome of the test. Therefore, especially with regard to respiratory allergy, standardized and validated dose-response test methods are urgently required in order to be able to recommend safe exposure levels for allergens at the workplace.

Allergens↗

Allergenic fungi spore records (15 years) and sensitization in patients with respiratory allergy in Thessaloniki-Greece.

BACKGROUND: The prevalence of respiratory allergy to fungi spores (FS) is not precisely known but is estimated at 20-30% of atopic patients. There are no aerobiological records, necessary for respiratory allergy diagnosis and treatment, in Thessaloniki and generally in Greece. AIM: Creation of a database on FS circulation and investigation of skin sensitivity (SS) of asthmatics by using skin prick tests (SPT). MATERIAL AND METHODS: Daily records and identification of 15 airborne FS species were conducted, using a Burkard trap during 1987-2001. SS to 5 most common FS extracts was investigated, by using SPT in a total of 1311 asthmatics with atopy, submitted to the Out-Patient Clinic of Asthma (Pulmonary Dept, Aristotle Univ, Thessaloniki) in 1990-2001. RESULTS: The FS recorded in the 15-year period were as follows: Cladosporium spp. (72.2%), Alternaria spp. (9.8%), Ustilago spp. (8.1%), Ascospores (2.7%), Agrocybe spp. (1.5%), Helminthosporium spp. (1.4%), Leptosphaeria spp (1.2%), Agrogybe spp. (1.1%), whereas the species Botrytis, Stemphylium, Pleospora, Nigrospora, Epicoccum. Fusarium, Torula and Phoma presented concentrations <1%. The highest numbers of airborne FS were recorded during summer. Positive skin reaction to FS was observed in 421 (32%) patients of the 1311 asthmatics. Positive skin reaction to Altemaria species was observed in 177 patients (13.5%), in 98 (7.4%) to Cladosporium, 65 (5%) to Aspergillus, 45 (3.4%) to Fusarium and 36 (2.7%) to Rhizopus. FS sensitivity is much more frequent in younger men. CONCLUSIONS: For the first time in Thessaloniki-Greece, 15 allergenic FS species circulation has been recorded for the last 15 years. SS was more frequently detected for the species of Alternaria, Cladosporium and Aspergillus.

Air Microbiology↗

Allergen-specific sublingual immunotherapy for respiratory allergy.

Present knowledge regarding the clinical efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of respiratory allergy is reviewed. Allergen-specific immunotherapy is presently considered a 'biological response modifier' for the treatment of respiratory allergy, to be used in association with drug therapy and allergen avoidance. Its value in the treatment of these conditions has been established in position papers from the World Health Organization and the European Academy of Allergology and Clinical Immunology. Immunotherapy is usually administered subcutaneously (SCIT), and with this route several severe adverse events and fatalities have been described. Therefore, in the last 15 years, novel and safer routes of administration (local routes) have been developed. SLIT, in particular, has been investigated in 18 randomised controlled clinical trials. SLIT's clinical efficacy (improvement in symptoms and reduction in drug intake) in both asthma and rhinitis has been clearly assessed in 16 of these studies and for the most common allergens. SLIT's safety profile, derived from the clinical trials and from post-marketing surveillance studies, was shown to be satisfactory in both adults and children. The most frequently reported adverse events are gastrointestinal complaints, which can be avoided through appropriate dosage adjustment. For these reasons, SLIT has been accepted as a viable alternative to SCIT in recent position papers. The main advantages of SLIT are its safety (no severe systemic adverse event has ever been described) and good patient acceptance, especially in children; in addition, SLIT is a self-administered treatment that can be carried out at home by the patient. In contrast to injection immunotherapy, knowledge of the mechanisms of action of SLIT is still developing, albeit rapidly, although interesting data about its pharmacokinetics in humans are available. Data are also required concerning the possible preventive and long-lasting effects. SLIT is a viable alternative to SCIT, with the same rationale and indications. It is intended to be used in association with proper pharmacological treatment, at the earliest stages of the disease, for optimal management of respiratory allergy.

Administration, Sublingual↗

[The role of phadiatop in the screening of respiratory allergy].

Phadiatop is a new in vitro screening test for respiratory allergy. This test, based on the RAST procedure, detects in serum, the presence of specific IgE to a mixture of common inhalent allergens. Among 70 patients (26 children and 44 adults) consulting for respiratory syndrome, Phadiatop was positive in 31 cases. There were a good correlation between this new test and skin tests (59% for adults and 92% for children), total IgE (70% for adults and 65% for children) and RAST (93% for adults and 96% for children). Phadiatop, with a specificity of 100%, a sensitivity of 82% (76% for adults and 92% for children) and an efficiency of 90% (86% for adults and 96% for children), is a more accurate test than total IgE and could be an excellent in vitro screening test for respiratory allergy.

Adolescent↗