Therapeutic problems of allergy specific immunotherapy for treatment of upper respiratory tract allergies

BACKGROUND: The outcome of management in patients with osteosarcoma and pulmonary metastases at a Sydney teaching hospital was reviewed. METHODS: A retrospective review was undertaken of all patients diagnosed with osteosarcoma and treated by the Bone and Soft Tissue Unit and the Medical Oncology Department, Royal Prince Alfred Hospital between 1979 and January 1995. Information was collected on demographics, tumour site, tumour histology, primary management including surgery and adjuvant therapy, and the subsequent development and management of pulmonary metastases. RESULTS: A total of 56 patients with localized osteosarcoma was seen. Overall survival and survival following pulmonary metastases was assessed. There were 33 (59%) males and 23 (41%) females, with a median age of 27 years. Survival at 5 years, for patients with non-axial osteosarcoma was 60% (95% CI, 44-77%). Pulmonary metastases without other metastatic disease being apparent, developed in 22 patients, of whom 12 underwent surgical resection. The median disease-free interval of these latter patients was 20 months (95% CI, 8-32 months). Median survival among patients not undergoing surgical resection was 5 months from detection of metastases. Patients undergoing resection of pulmonary metastases had a median survival of 17 months following detection of pulmonary metastases (95% CI, 7-27 months). Actuarial 5-year survival was 16% (95% CI, 0-42%). CONCLUSIONS: A small proportion of patients with resectable pulmonary metastases from osteosarcoma achieve long-term disease-free survival following surgical resection. It is not possible to accurately identify these patients prospectively.     

Specific immunotherapy in allergies--evaluation of current status

Specific immunotherapy is the treatment of choice in the therapy of inhalant allergies. Application route and dose regimen, selection and quality of allergens, as well as the individual patient represent different variables of immunotherapy to be considered. Premedication by oral antihistamines is mandatory for the reduction of side effects. Histamine-intolerance represents a contraindication for immunotherapy. Specific immunotherapy is highly efficacious leading to a 50-100% reduction of symptoms in nearly 90% of patients.     

Food allergy in patients with respiratory allergy. Diagnostic possibilities and problems

In the past two years the authors examined 28 patients with abdominal complaints and allergic respiratory symptoms. Detailed internal, gastroenterological, allergological examinations were made. METHODS: 1 skin Prick-test (SPT) with inhalative and nutritive panel 2. measuring of food-specific (gliadin, alpha-lactalbumin beta-lactoglobulin, ovalbumin) IgG-antibody level detecting with ELISA method, 3. leukocyte migration inhibition (LMI) test against the same foodstuffs, 4. histological examination of the stomach and the duodenum especially for mucosal mastocytes (MMCs). RESULTS: 1. SPT was positive in 23/28 patients for inhalative, but in the 5 cases we did not identify any inhalative allergen. The SPT for the main foodstuffs were positive in 18 patients while in 3 other patients there was urtica only for the other antigens. 2. The food-specific IgG-antibody level was increased in 18/27 patients against one or more antigens. The SPTs and the antibody determination showed identity in 8/18 cases. 3. The LMI tests were positive against one or more main food-products in 23/27 cases. There was common positivity in respect of antigens (between LMI test and antibody identification) in 17 cases. Pathological immunological reactions were presented against the same main foodstuffs with at least two methods for flour in 11, for egg in 10 and for milk in 12 patients. Endoscopic examinations were performed in 27 cases. The number of the MMCs were increased in 22/27 patients. After a specific elimination diet open-food challenges were performed and they confirmed the results of the in vitro and in vivo examinations. CONCLUSION: It is common that the respiratory allergic symptoms in atopic patients accompanied with food allergy for the main foodstuffs caused not only more severe respiratory symptoms, but abdominal complaints too. In respect to the many positive LMI tests the late-type hypersensitivity have important pathogenetical role in it. This three methods together define well the main food-products, which can be antigens as well. The examination of the MMCs supports the local disturbance in the immunoregulatory system.     

Specific immunotherapy using allergens apropos of specific immunotherapy by the sublingual route

The present number of publications an allergen specific immunotherapy (ITa) by clinically controlled tests, double blind, is objective proof of the value of this treatment in the allergy pathologies mediated by IgE. The mechanisms of action of Ita are better understood, taking account of the intervention of TH2 and TH1 cells with the respective involvement of cytokines IL4-IL5, favouring the synthesis of IgE and interferon gamma (IFN gamma) slowing the synthesis of IgE. Adjuvants of bacterial origin influence the balance TH2/TH1 by blocking the production of TH2 cells. Ita by the sublingual route (SLIT) has been the objective of double blind clinical studies, with favourable results and good tolerance, of a number of allergens, pollens (grass, ragweed, parietaria, olive) and D. pteronyssinus mites. Application of this technique of SLIT to foods and drugs reveals more a mechanism of customisation than induction of cellular acticity, of a mucosal secretory IgA and an oral tolerance with systemic response, mechanisms that are involved in SLIT. Taking into account the restrictions of ITa, SLIT allows inclusion of other allergic patients, such as children receiving injections and subjects who are not inclined to observe and comply with treatment.... The different techniques used for classical ITa by the subcutaneous route are also useable for SLIT with a very good tolerance, apart from some transitory digestive problems. SLIT is no longer a technique of the future, but already one of the present time, currently used and which gives a renewal of value in the form of therapy that is ITa for IgE-mediated allergy pathology.     

Results of specific immunotherapy with Allergovit in patients with pollen allergy

The immunotherapy among patients with pollen allergy was performed by individuals composed Allergovit. The effects of this treatment was compared to patients with pollenosis who don't have desensitization because they would'nt it. This results indicated that is need to do the nasal provocation test before the choice of antigens for the specific immunotherapy because the prick skin test was very often positive but patients don't have the symptoms. Precise composition of the vaccine improved the course in first season in 77.9 per cent, in second season in 87.5 per cent and in third season in 91.6 per cent.     

Assessment of the indoor environment in respiratory allergy

Many types of allergens may be present in the indoor environment and may lead to sensitization and respiratory allergy. Common indoor allergens include dust mites, animal dander, cockroach exposure and molds. Exposure to indoor pollutants, such as tobacco smoke, wood-burning stoves or fireplaces and chemical sprays, can precipitate and exacerbate symptoms. An allergic reaction in the airways caused by natural exposure to allergens has been shown to lead to an increase in inflammatory reaction, increased airway hyperresponsiveness and increased eosinophils in bronchoalveolar lavage. Other research has demonstrated that asthma symptoms correlate with levels of domestic dust mite and cockroach exposure. In the case of dust mites, ending exposure results in symptomatic relief.     

Effects of birch pollen-specific immunotherapy on apple allergy in birch pollen-hypersensitive patients

Electrophysiological testing remains an important efficacy parameter in clinical neuropathy trials. The quality of nerve conduction studies in reported trials varies greatly, and may be responsible for negative results. We report the utilization of an expert core lab for electrophysiological testing. With the core lab, the variability of repeat testing is comparable to that of a single, excellent laboratory. Motor conduction velocities demonstrated a coefficient of variation of 3% and sensory conduction velocities 4% across 60 study sites. The distal motor evoked potential amplitudes varied by 13% at the ankle, and 10% at the wrist. The sensory potential amplitudes varied by 16% at the ankle, and 11% at the wrist in 60 sites. The overall monitoring rate in all submitted nerve conduction tracings was 36.6%. Our results show that an expert core lab can improve the electrophysiological quality of clinical trial data with the potential to show small changes in nerve conduction velocities and in both motor and sensory potential amplitudes.     

Occupational respiratory allergy in bakery workers: a review of the literature

Baker's asthma has long been recognized as a serious disease among workers in the bakery industry and the number of cases with baker's asthma is steadily increasing. This paper presents a review of the available literature on baker's allergy with a special focus on the allergens involved, the epidemiologic research and issues on exposure assessment, evidence of exposure-response-relationships, and possible prevention strategies. A large number of potential allergens have been identified and are described here. At present little is known about the incidence of baker's allergy. On the other hand, a large number of cross-sectional studies have been performed, showing that sensitization and work-related symptoms are common among bakery workers. Only atopy and exposure level have consistently been reported as determinants of this occupational disease. Age, gender, and smoking habits do not seem to be associated with sensitization or work-related respiratory symptoms. Recently, immunochemical methods have been developed to measure specific allergens in the bakery industry, which have been used to unravel the role of allergen exposure in the development of baker's asthma. Clear exposure-response-relationships have been found. The implications of these recent findings for prevention strategies and standard setting are discussed.     

Specific V beta T cell subsets are associated with cat and birch pollen allergy in humans

Cognate interaction between TCRs and MHC class II molecules plays an important role in initiating the allergen-specific immune response. Therefore, we analyzed the TCR distribution of human PBLs of 56 atopic and nonatopic (NA) individuals, including 4 monozygotic twin pairs, from two extended and four nuclear families. The expression of 23 V beta and 3 V alpha elements was analyzed. The blood samples of symptomatic birch pollen-sensitized individuals that were taken < or = 6 wk after the birch pollen season (n = 8) showed a significantly higher frequency of V beta 16.1+ and V beta 20.1+ T cells compared with the blood samples of birch pollen-sensitized individuals that were obtained out of allergen season (n = 10) or from NA individuals (p < 0.0005 and p < 0.0001, respectively). Allergen-specific lymphocyte proliferation was detected in the allergic individuals, and the distribution of V beta 16.1+ and V beta 20.1+ T cells returned to normal levels after the pollen season. The frequency of these V beta-expressing T cells correlated with the levels of allergen-specific IgE Abs. In addition, cat-sensitized individuals (n = 8) showed a significantly higher frequency of V beta 17.1-expressing T cells than did NA individuals (p < 0.005). Our results indicate restricted TCR-V beta gene usage in cat and birch pollen allergies; we suggest that both genetic and environmental factors contribute to TCR-V beta gene expression and to the development of a specific T cell response.     

Factors influencing immediate responses to intradermal allergen administration in patients with respiratory allergy

BACKGROUND: Immediate skin reactions to allergens are influenced by several factors, such as the amount of administered allergen, the level of specific IgE, releasability of mast cells and hyperresponsiveness of the target organ. METHODS: For the evaluation of factors influencing immediate skin response to intradermal allergen administration, we measured the wheal size 15 min after intradermal injection of 0.01-0.02 ml of the following agents: whole-body extract of Dermatophagoides farinae, 1,000 allergy units/ml; histamine, 0.1 mg/ml, and codeine sulfate, 0.09% in saline, and determined total IgE level, specific IgE and IgG subclass antibodies to D. farinae in 53 patients with respiratory allergy. RESULTS: Multiple regression analysis for factors influencing wheal size after intradermal injection of D. farinae, specific IgE antibody level to D. farinae and wheal size after intradermal administration of histamine showed statistically significant results (R2 = 0.42739, p = 0.0000; R2 = 0.50243, p = 0.0185, respectively). Multiple regression analysis for factors influencing wheal size after intradermal administration in the group with high levels of specific IgE to D. farinae (RAST class 3 or more) showed that wheal size after intradermal administration of codeine was the only factor exerting a statistically significant influence (p = 0.0119). CONCLUSION: Based on the above results, we can state that immediate responses to intradermal allergen administration were influenced by the level of specific IgE and hyperresponsiveness of the target organ to histamine, but that the immediate skin allergic responses in the presence of high levels of specific IgE were partially but significantly influenced by the releasability of skin mast cells.     

Chemical respiratory allergy, IgE and the relevance of predictive test methods: a commentary

Polycystic ovary syndrome is a diagnosis made in 5%-10% of women between late adolescence and the menopause. Patients may present with oligomenorrhoea or amenorrhoea, anovulation or infertility, hirsutism or acne. Women with the syndrome have at least seven times the risk of myocardial infarction and ischaemic heart disease of other women, and by the age of 40 years up to 40% will have type 2 diabetes or impaired glucose tolerance. Polycystic ovary syndrome is associated with insulin resistance, with consequent hyperinsulinaemia and (frequently) hyperlipidaemia and obesity. Recent research has shown that the application of diabetes management techniques aimed at reducing insulin resistance and hyperinsulinaemia (such as weight reduction and the administration of oral hypoglycaemic agents) can not only reverse testosterone and luteinising hormone abnormalities and infertility, but can also improve glucose, insulin and lipid profiles. The management of polycystic ovary syndrome should now include patient education and attention to diabetes and cardiovascular risk factors such as hyperlipidaemia, obesity, physical exercise, glucose intolerance, hypertension and cigarette smoking.     

Codfish allergy in adults. Specific tests for IgE and histamine release vs double-blind, placebo-controlled challenges

BACKGROUND: At present, several in vitro tests for immunoglobulin E (IgE)-mediated food allergy are available. An estimation of the diagnostic accuracy of the various tests used in predicting clinical sensitivity to codfish in a well-characterized allergic material is necessary. OBJECTIVES: To compare the diagnostic value of four specific IgE tests, and histamine release from basophils (HR) in identifying clinical type I allergy to codfish. As a true diagnosis, double-blind, placebo-controlled food challenges (DBPCFC) were employed. METHODS: Eight clinically codfish-allergic adult patients were investigated together with 30 codfish-tolerant control subjects for evidence of codfish-specific reactivity by Phadebas RAST (PHA), Pharmacia CAP System RAST (CAP), Magic Lite (ML) and HR. To characterize the diagnostic properties of a freshly prepared raw codfish extract, experiments were conducted employing an in-house radioallergosorbent test (RAST), the Maxisorp RAST (MAXI) and HR. Finally, protein profile and IgE-reacting allergens were detected by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. RESULTS: The sensitivities of HR with commercial extract and the three commercially available specific IgE analyses were 0.83 and 1.00 respectively. Specificities were 1.00 (HR) and 0.87-1.00 (specific IgE tests). Freshly prepared codfish extracts improved the sensitivity of HR. SDS-PAGE revealed approximately 29 bands (< 14.3-200 kDa) including a band of 12-13 kDa, and in immunoblotting 18 sera identified 17 IgE-binding bands. The protein migrating at 12-13 kDa was identified in the fresh codfish extract tested with sera from all clinical codfish allergics, while no significant reaction was seen in the control subjects. CONCLUSION: Based on the small number of adult patients included in our study, the in vitro assays with commercial and fresh extracts have high sensitivity and are acceptable for screening for codfish allergy. Specificity of Phadebas, CAP, and our in-house RAST was less than unity, whereas ML and strong binding of IgE to a 12-13 kDa protein completely matches DBPCFC results, and thus seems sufficient for establishing the diagnosis.     

Induction of allergy to new aeroallergens during specific immunotherapy (SIT) in grass pollen sensitive patients

In the group of 50 patients suffering from grass pollen allergy and successfully treated with SIT for three consecutive years, we observed in 5 persons after the end of this treatment the induction of allergy to new allergens (to weeds, mites or tree) manifested by the change of the symptoms season. The induction of the new kind of allergy was confirmed by revealing of the positive skin prick tests to new allergens and by an increase of the specific IgE serum level to them. Despite disappearance of the symptoms of the illness during grass pollen season in all 5 patients we noted the higher total IgE as well as specific to grasses IgE serum level, in comparison to the value at the start of SIT. In the paper the possible mechanisms of this phenomenon are discussed, which seems to be not connected with the natural development of allergy and which confirms once more that during SIT individual changes in humoral and cellular immunity of the patient take place, sometimes very difficult to be predicted. They may among others switch clinical profile of allergy, what indicates that patient during SIT should be under the careful immunological supervision.     

Effects of air quality on chronic respiratory symptoms adjusted for allergy among preadolescent children

The aim of this study was to assess the respiratory effects of outdoor air pollution after correcting for allergy and indoor air quality. The respiratory health survey targeted 1,129 schoolchildren, 9 yrs of age, attending schools in Krakow located in city areas differing in outdoor air pollution levels. Chronic phlegm as a unique symptom was related neither to allergy nor to indoor variables, but was associated with the outdoor air pollution level (odds ratio (OR): 4.2; 95% confidence interval (CI): 1.1-16.9). The same relationship has been confirmed for the self-reported local sources of industrial air pollution in the area of residence (OR: 4.2; 95% CI: 1.5-11.7). Hay fever appeared to be related to outdoor air pollution level (OR: 1.43; 95% CI: 1.1-2.0) and self-reported heavy traffic (OR: 1.3; 95% CI: 1.0-1.7). In the total sample, wheezing was connected exclusively to allergy and parental atopy, while attacks of dyspnoea with wheezing and asthma diagnosed by physician only were associated with allergy. Since the effect of outdoor pollutants on chronic cough and wheezing (odds ratio: 1.85; 95% confidence interval: 1.03-3.33) was only shown to be significant in the subsample of children without allergy and parental atopy, it may be postulated that either allergy is predisposing to respiratory reactions, or outdoor air pollution is coinvolved in an allergization process of the preadolescent children. Consequently, allergy should be considered as an important confound in epidemiological studies on the respiratory effects of air pollution.     

Comparison of two techniques of automated screening in respiratory and food allergy (UniCAP versus IMMULITE)

Screening tests plays an essential part in primary allergy diagnosis, therefore they have to show the highest level of reliability. In order to assess how UniCAP system fulfill these requirements, in comparison with Immulite, we analysed the results obtained with Phadiatop, (UniCAP) and AlaTOP (IMMULITE) in 110 patients with a clinical positive diagnosis for inhalant allergy. Furthermore we compared the results from food allergy screening tests performed in 103 patients with a clinical positive diagnosis for food allergy and we analysed 110 tests results of controls with negative diagnosis for allergy. We obtained the following results: [table: see text] Samples for which the tests results were not in concordance with the clinical diagnosis were tested with the follow up panel of the different screening tests. We obtained a better concordance with Phadiatop, than with Alatop. Specificity of the inhalant allergy screening tests is the same in the two systems. We also obtained a better concordance with fx5 than with fp5. We conclude on the basis of their respective clinical sensitivity that both Phadiatop and fx5, available on UniCAP, better answer inhalant and food allergy screening needs than Alatop and fp5, available on Immulite.     

Genetics and allergy

Complex diseases, including diseases of allergic origin (asthma, rhinitis, dermatitis), tend to cluster in families, suggesting the existence of a genetic predisposition that has been confirmed by the family and twin studies. However, it is difficult to establish a clear Mendelian pattern of inheritance and it is accepted that multiple genes exist which have an additive effect (polygeny) and interact with environmental factors (multifactorial polygenic mechanism) to cause not only the atopic constitution but also the pathology that derives from it. Advances in genetics and molecular biology, through linkage studies in chosen family nuclei and different population groups, are facilitating the location of chromosomal regions related with allergic pathology. The genes situated in these regions are considered candidate genes, and the genes themselves and the functions that they control are studied in relation to allergic disease. Although there are regions and candidate genes distributed throughout the genome, chromosomes 5, 6, 11, and 14 contain genes whose responsibility for susceptibility to atopy, asthma and bronchial hyperreactivity is accepted and whose polymorphisms could be risk factors. The study of these genes and many other candidate genes may clarify some etiopathogenic aspects of diseases of allergic origin and improve their prophylaxis and therapy.