Showing papers in "Allergy in 1997"

A comparison of the efficacy and safety of inhaled corticosteroids in asthma.

Abstract: Since its development in the early 1950% glucocorticosteroid (GCS) therapy has been an important and often life-saving form of therapy in patients with severe asthma. The long-term use of systemic GCS therapy is, however, limited by major unwanted effects These include adrenal suppresdion, adverse changes in skin, bone and other connective tissues, and growth impairment in children. The severe systemic side-effects of long-term oral GCS therapy stimulated the development of GCS preparations that could be inhaled, in the hope of achieving a local effect in the lungs without a significant risk of unwanted systemic effects The initial inhaled therapy with compounds such as dexamethasone proved disappointing because the GCSs used had inadequate topical potency, and they were not rapidly metabolised to inactive compounds by the liver. The balance of wanted and unwanted effects changed greatly when the topically potent inhaled GCSs such as beclomethasone dipropionate (BDP) and budesonide (BUD) were introduced. This shows especially where high firstpass metabolism to inactive compounds in the liver has been demonstrated, as with BUD and fluticasone propionate (FP). The high safety margin of inhaled therapy with GCSs has encouraged an increasingly widespread use of these compounds in patients with moderate to severe asthma over the past 20 years Many S. Pedersen', P. O'Byme2

"Latex-fruit syndrome": frequency of cross-reacting IgE antibodies.

Abstract: An association between allergies to latex proteins and to various foods has been reported and confirmed by RAST and immunoblotting inhibition. However, no significant data had been collected on the frequency of specific IgE antibodies to fruits in these patients and the frequency of a history of fruit intolerance. Serum samples of 136 patients with well-documented, clinically relevant, immediate-type hypersensitivity against latex proteins were analyzed for IgE antibodies against a panel of different fruits. Patient history of food intolerance was documented by a standardized questionnaire. Fruit-specific IgE antibodies were detected in 69.1% of serum samples. Cross-reacting IgE antibodies recognizing latex and fruit allergens (papaya, avocado, banana, chestnut, passion fruit, fig, melon, mango, kiwi, pineapple, peach, and tomato) were demonstrated by RAST-inhibition tests. Of our patients, 42.6% reported allergic symptoms after ingestion of these fruits and a total of 112 intolerance reactions were recorded. However, fruit-specific IgE antibodies were detected only in serum samples from 32.1% of the patients who perceived symptoms due to these fruits. Thus, serologic tests seem to be of low significance for prediction of food allergy in latex-allergic patients.

Citations and journal impact factors: questionable indicators of research quality.

Abstract: Evaluation of research quality is one of the most important, yet one of the most difficult aspects of the scientific process. The traditional method of evaluation is peer review, whereby research plans or scientific results are scrutinized by scientific colleagues, assumed to possess the necessary expertise. However, peer review is all too often performed either by narrow specialists who are unable to compare different projects, or by people with broad scientific qualifications, but without the specific insight required to evaluate the ingenuity and originality of results generated within a scientific specialty. As a consequence, evaluation committees tend to produce reports lacking in internal consistency and fairness as well as in quahty. Resort is often had to secondary, superficial criteria, such as personal or institutional reputation, project relevance, journal prestige, crude publication counts, etc., giving the whole process the character of a lottery (1-4).

The role of diesel exhaust particles and their associated polyaromatic hydrocarbons in the induction of allergic airway disease

Abstract: The increase in allergic airway disease has paralleled the increase in the use of fossil fuels. Studies were undertaken to examine whether extracts of polyaromatic hydrocarbons (PAH) from diesel exhaust particles (DEP) (PAH-DEP) acted as mucosal adjuvants to help initiate or enhance immunoglobulin E (IgE) production in response to common inhaled allergens. In vitro studies demonstrated that PAH-DEP enhanced IgE production by tonsillar B-cells in the presence of interleukin-4 (IL-4) and CD40 monoclonal antibody, and altered the nature of the IgE produced, i.e. a decrease in the CH4'-CHe5 variant, a marker for differentiation of IgE-producing B-cells, and an increase in the M2' variant. In vivo nasal provocation studies using 0.30 mg DEP in saline also showed enhanced IgE production in the human upper respiratory mucosa, accompanied by a reduced CH4'-CHe5 mRNA splice variant. The effects of DEP were also isotype-specific, with no effect on IgG, IgA, IgM, or albumin, but it produced a small increase in the IgG4 subclass. The ability of DEP to act as an adjuvant to the ragweed allergen Amb a I was examined by nasal provocation in ragweed allergic subjects using 0.3 mg DEP, Amb a I, or both. Although allergen and DEP each enhanced ragweed-specific IgE, DEP plus allergen promoted a 16-times greater antigen-specific IgE production. Nasal challenge with DEP also influenced cytokine production. Ragweed challenge resulted in a weak response, DEP challenge caused a strong but non-specific response, while allergen plus DEP caused a significant increase in the expression of mRNA for TH0 and TH2-type cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) with a pronounced inhibitory effect on IFN-gamma gene expression. These studies suggest that DEP can enhance B-cell differentiation, and by initiating and elevating IgE production, may play an important role in the increased incidence of allergic airway disease.

The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

Abstract: Numerous studies published in the last 10-15 years have shown that nerve growth factor (NGF), a polypeptide originally discovered in connection with its neurotrophic activity, also acts on cells of the immune system. NGF has been found in various immune organs including the spleen, lymph nodes, and thymus, and cells such as mast cells, eosinophils, and B and T cells. The circulating levels of NGF increase in inflammatory responses, in various autoimmune diseases, in parasitic infections, and in allergic diseases. Stress-related events both in animal models and in man also result in an increase of NGF, suggesting that this molecule is involved in neuroendocrine functions. The rapid release of NGF is part of an alerting signal in response to either psychologically stressful or anxiogenic conditions in response to homeostatic alteration. Thus, the inflammation and stress-induced increase in NGF might alone or in association with other biologic mediators induce the activation of immune cells during immunologic insults. A clearer understanding of the role of NGF in these events may be useful to identify the mechanisms implicated in certain neuroimmune and immune dysfunctions.

Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20‐year survey

Abstract: Studies on the epidemiology of common adverse cutaneous drug reactions have rarely been reported, since they can only be successfully conducted in clinics of internal medicine employing consultant dermatologists and having a comprehensive or intensive system of monitoring. Between 1974 and 1993, the adverse skin reactions occurring in divisions of general internal medicine of three different hospitals were monitored by a computerized comprehensive system. The "drug-monitoring patient" was defined as the recipient of at least one drug during hospitalization. The relationship of the skin reactions to drug causality in these patients had to be either definite (proven by re-exposure) or probable (drug relation greater than that of nondrug causality). The skin reactions were classified into four diagnostic groups. Maculopapular exanthema, urticaria, and vasculitis were the three main groups. The fourth group comprised cases of nonhomogeneous but clinically well-defined special exanthema. For selected drugs and years of observation, special emphasis was placed on the study of time patterns (reaction time, exposure time). A total of 1317 definite or probable drug-induced skin reactions occurred during the hospitalization of 48,005 consecutively admitted "drug-monitoring patients": 1201 cases of maculopapular exanthema, 78 cases of urticaria, 18 cases of cutaneous vasculitis, and 20 cases of special exanthema (five of erythema multiforme minor, six of fixed eruption, one of photosensitivity reaction, and eight of acneiform eruption). The main drugs involved did not differ for the three main types of skin reactions, penicillins ranking in the first place, followed by sulfonamides--most often combined with trimethoprim--and in the third place nonsteroidal anti-inflammatory drugs. The reaction time (time from last drug exposure to first skin manifestation) for urticaria showed a relevant proportion of the acute type (within 1 h) and most of the subacute type (1-24 h). For maculopapular exanthema, the subacute or, rarely, the latent type (1-8 days, exceptionally more than 8 days) predominated. For aminopenicillins, the rate of occurrence of skin reactions increased with increasing exposure time up to 12 days, and then markedly diminished. Possibly due to the tendency to withdraw suspected drugs even in the case of minor (e.g., maculopapular) skin reactions, no severe events such as erythema multiforme major/Stevens-Johnson syndrome or toxic epidermal necrolysis occurred.

Correlations between skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges

Abstract: The skin prick test is the most widely used test for detecting IgE-mediated food hypersensitivity. Our study aimed to define firstly the correlations between results obtained with prick tests using commercial extracts and fresh foods, and secondly the correlations between these results and those obtained with labial and/or oral challenge. We compared the wheal diameters read at 15 min with commercial extracts and fresh foods, for four foods, in 430 children with suspected food allergy. For cow's milk, wheal diameters were larger with commercial extracts, but the difference was not significant. Conversely, wheal diameters were significantly larger with fresh foods for the other food allergens. Skin prick tests were positive in 40% of cases with commercial extracts and in 81.3% with fresh foods. The overall concordance between a positive prick test and positive challenge was 58.8% with commercial extracts and 91.7% with fresh foods. These results indicate that fresh foods may be more effective for detecting the sensitivity to food allergens. Fresh foods should be used for primary testing for egg, peanut, and cow's milk sensitivity.

Quality of life in adults and children with asthma and rhinitis.

Abstract: Many clinicians now recognize the importance of incorporating an assessment of health-related quality of life (HRQL) into their clinical studies and practice. Conventional clinical measures provide valuable information about the status of the affected organ system, but they rarely capture the functional impairments (physical, emotional, and social) that are important to the patients in their everyday lives. In order to obtain a complete picture of a patient's health status, both the conventional clinical indices and the patient's HRQL must be measured. Both adults and children with asthma and rhinitis are distressed by the symptoms, and they are limited in their day-to-day activities such as sports, work or school work, and participation in other activities with friends. In addition, both adults and children experience emotional strain as a result of both conditions. Disease-specific HRQL questionnaires have been developed and validated for both adults and children with asthma and rhinitis. These questionnaires have good measurement properties and validity and can be used in both clinical trials and clinical practice to assess the impact of the condition on a patient's life. Since one of the aims of treatment is to ensure that patients benefit from it, an essential component of clinical assessment should be an evaluation of HRQL.

Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long-term (6-year) follow-up

Abstract: The long-term effect of tree pollen extract immunotherapy was investigated 6 years after termination of the treatment. Subjective symptom evaluation of 36 patients 6 years after a 3-year period of immunotherapy showed that rhinitis and asthma symptoms remained at the improved level reached just after termination of the treatment. Some 86% of the rhinitis patients and 68% of the asthma patients maintained improvement. None of the rhinitis patients developed asthma in the study period. Skin prick tests reflected the outcome of the subjective symptom assessment. The skin sensitivity of the patients decreased significantly during immunotherapy, and the skin reactions 6 years after specific immunotherapy were still significantly lower than the pretreatment levels. Total IgE and birch-specific IgE levels were constant throughout the study period, and both the affinity and epitope specificity of the IgE antibodies of the patients were the same before, during, and 6 years after treatment. In conclusion, specific immunotherapy reduces symptoms in patients suffering from rhinitis and asthma, and the effect is maintained 6 years after termination of the treatment. Specific immunotherapy seems to prevent long-term development of asthma in rhinitis patients. IgE measurements do not reflect the overall status of the patients.

Evaluation of the prevalence of skin prick test positivity to Alternaria and Cladosporium in patients with suspected respiratory allergy. A European multicenter study promoted by the Subcommittee on Aerobiology and Environmental Aspects of Inhalant Allergens of the European Academy of Allergology and Clinical Immunology

Abstract: D'Amato G, Chatzigeorgiou G, Corsico R, Gioulekas D, Jager L, Jager S, Kontou-Fili K, Kouridakis S, Liccardi G, Meriggi A, Palma-Carlos A, Palma-Carlos ML, Pagan Aleman A, Parmiani S, Puccinelli R Russo M, Spieksma FThM, Torricelli R, Wuthrich B. Evaluation of the prevalence of skin prick test positivity to Alternaria and Cladosporium in patients with suspected respiratory allergy. A European multicenter study promoted by the Subcommittee on Aerobiology and Environmental Aspects of Inhalant Allergens of the European Academy of Allergology and Clinical Immunology. This trial was undertaken to study, in several geographically spread European countries, the prevalence of skin prick test (SPT) positivity to Alternaria (A) and Cladosporium (C) in subjects with nasal and/or bronchial symptoms of suspected allergic cause. Each patient completed an anamnestic questionnaire and underwent SPT with a panel of common inhalant allergens and also A and C supplied by three different laboratories, to allow for manufacturer bias. Specific scrum IgE determination was carried out only in subjects with SPT positivity to A and/or C with an immunoassay system. In nine European allergology centers, a total of 877 subjects was enrolled in the trial; 83 of them showed SPT positivity to A and/or C; only nine patients showed monosensitization to A, and none to C The highest percentage of positive subjects was found in Spain (20%); the lowest in Portugal (3%). In the other seven centers, the variation was 7–10%. The age range of mold-positive subjects was 5–60 years. Rhinitis was by far the most common symptom, whether associated or not with asthma and/or conjunctivitis.

Effect of tea polyphenols on histamine release from rat basophilic leukemia (RBL-2H3) cells: the structure–inhibitory activity relationship

Abstract: We studied the effect of tea polyphenols on histamine release from rat basophilic leukemia (RBL-2H3) cells. Among tea polyphenols, (-)- epigallocatechin gallate (EGCG) most strongly and dose-dependently inhibited histamine release from cells stimulated with a calcium ionophore, A23187. (-)-Epigallocatechin (EGC) and (-)-epicatechin gallate (ECG) with a triphenol residue moderately inhibited histamine release, whereas diphenolic (+)-catechin (C) and (-)-epicatechin (EC) did not. The magnitude of the inhibitory effect was in the order EGCG > ECG > EGC. Among simple polyphenols, the triphenol compounds, pyrogallol (PG) and gallic acid (GA) exerted inhibitory activity, but the diphenols, pyrocatechol, hydroquinone, and resorcinol did not. In addition, the mixture of PG and GA inhibited histamine release as strongly as EGCG with two triphenol residues. Similarly, they inhibited histamine release induced by IgE-antigen complex stimulation more efficiently than that induced by A23187 stimulation. EGCG did not inhibit the increase of intracellular Ca2+ in RBL-2H3 cells stimulated with A23187 or IgE antigen. These results indicate that the triphenol structure plays an important role in the inhibitory activity of tea polyphenols. Their activity seemed to be exerted through the metabolic events occurring after the elevation of intracellular Ca2+ concentration.

Epidemiology of allergic diseases

Abstract: The escalation of allergic diseases (hay fever, asthma, atopic eczema) over recent decades has been linked to an increase in environmental pollutants. The prevalence of hay fever is associated with genetic predisposition, and some reports show an association with urban areas, socioeconomic status, and combined high allergen and automobile exhaust exposure. In asthma, there is also some evidence for geographical variations in prevalence; exercise challenge tests prove positive more often in urban areas than in rural areas. Although genetic predisposition is the strongest single risk factor for atopic eczema, air pollutants may aggravate the condition by acting as unspecific irritants and immunomodulators, leading to increased immunoglobulin E expression. In a study of 678 pre-school children, the influence of maternal smoking habits on individual measures of atopy revealed a positive association between smoking during pregnancy/lactation, and a positive history of atopic eczema. An East-West German comparative study examining different types and levels of air pollution, i.e. sulphurous (industrial; East) and oxidising (urban; West), showed that the prevalence of atopic eczema was greatest in East Germany. When various direct and indirect parameters of air pollution exposure were measured, the greatest association with atopic eczema was found with NOx exposure (indoor use of gas without a cooker hood), and close proximity to roads with heavy traffic. The increased prevalence of atopic eczema cannot be explained by changes in study methodology over time, or conventional risk factors alone; environmental risk factors may be an important contributing factor.

Low‐dose cyclosporin A in the treatment of severe chronic idiopathic urticaria

Abstract: In a limited number of severe chronic idiopathic urticaria (CIU) patients, low-dose cyclosporin A (CsA) treatment was found to be effective. This open study aimed to extend this clinical observation and determine the safety of treatment with CsA. In addition, it aimed to determine the prevalence and characteristics of the autologous serum skin test (AST) in such patients, and whether this test is affected by CsA treatment. Thirty-five patients who suffered from severe CIU (score 3), and who were followed for 6 months (using a clinical urticaria-severity score [range 0-3]) were divided into three groups: 19/35 were treated for 3 months with low-dose CsA, and thereafter followed for an additional 3 months; 6/35 dropped out of protocol treatment; and 10/35 untreated patients (followed for the same period) served as a disease controls. In the treated group, no side-effects were observed, and by the end of treatment, 13/19 (68%) patients were in full remission (score 0) and the remainder scored 1. In contrast, the 10 CsA-untreated patients scored 3 for the whole follow-up period of 6 months. Positive AST was found in 14/35 (40%) of patients, whereas none were detected in 20 healthy control subjects. AST neither correlated with disease activity nor predicted response to treatment. This uncontrolled study shows that low-dose CsA is effective in treating CIU patients, and can be given safely for 3 months. However, CIU patients requiring initially high doses of glucocorticosteroids and with a long clinical history are less amenable to CsA treatment.

Genes, environments, and sex: factors of importance in atopic diseases in 7—9–year‐old Swedish twins

Abstract: Various atopic manifestations among adults have been shown to be influenced mainly by genetic factors. With the increase in prevalence of atopic diseases in recent years, especially among children, a great deal of attention has been given to environmental causes. In a study of 1480 Swedish twin pairs, 7-9 years old, we examined the importance of genetic and environmental factors in asthma, hay fever, eczema, and urticaria. Structural equation model fitting showed 33-76% of the variation in liability to the diseases to be due to genetic effects. Shared environmental effects were also important for hay fever and urticaria in both sexes and for eczema among girls. The clustering of atopic disease in families was almost entirely due to a common set of genes, but each disease manifestation also seemed to have specific genes of importance. Investigation of unlike-sex twins showed that boys had a higher cumulative incidence of asthma and hay fever than girls, whereas girls had a higher incidence of eczema. Thus, it may be concluded that although genetic factors are of major importance in atopic manifestation in children, both environmental and sex-related factors play a role.

Anisakis simplex, a relevant etiologic factor in acute urticaria

Abstract: Del Pozo MD, Audicana M, Diez JM, Munoz D, Ansotegui IJ, Fernandez E, Garcia M, Etxenagusia M, Moneo I, Fernandez de Corres L. Anisakis simplex, a relevant etiologic factor in acute urticaria. Anisakis simplex, a parasite of fish and cephalopods, can induce IgE-mediated reactions. This study aimed to determine the etiologic role of A. simplex in patients affected by urlicaria/angioedema ‘AE’ or anaphylaxis. We studied 100 adult subjects suffering acute episodes of urticaria/AE, by anamnesis, prick tests with A. simplex and fish-mix extracts, and total and specific IgE to both A. simplex and cod. The following criteria of A. simplex allergy were considered: 1’ urticaria/AE within 6 h after fish ingestion; 2’ specific IgE to A. simplex; 3’ positive prick test to A. simplex extract; 4’ exclusion of other suspected causes. Double-blind, placebo-controlled food challenge was not carried out because ethical considerations forbid challenge with a parasite. Specific IgE to A. simplex‘<0.7 kU/1’ was found in 22 subjects, but only eight were diagnosed as having A. simplex allergy. Other allergens were involved in 37 patients, and 55 cases were considered idiopathic. Specific IgE to fish ‘<0.7 kU/1’ was found in two patients, but only one was diagnosed as having fish allergy. We concluded that A. simplex is an important etiologic factor in acute urticaria. We suggest that it should be considered in cases of urticaria/AE or anaphylaxis, especially after fish ingestion.

Incidence of asthma in adults – report from the Obstructive Lung Disease in Northern Sweden Study

Abstract: Incidence studies offer a better opportunity to study risk factors for asthma than do prevalence studies. However, regular prospective follow-ups of large cohorts are difficult to perform, and that is why direct measurement of the incidence rate of asthma is almost impossible. Thus, cross-sectional follow-up studies of defined cohorts can be used to provide data on incidence. In 1986, a postal questionnaire survey on respiratory symptoms and diseases was performed in the northernmost province of Sweden. The population sample comprised all subjects born in 1919-20, 1934-5, and 1949-50 in eight representative areas of the province, which comprises 25% of the total area of Sweden. Completed answers were given by 5698 subjects (86%) of the 6610 subjects invited to the study. In 1992, the cohort was invited to a follow-up survey during the same season as in 1986, and 6215 subjects were traced. Of the 5393 subjects who answered the questionnaire, 4932 had participated in the 1986 survey, or 87% of those who participated in 1986. For the period 1986-92, the cumulative incidences of asthma were 4.9 and 5.0%, respectively, as assessed by the questions, "Have you ever had asthma?" and "Have you been diagnosed as having asthma by a physician?" Thus, the results indicate a mean annual cumulative incidence of asthma of 0.8%. After correction of the results for subjects who were diagnosed as having asthma in the clinical part later in the 1986 study, the mean annual cumulative incidence of asthma was found to be 0.5%. Risk factors were family history of asthma (OR 3.46) and current and former smoking, while female sex was a strong trend.

Allergenicity of α‐caseins from cow, sheep, and goat

Abstract: The allergic potential of alpha-caseins from bovine, ovine, and goat's milk sharing more than 85% identical amino acids was compared. Caseins were purified by anion-exchange chromatography and used for a specific IgE and IgG ELISA with diluted human sera. Sera were from 17 children with immediate-type allergy to cow's milk, from 59 children with atopy but without food allergy, and from 27 healthy children without atopy disease. The sera of cow's milk-allergic children showed a significantly higher IgE and IgG binding to alpha-caseins from all three species than the sera of the other groups. All groups showed an increased antibody binding to bovine alpha-casein compared to the sheep and goat proteins, but the differences were significant only in the groups of atopic children and of healthy controls. Furthermore, inhibition of the IgE binding to bovine alpha-casein with alpha-casein from cow, goat, and sheep revealed that the alpha-casein from these species are highly cross-reactive; on the basis of the small differences in their primary structure. In conclusion, the milk of goat and sheep harbor an allergic potential and is not suitable for the nutrition of milk-allergic patients.

Cross-reactivity between IgE-binding proteins from Anisakis German cockroach, and chironomids

Abstract: Pascual CY, Crespo JF, San Martin S, Ornia N, Ortega N, Caballero T, Munoz-Pereira M, Martin-Estaban M. Cross-reactivity between IgE-binding proteins from Anisakis German cockroach, and chironomids. Anisakis simplex larvae parasitize animals used as seafood and can produce a specific immune response in man. The ingestion of seafood contaminated with stage three of A. simplex larvae can induce a specific IgE response with clinical symptoms, usually urticaria, even if the fish is cooked before ingestion and the invasive infestation power destroyed by heating. Our preliminary studies showed a strong association of A. simplex sensitization with Ascaris lumbricoides, Daphnia chironomid spp., Atlantic shrimp ‘Pandalus borealis’ and German cockroach ‘Blattella germanica’. We conducted the cross-reactivity study with cockroach, a ubiquitous insect, and Chironomidae ‘red mosquito larvae’, a work-related allergen, without any possibility of Anisakis contamination. Serum samples were collected from 60 pediatric patients, with serum specific IgE to A. simplex. Both specific-IgE and immunoblot-inhibition studies, with a serum pool from 18 patients, were performed to determine whether the association of sensitizations to nematodes and arthropods was due to immunologic cross-reactivity. In addition, serum samples from 21 of 60 patients who showed also sensitization to German cockroach were used for individual immunoblot studies. In the serum pool, dose-dependent inhibition of B. germanica and Chironomus spp. was observed after preincubation with the A. simplex extract. Immunoblot of Anisakis inhibited with Chironomus and German cockroach, yielded a partial blot inhibition but mainly on bands below 41 kDa. Blot inhibition of German cockroach and Chironomus with Anisakis was dose related. The band patterns in individual blots were heterogeneous, but most of them had bands of 30–43 kDa. None of these sera recognized allergens in the 14–kDa area. In our study, CAP-inhibition and immunoblot-inhibition analysis of Anisakis showed that several IgE-binding components could be shared by the three allergens.

Mechanisms of pollution-induced airway disease: in vitro studies in the upper and lower airways.

Abstract: Evidence from both epidemiological and laboratory-based studies suggests that increased exposure to liquid petroleum and gas-derived air pollutants [nitrogen dioxide (NO2), ozone, and respirable particulate matter] may play a role in the clinical manifestation of both allergic and non-allergic airway disease. The mechanisms and cell types involved in pollutant-mediated effects in the airways, however, are not clear. In vitro studies have suggested that human fibroblasts, B-lymphocytes, alveolar macrophages, and epithelial cells/cell lines may be involved. Studies of fibroblasts and macrophages have demonstrated that exposure to ozone results in decreased cell viability and increased release of pro-inflammatory mediators from macrophages. Similarly, studies of B-lymphocytes have demonstrated that exposure to diesel exhaust particles (DEP) enhances the synthesis of immunoglobulin E by these cells. The airway epithelial cells have received the greatest attention in mechanistic studies of air pollution-induced airway disease and suggest that these cells are likely to play a pivotal role in the pathogenesis of airways disease. Various studies have demonstrated that exposure of nasal or bronchial epithelial cells to NO2, ozone, and DEP results in significant synthesis and release of pro-inflammatory mediators, including eicosanoids, cytokines, and adhesion molecules. Additionally, evidence suggests that epithelial cells of atopic individuals release significantly greater amounts of cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-8, and regulated on activation, normal T-cell expressed and secreted (RANTES), on exposure to NO2 and ozone. Studies investigating the biological relevance of epithelial cell-derived pro-inflammatory mediators have shown that these enhance eosinophil chemotaxis and eosinophil adherence to endothelial cells, suggesting that pollution-induced inflammation of the airways is likely to be influenced by modulation of epithelial synthesis and release of these mediators.

Definition, prevalence and development of nasal obstruction

Abstract: Nasal obstruction is defined as discomfort manifested as a feeling of insufficient airflow through the nose. Thus defined, nasal obstruction is a subjective complaint. Common synonyms for nasal obstruction are nasal stuffiness and nasal blockage. However, some authors have considered the word “obstruction” to imply the existence of an obstacle in the nose, thus suggesting the term to have an objective importance. Regarding the term nasal patency, prevailing opinion in the literature is that it denotes an objective measure of how open the nose is. The practically useful methods, which in a strict sense measure nasal patency, are acoustic rhinometry, computed tomography and magnetic resonance imaging. Often rhinomanometry and nasal peak flow measurements are also included among the methods for measuring nasal patency, although they record nasal airflow with and without, respectively, simultaneous pressure recordings. The latter methods yield data on the dynamic function of the nose, whereas acoustic rhinometry and imaging provide a static impression of nasal function. “Congestion” is another word often used regarding the nose. It is used by the clinician examining the nose, or in research to denote swollen mucosa caused by dilatation of the capacitance vessels. Decongestants act by constricting blood vessels. Increased nasal obstruction is not always accompanied by increased nasal airway resistance (NAR), decreased nasal peak flow, or reduced acoustic rhinometry values. Nasal obstruction is also one of the complaints of patients with atrophic rhinitis, a disorder with wide nasal cavities. In the presence of a common cold, NAR may, at least periodically, be within normal limits, despite the patient’s sensation of nasal obstruction. On the other hand, spraying the nose with menthol increases the sensation of nasal patency withMax Jessen’, Lars Malrn2

Latex allergy diagnosis: in vivo and in vitro standardization of a natural rubber latex extract.

Abstract: For the diagnosis of IgE-mediated (immediate) hypersensitivity to natural rubber latex (NRL), skin prick testing with extracts of latex gloves has been widely used, but such extracts are difficult to standardize. The present study aimed to produce on an industrial scale an NRL extract from freshly collected NRL and to evaluate, calibrate, and standardize the extract by both in vivo and in vitro testing. The source material, latex of the rubber tree, Hevea brasiliensis (clone RRIM 600), was frozen immediately after collection in Malaysia and shipped in dry ice to Stallergenes SA, France. Protein and allergen profiles were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, isoelectric focusing (IEF), crossed immunoelectrophoresis (CIE), and crossed radioimmunoelectrophoresis (CRIE). Allergen quantification was effected by RAST inhibition. The capacity of the preparation to elicit immediate hypersensitivity reactions in vivo was measured by skin prick testing in 46 latex-allergic patients and 76 nonallergic control subjects. SDS-PAGE and immunoblot profiles of the extract and an NRL standard (E8) provided by the US Food and Drug Administration were almost identical, disclosing several distinct IgE-binding proteins with apparent molecular weights of 14, 20, 27, 30, and 45 kDa, conforming to reported molecular weights of several significant NRL allergens. An arbitrary index of reactivity (IR) of 100 was assigned to the extract at 1:200 dilution (w/v), having a protein content of 22 micrograms/ml. Skin prick testing of latex-allergic patients and controls using the extract at 100 IR revealed 93% sensitivity, 100% specificity, 100% negative predictive value, and 96% positive predictive value. In conclusion, a skin prick test reagent for diagnosis of type I NRL allergy was successfully standardized. The reagent was demonstrated to contain most, if not all, of the currently known clinically significant NRL allergens, and it showed high sensitivity and specificity.

Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels.

Abstract: After observing a patient allergic to cat dander and pork but devoid of other allergies, we prospectively screened patients known to be allergic to cat for a second sensitization to pork. After collecting the sera of 10 young patients found to contain specific IgE to cat dander and pork, we undertook this study to detect the possible cross-reactive allergen, define its molecular characteristics, and evaluate its clinical relevance. Through immunoblotting techniques, cat and porcine serum albumin were found to be jointly recognized molecules. These findings were further analyzed by specific anti-albumin IgE titrations and cross-inhibition experiments. Cat serum albumin cDNA was obtained from cat liver, and the corresponding amino acid sequence was deduced and compared to the known porcine and human serum albumin sequences. Inhibition experiments showed that the spectrum of IgE reactivity to cat serum albumin completely contained IgE reactivity to porcine serum albumin, suggesting that sensitization to cat was the primary event. In two cohorts of cat-allergic persons, the frequency of sensitization to cat serum albumin was found to lie between 14% and 23%. Sensitization to porcine albumin was found to lie between 3% and 10%. About 1/3 of these persons are likely to experience allergic symptoms in relation to pork consumption. Sensitization to cat serum albumin should be considered a useful marker of possible cross-sensitization not only to porcine serum albumin but also to other mammalian serum albumins.

Mechanism of aspirin-induced asthma

Abstract: Shortly after its introduction into therapy, aspirin was implicated as the cause of a violent bronchospasm. Tlie association of aspirin sensitivity, asthma, and nasal polyps was described by F. Widal and eolleagues in 1922. Tliis clinical entity, subsequently named the aspirin triad, was brought to physicians' attention by Samter & Beers (1), who, in the late 1960s, presented a perceptive description of the elinical course of the syndrome. Adverse reactions to aspirin and other nonsteroidal anti-inflammatory drugs (NSAID) may have various clinical presentations and different pathogeneses (2-4). Here we discuss one of these presentations. It affects asthmatics and indeed constitutes a special type of asthma called aspirinindueed asthma (AIA).

Prevalence of lysozyme sensitization in an egg‐allergic population

Abstract: An egg protein, lysozyme, is a still unlabeled additive currently used in cheese preparation. Furthermore, the WHO-FAO committee considers it innocuous. However, 31% of children and 8% of adults with food allergies are allergic to eggs. This work aimed to determine the percentage of patients sensitized to lysozyme from a population of egg-allergic patients. Specific IgE was determined with Cap RAST in 52 patients clinically allergic to egg. Thirty-five percent of egg-allergic patients had antilysozyme IgE. Given this high incidence of lysosozyme sensitization, it seems that the presence of lysozyme should be indicated on food labels.

Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity

Abstract: To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double-blind, placebo-controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo-treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo- and verum-treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum-treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite-allergen-induced asthma may reduce not only immediate, IgE-mediated symptoms but, after a rather long time period of 12-18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.

A 1‐year, placebo‐controlled, double‐blind house‐dust‐mite immunotherapy study in asthmatic adults

Abstract: Thirty-one adult patients with asthma caused by house-dust mites (HDM) were included in this placebo-controlled, double-blind study to evaluate the efficacy and safety of specific immunotherapy (SIT) with biologically standardized extracts of HDM. The specific diagnosis was confirmed by skin prick tests, specific IgE, and bronchial provocation tests with HDM allergens. The patients were randomized to receive active treatment with extracts of either Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard® SQ, ALK, Denmark) or placebo injections. Twenty-three patients completed the study. After 1 year of treatment, we found a clinically important and significant reduction in both asthma medicine consumption (inhaled steroids 38% and β 2 -agonists 46%) and symptom score (57%) in the actively treated group, but not the placebo group. These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group. Additionally, there was a significant difference in the patients' scores for effect in favor of the actively treated group. Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group. Spirometric lung-function measurements showed a significant increase in forced expiratory volume in 1 s (FEV 1 ) from 85% before to 89% of predicted values after treatment for the actively treated group. Peak-flow measurements at home showed no significant changes during the study. It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM.

Microvascular anatomy of the nose

Abstract: The microvasculature of the nose consists of: 1) A dense subepithelial network of capillaries, with fenestrations between the endothelial cells. This network provides nutrients to the epithelium and glands, and allows passage of water into the lumen for evaporation and air-conditioning. 2) A system of capacitance vessels or sinuses, which when they distend, block the nasal lumen, and when they empty, open the nasal passages. Changes in their volume will affect the filtering and air-conditioning functions of the nose. 3) Arteriovenous anastomoses which allow rapid passage of blood through the mucosa. They are probably important in air-conditioning, and in the countercurrent mechanisms that tend to keep the brain cool in a hot dry climate. The anatomical interrelationships between these different systems is not well understood, nor is their differential control in terms of actions of mediators and nerves. In neurogenic inflammation sensory nerves are excited and release local mediators such as substance P via axon reflexes. These sensory neuropeptides will cause vasodilatation, vascular congestion and extravasation of liquid from the postcapillary venules, with resultant oedema and exudate. They may also cause secretion from the submucosal glands.

Provocation tests with allergens

Abstract: It seems that the first allergen challenge was performed by Blackley in 1873 (1). He applied fresh pollen to the lining membrane of his nares provoking itching, rapidly followed by sneezing and discharge of serum. Moreover, he provoked positive bronchial responses by inhaling particles, including fungal spores. Lowell & Schiller (2) were the first to demonstrate that allergen could be administered by inhalation employing aerosols of allergen extracts, and the responses could be measured quantitatively with a spirometer. Subsequently, the improved techniques for pulmonary function testing, the advent of nebulizers that give reproducible doses, and good penetration and deposition of particles in the lower airways (3) together with standardized allergen extracts have significantly improved the methods of provocation so that results may be considered satisfactory and data from different centers may be compared. Several articles have appeared regarding standardized bronchoprovocation testing (BPT). A science citation search revealed that the standardized method of BPT proposed by the United States National Institute of Health Committee, later adopted by the American Academy of Allergy and Immunology, is one of the most highly referenced in world literature (4). This technique requires the intermittent administration of graded doses of aerosol, repeated pulmonary function tests, the construction of a dose-response curve and the determination of the PD,, FEV,: the provocation dose necessary for a 20% decrease in FEV, which may be interpolated from the curve. Another technique requires tidal volume breathing of graded concentrations of aerosols for 2-minute periods, with periodic pulmonary function tests and also the construction of a dose-response curve (5 ) . The PC,,, or the concentration necessary for a 20% decrease in FEV,, is determined from this curve. Another recently proposed method involves the use of a powder device to deliver a dry powder aerosol to the lung (6). With this innovative technique, incremental doses of dry powder capsules that contain lyophilized antigen are inhaled, and a dose-response curve is constructed after the determination of sequential pulmonary function tests. All three methods have a good reproducibility and there is a good correlation between the two aerosol techniques (7, S), between provocation with allergen in solution and in powder form (9) and between the dosimeter and powder method (10). Because of inter-laboratory differences, however, each laboratory should be responsible for its own coefficient of reproducibility. Care should be taken not to confuse PD,, (breath units) with PC,, (a derived concentration). Details of the respective techniques can be found in the source literature for the intermittent method (ll), the continuous method (5, 12) and the dry powder method (6). Although BPT are widely used, there is no international consensus as to how the tests should be performed, nor is there agreement on their standardization, indication and uses. In an attempt to rectlfy somewhat this situation, an international committee produced an update of guidelines for standardization of BPT with allergens (11). Furthermore, in 1990, the European Academy of Allergy and Clinical Immunology (EAACI) established a Subcommittee on Bronchial Provocation Tests with Allergens. The aims of the Subcommittee were to define indications, to describe the types of allergen extracts, to define the methods for BPT, to define the sensitivity, specificity and reproducibility of the results and to provide cautions and contraindications Initially, the subcommittee’s mandate was limited to bronchial provocation tests; later it was extended to nasal and conjunctival tests. A Steering Committee was appointed to draw up the various chapters, which were circulated to other EAACI members who expressed an interest in the topic.

The pharmacological basis for the treatment of perennial allergic rhinitis and non‐allergic rhinitis with topical corticosteroids

Abstract: The currently available respiratory topical corticosteroids are all effective at reducing the nasal symptoms of itch, sneezing, rhinorrhoea and obstruction associated with allergic rhinitis. The mechanism of action of corticosteroids is related to their anti-inflammatory activities. They have been documented to prevent fluid exudation and reduce the number of circulating inflammatory cells, including lymphocytes, mast cells, basophils, eosinophils, macrophages, and neutrophils. This occurs through multiple mechanisms, e.g. eosinophil infiltration is suppressed by preventing cytokine production, reducing local mechanisms of tissue infiltration, and decreasing eosinophil survival. Furthermore, corticosteroids also reduce preformed and newly-generated mediators (e.g. histamine, tryptase, prostanoids, leukotrienes), and inhibit production of cytokines and chemokines by inflammatory cells (e.g. IL-1 through IL-6, IL-8, RANTES, TNF-alpha, IFN-gamma and GM-CSF). The currently available corticosteroids differ pharmacologically. Fluticasone propionate appears to have the greatest affinity for the glucocorticoid receptor, and binds more quickly and dissociates more slowly from the receptor compared with other corticosteroids, suggesting a more prolonged duration of action. Its increased specificity for respiratory tissue may lead to greater potency with less potential for systemic adverse effects. Fluticasone propionate has been compared with other corticosteroids in animal models for relative topical and systemic potency, and according to these data, it has the most favourable risk-benefit ratio.