bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defence against allergic sensitization in the healthy lung: the role of inhalation tolerance
Authors: HOLT P. G. , McMENAMIN C. 
Published: April 2006

SummaryExperimental animal studies indicate that under normal steady‐state conditions, initial encounters with non‐pathogenic antigens (i.e. inert proteins, such as pollens) do not trigger immune responses, but instead activate antigen‐specific suppressor T cells which protect against subsequent allergic sensitization by inducing a state of immunological tolerance towards the inhaled antigen. This inhalation tolerance phenomenon appears analogous to the more familiar process of oral tolerance in the gastrointestinal tract, and is proposed to serve as the ‘last line of defence’ against sensitization to aero‐allergens which have evaded other levels of containment in the respiratory tract. It is postulated that this tolerance process plays a similar protective role in man, as the final component of a multi‐layer defence system centering upon the respiratory epithelium. Recent findings which indicate that both oral and inhalation tolerance mechanisms are relatively slow to develop postnatally, provides a possible basis for the increased risk of allergic sensitization recognized in infancy.
IgE‐mediated allergy in adults with severe atopic eczema
Authors: BARNETSON R. StC. , WRIGHT A. L. , BENTON E. C. 
Published: April 2006

SummaryA study was carried out of 45 adults with atopic eczema sequentially admitted to the Dermatology wards in the Royal Infirmary, Edinburgh. The clinical course of the eczema, the associated atopic conditions and the possible role of inhalant and food allergens were assessed. Most subjects had developed eczema in early childhood, but nine of the 45 developed it for the first time after the age of 15 yr. Eleven subjects outgrew their eczema around puberty only to experience recrudescence in their late teens. In 18 subjects the eczema was flexural until the late teens, when it became widespread. In this group of severely affected subjects, 25 had a history of asthma, 29 had either seasonal or perennial rhinitis, and 10 had current symptoms of food allergy. All but one had elevated total serum IgE concentrations (range 63–50 000 kU/1). Using dilutions of the subjects' serum in the radio‐allergosorbent test, an estimate of the specific IgE to 10 allergens (three inhalants, seven foods) was obtained, where 1 RAST unit is roughly equivalent to 1 IU total IgE. Most of the IgE was produced in response to the inhalant allergens tested (grass pollen, house dust mite and cat epithelium), 32 of the subjects having a RAST score of 3 or 4 to each of the three inhalant allergens, with the remaining 13 having a RAST score of 3 or 4 to at least one. The highest levels were to house dust mite, exceeding 1000 RAST units in 13 subjects. Thirteen subjects had a RAST score of 4 to at least one food allergen, with levels up to 1000 RAST units. Although this usually correlated with a history of allergy to the food (except in the case of wheat), some subjects with a positive RAST to a specific food could eat the food without problem. Overall these findings indicate that almost all subjects with severe atopic eczema have inhalant allergy, and produce high concentrations of IgE to inhalant allergens: roughly 25% of such subjects also have IgE‐mediated food allergy, and they have high IgE concentrations to certain food allergens. The role of inhalant and food allergy in adult atopic eczema remains questionable, but should be considered in the overall management of the subject.
The effect of histamine‐H1 receptor antagonism with terfenadine on concentration‐related AMP‐induced bronchoconstriction in asthma
Authors: PHILLIPS* G. D. , POLOSA R. , HOLGATE S. T. 
Published: April 2006

SummarySelective histamine‐H1 receptor antagonists inhibit adenosine 5′‐monophosphate (AMP)‐induced bronchoconstriction by > 80% when expressed as a percentage inhibition of the FEV1 time–response curve following inhalation of the provocation concentration of AMP required to produce a 20% decrease in FEV1 from baseline (PC20). To investigate this further we have determined that, in eight mild atopic asthmatic subjects, terfenadine (180 mg), administered 3 hr pre‐challenge, increases the geometric mean PC20 for histamine from 0.4 (range 0.03–3) mg/ml after placebo, to 20.2 (range 0.6–64) mg/ml following active treatment (P<0.0001). For AMP, the PC20 increased from 9.3 (range 1.0–113.3) mg/ml after placebo, to 150.2 (range 32.1–1177.7) mg/ml with terfenadine (P<0.0001). This 16.2‐fold (range, 5.5–47.9) displacement to the right of the AMP concentration–response curve by a selective histamine‐H1 receptor antagonist emphasizes the central role of histamine in the airways response to this nucleotide.
Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age—in‐vivo results
Authors: LILJA G. , DANNAEUS A. , FOUCARD T. , GRAFF‐LONNEVIG V. , JOHANSSON S. G. O. , ÖMAN H. 
Published: April 2006

SummaryOne hundred and sixty‐two women with respiratory allergy to animal danders and/or pollens were randomly allocated to a diet consisting of either a very low ingestion of hens' egg and cows' milk or a daily ingestion of one hens' egg and about 11 of cows' milk during the last 3 months of pregnancy. One hundred and sixty‐three infants were followed prospectively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly. No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy. The numbers of skin‐prick tests positive to ovalbumin, ovomucoid, β‐lactoglobulin and cows' milk were likewise not influenced by differences in the maternal diet during late pregnancy. Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy.
Aspirin‐like effects of selected food additives and industrial sensitizing agents
Authors: WILLIAMS W. R. , PAWLOWICZ ANNA , DAVIES B. H. 
Published: April 2006

SummaryA number of food additives and industrial chemicals, responsible for inducing symptoms of intolerance in some individuals, have been studied in tests measuring platelet activation by noradrenaline. All the investigated agents inhibited platelet aggregation and this was associated with inhibition of the cyclo‐oxygenase‐thromboxane pathway. Suboptimal inhibitory concentrations of the agents studied had additive inhibitory effects on platelet aggregation when they were tested in pairs, or when tested with salicylate or aspirin. The results support the theory that some food additives and industrial chemicals induce intolerance because of their aspirin‐like properties.
The subclass of IgG antibody in allergic disease: II. The IgG subclass of antibodies produced following natural exposure to dust mite and grass pollen in atopic and non‐atopic individuals
Authors: KEMENY D. M. , URBANEK R. , EWAN P. , MCHUGH S. , RICHARDS D. , PATEL S. , LESSOF M. H. 
Published: April 2006

SummaryIn an attempt to understand the role of the different IgG subclasses in allergic disease, we have studied the subclass of IgG antibody to dust mite (HDM) and grass pollen (GP) produced as a result of natural exposure. Studies were carried out on 40 atopic children and 100 atopic adults who had never received immunotherapy. Thirty‐two non‐atopic adult controls were also studied. The specificity of the assay for IgG antibodies to dust mite was confirmed by inhibition with the homologous extract but not mite culture medium or fetal calf serum. IgG1 antibodies to HDM could be detected in most atopics (94%) and non‐atopics (97%), and similar results were obtained for GP (81% and 100%, respectively). IgG4 antibodies to HDM were detected in more atopics (66%) than non‐atopics (53%) and the difference was more marked for GP (72% vs. 19%). While the levels of IgG1 antibodies were not significantly different in the two groups, the levels of IgG4 antibodies were much lower in the non‐atopics (P < 0.001, Mann–Whitney U‐test). These data show that all subjects were capable of recognizing and mounting an IgG1 antibody response to these inhaled antigens. Atopic individuals differed from normal subjects in the frequency with which they made IgG4 antibodies in response to natural exposure to both dust mites and pollen.
Pigeon breeders' disease: quantitative immunoelectrophoretic studies of pigeon bloom antigen
Authors: LONGBOTTOM JOAN L. 
Published: April 2006

SummaryThis study employed quantitative immunoelectrophoretic techniques, on sera from confirmed cases of pigeon breeders' disease (PBD), to investigate the antigenicity of a pigeon bloom extract, implicated as a sensitizing agent in this disease. On crossed immunoelectrophoresis the maximum number of antigenic components identified was 29 for the bloom compared to 10 for pigeon serum. A majorcomponent was shown to be closely related to pigeon IgA, and demonstrated partial crossreactivity to the pigeon IgG. This component also showed identity with the major component of a pigeon droppings extract, considered to be derived from intestinal IgA. Only trace amounts of serum albumin were detected and most other bloom components were not serum‐related. Although greater overall antigenic similarity was found to pigeon droppings extract, at least three of the bloom components appeared to be specific. The bloom extract also contained a low amount of an α‐techoic acid‐like component, causing some non‐specific reactivity. Pigeon feather dust or ‘bloom’, like pigeon droppings, is therefore a potent source of antigens associated with PDB–pigeon IgA being a major component of both antigens.
Histamine, antihistamines and atopic eczema
Authors: BEHRENDT H. , RING J. 
Published: April 2006

SummaryHistamine is known to be a classical inducer of pruritus. In atopic eczema, itch is a prominent feature (regarded by some even as a‘primary lesion’!). One of the most potent chemical mediators of itch is histamine. Histamine, together with other mediators may play a role in the pathophysiology of atopic eczema: the increased release of histamine from basophil leucocytes of atopic patients has been described, as well as elevated histamine levels in plasma and skin during acute exacerbations of eczematous lesions. Therefore, application of H1 antagonists seems to be a rational regime in the symptomatic treatment of atopic eczema. Nevertheless, some controversy exists regarding the clinical efficacy of orally applied H1 antagonists in this disease, especially with regard to the newer non‐sedating compounds such as terfenadine, astemizole, loratadine and cetirizine. Review of the literature shows that there are studies demonstrating a clear‐cut antipruritic effect of non‐sedating H1 antagonists. Thus the sedative action does not seem necessarily to be connected with therapeutic efficacy in treating itch in atopic eczema. Newer studies show that cetirizine exerts an additional inhibitory effect on eosinophils. This may broaden the therapeutic spectrum of this H1 antagonist in diseases with eosinophil involvement.
Atopic dermatitis: a defect of intracellular secondary messenger systems?
Authors: HOLDEN C. A. 
Published: April 2006

SummaryThe clinical manifestations of atopie dermatitis comprise a complex mixture of pharmacological, physiological and immunological responses. Circumstantial evidence suggests that atopic disease may arise consequent upon the migration of bone marrow‐derived cells into the target tissue of skin or respiratory mucosa. Mediator release from such cells has been shown to be abnormal in atopic dermatitis, and itch, the hallmark of the disease, may be the result of chronic inflammatory mediator release into the skin. Abnormal release of mediators has been shown to correlate with inadequate nucleotide control of cell function. In particular, elevated cyclic AMP‐specific PDE activity causing cyelic AMP hyporesponsiveness has been found in peripheral blood mononuclear leucocytes in atopic dermatitis. Investigation of this pathway has led to the discovery of additional abnormalities of other secondary messenger systems, including abnor‐malities of protein kinase C activity and of inositol activation. The biochemical abnormalities may be a consequence of down‐regulation of the second messenger systems because of chronic exposure to low levels of inflammatory mediators, but may themselves subsequently permit further mediator release. They may provide a biochemical mechanism for many of the immunological abnormalities seen in atopic dermatitis. In particular, they offer a biochemical explanation for the paradox of increased type 1‐mediated immunity and diminished cell‐mediated immunity commonly observed in this complex disease.
The effect of an inhaled steroid on the hypothalamic‐pituitary‐adrenal axis‐which tests should be used?
Authors: HOLT P. R. , LOWNDES D. W. , SMITHIES ELIZABETH , DIXON G. T. 
Published: April 2006

SummaryInhaled corticosteroids may produce systemic effects which include decreased hypothalamic pituitary‐adrenal (HPA) axis activity. Four tests of HPA axis function were assessed in 12 healthy volunteers, during inhalation of two actuations of beclomethasone dipropionate (250 μg) aerosol four times daily for 15 days, to determine the most appropriate test for this effect of inhaled corticosteroids. Measurement of basal adrenal activity showed that both 24‐hr urinary free cortisol and 0900 hr plasma cortisol were decreased by the fourth day of steroid treatment. All 12 subjects had decreases in basal adrenal activity. Overall the 24‐hr urinary free cortisol showed the greater change, with mean pre‐steroid baseline values of 497 and 515 nmol/24 hr reduced to 167 nmol/24 hr on the ninth day of treatment (P < 0.001). The single‐dose metyrapone test showed marked changes in each of the six subjects tested. The mean 11‐deoxycortisol response was 96 nmol/l on the eleventh day of treatment, compared to baseline and eighth‐day post‐treatment values of 439 and 407 nmol/1 respectively (P < 0.001). In contrast, no consistent treatment‐related changes were observed with the short tetracosactrin test. Only two out of six subjects had an abnormal short tetracosactrin test, although all showed a decrease in basal adrenal activity. From these results, the 24‐hr urinary free cortisol and single‐dose metyrapone test at 0600 hr are recommended to assess the effect of inhaled glucocorticoids on the HPA axis. The short tetracosactrin test failed to detect an effect from the same dose of inhaled beclomethasone dipropionate and cannot therefore be recommended to exclude the systemic effect of an inhaled steroid.
Effect of cetirizine in a conjunctival provocation test with allergens
Authors: SCHOENEICH MAGDALENA , PÉCOUD A. R. 
Published: April 2006

SummaryCetirizine is a new selective H1‐antagonist. In a double‐blind and placebo‐controlled study, 11 subjects underwent a conjunctival provocation test (CPT) with a grass pollen extract to determine the effect of cetirizine on allergen‐induced itching and redness of the eye. Results of CPTs were reproducible, as no difference was observed between the CPTs performed without any pre‐treatment and the CPTs after placebo. Compared to placebo, cetirizine administered orally (10 mg twice a day for 4 days) and in double‐blind fashion increased the conjunctival reaction threshold (P < 0.004) by inhibiting both redness and itching of the eye. Cetirizine should protect patients against allergic conjunctivitis.
Comparison of a multi‐allergen dipstick IgE assay to skin‐prick test and RAST
Authors: IWAMOTO I. , YAMAZAKI H. , KIMURA A. , OCHIAI K. , TOMIOKA H. , YOSHIDA S. 
Published: April 2006

SummaryA multi‐allergen dipstick enzyme immunoassay ‘Quidel Allergy Screen’ (QAS) has recently been developed commercially for measuring IgE antibodies against nine allergens (house dust 1, house dust 2, Dermatophagoides pteronyssinus, D. farinae, Japanese cedar, ragweed, cat dander, sweet vernal grass, and egg white) at one time. To assess whether this assay is useful in screening allergen‐specific IgE antibody, we compared the titres of IgE antibodies against the nine allergens measured by QAS to those in the skin‐prick test and by RAST in 93 atopic asthmatics and 22 normal subjects. We found a good overall agreement between the results of the skin‐prick test and the results of QAS (sensitivity = 47.1‐81.4%, specificity = 84.5‐100%, and agreement =78.9‐88.9%). The sensitivities against house dust I, D. pteronyssinus. and D. farinae ranged from 77.2 to 81.4%. However, the sensitivities against house dust 2, Japanese cedar, ragweed, and cat dander were low (47.1‐68.8%). We also found a good overall agreement between the results of RAST and the results of QAS, except for egg white (sensitivity = 46.2‐94.4%, specificity = 87.4‐100%, and agreement = 77.4‐96.5%). The sensitivities against house dust 1 and 2, D, pteronyssinus, D. farinae, and Japanese cedar ranged from 86.0 to 94.4%. The sensitivities against ragweed, cat dander, and sweet vernal grass were low (46.2‐52.6%). There were strong correlations between the titres of RAST and the titres of QAS except cat dander and egg white (r= 0.701 0.924 for the seven allergens). Thus, we conclude that QAS is useful in screening IgE antibodies against multiple allergens at one time. However, because the sensitivities against some allergens tested were low, further improvement of some allergen preparations seems to be necessary in the assay.
Ecology of house dust mites in Oxfordshire
Authors: HART B. J. , WHITEHEAD L. 
Published: April 2006

SummaryIn a survey of the mite fauna in 30 homes in Oxfordshire, Dermatophagoides pteronyssinus and Euroglyphus maynei were found to be the most abundant species but D. farinae was absent. Of a total of 14 parameters investigated for their influence on mite numbers, relative humidity was apparently the most important factor. Bedrooms with humidities above 64% contained significantly more mites in mattresses than those with lower humidities. Bedroom humidity and thus mattress mite numbers were apparently related and were influenced by the bedroom minimum temperature, the age of the house and the use of central heating. These trends were not seen in the numbers of mites found in living‐room carpets. Atopic and non‐atopic participants involved in this study did not differ significantly in the numbers of mites found in their homes.
The role of activated T lymphocytes in gastrointestinal disease
Authors: MACDONALD T. T. 
Published: April 2006

SummaryActivated T cells can be visualized in the intestinal lamina propria in a number of gastrointestinal diseases including food‐sensitive enteropathy (coeliac disease), inflammatory bowel disease and intractable diarrhoea of infancy. Experimental studies have shown that T‐cell activation in human intestinal lamina propria in vitro produces an increase in crypt cell proliferation, villous atrophy, increased HLA‐DR expression on enterocytes, increased intra‐epithelial lymphocyte numbers, and phenotypically, macrophage activation. All of these features are seen in human gastrointestinal disorders and it is proposed that T‐cell activation to wheat (in coeliac disease), milk (cows'milk‐sensitive enteropathy), and unidentified luminal antigens (Crohn's disease) plays a primary role in the pathogenesis of these disorders.
The inhibitory effect of terfenadine and flurbiprofen on early and late‐phase bronchoconstriction following allergen challenge in atopic asthma
Authors: HAMID M. , RAFFERTY P. , HOLGATE S. T. 
Published: April 2006

SummaryWe have studied the effect of cyclo‐oxygenase inhibition and H1‐receptor antagonism on the early and late bronchoconstrictor responses to inhaled allergen in mild atopic asthmatics. In the first phase of the study histamine inhalation challenge tests were performed in seven mild, atopic asthmatics 2 h after treatment with placebo or flurbiprofen (50, 100 or 150 mg). Flurbiprofen in these single doses had no effect on histamine reactivity. Ten atopic asthmatics participated in the second phase of the study in which the time course of the bronchoconstrictor response to inhalation of allergen was observed on four separate occasions after treatment with (a) placebo, (b) flurbiprofen, 150 mg, (c) terfenadine 180 mg, and (d) the combination of flurbiprofen and terfenadine. On each occasion subjects inhaled a concentration of allergen (Dermatagaphoide & pteronyssinus, grass pollen) that had previously been shown to produce a 30% fall in FEV1 (PC30 allergen). The mean maximum fall in FEV1 during the early reaction was 33·2 ± 3·3% from the post‐saline baseline value following placebo and this was reduced to 27·5 ± 5·3% after flurbiprofen (n.s.), 20·3 ± 3·2% after terfenadine (P < 0·05), and 23·1 ±2·3 after the treatment combination (P < 0·05). Seven subjects developed late asthmatic reactions (LAR) after placebo and in these subjects the mean maximum fall in PEFR during the LAR was reduced from 22·6 ± 3·1 % after placebo to 16·7 ± 3·2% after flurbiprofen (P < 0·05), 15·2 ± 2·3% after terfenadine (P < 0·05) and 11·5 ± 3·1% after the treatment combination (P < 0·01). Both terfenadine and flurbiprofen exhibited inhibitory effects on the early and late bronchoconstrictor responses to inhaled allergen implying roles for histamine and cyclo‐oxygenase products in both phases of the response. As the inhibitory effect of the drugs was not purely additive when administered in combination, this implies that the bronchoconstrictor actions of histamine and the prostaglandins are not independent following allergen challenge.
Symptoms of respiratory allergies are worse in subjects with coexisting food sensitization
Authors: FIORINI G. , RINALDI G. , BIGI G. , SIRONI D. , CREMONINI L. M. 
Published: April 2006

SummaryFood sensitization was evaluated in 78 subjects with respiratory allergies, both by skin tests with commercial and fresh allergens, and by specific IgE determination. On the basis of the presence or absence of the latter the population was divided into two groups. The group with food‐specific IgE showed more severe features of respiratory allergy, including a greater number of positive skin tests and specific IgE. determinations, more class 3 and 4 reactions, and more symptoms. The hypothesis that early food sensitization can predispose to severe inhalant allergy is discussed.
Ketotifen reduces sneezing but not histamine release following nasal challenge with antigen
Authors: MAJCHEL A. M. , PROUD D. , KAGEY‐SOBOTKA ANNE , LICHTENSTEIN L. M. , NACLERIO R. M. 
Published: April 2006

SummaryWe evaluated the effect of pre‐treatment with 1 and 2 mg b.i.d. of ketotifen on the early response to nasal challenge in a double‐blind cross‐over trial. Weekly nasal challenges were performed in 10 allergic subjects after 1 hr and 1, 2, 3 and 4 weeks of ketotifen administration. The response to nasal challenge was monitored by counting the number of sneezes, the assessment of subjective symptoms, and by measuring the levels of histamine and TAME‐esterase activity in recovered nasal lavages. The number of sneezes diminished significantly after a single dose of drug with both the 1 and 2 mg doses. Prolonged pre‐treatment did not improve the results. The levels of histamine and TAME‐esterase activity in recovered nasal lavages were not changed significantly by either pre‐treatment at either dose. Although the number of subjects was small, our data suggest that ketotifen diminishes allergic symptomatology by its antihistaminic properties rather than by inhibiting histamine release from mast cells. As we did not look into the effects of ketotifen on other products generated by mast cells (prostanoids, leukotrienes and tryptase), we cannot fully rule out an effect on mast cells.