bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of ketotifen on allergen‐induced bronchoconstriction and skin weal
Authors: TAMURA G. , MUE S. , TAKISHIMA T.
Published: April 2006

Abstract. A single‐blind cross‐over method was used to investigate the effects of ketotifen on the total respiratory resistance response curve to inhalation of a high concentration of allergen (1:5 w/v house dust or 1:10 w/v Japanese cedar pollen) and the weal response to intradermal injection of serially diluted allergen (1:103–1:106 w/v). Five subjects received 2 mg of ketotifen every 12 hr for the first week and an inactive placebo in the same manner for the second week. The remaining five subjects received the placebo for the first week and ketotifen for the second week. Ketotifen did not alter base‐line pulmonary function, but significantly delayed the time from the start of allergen exposure to the beginning of elevation of total respiratory resistance (P<0·02), and the time from the start of allergen exposure to the point at which total respiratory conductance decreased by 35% from the base‐line value (P<0·01). Ketotifen also decreased skin test sensitivity significantly (P<0·01)
Reproducibility of responsiveness to a standardized bronchial allergen provocation—Rt compared to FEV1 as measurement of response to provocation
Authors: FRØLUND L. , MADSEN F. , SVENDSEN U. G. , NIELSEN N. H. , WEEKE B.
Published: April 2006

Standardized bronchial allergen provocation was performed twice in nineteen extrinsic, well defined, stable asthmatic patients, with an interval of median 15 days (range 14–19) to study the reproducibility of the bronchial response. Smoking and medications were withheld prior to the provocation after a rigid scheme. Ten‐fold increasing concentrations of allergen solution 0.9 ml were inhaled by tidal volume breathing for 5 min with intervals of 10 min. The bronchial response to inhaled allergen was determined by forced expiratory volume in the first sec (FEV1) and by total resistance to breathing (Rt) determined by an opening interrupter method. The provocation was continued until an allergen concentration causing at least 20% decrease of the postsaline FEV1 or a 40% increase in Rt was reached. A PC20‐FEV1 and a PC40‐Rt was calculated by interpolation on the log‐dose‐response curve. The reproducibility of PC20‐FEV1 allergen was high with a 95% confidence interval (CI) for a single determination being the observed value ±0.83, ten‐fold concentration difference, the intraclass correlation (IC) was 0.99 and the coefficient of variation 8.46%. Concerning PC40‐Rt a 95% CI for a single determination was calculated being the observed value ±0.58, ten‐fold concentration difference, IC was 0.99 and the coefficient of variation was 5.79%. No significant correlation was found between differences in pre‐challenge FEV1 and Rt values and the corresponding PC20‐FEV1 and PC40‐Rt values. Least square regression between PC20‐FEV1 and PC40‐R1 was performed for the first and the second provocation (P < 0.05). We conclude that bronchial allergen challenge performed in stable asthmatics is highly reproducible and as such a valuable test in the diagnosis of allergic asthma when connected with anamnesis, skin‐prick test and the level of specific immunoglobulin E in peripheral blood.
Diagnostic value of the skin‐prick test and RAST assay in insect sting allergy
Authors: GREEN‐GRAIF Y. , EWAN PAMELA W.
Published: April 2006

The results of skin‐prick tests to four concentrations of venom (0.1, 1, 10 and 1000 μg/ml) carried out on two occasions were analysed in relation to the history of adverse reactions to stings and to the level of venom‐specific IgE antibody in serum, in forty‐two subjects allergic to insect stings (sixteen to bee and twenty‐six to wasp). Fifty control subjects (some of whom had never been stung by bee or wasp) with no history of adverse reaction to stings were also studied. No subject gave a positive skin‐test reaction to 0.1 μg/ml, and small numbers reacted to either 1 or 10 μg/ml. The lowest concentration of venom to which most subjects had a positive skin test was 100 μg/ml. Our data suggest that in wasp‐allergic patients a positive skin test to 100 μg/ml is normally significant (reflecting the presence of specific IgE), whereas in bee‐allergic patients a skin test reaction to 100 μg/ml is usually non‐specific for the following reasons.

(i) In the allergic patients when skin tests were repeated, a reaction to 100 μg/ml bee venom often became negative (in six of eight), whereas for wasp venom the reaction became more positive (at 10 or 1 μg/ml) in seven of eight patients. Whilst this might reflect lack of reproducibility, the consistent direction of change for either bee or wasp venom suggests responses to this concentration of these venoms may have different interpretations.

(ii) In bee‐allergic patients, where positive skin tests to 100 μg/ml wasp venom were found they were repeatable in all patients, and occurred only in patients who had been stung by a wasp. In wasp‐allergic patients, skin test reactions to 100 μg/ml bee venom were not reproducible between studies in any patient and often occurred in subjects never stung by a bee.

(iii) A better correlation between skin test and RAST occurred for wasp venom when a skin‐test reaction to 100 μg/ml was included as a positive (rather than reactions to 1 or 10 μg/ml only). For bee venom the correlation did not improve when skin‐test reactions to 100 μg/ml were included.

(iv) In the control group, skin‐test reactions to 100 μg/ml bee venom were often false positives (seven of eight had never been stung by a bee). Four out of fifty controls reacted to wasp venom 100 μg/ml, but three of these had received a wasp sting.

These findings suggest that in routine clinical practice skin tests should be carried out over the range 1–10 μg/ml in bee‐allergic subjects but in wasp‐allergic patients 100 μg/ml should also be included. Extracts of 0.1 μg/ml need not be used.
Nasal challenge with pollen grains, skin‐prick tests and specific IgE in patients with grass pollen allergy
Authors: BOUSQUET J. , LEBEL B. , DHIVERT HENRIETTE , BATAILLE Y. , MARTINOT B. , MICHEL F. B.
Published: April 2006

Nasal challenges with pollen grains are as close as possible to natural pollen exposure, but they are not well documented in grass pollen allergy. Forty‐four grass pollen allergic patients and ten non‐allergic volunteers were tested by means of nasal challenge, quantitative skin‐prick tests with a standardized orchard grass pollen extract and serum‐specific IgE. Nasal challenges were performed with lactose and increasing concentrations of orchard grass pollen grains (15–3645 grains, three‐fold increase). The test was considered to be positive when a symptom score over 5 was obtained, since this score had been previously correlated with the release of PGD2 in nasal secretions. All control subjects and 3/44 patients had a negative challenge. The number of orchard pollen grains required to elicit a positive challenge was 332 ± 440 (range: 15–1215 grains) and the distribution was Gaussian. This number is higher than expected according to pollen calendars performed during the season, but owing to the priming effect of the nasal mucosa by allergens it is compatible to natural exposure. The correlation between nasal provocation tests and skin‐prick test end‐points was significant (P < 0.005, Spearman rank test). Conversely there was no correlation between nasal challenge or skin‐prick test end‐point and serum‐specific IgE.
Lack of allergenic cross‐reactivity between storage mites and Dermatophagoides pteronyssinus
Authors: VAN HAGE‐HAMSTEN MARIANNE , JOHANSSON S. G. O. , JOHANSSON EVA , WIREN A.
Published: April 2006

The allergenic cross‐reactivity between storage mites (Lepidoglyphus destructor, Glycyphagus domesticus, Tyrophagus putrescentiae and Acarus siro) and the house dust mite Dermatophagoides pteronyssinus was studied with the radio‐allergo‐sorbent test (RAST) and the RAST inhibition technique. RAST‐positive sera were obtained from fifty‐three farmers who were positive to at least one of the four storage mites. Sera from twelve of these farmers, eight of whom were also positive to D. pteronyssinus, were investigated with the RAST inhibition technique. No significant correlations were found between IgE‐antibody levels to any single storage mite and D. pteronyssinus. There was no correlation between the RAST results to A. siro and G. domesticus, whereas a significant correlation was found between L. destructor, G. domesticus and T. putrescentiae. The RAST inhibition studies confirmed the greater allergenic similarity between L. destructor, G, domesticus and T. putrescentiae than between A. siro and the other three storage mites. The results of our studies support the hypothesis that each of the storage mites and D. pteronyssinus possess their own unique allergen or allergens. Furthermore, L. destructor, G. domesticus and T. putrescentiae seem to be allergenically more closely related to each other than to A. siro.
Prevention of fog‐induced bronchospasm by nedocromil sodium
Authors: ROBUSCHI M. , VAGHI A. , SIMONE P. , BIANCO S.
Published: April 2006

A single dose double‐blind crossover study was performed to compare the efficacy of nedocromil sodium (4 mg) and placebo administered from pressurized aerosols against bronchoconstriction induced by the inhalation of ultrasonically nebulized distilled water (fog) in twelve asthmatic subjects. Neither active nor placebo pre‐treatment produced any significant change in baseline FEV1 and SRaw. Nedocromil sodium significantly attenuated fog‐induced falls in FEV1 (P < 0.001) and increased specific airways resistance (SRaw, P < 0.01). The results provide further evidence of the potential therapeutic usefulness of nedocromil sodium in the management of chronic obstructive airways disease.
Allergy to venom from bee or wasp: the relation between clinical and immunological reactions to insect stings
Authors: HEINIG J. H. , ENGEL T. , WEEKE E. R.
Published: April 2006

Sixty‐three patients, applying to the casualty ward after a bee or wasp sting, were tested. On the day of admission, and 4 weeks later, blood was sampled to measure specific IgE and IgG against bee and wasp venom and total IgE. Four weeks after the insect sting, all patients were examined with skin‐prick test (1, 10 and 100 μg/ml), and intracutaneous test (0.05 ml of extract 1.0 μg/ml). The amount of venom‐specific IgE and IgG increased significantly during the 4‐week period, venom‐specific IgE was most pronounced in patients experiencing the most severe clinical reactions. However, no significant correlations were found between the results of the immunological tests carried out 4 weeks after the insect sting and the clinical reaction upon the insect sting.
ELISA method for measurement of airborne levels of major laboratory animal allergens
Authors: PRICE JILL A. , LONGBOTTOM JOAN L.
Published: April 2006

Three types of air‐sampling apparatus (the Air‐Sentinel, Burkard Personal Sampler and Casella Personal Sampler) were compared for their use in sampling the air in situations where individuals are exposed to laboratory animals, and a cascade impactor was used to determine the sizes of particles carrying the allergens under investigation. An ELISA, using monospecific antisera raised to selected major allergens of the mouse, rat and rabbit, i.e. mouse Ag 1 (mouse urinary prealbumin), rat Ag 4 (rat urinary prealbumin) and rabbit Ag R1, was developed to assay the extracts obtained from the samplers. This ELISA system was able to detect < 5 ng/m3 of allergen in sampled air. The rat and mouse allergens were shown to be carried mainly on particles of 6–18 μm, whereas the rabbit allergen was also found on particles of 2 μm and smaller. Allergen levels correlated well with the number of animals present in the room and the degree of activity during sampling. A protective filtered‐air hood, when worn during surgical operation procedures, was shown to reduce effectively the level of rat allergen breathed by an individual.
Need for theophylline in severe steroid‐requiring asthmatics
Authors: BRENNER MANON , BERKOWITZ R. , MARSHALL NANCY , STRUNK R. C.
Published: April 2006

Concern about side‐effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi‐medication regimen of severe asthmatics. We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti‐asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability. Five in‐patients, 12–15 years old, completed a double‐blind, cross‐over trial of theophylline vs placebo. All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes. Regular medications consisted of long‐acting theophylline with levels between 12 mcg/ml and 16 mcg/ml, and prednisone 10–30 mg on alternate days. In addition, they were all taking inhaled metaproterenol, cromolyn sodium, atropine sulphate, and beclomethasone dipropionate four times daily (qid). Patients received either theophylline or placebo during two drug periods. All other medications were unchanged. Parameters measured were symptom score, number of extra respiratory treatments (prn RTs), increase in steroid dosage, and daily spirometry. During the placebo period, all five patients required increased steroids, daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection. A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all. These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who cannot be controlled with all other available bronchodilators, cromolyn, and inhaled and systemic steroids.
Tryptase from human mast cells does not activate purified human Hageman Factor
Authors: ALTER S. C. , LÄMMLE B. , GRIFFIN J. H. , SCHWARTZ L. B.
Published: April 2006

The effect of tryptase, a neural protease released from human lung mast cell secretory granules, on purified human Hageman Factor(Factor XII) was examined. No increase in Hageman Factor enzymatic activity was detected after incubation with tryptase at 37°C; activation of Hageman Factor by bovine trypsin served as a positive control. Furthermore, pre‐incubation of Hageman Factor with tryptase did not diminish the subsequent activation of Hageman Factor by trypsin. Polyacrylamide gel electrophoresis was also performed to show that incubation with tryptase does not alter the molecular weight of Hageman Factor. Therefore, tryptase neither activates nor destroys human Hageman Factor.
Nasal response to allergen and hyperosmolar challenge
Authors: KRAYENBUHL M. C. , HUDSPITH B. N. , SCADDING G. K. , BROSTOFF J.
Published: April 2006

Rhinitis causes both clinical and social discomfort to patients, and in clinical practice is often underdiagnosed. We have examined a simple method for the assessment of a positive nasal provocation test to help in the diagnosis of rhinitis. In patients with histories suggestive of house dust mite (HDM) sensitivity and positive skin‐prick tests or specific IgE to Dermatophagoides pteronyssinus, there was a fall in nasal inspiratory peak flow (NIPF) following nasal challenge with allergen. This was not seen in control subjects or in pollen‐sensitive patients when challenged with house dust mite. Frequency of sneezing and degree of rhinorrhoea increased in these patients following challenge, and based on these findings we propose a simplified scoring system for the diagnosis of allergic rhinitis. We examined non‐specific nasal reactivity using hyperosmolar solutions as a challenge system and found that allergic subjects responded with a fall in NIPF, although the clinical response was not identical to that seen with allergen. Control subjects did not respond to hyperosmolar challenge.
Allergenicity and cross‐reactivity of cat and dog allergenic extracts
Authors: BOUTIN Y. , HÉBERT H. , VRANCKEN E. R. , MOURAD W.
Published: April 2006

This study aims to confirm that cat allergen 1 (CAT‐1) is a major allergenic determinant in cat‐sensitive patients, and to further define the role of other determinants, as well as to identify the determinants responsible for the cross‐reactivity between cat and dog extracts. Firstly, the allergenic determinant with an electrophore‐tic mobility of 18 kD (corresponding to CAT‐1) is indeed a major allergenic determinant being recognized by the majority (75%) of cat‐sensitive subjects. Secondly, the cross‐reactivity between the two species was confirmed by RAST inhibition. Cat and dog soluble allergens could inhibit, to variable degrees, the binding of serum IgE from cat‐ and dog‐sensitive patients to insolubilized allergens. Binding of serum IgE from subjects sensitive only to cats was inhibited by cat extracts only. These observations suggest the presence of determinants common to the two sources of extracts, and others specific for each species. These data were confirmed by immunoblot analysis. Indeed, an allergenic determinant of 69 kD was found in both cat and dog extracts. Conversely the allergenic determinants with an electrophoretic mobility of 18 and 32 kD were found only in cat extracts, and those at 22 and 24 kD were dog specific. However, surprisingly, serum IgE antibodies from patients sensitive only to cats reacted on immunoblot differently from those of both cat‐ and dog‐allergic subjects. Indeed, the 18 kD determinant was the only one recognized by serum IgE antibodies from subjects sensitive to cats only, as opposed to the patients allergic to both species: then, the 69 kD determinant was strongly recognized and the 18 kD only slightly recognized. If these observations confirmed that CAT‐1 is a major allergen in cat‐sensitive subjects, they also showed a different profile of reactivity in patients sensitive to cats only and those sensitive to both cats and dogs, which could have diagnostic and therapeutic implications.
Identification of allergens and antigens of Bermuda grass (Cynodon dactylon) pollen by immunoblot analysis
Authors: SHEN HORNG‐DER , WANG S. R. , TANG R. B. , CHANG ZO‐NAN , SU S. N. , HAN S. H.
Published: April 2006

Allergens and antigens of Bermuda grass pollen fractionated by SDS‐polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes were identified using twenty‐one sera of Bermuda grass pollen‐allergic patients. The IgE‐ and IgG‐binding pollen components transferred to nitrocellulose were detected by reaction with enzyme‐labelled anti‐human IgE and anti‐human IgG, respectively. There was heterogeneity in both IgE‐ and IgG‐binding patterns of the allergic sera tested. Fourteen pollen components, ranging in molecular weight from 16000 to 88000 daltons, bound to IgE antibodies. Only two of the fourteen allergens identified reacted with IgE antibodies of more than 50% of the twenty‐one allergic sera. The pollen component with a molecular weight of 32000 daltons showed by far the highest frequency of IgE binding, being recognized by sixteen (76%) of the twenty‐one sera examined. Fifteen (71 %) of the twenty‐one sera tested had IgE antibodies that reacted with more than one of the fourteen allergenic components identified. Pollen components recognized by IgE antibodies also reacted with IgG antibodies, and there were components only recognized by IgG antibodies. Results obtained from this study should be useful both clinically and in research.
Nasal secretory response to allergen provocation
Authors: COHEN R. A. , BRESTEL E. P.
Published: April 2006

Nasal provocation with ragweed pollen extract was performed on ragweed‐sensitive and non‐atopic subjects. Nasal lavage fluids were collected 15 min after saline and allergen challenges, and assayed for total protein, albumin, potassium, lysozyme activity and peroxidase activity. There was no statistically significant increase in any of these lavage fluid constituents in non‐atopic subjects after allergen provocation, compared with after saline provocation. The lavage fluids of ragweed‐sensitive subjects had significant rises in each of the constituents following allergen provocation. This method provides a simple mechanism for quantitating the nasal secretory response to allergen provocation.
A study of allergens in celery with cross‐sensitivity to mugwort and birch pollens
Authors: VALLIER PAULETTE , DECHAMP CHANTAL , VIAL ODILE , DEVILLER P.
Published: April 2006

Sixty‐one sera with positive RAST to mugwort pollen (Artemisiae vulgaris) were submitted to RASTs for birch pollen (Betula verrucosa) and celery (Apium graveolens). In 36 cases RAST results were positive for celery. In addition, 23 sera presented specific IgE to birch pollen. The binding of specific IgE to individual allergens in celery, mugwort pollen and birch pollen was studied by the immunoblotting technique. This involved electrophoretic separation of allergenic extracts, electrotransfer of proteins onto nitrocellulose sheets and sensitive immunoenzymatic detection. Eighteen sera had specific IgE binding to two celery components of molecular weight around 15 kD. All these sera also detected a 15 kD allergen in mugwort and two allergens in birch of 14 kD and 16 kD molecular weight. The sera that did not detect the 15 kD bands in celery failed to react with both the 15 kD mugwort component and the 14 and 16 kD birch components. Specific cross‐inhibitions of the detection of these allergens on immunoblots were obtained by pre‐incubation of the sera with crude extract of the three species. These results strongly suggest that such allergens display some structural identity and that they could be at the origin of some cases of crossed hypersensitivity to celery, mugwort pollen and birch pollen.
City spore concentrations in the European Economic Community (EEC). VII. Oleaceae (Fraxinus, Ligustrum, Olea)
Authors: D'AMATO G. , MULLINS J. , NOLARD N. , SPIEKSMA F.Th.M. , WACHTER R.
Published: April 2006

In this paper we present the results of volumetric sampling of the airborne pollen grains of the Oleaceae family (Fraxinus, Ligustrum and Olea) in some European towns, in the period from 1982 to 1986. The sampling and appraisal of pollen content in the air is of particular interest to clinicians and allergic patients in order to assess exposure to the various pollen types in relation to allergy. In the Oleaceae family, the most allergenic pollen is produced by Olea europaea, the olive tree, which in the Mediterranean area has a pollination period lasting from May to the end of June and sometimes causes severe symptoms of pollinosis. In Northern and Central Europe, where there are no olive trees, there are two other commonly occurring genera of the Oleaceae family, namely Fraxinus and Ligustrum, but these have a low frequency of allergic sensitization.
Late asthmatic reactions and bronchial variability after challenge with low doses of allergen
Authors: IHRE ELISABETH , AXELSSON I. G. K. , ZETTERSTRÖM O.
Published: April 2006

Late allergic inflammatory reactions are probably of major importance for the development of asthma. In order to study the occurrence of early and late asthmatic reactions after challenge with different doses of allergen, inhalation provocation tests were performed in 13 patients with mild or moderate symptoms of allergic asthma. The provocation series was started with a low allergen dose (0.1–10 BU), which was then increased in successive ten‐fold increments at intervals of 1 week until a pronounced bronchial reaction developed. Three different reaction patterns were observed. Six patients showed an isolated late reaction to relatively low doses of allergen. In four patients an immediate reaction was followed by a late reaction—a so‐called dual response, and in three patients only an immediate reaction occurred. In four of the six patients who showed only a late reaction a higher allergen dose was given and this resulted in dual reactions in all four. One patient was challenged with an even higher dose, to which she reacted with an immediate response alone. After a late reaction, bronchial variability with low PEF values was observed over a period of several days. It is thus possible for an isolated late asthmatic reaction to be provoked by a low dose of inhaled allergen. This can be of clinical importance, repeated small doses of allergen may be unnoticed but still give bronchial inflammation and asthmatic symptoms.
The relationship between viral infections and onset of allergic diseases and asthma
Authors: BUSSE W. W.
Published: April 2006

The pathogenesis of both allergic diseases and asthma remains an unsolved mystery. Of considerable interest, and perhaps insight, into this problem are clinical observations that viral illnesses play an important role in the allergic diathesis. Conclusive evidence to establish a relationship linking viral illnesses to clinical allergy has yet to be established. Nonetheless, recent observations in this arena are intriguing to scientist and clinician alike. The following discussion reviews recent investigations that evaluate the relationship between viral illnesses and development of allergic disease and asthma.
Inhaled lignocaine does not alter bronchial hyperresponsiveness to hyperventilation of dry cold air in asthmatic subjects
Authors: CAIRE N. , CARTIER A. , GHEZZO H. , L'ARCHEVÊQUE J. , MALO J.‐L.
Published: April 2006

It has been hypothesized that bronchoconstriction due to exercise and hyperventilation is caused by the stimulation of irritant receptors in the upper airways. However, controversial results have been reported on the effect of lignocaine, which can inhibit the stimulation of these receptors. The aim of this study was to investigate the effect of inhaled lignocaine on bronchial responsiveness to hyperventilation of cold dry air in asthmatic subjects. Eight adult asthmatic subjects in a clinical steady state came on four different days (two placebo and two active days in random order) with a maximum interval of 3 weeks. After assessment of forced expiratory flow rates, inhalation of either phosphate‐buffered saline (placebo) or lignocaine solution (40 mg) was carried out in a single‐blind fashion. The technician was not aware which medication was being inhaled, but the asthmatic subject knew which drug it was by the sensation in his or her throat. Forced expiratory flow rates were reassessed 15 min after the nebulization; then, the subjects were asked to inhale cold dry air (−20°C) in progressively increasing levels of ventilation (7.5, 15, 30 and 60 1/min and maximum voluntary ventilation). PD20 was interpolated from the dose‐response curve, relating the dose of cold air on a noncumulative logarithmic scale on the abscissa and the percentage change in FEV1 on the ordinate. There were no significant changes in FEV1 and PD20 after inhalation of lignocaine as compared to the placebo. We conclude that inhaled lignocaine does not significantly alter bronchial hyperresponsiveness to hyperventilation of cold air in asthmatic subjects. It is therefore unlikely that receptors in the upper airways could modulate this type of bronchoconstriction.
The clinical efficacy of budesonide in hay fever treatment is dependent on topical nasal application
Authors: LINDQVIST N. , ANDERSSON M. , BENDE M. , LÖTH S. , PIPKORN U.
Published: April 2006

During the last decade topical glucocorticoids have been established as the first hand choice for the treatment of allergic rhinitis. Although they are clinically effective, their precise mode of action has not been sufficiently clarified. In order to evaluate whether the clinical effect is dependent on the topical administration a randomized, double‐blind, double‐dummy study was performed. Ninety‐eight patients with allergic rhinitis due to birch pollen were recruited at two centres in southern Sweden. The patients received one of the following three treatment alternatives: 200 μg of nasally applied budesonide twice daily, 250 μg of budesonide given orally twice daily or a placebo. The selection of the doses was based on previous pharmacokinetic studies giving almost equal plasma levels of the nasally and orally administered budesonide. To evaluate the possible clinical efficacy of the treatment, the patients kept a diary in order to register symptoms according to a 0–4 scale. After a run‐in week with no treatment the patients entered the treatment period which lasted for 3 weeks. A total of 96 patients completed the study. The symptom data showed that topically applied budesonide was clinically effective with a pronounced reduction in all the nasal symptoms registered and compared with placebo treatment there was a statistically significant difference in favour of the budesonide treatment (P < 0.001). The nasal symptoms of the patients receiving oral budesonide did not differ from those receiving placebo. Intranasally administered budesonide proved to be significantly more effective than orally applied budesonide (P < 0.01). Thus, this study clearly demonstrates that the clinical effect of budesonide in recommended doses for hay fever treatment is dependent on the nasal application.
A prospective study of bronchial hyperresponsiveness and respiratory symptoms in a population of Australian schoolchildren
Authors: PEAT J. K. , SALOME C. M. , SEDGWICK C. S. , KERREBIJN J. , WOOLCOCK A. J.
Published: April 2006

To examine the relationship between bronchial hyperresponsiveness (BHR) and respiratory symptoms associated with asthma, we studied a sample of 380 schoolchildren on three occasions at 2‐yr intervals. The age of the children at the first study was 8–10 yr. Respiratory symptoms history was assessed by questionnaire, BHR was measured by a histamine inhalation test and atopy was assessed by skin‐prick tests to 13 allergens. The cumulative prevalence of BHR in this sample was 27%. The severity of BHR was categorized as severe, moderate, mild or slight. The distribution of severe, moderate and mild BHR was similar at each of the studies. At the third study, when the children were aged 12–14 yr, the prevalence of slight BHR decreased. Children with severe or moderate BHR at age 8–10 yr were atopic, reported current symptoms during the 4 yr of the study and had a high prevalence of severe or moderate BHR in later studies. In this group, 87% of children had current respiratory symptoms and 73% were using asthma medication at age 12–14 yr. In children with mild or slight BHR when first studied, the prevalence of atopy, continuing respiratory symptoms and medication use was much lower. We conclude that severe or moderate BHR is an important risk factor for ongoing morbidity and that comparisons of the prevalence of this severity of BHR in populations may be more informative than comparisons of BHR defined by present criteria.
The incidence of IgE and IgG antibodies to chlorhexidine
Authors: LAYTON G. T. , STANWORTH D. R. , AMOS H. E.
Published: April 2006

IgE antibodies to the antiseptic agent chlorhexidine have recently been detected in the majority of sera from a small group of predominantly Japanese individuals showing anaphylactic‐type adverse reactions towards chlorhexidine. In this study the prevalence of IgE and IgG antibodies with specificity for chlorhexidine was investigated in groups of Japanese and British individuals. The RAST data, using a better defined semi‐chlorhexidine‐HSA antigen than previously employed, revealed that chlorhexidine‐specific IgE was only detected in Japanese individuals who had experienced anaphylactic‐type reactions and was not detected in groups of Japanese nurses and patients, or in groups of British nurses and hospital staff, all in regular contact with chlorhexidine. A group of British blood donors was also negative. In contrast, IgG antibodies were detected not only in sera from chlorhexidine‐sensitive Japanese patients, but also in several sera from Japanese nurses, non‐sensitive Japanese patients and several British individuals. The possible reasons for these observations are discussed.
The human skin mast cell
Authors: BENYON R. C.
Published: April 2006

The abundance of mast cells in human dermis, together with their ability to release a variety of vasoactive and pro‐inflammatory mediators following cross‐linkage of their cell‐surface receptors for IgE, enables these cells to provide an effective defence mechanism within this organ. A similar defensive function is attributed to mast cells of other human organs such as intestine and lung which are in contact with the external environment and therefore susceptible to infiltration by foreign allergens and microorganisms. However, mast cells of the skin apparently differ from those present in lung and intestine in being activated for histamine release by a variety of endogenous neuropeptides which stimulate the rapid release of histamine in the virtual absence of eicosanoids. This would provide a mechanism of neurogenic control of a variety of homeostatic functions such as blood flow, angiogenesis and fibroblast proliferation. Such processes would aid in the remodelling of tissue during wound healing, and increased numbers of mast cells have been noted around healing wounds of rat skin [57] and areas of developing fibrosis [146]. Neuropeptides modulate the activity of a variety of immuno‐competent leucocytes including macrophages, monocytes and lymphocytes [147–149]. The findings that skin mast cells are activated by neuropeptides suggest that these cells may also be included amongst those involved in neuro‐immune interactions. Activation of skin mast cells by non‐immunological stimuli may contribute to the aetiology of some forms of skin disease. Patients with chronic idiopathic urticaria appear to have enhanced vascular responsiveness to intradermal injections of the histamine liberator codeine [139] suggesting that this disease may involve hyper‐responsiveness of their mast cells to endogenous non‐immunological stimuli. The findings of large increases in histamine accompanied by small increases in PGD2 in venous effluent of thermally challenged limbs of patients with cold‐ or heat‐induced urticaria [94,95] may suggest that their mast cells had been activated by a non‐immunological stimulus. However, the interpretation of results gained using such relatively complex in‐vivo systems are difficult, as the cellular origin of the detected mediators is by no means clear. However, it is hoped that in the future the alliance of newly developed in‐vitro techniques to investigate mast cell function together with in‐vivo methods to investigate their interaction with elements in their tissue environment will greatly increase our understanding of the role of the human skin mast cell in health and disease.
The relative risks of sensitivity to grass pollen, house dust mite and cat dander in the development of childhood asthma
Authors: SEARS M. R. , HERBISON G. P. , HOLDAWAY M. D. , HEWITT C. J. , FLANNERY ERIN M. , SILVA P. A.
Published: April 2006

The associations between skin sensitivity to various common allergens and the development of childhood asthma were ascertained in a longitudinal study of a birth cohort of New Zealand children up to the age of 13 years. Of 714 children skin‐tested, 45.8% were sensitive to at least one of 11 allergens, the most common responses being to rye grass pollen (32.5%), house dust mite (30.1%) and cat dander (13.3%). Allergen‐specific relative risk analysis, controlled for the effect of sensitivity to other allergens, demonstrated that sensitivity to house dust mite and to cat dander were highly significant independent risk factors associated with the development of asthma (whether defined as recurrent typical respiratory symptoms, increased airway responsiveness, or the concurrent presence of both), whereas grass sensitivity was not a significant independent risk factor for asthma.
Food specific skin‐test reactivity in atopic subjects
Authors: MORGAN J. E. , DAUL C. B. , HUGHES J. , McCANTS M. , LEHRER S. B.
Published: April 2006

It has been proposed that a permanent or transitory increase in gut permeability is an important facet in the development of food allergy. If this occurs, then individuals with a history of a specific food allergy should have a higher incidence of immunological reactivity to other food allergens as compared to food tolerant subjects. To test this hypothesis, we evaluated the prevalence of food‐specific IgE responses by skin‐prick testing in 60 individuals. Subjects were classified by a history of food allergy (shrimp hypersensitivity) and atopic status. Prevalence of skin‐prick test reactivity to shrimp and a panel of nine other food extracts was determined. Skin‐test reactivity to shrimp was related both to a history of shrimp sensitivity and atopic status. However, the prevalence of skin‐test reactivity to other foods was not related to clinical history of shrimp allergy, although it was related to atopy. A subset of subjects with shrimp allergy had multiple positive skin reactions to many of the nine other foods. This reactivity was associated with a history of pulmonary symptoms following shrimp ingestion. In general our results do not support non‐specific increases in gut permeability being important in the development of food allergy.
The effect of topical nasal anaesthesia on allergen‐induced symptoms, obstruction and blood flow
Authors: HOLMBERG K. , BAKE B. , PIPKORN U.
Published: April 2006

The effect of topical anaesthesia on the nasal mucosa before and after allergen challenge was evaluated in 12 subjects with strictly seasonal allergic rhinitis. A single‐blind randomized placebo‐controlled design was used. The nasal challenge was carried out after pre‐treatment of the nasal cavity with 52 mg of lidocaine/nasal cavity, or placebo applied topically in spray form. The number of sneezes was counted. The amount of nasal secretion was estimated by weighing used paper handkerchiefs. The capacitance and resistance vessel reactions were monitored by determining nasal peak flow and 133Xe wash‐out respectively. After placebo pre‐treatment the two doses of allergen induced moderate symptoms and vascular changes. Pre‐treatment with local anaesthesia did not affect any of the symptoms nor did it affect the decrease in the tone of the capacitance vessels. It was found that topically applied lidocaine per se did not have any effect on nasal mucosal blood flow as measured using the 133Xe wash‐out technique. However, the local anaesthesia did block the allergen‐induced increase in the tone of the resistance vessels. In conclusion, a redundancy of systems appears to be involved in nasal allergic reactions. Although a reflex‐induced mechanism may well play a significant role in the induction of the signs and symptoms of nasal allergic reactions, the redundancy of systems involved may well override any reduction in one single system, as appears to be the case in the present study. Lidocaine peer se did not influence the nasal mucosal blood flow.
Inflammatory and immunological cell profiles in a rat model of conjunctival immediate hypersensitivity
Authors: DOHERTY MELANIE J. , EASTY D. L.
Published: April 2006

A modified model of conjunctival immediate hypersensitivity in the rat is described. The advantages of this model over previously reported rat models are that it does not require invasive challenges, pre‐treatment with mucolytic agents to enhance antigen penetration, or the use of haptens, and is therefore more representative of the mode of allergen challenge seen in human hay fever conjunctivitis. This model has been shown to have both early and late‐phase cellular responses but only early phase clinical signs. During the early phase of the response the tarsal region accommodates a massive neutrophil infiltration and the fornix‐bulbar region participates to a greater extent during the late‐phase reaction, with a significant eosinophil infiltration. The development of this model has allowed us to gain a clearer insight into the mechanisms involved during conjunctival immediate hypersensitivity in the rat; and the simplicity of this model makes it attractive to use in the evaluation of new drug therapies prior to their introduction into human clinical trials.
Immunological specificity of chloramine‐T‐induced IgE antibodies in serum from a sensitized worker
Authors: WASS U. , BELIN L. , ERIKSSON N. E.
Published: April 2006

A procedure for the preparation of chloramine‐T (CT) conjugates used to assay IgE antibodies was developed using response surface methodology and serum from a subject occupationally exposed to the substance. The conjugates, synthesized by reacting CT with human serum albumin (HSA) and other protein carriers, were used as antigens in a radio‐allergosorbent test (RAST). Human serum albumin was found to be a suitable carrier, although other protein carriers also gave specific IgE‐binding of a similar extent. The CT‐HSA conjugates used in the RAST were characterized by high performance liquid chromatography, electrophoresis, immunodiffusion and ammonium sulphate precipitation. However, no strong correlation was seen between the ability of the conjugates to bind IgE and their physical or immuno‐chemical properties. The hapten and carrier specificity of CT‐induced IgE antibodies in the subject's serum were studied by direct RAST and RAST inhibition. No existence of new antigenic determinants related to the carrier could be demonstrated. Although HSA as a carrier was altered immunochemically by CT, the IgE antibodies were found to be specific to hapten only. Chloramine‐T‐specific IgG antibodies could not be demonstrated in the subject's serum.
Measurement of specific IgE antibodies in individuals exposed to formaldehyde
Authors: KRAMPS J. A. , PELTENBURG LUCY T. C. , KERKLAAN P. R. M. , SPIEKSMA F. TH. M. , VALENTIJN R. M. , DIJKMAN J. H.
Published: April 2006

Using an in‐vitro test, the presence of formaldehyde‐specific IgE antibodies was investigated in sera from four groups of individuals exposed to formaldehyde by different routes and concentrations. Group (A) 28 subjects living or working in rooms or places where formaldehyde‐containing construction materials were used: (B) 18 subjects occupationally exposed to relatively high concentrations of formaldehyde; (C) 12 paramedic employees working in a renal dialysis unit where formaldehyde‐sterilized dialysers were being used; and (D) 28 subjects undergoing haemodialysis with these formatdehyde‐sterilized dialysers. Formaldehyde‐specific IgE antibodies could be detected in only one of the 86 serum samples. This particular sample was from a worker occupationally exposed to formaldehyde (group (B)), but who did not show any work‐related symptoms. In two pools of control sera from unexposed subjects no specific IgE antibodies to formaldehyde were detected. It is concluded that exposure to formaldehyde, even in relatively high concentrations, rarely evokes the production of specific IgE antibodies. The presence of these specific antibodies is not necessarily attended by allergic symptoms. On the other hand, the symptoms supposed to be related to formaldehyde exposure and reported in this study by 24 out of 28 subjects in group (A), and some of the subjects in groups (B) and (C), cannot be attributed to an IgE‐mediated sensitization to formaldehyde.
Comparison of a new type of skin test (Phazet) with existing skin test methods and the radioallergosorbent test (RAST)
Authors: KEMENY D. M. , LAMBOURN E. M. L. , PATEL S. , LESSOF M. H.
Published: April 2006

A new skin test method (Phazet) for diagnosis of immediate‐type allergic disease was tested in 232 patients attending the Guy's Hospital Allergy Clinic, and compared with conventional skin test methods, using Bencard and Pharmalgen allergen solutions, and with serum IgE antibody tests (RAST). Six allergens (cat, dust mite, Cladosporium. grass pollen birch pollen and plantain pollen) were used, as well as histamine and a negative control. Phazet proved easy to use and was popular with inexperienced operators (medical and dental students). For the majority of allergens there was reasonably good agreement with the different tests, but overall Phazet and RAST produced fewer positive results than the other skin tests methods. In particular, the frequency of positive histamine tests was lower with Phazet (82%) than with Bencard or Pharmalgen (99′%), but this discrepancy was lower in the second part of the study when the minimum time for the insertion of the needle (1 sec) was more scrupulously observed. Phazet offers a convenient and practical alternative to conventional ‘wet’ skin test methods.
Substance P activation of bronchoalveolar macrophages from asthmatic patients and normal subjects
Authors: PUJOL J.‐L. , BOUSQUET J. , GRENIER J. , MICHEL FRANCOISE , GODARD P. , CHANEZ P. , DE VOS CHRISTINE , DEPAULET A. CRASTES , MICHEL F.‐B.
Published: April 2006

The role of substance P in the pathogenesis of asthma is unclear. Animal studies suggest that it may be important, whereas human studies do not confirm this. Alveolar macrophages can be recovered easily by bronchoalveolar lavage (BAL) and stimulated in vitro. To assess the role of substance P in humans, we tested its ability to stimulate alveolar macrophages from six normal subjects and seven asthmatic patients. BAL cells were separated by adherence and alveolar macrophages constituted 95% of the adherent cell population. Four concentrations of substance P were used (10−7, 10−6, 10−5, 10−4 M). To assess the non‐specific activation of alveolar macrophages we used three concentrations of lipopolysaccharides (LPS) (5, 10, 20 μg/ml). The stimulation of alveolar macrophages was assessed by the release of thromboxane B2 by radioimmunoassay. This study indicates that alveolar macrophages are stimulated by LPS but are poorly activated or not at all by substance P.
The effect of topical steroid application on natural killer cell activity
Authors: LESKO M. J. , LEVER ROSEMARY S. , MACKIE RONA M. , PARROTT DELPHINE M. V.
Published: April 2006

Peripheral blood natural killer (NK) cell activity of a group of 10 healthy non‐atopic volunteers was reduced following the topical application of 15 g of 0.1 % betamethasone valerate ointment to the skin nightly for 1 week. In contrast, no such effect was observed when the inactive base of the steroid ointment was used. NK cell activity dropped significantly by day 7 (P < 0.05) and then recovered, although NK cell activity at day 22 was still lower than that observed at the start of the experiment. These findings suggest that topically applied steroid is absorbed in sufficient amounts to cause a systemic effect on NK cell function. This may have implications in a number of dermatological disorders, including atopic dermatitis, where topical steroids form the mainstay of treatment.
Abnormal platelet hydrogen peroxide metabolism in aspirin hypersensitivity
Authors: PEARSON D. J. , SUAREZ‐MENDEZ V. J.
Published: April 2006

The generation and degradation of hydrogen peroxide (H2O2) by platelets was investigated in aspirin hypersensitive and tolerant allergic subjects, and compared to that in general medical patients and healthy controls. H2O2 generation following triggering with anti‐IgE. specific allergen, and with aspirin (ASA) and indomethacin was examined using a chemiluminescence assay. Platelet levels of the main intracellular enzyme responsible for H2O2 metabolism–glutathione peroxidase–were measured by a quantitative functional assay. H2O2 secretion could be triggered by anti‐IgE in platelets from 15/29 ASA‐tolerant atopies, and by relevant allergen in platelets passively sensitized with allergen‐specific IgE. A similar response was observed following triggering with ASA, and with indomethacin, in platelets from 8/25 ASA‐sensitive subjects. Mean platelet glutathione peroxidase activity was significantly lower in subjects with ASA‐induced asthma, but not in subjects with non‐asthmatic reactions to ASA, compared to all other groups. Within the ASA‐sensitive group there was no correlation between low peroxidase activity and ASA‐triggered chemiluminescence. Our findings emphasize the heterogeneity of ASA‐intolerance syndromes and point to abnormal oxygen/peroxide metabolism as a common pathway underlying ASA‐induced asthma.