bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the levels of house dust mite specific IgG4during immunotherapy in asthmatic children
Authors: TSAI L. C. , TANG R.‐B. , HUNG M.‐W. , CHANG Z.‐N.
Published: April 2006

Serum levels of IgG subclass and house dust mite (Dermatophagoides pteronyssinus, Dpt) specific IgG4were evaluated during immunotherapy in asthmatic children. Asthmatic children undergoing long‐term immunotherapy (more than 2 years) posed a mean value of total serum IgG4orDpt‐specific IgG4antibodies significantly higher than that of patients prior to receiving immunotherapy, asthmatic (placebo) controls, or patients undergoing short‐term immunotherapy (less than 1 year) (P< 0.05). The mean levels of serumDpt‐specific IgG4in all asthmatic groups were also significantly higher than in the non‐allergic controls (P< 0.01). Moreover, the mean level ofDpt‐specific IgG4tended to increase during immunotherapy. A significant correlation between total serum IgG4andDpt‐specirk IgG4antibodies was noted (r= 0.6243;P< 0.001). Serial follow‐up reveals thatDpt‐specific IgG4levels usually rose significantly with clinical improvement in asthmatic children during immunoiherapy. These results suggest that the anti‐mite‐specific IgG4antibody may serve as an indicator for clinical outcome of mite allergy during immunotherapy.
Domestic endotoxin exposure and clinical severity of asthma
Authors: MICHEL O. , GINANNI R. , DUCHATEAU J. , VERTONGEN F. , LE BON B. , SERGYSELS R.
Published: April 2006

Endotoxins are potent pro‐inflammatory substances present in several natural environments and in commercial house dust extracts. To investigate the possible effect of chronic endotoxin exposure on asthma, 28 patients with perennial chronic asthma (20 allergic to house dust mite and eight intrinsic asthmatics) were evaluated during a 4‐month period (lung function, clinical and immunological criteria). At the same time, two house dust samples were collected from each patient's home to determine total house dust weight (mg/m2), endotoxin concentration and house dust mite antigen content (evaluated indirectly by guanine content with HPLC method). The mean (± s. d.) endotoxin concentration, as measured by quantitative Limulus assay was 2.59 (± 3.41) ng/mg house dust, ranging from 0.12 to 20 ng/mg. The mean guanine content was 0.13 (± 0.16) mg/100 mg house dust. There was no correlation between endotoxin and house dust mite concentrations. Patients were compared according to the low or high grade exposure to dust, endotoxins and guanine. Compared with patients with low grade (≤ 5.6 ng/ml) exposure, subjects exposed to high endotoxin concentrations (> 5.6 ng/ml) showed a significant increase in dyspnea (median 2.6 vs 3.3; P<0.05) and treatment (median 14 vs 44.3; P<0.01) scores, oral corticosteroid (median 0.0 vs 13.5 mg/24 hr; P<0.01) and β2‐mimetics (median four vs eight puffs/day; P<0.01) intake, and a significant decrease in FEV1/FVC (median 84.5 vs 67% of predicted value; P<0.01). In contrast, no differences were found between the two groups exposed to low (< 0.07 mg/100 mg house dust) and high (≥ 0.07 mg/100 mg house dust) concentrations of guanine, respectively. We conclude that endotoxins are present in normal domestic environment and could have a deleterious effect on the chronic asthmatic disease.
Immunoblot multi‐allergen inhibition studies of allergenic cross‐reactivity of the dust mites Lepidoglyphus destructor and Dermatophagoides pteronyssinus
Authors: JOHANSSON E. , BORGÅ Å. , JOHANSSON S. G. O. , VAN HAGE‐HAMSTEN M.
Published: April 2006

The allergenic similarity of the pyroglyphid mite D. pteronyssinus and the glycyphagid mite L. destructor was investigated with a new immunoblotting inhibition technique allowing simultaneous comparison of several allergens. Extracts of D. pteronyssinus and L. destructor were separated by SDS‐PAGE and electroblotted to nitrocellulose (NC). A serum pool containing IgE specific to the major allergens in both mites was mixed with serially diluted extracts of D. pteronyssinus and L. destructor and incubated with the mite allergens of NC. The inhibition of the IgE binding to NC was evaluated by densitometric scanning and percentage inhibition was calculated. The IgE antibodies to the 25‐kD component in D. pteronyssinus, were inhibited to the same degree by extracts of D. pteronyssinus and L. destructor. Another major allergen component in D. pteronyssinus (16 kD) was also inhibited by L. destructor extract but to a lesser degree: 400 times more of the heterologous than of the homologous extract was needed for 50% inhibition. To produce 50% of heterologous inhibition of the two major allergen components at 15 and 53 kD of L. destructor, 2000 and 10000 times more, respectively, of D. pteronyssinus than of L. destructor extract were needed. Two minor allergen components of L. destructor showed some cross‐reactivity with D. pteronyssinus. However, L. destructor was a stronger inhibitor of D. pteronyssinus than vice versa, probably because the sera were obtained from persons more sensitized to L. destructor than to D. pteronyssinus.
A gap in surface therapy: topical antihistamines
Authors: VAN DE HEYNING P. H. , CLAES J. , VAN HAESENDONCK J. , ROSSEEL M.
Published: April 2006

Allergic and non‐allergic rhinitis have been treated by many drugs with different modes of action such as topical disodium cromoglycate and ipratropium bromide, systemic antihistamines and corticosteroid drugs and topical corticosteroids. Yet, these therapies are not entirely satisfactory for all symptoms. The rationale for the topical, intranasal use of antihistamines in patients is discussed. Topical antihistamine agents arc administered in order to avoid the side effects of systematically applied medications, and to reach higher local drug concentrations. H1receptors of the nasal mucosa play an important role in the physiopathology of allergic and non‐allergic rhinitis and even of infectious rhinitis. Most studies using topical antihistamines in rhinitis, had an experimental physiopathological aim and did not explore clinical efficacy. Recently, topical application of levocabastine—a potent H1antagonist—yielded good clinical results in allergic conjunctivitis, seasonal allergic rhinoconjunctivitis, and non allergic perennial rhinitis.
Reliability of respiratory symptoms to diagnose atopy
Authors: VERVLOET D. , HADDI E. , TAFFOREAU M. , LANTEAUME A. , KULLING G. , CHARPIN D.
Published: April 2006

As reliance of responses to epidemiological questionnaires on atopic symptoms is doubtful, we studied the predictive value of these questions relative to atopy, defined by the presence of serum specific IgE, taking into account some extraneous variables such as age and sex. The study population included 2067 adults, 20‐60 years old. The protocol consisted of a standardized questionnaire and an evaluation of serum specific IgE using the Phadiatop® (Pharmacia Diagnostics, Uppsala, Sweden) test. The predictive value of each symptom suggestive of atopy was quite low, but was much dependent on age and sex. Women more often than men reported atopic symptoms in the absence of atopy. Similarly, the predictive value of each symptom decreased with age. Thus atopic symptoms do not have the same value as predictors of atopy. These findings have both clinical and epidemiological important implications.
Changes in mite allergen Der p I in house dust following spraying with a tannic acid/acaricide solution
Authors: TOVEY E. R. , MARKS G. B. , MATTHEWS M. , GREEN W. F. , WOOLCOCK ANN
Published: April 2006

The beds, carpets and furnishings in 15 houses were sprayed with a solution containing tannic acid and an acaricide in an attempt to reduce allergen concentrations. Dust was collected from these sites for 4 weeks following spraying and the mite allergen Der p I concentration was measured and compared with baseline concentrations. In a subgroup of houses, counts of live mites and estimates of aeroallergen were also made. Four untreated houses were monitored over the same period. In dust samples collected 3 days after spraying, the mean concentrations of Der p I in beds, carpets and furniture were 23%, 28% and 26% of the pretreatment levels. All these reductions were significant compared to untreated controls. Samples collected 4 weeks after treatment were not significantly different to baseline for each group. After the initial reduction, the rate of increase in allergen concentration was significantly greater in the spray‐only beds than in the beds which had been both sprayed and fitted with occlusive covers. Both aeroallergen and live mites continued to be detected in houses after treatment with the spray. These studies suggest that such sprays are only temporarily effective when applied at the manufacturer's recommended volumes and additional approaches are required to control the bulk of allergens in houses.
Comparison between MAGIC LITE®‐ and CAP®‐system: two automated specific IgE antibody assays
Authors: KLEINE‐TEBBE J. , EICKHOLT M. , GÄTJEN M. , BRUNNÉE T. , O'CONNOR A. , KUNKEL G.
Published: April 2006

The MAGIC LITE system, a newly developed immunochemiluminometric assay for specific and total IgE antibody using paramagnetic particles coupled with standardized allergens as solid phase, was compared to the CAP system, a recently introduced immunoassay based on a cellulose polymer encased in a capsule. A total of 357 serum samples of patients with suspected inhalant allergies and a positive skin prick test (SPT) to common allergens (birch, timothy‐grass, mugwort, cat dander, Dermatophagoides pteronyssinus, Alternaria) were investigated. Fifty SPT negative subjects served as controls (total number of tests in each assays = 1600). Both assays were highly precise (overall intra‐assay and inter‐assay coefficients of variation were 2.9% and 4.5% in MAGIC LITE, 4.7% and 5.5% in CAP) and showed excellent linearity (mean r2 of eightfold log2 serum dilutions were 99.7% and 99.3% in MAGIC LITE and CAP). Good correlations were found between the absolute specific IgE antibody values detected by both methods (correlation coefficient r: birth 0.86, grass 0.93, mugwort 0.96, cat 0.91, D. pteronyssinus 0.73, Alternaria 0.90). Excellent specificity (.98%) occurred in both assays and with all allergens, and sensitivity was related to the allergen (MAGIC LITE/CAP): birch 91%/89%, grass 83%/90%, mugwort 50%/69%, cat 83%/83%, D. pteronyssinus 72%/78%, Alternaria 75%/81 %. Our results indicate that both in vitro tests are useful tools for the detection of specific IgE antibody.
The association of perennial rhinitis with Trichophyton infection
Authors: KIVITY S. , SCHWARZ Y. , FIREMAN E.
Published: April 2006

Trichophyton was recently reported to be the cause of respiratory allergy in patients with severe bronchial asthma. We describe eight patients with perennial rhinitis in combination with skin or toe‐nail infection, in whom Type I hypersensitivity reaction to Trichophyton was confirmed by skin test, RAST and nasal provocation. When treated with oral fungicidal therapy, there was significant improvement in both their skin and nasal symptoms. Local therapy produced only a mild, transient improvement. We emphasize the need for thorough evaluations in patients with respiratory allergies and negative routine skin tests.
Oilseed rape—a new allergen?
Authors: FELL P. J. , SOULSBY S. , BLIGHT M. M. , BROSTOFF J.
Published: April 2006

Oilseed rape (Brassica napus) is a commonly grown crop in Europe and it has been suggested that its pollen may be a potent new allergen. The prevalence of sensitization in a normal exposed population and an objective study of those patients found to be allergic to the rape pollen is described. The results show a low prevalence of allergy to oilseed rape pollen (less than 0.2%) unless the subjects were occupationally exposed. Those affected, with one exception, were already atopic and allergic to other pollens. The role of volatile materials given off by the plant remains to be elucidated.
Comparison of a video questionnaire* with the IUATLD written questionnaire for measuring asthma prevalence
Authors: SHAW R. A. , CRANE J. , PEARCE N. , BURGESS C. D. , BREMNER P. , WOODMAN K. , BEASLEY R.
Published: April 2006

A video questionnaire (VQ) for measuring asthma prevalence in adolescents was assessed for repeatability and validity in relation to bronchial hyperresponsiveness (BHR) (PD20 ≤ 7.8 μmol methacholine). Comparison was also made with a standard, self completed written questionnaire (SQ), based on the IUATLD Bronchial Symptoms Questionnaire, which included five questions seeking comparable data to those in the VQ. Both the VQ and SQ were administered to 707 schoolchildren (13–16 years), in whom English was the primary language. One hundred and six randomly selected children subsequently underwent bronchial challenge to methacholine. Both the sensitivity and specificity for BHR were higher for a combination of three or more positive responses to the VQ (0.73 and 0.88), than to the SQ (0.63 and 0.82), although these differences were not statistically significant (P= 0.24). When administered again after a two week interval, the VQ had a significantly higher (P= 0.03) coefficient of repeatability (0.79) than the SQ (0.50). We conclude that the VQ is a valid and reliable method of determining asthma prevalence, and propose that by providing data relatively free from biases due to language, culture, literacy or interviewing techniques it may be particularly useful when comparing asthma prevalence and severity in different populations.
Heterogeneity of IgE antibody response to reactive dye in sera from four different sensitized workers
Authors: HONG C.‐S. , PARK H. S.
Published: April 2006

We studied RAST and RAST inhibition tests to black GR, the most frequent sensitizer among several reactive dyes in our previous study, in order to evaluate the specificity of IgE antibodies to hapten or new antigenic determinants and the crossreactivity between two reactive dyes, black GR and orange 3R, in sera from four different sensitized workers. RAST inhibition studies with black GR‐human serum albumin (HSA) conjugate discs demonstrated that black GR‐HSA conjugates were the most effective inhibitors. Orange 3R‐HSA conjugates, unconjugated forms of black GR and orange 3R were weak inhibitors in two patients and non‐inhibitory in one patient, whereas they caused strong dose‐dependent inhibitions in one patient. These results suggested that the IgE response to black GR‐HSA conjugates might be heterogenous and the cross‐reactivity between two reactive dyes differed from one patient to another.
Comparative inhibition profiles of three non‐sedating antihistamines assessed by an extended Lewis model*
Authors: SHALL L. , THOMPSON D. A. , BARKLEY A. S. J. , MILLARD L. G.
Published: April 2006

Antihistaminic drugs are widely prescribed across a multitude of medical specialities such as Allergy and Dermatology. The potentially serious sedative effect of these valuable agents has previously restricted their full use and the choice of drug has been dictated more by individual patient acceptability than by any laboratory demonstrations of comparative efficacy. Unsurprisingly therefore, there is a trend towards prescribing those newer preparations which leave the central nervous system unclouded. We have studied the most frequently prescribed non‐sedating antihistamine preparations, terfenadine (Triludan, Triludan Forte), cetirizine (Zirtek) and loratadine (Clarityn) in pharmacodynamic and relative efficacy trials using a quantifiable and reproducible extension of the classic Lewis model. The results indicate that two preparations, terfenadine 120 mg (Triludan Forte) and cetirizine 10 mg (Zirtek) are superior to their immediate rivals in degree of efficacy and/or speed of action. These results should assist clinicians in the positioning of effective, rapidly acting antihistamines for the symptomatic treatment of immediate hypersensitivity reactions such as urticaria and rhinitis.
The influence of terfenadine and ipratropium bromide alone and in combination on bradykinin‐induced nasal symptoms and plasma protein leakage
Authors: RAJAKULASINGAM K. , POLOSA R. , LAU L. C. K. , CHURCH M. K. , HOLGATE S. T. , HOWARTH P. H.
Published: April 2006

Nasal instillation of bradykinin elicits many of the characteristic features of rhinitis. To assess the relevance of histamine release from metachromatic cells and the activation of cholinergic pathways, we investigated the effects of terfenadine, a histamine H1‐receptor antagonist, and ipratroprium bromide, a selective antimuscarinic agent, on bradykinin induced rhinorrhoea, nasal airways resistance (NAR), nasal pain and plasma protein leakage. Oral terfenadine (120 mg) or matched placebo and nasal ipratropium bromide (80 μg) or matched placebo were administered at 4 hr and 30 min respectively prior to bradykinin nasal challenge in two randomized, double‐blind and cross‐over studies on eight non‐rhinitic subjects. Thus subjects received either double‐placebo, oral terfenadine and nasal placebo, oral placebo and nasal ipratopium bromide or oral terfenadine and nasal ipratropium bromide, as pretreatment. Bradykinin challenge induced mean maximal increases of 57%, 59%, 77% and 72% in NAR on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratropium bromide pretreatment days respectively. These increments were not significantly different. Similarly rhinorrhoea and nasal pain induced by bradykinin nasal challenge were not significantly different on the four challenge days. Bradykinin nasal challenge caused a mean maximal increase in albumin levels in recovered nasal lavages of 11.5, 13.0, 12.2 and 12.3 times of baseline levels on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratroprium bromide pretreatment days respectively. Similarly total protein levels achieved a mean maximal increase of 8.0, 8.2, 7.9 and 8.8 times of baseline levels on these challenge days. The increments in both albumin and total protein did not significantly differ on the 4 challenge days. This study, therefore, demonstrates that cholinergic pathways and mast cell release of histamine do not contribute to increase in NAR, rhinorrhoea and plasma protein extravasation induced by bradykinin.
In vitro evaluation of acaricidal and fungicidal activity of the house dust mite acaricide, Allerbiocid
Authors: HART B. J. , GUÉRIN B. , NOLARD N.
Published: April 2006

The acaricidal and fungicidal activities of a new acaricide Allerbiocid, formulated for the control of house dust mites, were investigated. The components of the Allerbiocid formula are: 3% benzyl benzoate (acaricidal and fungicidal), 1% tannic acid (protein denaturant) and 0.5% Tween (surface active agent) in 70% isopropyl alcohol (antiseptic). At application rates of both 150 and 250 ml/m2, the acaricidal activity appeared to work by both ingestion and contact and remained active upon contact with mites for up to 10 weeks. When Sabouraud agar was treated with Allerbiocid at a concentration of 5 ml/20 ml medium, the preparation was also found to have fungicidal and fungistatic activities on various species of fungi commonly found in house dust. Allerbiocid contains tannic acid which is a protein denaturant. Levels of Der p I in dust were found to be reduced by over 90% after treatment with Allerbiocid. The importance of denaturation of mite faecal allergens and allergens associated with dead fungal spores is discussed.
Double‐blind group comparative study of 2% nedocromil sodium eye drops with 2% sodium cromoglycate and placebo eye drops in the treatment of seasonal allergic conjunctivitis
Authors: LEINO M. , ENNEVAARA K. , LATVALA A.‐L. , NORDGREN P. , POSTI A.‐M. , SUVES R. , TAKALO E.
Published: April 2006

A 4 week, multicentre, double‐blind, double dummy, placebo controlled group comparative study was carried out during the birch pollen season to compare the efficacy and tolerability of 2% nedocromil sodium eye drops (twice daily) and 2% sodium cromoglycate eye drops (four times daily). Participants with a history of seasonal allergic conjunctivitis (SAC) were randomized to receive nedocromil sodium (60), sodium cromoglycate (61) or placebo (64). Clinical assessment of SAC showed improvement with both active treatments compared to placebo but symptomatology was low and only changes in photophobia and grittiness reached significance (P < 0.05). Patient diaries showed significant control of itching by both active treatments, compared to placebo, with no differences between the active preparations. Patients’ opinions indicated a marked placebo effect: 73% of this group reported full or moderate control of symptoms, compared with 75% in sodium cromoglycate and 80% in the nedocromil sodium group. Unusual symptoms were most common (27 patients) with nedocromil sodium eye drops: P < 0.05 vs. placebo (15 patients). There were no serious adverse events. Nedocromil sodium eye drops (b.d.) and sodium cromoglycate eye drops (q.i.d.) were both considered clinically more effective than placebo in controlling symptoms of SAC due to birch pollen.
Higher risk of infantile atopic dermatitis from maternal atopy than from paternal atopy
Authors: RUIZ R. G. G. , KEMENY D. M. , PRICE J. F.
Published: April 2006

The risk of infantile atopic dermatitis (AD) posed by maternal atopy and paternal atopy, respectively, were compared in the infants from a birth cohort in whom one of the parents had been designated atopic by skin prick testing. Nineteen with atopic mothers were compared with 20 with atopic fathers. AD, other atopic manifestations and potentially influential factors such as breast‐feeding were documented prospectively during the first year in all infants. At 3, 6 and 12 month assessments skin prick sensitivity and total serum IgE concentration were determined. Nine of 19 infants with atopic mothers and two of 20 with atopic fathers had AD (P= 0.023) giving a relative risk of 4.7 (95% confidence interval 2.5 to 9.0). Seven of 19 with atopic mothers and none with atopic fathers had AD with onset before 6 months (P= 0.007). When all types of disease evidence (AD, recurrent wheeze and food reactions) were analysed together no significant difference was apparent between the groups. The two groups were found to be well matched with regard to breast‐feeding, time of starting cow's milk, solids and egg, sex, month of birth, parental AD and smoking, race, household pets and neonatal IgE concentration. IgE concentrations at each age and the prevalence of skin prick positivity were similar between the groups. Maternal atopy poses a higher risk for infantile AD and paternal atopy. Whether this may be due to genetic or congenital factors or both is uncertain, but clearly the finding is of relevance in the prediction of allergy in childhood.
Adrenergic response in children with asthma on exogenous stimuli
Authors: VAN AALDEREN W. M. C. , POSTMA D. S. , KÖETER G. H. , DE MONCHY J. G. R. , KNOL K.
Published: April 2006

In asthmatic children it was investigated whether the degree of impairment of the adrenergic response on exogenous stimuli is related to the magnitude of the 24‐hour amplitude in airflow obstructions. Urinary‐adrenaline and noradrenaline excretion after house dust mite (HDM) inhalation and after exercise was measured. Nine children with (group I), and nine without increased airflow obstruction overnight (group II) and nine age matched healthy children (group C) were included in the study. All patients showed an early obstructive reaction (EOR) after HDM challenge. Six children in group I and five in group II developed an EOR on exercise. A Significant increase in urinary adrenaline excretion was observed after exercise in the control group (P<0.05, values on the control and challenge day being 5.4±0.9 and 10.0±1.6 μmol mol creat.). The same occurred for noradrenaline (P<0.01, values being 28.2±2.5 and 49.0±5.7 μmol mol creat.). Adrenergic response after both stimuli was impaired in the asthmatic groups, in group I more pronounced than in group II. Values from group I for adrenaline on the control day. HDM and exercise challenge were 6.0±0.8, 4.7±0.6, 6.0±1.0 and for noradrenaline 36.1±2.7, 27.2±2.3, 38.4±4.9 μmol mol creat., respectively. Values from group II for adrenaline on these days were 5.6±1.0, 3.7±0.6 and 9.0±1.3 and for noradrenaline 28.3±3.2, 22.4±2.5, 41.3±5.9 μmol/mol creat., respectively. The results of this study suggest that the degree of impairment of the adrenergic response on exercise in asthmatic children is related to the magnitude of the 24 hr amplitude in pulmonary function.
Specific IgE antibodies to nickel in workers with known reactivity to cobalt
Authors: SHIRAKAWA T. , KUSAKA Y. , MORIMOTO K.
Published: April 2006

Twenty‐one workers with hard metal asthma, including eight atopics, diagnosed on the basis of peak flow diaries and positive reaction to cobalt chloride (CoCl2) and/or nickel sulphate (NiSO4) in skin and provocation tests were studied for sensitization by detection of specific antibodies to nickel‐conjugated human serum albumin (Ni‐HSA), and nickel‐conjugated exchange resin (Ni‐resin). Their results were compared with those of sera obtained from control sera from 60 asthmatic patients and pair‐matched asymptomatic control workers in the hard metal plant. In the RASTs (radioallergosorbent tests), sera from the same six subjects developed positive reactions both to Ni‐HSA (RAST index > 2.0, P < 0.01) and Ni‐resin (RAST index > 2.0, P < 0.01), while the counts measured for the others of the 15 subjects (RAST index < 1.52) were about the same as those for control groups (RAST index < 1.58). Subject HSA RAST and resin RAST results (378.52 c.p.m. in HSA RAST and 324.56 in the resin RAST) were about the same as those of the control sera (388.65 c.p.m. and 398.59 c.p.m., respectively). There was no difference in the prevalence of smoking habit and high IgE between Ni‐RAST positive and negative subjects. However, subjects with simultaneous sensitivity to nickel and/or cobalt still developed asthmatic attacks following medications, while those without sensitivity to these metals were almost symptom free. The positive sera had simultaneous sensitivity to both cobalt and nickel, suggesting the presence in them of specific IgE antibodies to nickel playing some role in the aetiology of hard metal asthma.
Bronchial allergen challenge: dose versus concentration
Authors: FRØLUND L. , MADSEN F. , SCHARLING B. , HEINIG J. H. , SVENDSEN U. GERNER
Published: April 2006

This study was designed to investigate if two equivalent doses of allergen administered by different dosing regimes—two breaths and 10 breaths of each concentration—would result in the same magnitude of the early and late asthmatic response. Fifteen patients with extrinsic allergic asthma were challenged twice with either two or 10 breaths of twofold increasing allergen concentrations. The challenge was continued until a 20% decrease in FEV1 had been achieved. A non‐cumulative PC20FEV1 allergen was derived, and the cumulative dose of allergen given was similarly derived. In order to assess the reproducibility of the challenge, seven patients were challenged twice with two‐breath regime. The mean value of allergen PC20 obtained by the two‐breath regime was 4.1 fold (95% CI: 2.3–7.1 fold) greater than those obtained by the 10‐breath regime (P < 0.05), whereas the difference was 1.4 fold (95% CI: – 3.3–0.5 fold) for the cumulative dose (P > 0.05). A statistically significant larger magnitude of the early asthmatic response, as determined by the maximum per cent fall in FEV1, and late asthmatic response determined by the maximum per cent fall in peak expiratory flow domiciliary recorded during the following 24 hr after challenge, was observed in favour of the 10‐breath regime compared to the two‐breath regime (mean difference 6%, 95% CI: 0.6–11%). The reproducibility of the provocation test was acceptable (± 1.8 two‐fold concentration difference). These results confirm the ‘equivalent dose hypothesis’, and demonstrates that dosage rather than concentration appears to determine the early and late asthmatic response after bronchial allergen challenge.
Application of monoclonal antibodies against major basic protein (BMK‐13) and eosinophil cationic protein (EG1 and EG2) for quantifying eosinophils in bronchial biopsies from atopic asthma
Authors: MOQBEL R. , BARKANS J. , BRADLEY B. L. , DURHAM S. R. , KAY A. B.
Published: April 2006

A monoclonal antibody prepared against the eosinophil major basic protein (MBP) was compared with the anti‐eosinophil cationic protein (ECP) antibodies (Eg1 and EG2) in immunostaining of bronchial biopsies from atopic asthma and controls. Anti‐MBP (designated BMK‐13) did not cross‐react with other eosinophil basic proteins (i.e. ECP, eosinophil peroxidase [EPO] or eosinophil‐derived neurotoxin [EDN]) and stained more than 98% of peripheral blood eosinophils irrespective of their degree of activation. EG2 stained 15% of resting and 75% of activated eosinophils; EG1 recognized 74% and 78% of resting and activated cells, respectively.

The numbers of BMK‐13, EG1 or EG2‐positive staining cells in bronchial biopsies from asthma were significantly greater than atopic non‐asthmatics (P < 0.02, P < 0.01 and P < 0.05, respectively) and normal non‐atopic controls (P < 0.001). For each of the various groups studied, the rank order for the number of eosinophils stained was BMK‐13 > EG1 > EG2. BMK‐13 stained significantly more cells from bronchial biopsies of atopic asthma and atopic non asthma when compared to EG2(P < 0.001 and P < 0.05, respectively). Since only a proportion of BMK‐13+ cells were EG2+, these results suggest that not all tissue eosinophils are actively secreting. Thus, BMK‐13 can serve as a useful pan‐eosinophil marker in tissue sections since it appears to stain most eosinophils.
Specificity mapping of patients IgE response towards the tree pollen major allergens Aln g I, Bet v I and Cor a I
Authors: IPSEN H. , WIHL J.‐Å. , PETERSEN B. NÜCHEL , LØWENSTEIN H.
Published: April 2006

The specificity pattern of IgE from non‐treated tree pollen allergic patients (n= 38) were evaluated by solid phase absorption of serum samples followed by CRIE on alder, birch and hazel CIE precipitation profiles. The majority of the serum samples seemed to contain IgE antibodies with the following characteristics: specific towards Bet v I alone and common between Aln g I, Bet v I and/or Cor a I, ‘II’. The IgE specificity profiles observed for 95% of the sera tested are compatible with birch pollen allergens being the only sensitizing allergens, indicating that the patients react to allergens from other tree pollens of the Fagales order due to IgE cross‐reaction with the major allergens of birch and alder and/or hazel pollens.
Early neutrophil but not eosinophil or platelet recruitment to the lungs of allergic horses following antigen exposure
Authors: FAIRBAIRN S. M. , PAGE C. P. , LEES P. , CUNNINGHAM F. M.
Published: April 2006

Previous studies have shown that bronchoalveolar lavage fluid from horses with allergic respiratory disease and showing clinical symptoms contains increased numbers of neutrophils. In some cases, the eosinophil count is also increased. In this study the time course of changes in lung function and the accumulation of radiolabelled leucocytes and platelets in the lungs of allergic and normal horses has been examined during a 7 hr allergen exposure. Antigen challenge had no effect on pleural pressure or the distribution of radiolabelled neutrophils, eosinophils or platelets in normal horses. In contrast, in 6/8 allergic horses, there was an increase in pleural pressure and neutrophil accumulation in the lungs, both of which were evident after 4–5 hr. However, during the 7 hr challenge period radiolabelled eosinophils were detected in the lungs of only 1/6 horses exhibiting an increase in pleural pressure and in 1/7 horses that failed to show a change in airway function despite a clinical history of allergic respiratory disease. Antigen challenge did not alter the distribution of radiolabelled platelets in the five allergic horses tested. These results demonstrate that increased pleural pressure is not accompanied by eosinophil or platelet accumulation in the lungs of horses with allergic respiratory disease following exposure to antigen. However, changes in airway function can be associated with neutrophil accumulation but can also take place in the absence of this cell recruitment. This raises the possibility that the presence of neutrophils in the lung is not a prerequisite for changes in lung function.
Inhibition of bronchial hyperresponsiveness to histamine induced by intravenous administration of leukotriene C4 by novel thromboxane A2 receptor antagonists ONO‐NT‐126 and ONO‐8809 in guinea‐pigs
Authors: KUROSAWA M. , YODONAWA S. , TSUKAGOSHI H.
Published: April 2006

We studied the effect of intravenous administration of leukotriene (LT) C4 on bronchial responsiveness to histamine and airway wall thickening in guinea‐pigs. Guinea‐pigs were killed and the lungs were fixed in formalin. Slides from paraffin‐embedded sections of the lungs were stained and the airways that were cut in transverse sections were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two incides, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline‐Raw and peak‐Raw following intravenous administration of histamine before and after the intravenous administration of LTC4. Intravenous administration of 3 μg/kg LTC4 for 1 hr induced an increase of the relative thickness of the airway wall in peripheral bronchi by the histological examination. In analysis of airway function, intravenous administration of 3 μg/kg LTC4 for 1 hr induced airway hyperresponsiveness to histamine with airway wall thickening. Thromboxane A2 receptor antagonists ONO‐NT‐126 and ONO‐8809 inhibited the LTC4‐induced airway hyperresponsiveness to histamine in a dose‐dependent manner, but not the airway wall thickening induced by LTC4, suggesting that the effect of LTC4 on bronchial hyperresponsiveness is likely to be mediated through TXA2.
Genetic polymorphism of the β‐2 adrenergic receptor in atopic and non‐atopic subjects
Authors: POTTER P. C. , VAN WYK L. , MARTIN M. , LENTES K. U. , DOWDLE E. B.
Published: April 2006

To investigate a possible genetic basis for reported differences in β‐2 receptor expression in atopic subjects, DNA from 42 atopic children (22 asthmatics and 22 with allergic rhinitis) and 30 non‐atopic subjects was Southern blotted and Ban‐1 restriction fragment polymorphisms (RFLPS) were studied using a 2.6 kb probe of the human β‐2 receptor gene. Two alleles 3.1 kb and 2.9 kb were identified. Homozygotes and heterozygotes for the two alleles were found with equal frequency in the atopic patients who had asthma and in those who had allergic rhinitis only. The gene frequencies for the upper and lower alleles were 0.45 and 0.55 respectively. Our studies do not provide evidence for an association between a particular polymorphic form of the human β‐2 receptor gene and atopy.
Atopy in childhood. I. Gender and allergen related risks for development of hay fever and asthma
Authors: SEARS M. R. , BURROWS B. , FLANNERY E. M. , HERBISON G. P. , HOLDAWAY M. D.
Published: April 2006

Reasons for the gender differences in prevalence rates for asthma remain unclear. We have examined the relationships between allergen skin‐test reactions and diagnoses of hay fever and asthma in New Zealand hoys and girls examined at the age of 13 years. Information on current and past wheezing, diagnosed asthma, and hay fever was obtained for 662 subjects (341 boys) of a birth cohort followed longitudinally to the age of 13 years, using a physician‐administered questionnaire. Atopic status was determined by skin‐prick tests to 11 common allergens. The proportion of 13‐year‐old boys with current asthma was 1.6 times higher and of ever‐diagnosed asthma 1.4 times higher than in girls, but the prevalence of recurrent wheeze ( three episodes per year) not diagnosed as asthma, or of hay fever, was not significantly different between the sexes. The prevalence of diagnosed asthma increased with increasing numbers of positive skin tests, but hay fever without asthma was little affected above one positive skin‐test. Boys had a greater prevalence of any positive skin‐test (50.1 % vs 37.1%), two or more positive tests (29.3 % vs 21.8%), and responses to house dust mite (34.0% vs 23.1 %) and cat (14.7% vs 11.2%). Gender differences for asthma became insignificant when adjusted for skin‐test responsiveness to house dust mite and/or cat. The proportion of children with diagnosed asthma increased with increasing size of weals to house dust mite and cat dander. Gender differences in allergen sensitivities partly explain the gender differences in diagnosed asthma in children. In both sexes, risk of asthma was primarily associated with sensitization to indoor allergens (house dust mite and cat), and was related to the magnitude of the skin‐test response, while the risk of hay fever was primarily associated with grass pollen sensitivity.
Atopy in childhood. II. Relationship to airway responsiveness, hay fever and asthma
Authors: SEARS M. R. , BURROWS B. , HERBISON G. P. , HOLDAWAY M. D. , FLANNERY E. M.
Published: April 2006

While airway hyperresponsivencss is usually associated with a diagnosis of asthma or symptoms of wheezing, some individuals with rhinitis show airway hyperresponsiveness as do some with no symptoms whatsoever. We have studied the correlations between symptoms, airway hyperresponsiveness and atopy as determined by skin‐prick tests in a cohort of New Zealand children. A total of 662 members of a birth cohort were studied at age 13 years using a respiratory questionnaire, skin‐prick tests to 11 common allergens, and an abbreviated validated methacholine challenge test to determine airway responsiveness. Airway hyperresponsiveness (methacholine PC20 FEV1 8 mg/ml) was strongly correlated with reported asthma and current wheezing (P < 0.0001) and also with atopy, especially to house dust mite and cat (P < 0.0001). As weal size for both house dust mite and cat increased, so did the proportion of children with airway hyperresponsiveness. All children with diagnosed asthma and airway hyperresponsiveness were atopic. Skin‐test reactions to house dust mite and cat were strongly correlated with any degree of measurable airway responsiveness (PC20 FEV125 mg/ml) in children with rhinitis (P < 0.0001), and remained significantly correlated even in children without current asthma, without asthma ever and without rhinitis (P < 0.001). Atopy is a major determinant of airway hyperresponsiveness in children, not only in those with reported histories of asthma and wheezing, but also in the absence of any history suggesting asthma and rhinitis.
Peripheral blood mononuclear cells from house dust mite allergic patients produce IL‐2 in response to specific allergen challenge
Authors: MCHUGH S. M. , LACHMANN P. J. , EWAN P. W.
Published: April 2006

Proliferative responses and production of IL‐2 by peripheral blood mononuclear cells of patients with Dermatophagoitles pieronyssinus rhinitis ± asthma were measured at up to 24 hr intervals from 1–8 days, after stimulation with mitogen (PHA), antigen (SKSD) and specific allergen (D.pteronysxinus). IL‐2 was measured in culture supcrnaunts using the murine CTLL cell line bioassay. Compared to non‐atopic controls, patients had significantly higher prolilenitive responses to D. pteronyssinus and SKSD but similar responses to PHA. In patients, maximal proliferate responses to PHA, SKSD and D. piemnyxsinus were at 3, 6 and 7 days, respectively. IL‐2 levels in response to stimulation with D. pieronvssinus were significantly higher in patients than controls, where only background levels were found (15.4, 7.9–30.7− 10‐2 U/ml [mean, range] n=11;vs 2.2,0.1–8.4 × 10‐2 U/ml, n= 6; P< 0.05). In contrast, IL‐2 production to PHA and SKSD, although higher in patients, was not significantly different than controls. These results suggest allergic patients possess a population of T cells expandable by specific allergen which are induced to secrete IL‐2.
β2‐Adrenoceptor stimulation augments the IL‐4‐induced CD23 expression and release and the expression of differentiation markers (CD14, CD18) by the human monocytic cell line, U 937
Authors: PAUL‐EUGENE N. , DUGAS B. , GORDON J. , KOLB J. P. , CAIRNS J. A. , PAUBERT‐BRAQUET M. , MENCIA‐HUERTA J. M. , BRAQUET P.
Published: April 2006

The effect of β2‐adrenoceptor agonists and interleukin‐4 (IL‐4) on the CD23 expression on, and release from, the human promonocytic cell line, U 937, was investigated. As assessed by flow cytometry, incubation of U 937 cells in the presence of salbutamol, fenoterol or IL‐4 induced a concentration‐ and time‐dependent increase in CD23 expression, that was maximal after 48 hr and followed by a decrease thereafter. In addition, salbutamol potentiated the effect of IL‐4, the optimal concentration of the drug being a function of the concentration of this cytokine. This synergy between IL‐4 and β2‐adrenoceptor agonists was also observed for the release of the soluble form of CD23. The effect on CD23 expression of salbutamol and fenoterol, but not of IL‐4, was blocked in the Wesence of d, l‐propranolol (1 μm) or butoxamine (1 μm). The α‐adrenoceptor agonist, norepinephrine (1 μm), was ineffective in inducing CD23 expression or potentiating the one evoked by IL‐4. Salbutamol down‐regulated the expression of FcγRI (CD64) and Fc, RII (CD32) whereas IL‐4 was ineffective. Only when added together at the onset of the culture did salbutamol and IL‐4 induce, after 48 hr, the expression of the monocyte marker, CD 14. The expression of CD 18 was up‐regulated in response to salbutamol either alone or in combination with IL‐4, this cytokine alone being inefficient. These data suggest that IL‐4 and β2‐adrenoceptor agonists induce differentiation of U 937 cells into monocyte‐like cells.
Environmental exposure to Aspergillus fumigatus allergen (Asp f I)
Authors: SPORIK R. B. , ARRUDA L. K. , WOODFOLK J. , CHAPMAN M. D. , PLATTS‐MILLS T. A. E.
Published: April 2006

Asp f I is a major allergen produced by the mycelia of Aspergillus fumigatus. It is not present in spores and can be used as a specific marker for the detection of germination of this fungus. We investigated the domestic and outdoor concentration of Asp f I in Poole, U.K. and Charlottesville, VA, U.S.A. Asp f I was undetectable in 95% (281/296) of house dust extracts and present at low levels (< 0.17 μg/g of sieved dust, mean 0.038 μg/g) in the remainder. In contrast, Asp f I could be detected in 65% (15/23) of cultures of house dust, suggesting the presence of viable, but ungerminated, A. fumigatus in the majority of homes. Asp f I was detectable in 80% (28/35) of extracts of leaves and compost, but present in these outdoor samples at low levels (<0.11 μg/g, mean 0.27 μg/g). Air sampling for Asp f I was undertaken before and after vigorous disturbances at indoor (n= 5) and outdoor (n= 6) sites. Airborne Asp f I was not detected in domestic samples or in undisturbed outdoor samples. Following disturbance it could be measured in outdoor samples (range 7.6–29 ng/m3). The results suggest that while exposure to A. fumigatus is common, exposure to Asp f I and germinating A. fumigatus is uncommon. It is probable that those individuals who develop antibody responses to Asp f I have been exposed to A. fumigatus which has germinated in their respiratory tract.
Allergenicity of the cat flea (Ctenocephalides felis felis)
Authors: TRUDEAU W. L. , ÁNDEZ‐CALDAS E. FERN , FOX R. W. , BRENNER R. , BUCHOLTZ G. A. , LOCKEY R. F.
Published: April 2006

Adult fleas, spent and unspent culture media were extracted and the radio‐atlergosor‐bent test (RAST) performed with sera of 48 cat flea skin test‐positive individuals from the Tampa Bay area of Florida. Sixteen sera (33.6%) had a positive RAST to the cat flea extract prepared in our laboratory [1.7‐11.4% of the total counts (TC) added]. Six of the 16 sera (12.5%) also contained specific IgE to allergens in thespent medium (0.8‐3.3% TC). The allergen composition and strength were studied by RAST inhibition of two commercial cat flea extracts and compared with our in‐house flea extract. The results demonstrated similar allergen compositions and different potencies. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) of the in‐house flea extract showed several Coomassie blue‐stained bands (10–85 kD). SDS‐PAGE immunoblols revealed five IgE‐binding bands at 34, 35, 39, 54 and 60 kD. Flea allergens were quantified in eight house dust samples using RAST inhibition assays and expressed as RAST inhibition units; five of these samples contained detectable levels. Cat flea allergens may contribute to the allergenicity of house dust in areas of heavy llea infestation.
Cutaneous IgE‐mediated inflammatory lesion size is inhibited by an H1 antagonist (terfenadine) while mediator release is unaffected in vivo and in vitro
Authors: MASSEY W. A. , CHARLESWORTH E. N. , FREIDHOFF L. , COOPER P. , KAGEY‐SOBOTKA A. , LICHTENSTEIN L. M.
Published: April 2006

We are interested in understanding the pathogenesis of the cutaneous IgE‐mediated late phase reaction. A double‐blind, placebo‐controlled, randomized cross‐over study with 10 subjects of the effect of the non‐sedating antihistamine, terfenadine (Selddane), on the cutaneous reaction to antigen (ragweed or mixed grass) administered intradermally and over denuded blister bases was performed. The activity of terfenadine on anti‐IgE‐induced mediator release from the skin mast cell, lung mast cell and basophil was also examined in vitro. Terfenadine significantly inhibited the size of the cutaneous reaction at every hour between hours 1 and 9 (hr 9, control 2250 ± 500 mm2vs drug 1250 ± 250 mm2, P < 0.01, n=10) and showed some inhibitory effect at hours 10–12. While terfenadine blocks histamine release after nasal antigen challenge the release of mediators at skin blister sites was unaffected. The infiltration of leucocytes into the blister supernatant was unaffected by terfenadine although previous studies have shown significant inhibition with another antihistamine, cetirizine. In vitro, terfenadine. like other antihistamines, was found to have inhibitory activity on anti‐IgE‐induced mediator release at concentrations of 10−4‐10−5 M in lung and skin mast cells and basophils. We conclude that the effects of the newer antihistamines on cellular movement into the skin may be diverse, that terfenadine may show organ specificity in vivo and that terfenadine significantly decreases both the early and late gross inflammatory response of the skin to antigen. We cannot, as yet. explain the mechanism(s) by which this occurs.
A comparison of topical levocabastine and sodium cromoglycate in the treatment of pollen‐provoked allergic conjunctivitis
Authors: FROSTAD A. B. , OLSEN A. K.
Published: April 2006

A total of 71 patients with documented birch and grass pollen allergy participated in this randomized, double‐blind, parallel‐group study initiated to compare the long‐term therapeutic efficacy of twice daily levocabastine, a new topical H1‐receptor blocker, with that of sodium cromoglycate four times daily in the treatment of pollen‐provoked conjunctivitis. There was no statistically significant difference in therapeutic efficacy between the two treatment groups, although a positive trend in favour of levocabastine was observed. Global evaluations of therapeutic efficacy were similar in both treatment groups. A total of 94% of levocabastine‐treated patients rated treatment to be excellent or good compared with 86% of patients in the sodium cromoglycate group. Moreover, there were no significant differences in the severity of allergic symptoms reported on the patient diary cards. Patients were permitted to use rescue medication (oral terfenadine and betamethasone nasal spray) if symptoms became severe. The use of rescue medication was lower in the levocabastine group than in the sodium cromoglycate group. The mean number of days on which rescue medication was used was 12.8 and 26.9 in the two groups, respectively. The incidence, and type, of adverse reactions was similar in both patient groups. Levocabastine is well‐tolerated and at least as effective as sodium cromoglycate in the treatment of pollen‐provoked conjunctivitis.