bluuebunny/crossref_metadata_2025 huggingface dataset:
IgE antibodies to protein and mannan antigens of pityrosporum ovale in atopic dermatitis patients
Authors: LINTU P. , SAVOLAINEN J. , KALIMO K.
Published: April 2006

Background Pityrosporum ovale is a common saprophyte on the skin capable of inducing IgE antibody production in atopic dermatitis (AD) patients. Allergens ofP. ovale have been examined in several studies, but consensus on them is lacking.

Objective This study was carried out to obtain more information about the IgE antibody response against P. ovale. including niunnun.

Methods Sera from 64 AD patients and 10 healthy controls were analysed with immuno‐blotting and the nitrocellulose radio allergosorbent test (RAST) method specifically developed to detect antimannan P. ovale IgE antibodies.

Results In immunoblotting a total of 39 different IgE stained protein bands were seen. A high molecular weight staining was also seen especially in patients who displayed elevated mannan P. ovale RAST values. The most commonly stained protein bands in immunoblotting were 9 and 96 kD bands with antibodies in 73 and 65% of AD patients who had been positive in commercial P. orbiculare RAST with total serum IgE less than 4000 kU/I. Mannan RAST appeared positive in 77% of them. Positive immunoblotting to either of these bands was seen in 90% and, if added with staining with ihe 20 kD band, in 100% of these AD patients. A comhination of 9 kD IgE staining and mannan P. ovale RAST was positive in 92% of the patients and % kD and mannan P. ovale RAST in 85% of the patients. Conclusion It is evident that P. ovale has several allergens, the 9. 96 and 20 kD regions being the most important. According to our results mannan is also an important allegen of P. ovale
The inhibitory effect of TMK688, a novel anti‐allergic drug having both 5‐lipoxygenase inhibitory activity and anti‐histamine activity, against bronchoconstriction, leukotriene production and inflammatory cell infiltration in sensitized guinea pigs
Authors: TOHDA Y. , NAKAJIMA S. , SHIZAWA T. , MAEDA KAZUHA , OHMORI S. , SATOH H. , ISHII T. , KAMITANI T.
Published: April 2006

Background TMK688 is being developed as ati anti‐allergic drug having both 5‐lipoxygenasc inhibitory activity atid anti‐histaminc activity.

Method We compared the inhibition ol the late asthmatic rcsponses by TMK688 with that by other anti‐allergic agents in actively sensitized guinea pigs, and examined the relationship between 5‐lipoxygetiase inhibition and the late asthmatic responses

Results At 1–3.2 mg/kg, TMK688 inhibited the increases in respiratory resistance, leukotriene (LT) B4 and C4 production in the lungs and eosinophil infiltralion into the alveoli during the late asthmatic response, whereas the eliects tended to lessen at the dose of 10mg/kg. These effects are thought to be caused by the 5‐lipoxygenase inhibitory activity of TMK688 because Azelastine. an anti‐allergic drug having potent antihistamine activity, exhibited no effect. ONO‐1078. a peptide LT antagonist. inhibited the late‐phase bronchoconstriction at a dose of 100mg/kg p.o., but not the increase in the infiltration of inflammatory cells into the alveoli, suggesting that the late‐phase bronchoconstriction is induced, in part, by peptide LTs, i.e. LT C4, D4 and E4 atid that the inflammatory cell infiltration may be caused by LTB4, TMK688 inhibited the immediate bronchoconstriction dose‐dependently, and the effect was significant at a dose of 10mg/kg orally. Since Azelastine, Ketotifen and Oxatomide suppressed the bronchoconstriction at far lower doses than did TMK688, the inhibitory effect was mainly caused by its antihistamine activity.

Conclusions TMK688 appears to be a novel anti‐allergic drug having inhibitory effects on both the bronchoconstriction and the infiltration of inflatnmutory cells during late asthmatic responses.
The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity
Authors: NYFELER B. , PICHLER W.J.
Published: April 2006

Background The diagnosis of a drag allergy is mainly based upon a very detailed history and the clinical findings. In addition, several in vitro or in vivo tests can be performed to demonstrate a sensitization to a certain drug. One of the in vitro tests is the lymphocyte transformation test (LTT), which can reveal a sensitization of T‐cells by an enhanced proliferative response of peripheral blood mononuclear cells to a certain drag.

Objective To evaluate the sensitivity and specificity of the LTT, 923 case histories of patients with suspected drag allergy in whom a LTT was performed were retrospectively analysed.

Methods Based on the history and provocation tests, the probability (P) of a drag allergy was estimated to be >0.9, 0.5–0.9, 0.1–0.5 or <0.1, and was put in relation to a positive or negative LTT.

Results Seventy‐eight of 100 patients with a very likely drag allergy (P<0.9) had a positive LTT, which indicates a sensitivity of 78%. If allergies to betalactam‐antibiotics were analysed separately, the sensitivity was 74.4%. Fifteen of 102 patients where a classical drag allergy could be excluded (P<0.1), had nevertheless a positive LTT (specificity thus 85%). The majority of these cases were classified as so‐called pseudoallergic reaction to NSAIDs. Patients with a clear history and clinical findings for a cotrimoxazole‐related allergy, all had a positive LTT (6/6), and in patients who reacted to drags containing proteins, sensitization could be demonstrated as well (i.e. hen's egg lysozyme, 7/7). In 632 of the 923 cases, skin tests were also performed (scratch and/or epicutaneous), for which we found a lower sensitivity than for the LTT (64%), while the specificity was the same (85%).

Conclusion Although our data are somewhat biased by the high number of penicillin allergies and cannot be generalized to drag allergies caused by other compounds, we conclude that the LTT is a useful diagnostic test in drag allergies, able to support the diagnosis of a drag allergy and to pinpoint the relevant drag.
Stimulation of early eosinophil progenitors by a heat stable alveolar macrophage product from ovalbumin‐sensitized and non‐sensitized guinea pigs
Authors: ELSAS M. I. C. GASPAR , ELSAS P. XAVIER , JOSEPH D. , HAVET N. , DA SILVA L. A. ADELINO , SALGADO D. R. , SALIOU B. , VARGAFTIG B. B.
Published: April 2006

Background Alveolar macrophages (AM) may participate in brochopulmonary hyperreactivity by secreting cytokines that recruit mature eosinophils, or induce eosinophil production from recruited circulating progenitors.

Objective To define whether AM products can contribute to lung eosinophil production in immunized guinea pigs (GP), by analysing the effect of AM culture supernatatits (AM‐SN) on in vitro eosinophilopoiesis.

Methods Liquid and semi‐solid bone marrow (BM) cultures were seeded witb SN from 95% pure AM exposed to LPS.

Results AM‐SN increased very significantly the long‐term viability, cell proliferation and eosinophil production in liquid culture and supported formation of eosinophil‐bearing mixed colonies, by acting on progenitors depleted of mature eosinophils. The effect on eosinophil production was not duplicated by natural or recombinant sources of GM‐CSF (which nevertheless supported GM colony formation by GP BM), not by rhIL‐8 (which was active on GP cells) and was not due to residual LPS. FPLC separation of active AM SN yielded a peak of apparent m.w. 43 kDa, active on both liquid and semi‐solid cultures. The active moiety was heat‐ and trypsin‐resistant. Neutralizing monoclonal antibodies to hGM‐CSF, mGM‐CSF, hIL‐3 and mIL‐3 failed to deplete the activity in AM‐SN. Ovalbumin immunization induced its production by AM even without LPS challenge.

Conclusions The lack of T lymphocytes among factor‐producing AM, the properties of the active material, the inability of GM‐CSF to reproduce these effects, and the failure of MoAbs to GM‐CSF and to IL‐3 to neutralize the activity indicate it is not due to the major eosinopoietic factors GM‐CSF, IL‐3 or IL‐5.
The association of family size with atopy and atopic disease
Authors: JARVIS D. , CHINN S. , LUCZYNSKA C. , BURNEY P.
Published: April 2006

BackgroundStudies in children have shown that family size is negatively associated with atopy and atopic disease.

ObjectiveTo describe the association of family size with atopy and atopic disease in young adults.

MethodsA randomly selected sample of 1159 men and women aged 20–44 years provided information on respiratory symptoms, hay fever and eczema. Blood samples were taken for assessment of total IgE and specific IgE to house dust mite, grass, cat,Cladosporiumand birch. The association of family size and birth order with respiratory symptoms, atopy and total IgE was assessed by multiple logistic and linear regression.

ResultsThere was a negative association between family size and the reporting of ‘wheeze with breathlessness’ (adjusted odds ratio for an increase of one sibling 0.85; 95% confidence interval 0.75–0.98), ‘wheeze without a cold’ (adjusted odds ratio for an increase of one sibling 0.85; 95% confidence interva l0.75–0.98) and ‘asthma attacks’ in the last 12 months (adjusted odds ratio for an increase of one sibling 0.77; 95% confidence interval 0.61–0.97), current ‘hayfever and nasal allergies’ (adjusted odds ratio for an increase of one sibling 0.84; 95% confidence interval 0.75–0.94) and sensitization to grass (adjusted odds ratio for an increase of one sibling 0.87; 95% confidence interval 0.76–0.99). Birth order was negatively associated with ‘hayfever and nasal allergies’ only. A decreased risk of sensitization to grass in those from large families did not fully explain the negative association between family size and hayfever. No statistically significant (P> 0.05) association of family size or birth order with the reporting of other respiratory symptoms, eczema, sensitization to the other allergens or total IgE was observed.

ConclusionThere is a negative association between family size and some symptoms suggestive of asthma, ‘hayfever and nasal allergies’ and sensitization to grass in young adults. There is no consistent, significant association between family size and eczema, total IgE or sensitization to other allergens.
Allergen content in dust from homes and schools in northern Norway in relation to sensitization and allergy symptoms in schoolchildren
Authors: DOTTERUD L. K. , VAN T. D. , KVAMMEN B. , DYBENDAL T. , ELSAYED S. , FALK E. S.
Published: April 2006

Background Previous studies have shown a high prevalence of atopic diseases among school children in the community of Sør‐Varanger. Moreover, animal dander followed by pollen und house dust mite, were the most common allergens in skin prick tests.

Objective To assess the allergen content in homes (living‐rooms and mattresses) and classrooms of children living in an arctic area at 70° north. The presence of allergens in homes and schools and their relationship to atopy was of particular interest.

Methods Dust samples from 38 homes and seven schools in northern Norway were collected by vacuum cleaning. The presence of allergens of dog, birch, timothy, Cladosporium herbanun, codfish and hen egg‐white was investigated by radio‐allergosorbent test (RAST) inhibition and the presence of major allergens of cat Felis domesticus (Fel d I) and house dust mites (HDM) Dermatophagoides pteronyssinus (Derp I) and Dermatophagoides farinae (Derf I) by enzyme‐linked immunosorbent assay (ELISA).

Results Mattresses contained significantly more dust per unit area than living‐rooms and classrooms. No statistically significant differences in allergen content for dog. birch, timothy, Cladosporium, codfish and hen egg‐white were seen between HDM‐sensitized and non‐atopic children. Most dust samples contained dog allergens with the highest allergenic activity found in living‐rooms of those keeping dogs. An increased level of Feld I was detected in only one of 38 samples from living‐rooms (this family kept a cat) and in 25 of 38 samples from mattresses with ranges from 24 to 84ng/m2. The highest concentrations were found in mattresses of children keeping cats. Increased levels ( 25 ng/m2) of Derp I were found only in homes and virtually only in mattresses of HDM‐sensitized children. An increased level of Derf] was found in only one case, i.e. in the mattress of an HDM‐sensitized child where additionally Der p I and HDMs were demonstrated microscopically. When relating Der p I to HDMsensitization an odds ratio of more than 16 (95% Cl: 1.6–394.3) was found. All extracts from living‐rooms included codfish allergens. Low RAST inhibition values were detected for hen egg‐white, Cladosporium, birch and timothy pollen in most samples. Furthermore, the study demonstrated that dust from schools was relatively free of allergens.

Conclusion Previous findings indicating that the main allergen exposure problem in this geographical area is that of pet allergens were confirmed.
Allergic rhinitis in children: effects of flunisolide and disodium cromoglycate on nasal eosinophil cationic protein
Authors: SENSI L. G. , SERl A. , SIRACUSA A , PERTICI L. , MARCUCCI F.
Published: April 2006

Background Eosinophil cationic protein (ECP) is one of the major, cytotoxic molecules produced by eosinophils, which can be used as a marker of allergic inflammation.

Objective In this placebo‐controlled study we measured nasal and serum ECP levels to verify their possible role in monitoring the efficacy of anti‐inflammatory therapy in allergic chronic rhinitis in 38 children aged from 4 to 14 yr, allergic to house dust mites.

Method Nasal ECP, by the method of direct incubation on nasal mucosa, and serum ECP were determined before and after 3 weeks of treatment with flunisolide nasal spray 50 μg twice/daily (13 cases, Group 1), disodium cromoglycate (DSCG) 10.4mg three times/day (15 cases, Group 2) and placebo (10 cases, Group 3). The effectiveness of therapy was evaluated clinically and correlated to serum and nasal ECP values.

Results Before treatment no significant difference emerged in the clinical scores of the three groups of patients. Before and after treatment serum ECP levels were not statistically different from normal controls. Before treatment nasal ECP was significantly higher in all patients compared with controls (P < 0.001). Nasal ECP decreased significantly in flunisolide‐treated patients (P < 0.01) (before therapy: median 111 μg/L, range from 33.6 to 200 μg/L; after therapy: median 36.8 μg/L, range from 2.6 to 196 μg/D, but not in DSCG‐treated patients, (before therapy: median 66.2 μg/L, range from 32.3 to 200 μg/L; after therapy: median 60.4 μg/L, range from 7.9 to l44 μg/L). No significant variation was present in the placebo group. Clinical improvement was statistically significant after flunisolide therapy (P < 0.05), less evident after DSCG (P = 0.06).

Conclusion Serum ECP in chronic allergic rhinitis has been shown to be not useful in monitoring allergic inflammation, but nasal ECP, determined by mucosal incubation, may be used to evaluate the activity of eosinophils and monitor the anti‐inflammatory efficacy of therapy in chronic rhinitis.
Major allergens in soybean and clinical significance of IgG4 antibodies investigated by IgE‐ and IgG4‐immunoblotting with sera from soybean‐sensitive patients
Authors: AWAZUHARA H. , KAWAI H. , MARUCHI N.
Published: April 2006

Background Soybean occasionally causes food allergy but its major allergens have not been sufficiently confirmed. The relationship between food allergy and food‐specific IgG4 has also not been defined.

Objective We investigated the allergenicity of soybean proteins and the clinical significance of soybean‐specific IgG4.

Methods We detected IgE‐ and IgG4‐binding proteins in soybean by immunoblotting with sera from 30 soybean‐sensitive patients (including seven patients with positive soybean challenge tests). The extract from soybeans was fractionated into tbe whey fraction and the globulin fraction.

Results Ten and eight proteins were detected as IgE‐ and IgG4‐binding proteins, respectively, with a significant difference between tbe patient and control groups. Among the IgE‐binding proteins, the proteins with molecular weights of 20000 and 58000 in the whey traction, and 26000 and 31000 in the globulin Traction, had a particularly high IgE detection rate and high specificity. Two patients with positive challenge tests showed a quite different pattern in which only a protein with a molecular weight of 78000 in the globulin fraction was detectable with serum IgE in both patients. The majority of lgG4‐binding proteins were not consistent witb tbe IgE‐binding proteins. The strong reactivity of lgG4 was observed in all five infants among seven patients with positive challenge tests, and three of them had a very weak IgE reactivity.

Conclusions There were various antigenic proteins in soybean. Five proteins with molecular weights of 20000 and 58000 in the whey fraction, and 26000. 31000 and 78000 in the globulin fraction, were considered major allergens in the IgE‐mediated reaction. Results of IgE‐ and IgG4‐immunoblotting suggested that soybean‐specific IgG4 may act anaphy lactically in patients witb soybean allergy.
Nasal nitric oxide is increased in allergic rhinitis
Authors: ARNAL J.‐F. , DIDIER A. , RAMI J. , M'RINI C. , CHARLET J.‐P. , SERRANO E. , BESOMBES J.‐P.
Published: April 2006

Background Nitric oxide (NO) plays a major role in the regulation of vascular tone and in non‐specific host defence. The epithelium in the paranasal sinuses was recently identified as the major site of NO production in the upper airways.

Objective To investigate NO status in allergic rhinitis, we compared the NO concentration in the nasal cavities of control subjects (n= 19) and in patients with allergic rhinitis (n= 36) with symptoms (WS, n= 17) or without symptoms (WOS, n= 19) on the day of the test.

Methods NO concentration was measured using a chemiluminescent analyser aspiring from each nasal cavity at a sampling flow rate of 0.7L/min, before and 10min after administration of a nasal vasoconstrictor.

Results The mean NO concentration (± se) in the control was 235 ± 11 ppb and 225 ± 9 ppb in the right and left nostrils respectively, and was decreased by 14% and 12% by the nasal vasoconstrictor (P < 0.001). The NO concentration in patients with allergic rhinitis was significantly higher in the right and left nostrils (382 × 20 ppb and 396 ± 28 respectively, P < 0.0001 versus control). All WOS patients demonstrated normal or increased NO concentrations in both nostrils, whereas two WS patients showed decreased NO concentrations in the left nostril. Inhalation of a nasal vasoconstrictor increased NO concentration by 6% and 27% in the right and left nostrils respectively in WS patients.

Conclusion Nasal NO concentration is increased in patients with allergic rhinitis. Interestingly, patients without symptoms on the day of the test also showed a clear‐cut increase in nasal NO production, which could reflect a permanent inflammation of the sinus mucosa.
Prevalence of latex sensitization in subjects attending health screening: implications for a perioperative screening
Authors: PORRI F. , LEMIERE C. , BIRNBAUM J. , GUILLOUX L. , LANTEAUME A. , DIDELOT R. , VERVLOET D. , CHARPIN D.
Published: April 2006

Background Because latex is a common allergen, the rate of latex sensitization may be high in the general population. A major issue would then be to detennine whether a systematic preoperative screening in the general population should be recommended.

Objective The purpose of the study was to evaluate the prevalence of latex sensitization in a sample of the general population and to assess the role of possible risk factors.

Methods The subjects were 258 people, aged from 20 to 40 yr, visiting a health care centre for a check‐up. The protocol included: a questionnaire (occupation, symptoms of atopy, use of latex goods and possible reactions, history of previous surgery), a skin‐prick test, and a CAP RAST to latex. Atopy was evaluated by a skin‐prick test to common allergens and a Phadiatop® test.

Results Some 6.6% of the study group had either a positive skin test or a positive RAST to latex. These subjects had a four‐fold higher prevalence of symptoms when wearing gloves. The rate of latex sensitization was higher by fivefold in subjects with a history of reactions to latex goods and by fourfold in atopic subjects.

Conclusions Because the rate of latex sensitization is much higher than the anticipated rate of perioperative reactions due to latex allergy, a systematic preoperative screening for latex allergy should not be recommended for adults.
Microvascular actions of histamine: synergism with leukotriene B4 and role in allergic leucocyte recruitment
Authors: THORLACIUS H. , LINDBOM L. , HEDQVIST P. , RAUD J.
Published: April 2006

Background Previous studies have shown that antihistamities provide little or no protection against the recruitment of leucocytes in allergic inflammation.

Objective We wanted to examine if threshold doses of histamine can potentiate chemoattractant‐induced leukocyte adhesion and if complete inhibition of histamine‐induced microvascular effects is necessary to reduce allergic leucocyte recruitment.

Methods The role of histamine in allergic leucocyte recruitment was examined by use of intravital microscopy of the hamster cheek pouch microcirculation.

Results We found that topical administration of histamine caused a concentration‐dependent increase in microvascular permeability in the cheek pouch; i.e. 0.3 μM histamine caused no detectable plasma leakage, while 1 μM and 10 μM histamine resulted in 29 ± 9.3 and 356 ± 47 leakage sites/cm2 cheek pouch area, respectively. The percentage of postcapillary venules with more than five adherent leucocytes (an index of early leucocyte recruitment) was 1.1 ± 0.51% in the control situation, and did not increase significantly after stimulation with histamine alone (0.3–10μM) or with 1 nM ieukotriene B4 (LTB4). On the other hand, coapplication of 10μM histamine and 1 nM LTB4 increased leucocyte adhesion 24‐fold. In fact, the 10 times lower dose of histamine (1 μM) together with 1 nM LTB4 increased leucocyte adhesion to a similar extent (20 fold). The increase in vascular permeabihty evoked by exogenous 10μM histamine (with or without LTB4), or by histamine released from activated mast cells (antigen challenge), was completely reversed by local pretreatment with the H1‐receptor antagonist mepyramine. This mepyramine treatment also abohshed the enhanced leucocyte adhesion in response to coapplication of histamine and LTB4. Moreover, mepyramine, which had no effect on leucocyte recruitment evoked by 3 nM LTB4per se, reduced antigen‐induced recruitment of leucocytes to the extravascular tissue by 79.5 ± 14.8%.

Conclusion We conclude that threshold concentrations of histamine can strikingly potentiate chemoattractant‐induced leucocyte responses, and that in order to reduce allergic leucocyte recruitment it may be necessary to use antihistamines in doses high enough to abolish the microvascular actions of histamine.
Occupational asthma caused by triglycidyl isocyanurate (TGIC)
Authors: PIIRILÄ P. , ESTLANDER T. , KESKINEN H. , JOLANKI R. , LAAKKONEN A. , PFÄFFLI P. , TUPASELA O. , TUPPURA1NEN M. , NORDMAN H.
Published: April 2006

Background Polyester powder paints are extensively used in metal painting. Triglycidyl isocyanurate (TGIC), an epoxy compound, is often used as a hardener. Several cases of allergic eczema from occupational exposure to TGIC have been reported in the literature. Objective We examined a 36‐year‐old non‐smoking man who worked mainly as a spray painter, using a polyester powder paint containing 4% TGIC. During painting he used protective clothing and a motorized breathing protector. After 4 years he developed eczema on his hands, face and body, and an occupational allergic eczema caused by TGIC was diagnosed. He also suffered from powder‐paint‐related asthmatic symptoms.

Objective Occupational asthma was diagnosed in accordance with the accepted guidelines. Inhalation challenge tests were performed with the paint and TGIC

Results Spirometry showed slight obstruction; the blood eosinophils and serum IgE value were elevated. Skin‐prick tests with common environmental allergens were negative. The challenge test with lactose powder was also negative, A challenge test with a paint containing TGIC (4%) induced a dual reaction in PEF and a late 23% fall in FEV,. A test with TGIC (4%) mixed with lactose induced a dual PEF reaction, and also dual changes in spirometry. The PD15 in the histamine challenge test decreased significantly after the challenge tests.

Conclusions To our knowledge this is the first diagnosed case of occupational asthma caused by TGIC. This case report emphasizes the importance of protecting both the skin and respiratory tract of workers against chemicals such as TGIC, capable of causing skin and respiratory allergy.
Comparison of the ISAAC video questionnaire (AVQ 3.0) with the ISAAC written questionnaire for estimating asthma associated with bronchial hyperreactivity
Authors: LAI C. K. W. , CHAN J. K. W. , CHAN A. , WONG G. , HO A. , CHOY D. , LAU J. , LEUNG R.
Published: April 2006

Background A standardized protocol is essential for international comparisons of asthma prevalence and severity. The International Study of Asthma and Allergies in Childhood (ISAAC) used a standardized written questionnaire (WQ) and a video questionnaire (AVQ3.0) to survey the prevalence and severity of asthma in 13–14‐year‐old schoolchildren in different countries.

Objective To compare the effectiveness of WQ and AVQ3.0 in predicting bronchial hyperresponsiveness (BHR), defined as having a provocation dose of inhaled methacholine causing a 20% fall in baseline FEV1 of 7.8μmol.

Methods One hundred and eighty‐nine Chinese schoolchildren completed a written questionnaire followed by a video questionnaire on asthma symptoms. They then underwent bronchial challenge to methacholine.

Results Fair correlations were seen between the first two corresponding questions (moderate wheezing at rest and exercise wheeze) in the two questionnaires with Kapper indices of 0.44 and 0.43, respectively. The ability to predict BHR, as indicated by the Youden's index, was similar between the corresponding questions of the two questionnaires, except for ‘severe wheeze’ which had a significantly higher Youden's index in AVQ3.0 (0.44) than the corresponding question in WQ (0.11, P<0.05).

Conclusion The ISAAC International video questionnaire is at least as effective as the ISAAC written questionnaire in predicting BHR. It therefore provides a simple and valid tool for international comparisons of asthma prevalence and severity.
Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa
Authors: HALLEN H. , ENERDAL J. , GRAF P.
Published: April 2006

Background Controversy still exists about the treatment of rhinitis medicamentosa and treatment has never been objectively evaluated.

Objective To study the effect of fluticasone propionate aqueous nasal spray compared to placebo nasal spray in the treatment of rhinitis medicamentosa.

Methods A parallel randomized, double‐blind study was conducted to evaluate the treatment of rhinitis medicamentosa. Two groups containing 10 patients with rhinitis medicamentosa in each group stopped their overuse of nasal vasoconstrictor spray immediately and were treated with either fluticasone propionate nasal spray once daily 200 μg, or placebo nasal spray for 14 days. The nasal mucosal swelling was recorded with rhinostereometry, acoustic rhinometry and a peak inspiratory flow meter. Nasal stuffiness was estimated on a visual analogue scale in the morning and in the evening of each day.

Results The mucosal swelling decreased after 7 and 14 days of treatment with fluticasone propionate as well as placebo, but the reduction was significantly greater after treatment with fluticasone propionate. The symptom scores for nasal stuffiness showed a marked reduction during the treatment period in both groups, but there was a faster onset of symptom reduction after treatment with fluticasone propionate.

Conclusion Fluticasone propionate is more effective and has a faster onset of action than placebo in the treatment of rhinitis medicamentosa. An adequate treatment of these patients consists of a combination of vasoconstrictor withdrawal and a topical corticosteroid to alleviate the withdrawal process.
Localization of antigenic sites on Der p 2 using oligonucleotide‐directed mutagenesis targeted to predicted surface residues
Authors: SMITH A. M. , CHAPMAN M. D.
Published: April 2006

Background Understanding the molecular nature of allergen‐antibody interactions is important to understanding the mechanism of conventional immunotherapy as well as to designing alternative immunotherapeutic strategies. Many important allergens have been cloned and expressed, making it possible to apply recombinant DNA techniques to dissect antigenic determinants.

Objective The aim of this study was to use predictive algorithms and site‐directed mutagenesis to investigate monoclonal antibody and IgE antibody epitopes of the major house dust mite allergen Der p 2.

Methods Computer algorithms were used to assess the primary amino acid sequence of Der p 2 and to identify regions of hydrophilic and flexible sequence. Subsequently, site‐ directed mutagenesis was used to generate amino acid substitutions at hydrophilic residues at positions 44–46 and at position 100. The variants were tested in a competitive inhibition EL1SA with four group 2‐specific murine monoclonal antibodies and with human IgE antibody from mite allergic patients.

Results Conservative amino acid substitutions at position 44–46 did not distinguish IgE antibody epitopes. but did suggest that these residues are involved in the epitope defined by one monoclonal antibody, 15E11. Non‐conservative substitution of proline at this position reduced binding to all four monoclonal antibodies, as well as IgE antibody, by 50–80%. Point mutants at position 100 mapped the epitopes of two monoclonal antibodies. 7A1 and I3A4, previously shown to bind the same region of Der p 2. In addition, the two variants tested at this position showed distinct inhibition curves with these two monoclonal antibodies indicating differences in fine specificity.

Conclusions Using predictive algorithms, in the absence of tertiary structural information, we have been able to localize important B cell determinants on Der p 2. The results suggest that it is possible to modulate antibody recognition of allergens using site‐directed mutagenesis and that this approach may provide a new strategy for allergen specific immunotherapy.
Cetirizine treatment of rhinitis in children with pollen allergy: evidence of its antiallergic activity
Authors: CIPRANDI G. , TOSCA M. , RICCA V. , PASSALACQUA G. , RICCTO A. M. , BAGNASCO M. , CANONICA G. W.
Published: April 2006

Background
Cetirizine is an antihistamine, largely used in the treatment of allergic rhinoconjunctivitis, which also exerts anti‐allergic activity.

Objectives
To evaluate cetirizine as treatment for children with rhinitis due to pollen allergy, and to evaluate its anti‐allergic activity in such a clinical condition.

Methods
The study was designed as parallel groups, double‐blind, placebo‐controlled, randomized. Twenty allergic children were enroled and subdivided in two groups, receiving a 4 week treatment during the pollen season. The following parameters were monitored: clinical symptoms evaluated by the allergist before and after treatment and by the patients through a daily diary card, inflammatory cells count, expression of ICAM‐1 on nasal epithelial cells, inflammatory mediator levels in nasal Iavage and peripheral blood before and after treatment, and pollen counts.

Results
This study shows that cetirizine treatment is able to reduce: clinical symptoms (P < 0.01), inflammatory cell infiltrate (P < 0.03), ICAM‐1 expression on epithelial cells (P < 0.05), and soluble ICAM‐1 (P < 0.05) and ECP (P < 0.05) in nasal lavage.

Conclusion
Cetirizine is able to clinically improve nasal symptoms due to pollen allergy and to reduce allergic inflammation, which is related to allergen exposure.
Seasonal differences in airway hyperresponsiveness in asthmatic patients: relationship with allergen exposure and sensitization to house dust mites
Authors: VAN DER HEIDE S. , DE MONCHY J. G. R. , DE VRIES K. , DUBOIS A. E. J. , KAUFFMAN H. F.
Published: April 2006

Background The degree of airway hyperresponsiveness in allergic asthmatic patients may be influenced by changes in environmental exposure to inhalant allergens.

Objective This study investigates the relationship between seasonal changes in exposure to house dust mite (HDM) allergens and non‐specific airway hyperresponsiveness in asthmatic patients with multiple sensitizations to inhaled allergens.

Methods In 43 asthmatic patients sensitized to several inhalant allergens, lung function (FEV1), airway hyperresponsiveness (PC20 histamine), serum total IgE, house dust mite (HDM) specific IgE and number of peripheral blood eosinophils were measured during autumn 1990 (September‐November) and spring 1991 (March—May). During each season. floor dust samples were collected twice from living‐ and bedrooms and the concentration of the HDM allergens Der p 1 and Der p 2 determined.

Results More severe airway hyperresponsiveness (lower PC20 histamine) during autumn was only found in patients sensitized to HDM(n= 32; autumn: 2.05mg/mL, spring: 4.51mg/mL (geometric means), P <0.0 1), whereas in patients not sensitized to HDM (n= 11) similar values were observed in both seasons (3.44 and 4.52 mg/mL. respectively, P= 0.56). More severe airway hyperresponsiveness of HDM sensitized patients in autumn was significantly associated with higher Der p 1 concentrations in floor dust. Aside from airway hyperresponsiveness, seasonal changes in serum total IgE and number of peripheral blood eosinophils were seen in patients sensitized to HDM,

Conclusions In allergic asthmatic patients, airway hyperresponsiveness may increase during autumn, depending on sensitization to HDM and an increase of exposure to HDM allergen.
Occupational allergy in greenhouse workers: sensitization to Tetranychus urticae
Authors: DELGADO J. , ORTA J. C. , NAVARRO A. M. , CONDE J. , MARTÍNEZ A. , MARTINEZ J. , PALACIOS R.
Published: April 2006

Background Tetranychus urticae (TU) is a macroscopic mite which is found infesting a large number of plants of economic interest. It has rarely been described as a cause of occupational allergic disease in agricultural workers.

Objective To describe TU sensitization in greenhouse workers attending the outpatient allergy unit and its clinical associations, and to characterize the allergens involved. Materials and methods Twenty‐four consecutive carnation greenhouse workers with allergy‐related symptoms, referred to our outpatient clinic during a 6‐month period, were included. We made the diagnostic extract from carnation leaves heavily infested with TU. Skin‐prick test, specific IgE measurement and bronchial provocation test with TU extract were carried out in all subjects. Allergen characterization was achieved by SDS‐PAGE (sodium dodecylsulfate‐polyacrylamide gel electrophoresis) and immunoblotting

Results Sixteen patients (66%) presented positive skin‐prick test and specific IgE and were diagnosed allergic to TU. Fifteen patients suffered from bronchial asthma, 14 rhinitis and five urticaria. Twelve exibited positive bronchial provocation test to the TU extract. On RAST‐inhibition studies, there was no evidence of crossreactivity between TU extract and D. pteronyssinus. An allergen at 19 kDa was determined in the TU extract by SDS‐PAGE immunoblotting studies.

Conclusion TU could be an important occupational allergen in greenhouse workers showing allergic symptomatology. There is no crossreactivity between this mite and the house dust mite D. pteronyssinus.
Molecular cloning and expression of a Penicillium citrinum allergen with sequence homology and antigenic crossreactivity to a hsp 70 human heat shock protein
Authors: SHEN H.‐D. , AU L.‐C. , LIN W.‐L. , LIAW S.‐F. , TSAI J.‐J. , HAN S.‐H.
Published: April 2006

Background Penicillium citrinum has been identified as the most prevalent airborne Penicillium species in the Taipei area. However, detailed studies on allergens of this ubiquitous Penicillium species are still lacking.

Objective For the characterization of allergens of this prevalent Penicillium species, molecular cloning and expression of the allergen genes of P. citrinum were performed in the present study.

Methods Molecular cloning of the allergen genes was performed by using a λUni‐Zap XR cDNA library of P. citrinum and serum from an asthmatic patient. The cloned cDNA was excised from the phage vector as a recombinant pBluescript phagemid and sequenced. The cDNA of the IgE‐binding clone was expressed as fusion protein with the gultathione‐S‐transferase. The corresponding natural allergen was analysed by absorption immunoblotting using monoclonal antibody and serum from asthmatic patient. The frequency of IgE‐binding to the allergen cloned was analysed by dot immunoassay using recombinant allergen and by immunoblotting using the whole extract of P. citrinum.

Results In the screening of cDNA library of P. citrinum using serum from an asthmatic patient, IgE‐binding cDNA clones designated SC4 and XL were obtained. The 5′‐truncated, 0.7‐kb and 1.7‐kb cDNA inserts of clones SC4 and XL contained open reading frames of 163 and 503 amino acids, respectively. On alignment, the deduced amino acid sequences showed that 97 (60%) of the 163 amino acids and 376 (75%) of the 503 amino acids were identical to the corresponding amino acid sequence of the human heat shock protein in the hsp70 family. Both recombinant SC4 and XL showed positive SDS‐PAGE‐immunoblot reactivity to a monoclonal antibody MA3‐006 against the human hsp 70 protein. For characterization of the corresponding natural allergen, immunoblotting reactivities of MA3–006 and IgE antibodies to the 70kDa component of P. citrinum have been shown to be disappeared after absorption of these antibodies with the recombinant SC4 protein. Sera from 14 (41%) of 34 Penicillium‐allergic patients showed IgE‐binding to the recombinant XL protein and the 70kDa component in the extract of P. citrinum.

Conclusion Results obtained suggest that hsp 70 is an allergen of P. citrinum and that clones SC4 and XL contain partial cDNAs of this allergen gene.
Effects of JTV‐506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure
Authors: ANDO T. , KUME H. , URATA Y. , TAKAGI K.
Published: April 2006

Background ATP‐sensitive K+ (KATP) channel activators produce relaxation of smooth muscle in many tissues. However, this wide range of effects restricts their clinical usefulness in bronchial asthma because of a reduction in systemic blood pressure.

Methods We have now examined the effects of JTV‐506, a new benzopyran derivative, on airway smooth muscle contraction and systemic blood pressure and have compared this compound with cromakalim. We measured isometric tension records from guinea‐pig isolated trachea, as well as the respiratory resistance (Rrs) and systemic blood pressure in anesthetized guinea‐pigs.

Results JTV‐506 caused a concentration‐dependent inhibition of histamine‐induced contraction in guinea‐pig isolated tracheal smooth muscle, and was antagonized by glibenclamide. JTV‐506 was 7.6‐fold more potent than cromakalim. In anesthetized animals the intravenous injection of JTV‐506 reduced the increase in Rrs induced by intravenous application of 5 μg/kg of histamine in a dose‐dependent manner, 10μ/kg of JTV‐506 resulted in 57.0 17.9% inhibition of the increase in Rrs at 10 min. The inhibitory action on Rrs disappeared after 60 min. 10μg/kg of cromakalim caused 25.4 ± 5.8% inhibition of the increase in Rrs induced by histamine at 1 min. The ED50 values for JTV‐506 and cromakalim were 6.7 ± 3.5μg/kg and 60.1 ± 15.8μg/kg, respectively (P<0.05). Cromakalim was ± 9‐fold less potent in inhibiting the increased Rrs by histamine. and the inhibitory action lasted less than 10 min. The reduction of systemic blood pressure by JTV‐506 and cromakalim (each at a dose of 10μg/kg iv) was 11.3% and 21.5%, respectively

Conclusion JTV‐506 inhibits histamine‐induced contraction of tracheal smooth muscle by activation of KATP channels. This compound is more potent and longer‐lasting in the suppression of histamine‐induced increases in Rrs, and is less hypotensive than cromakalim. Our results suggest that this compound merits further investigation for utility as a bronchodilator in the clinic.
Clinical efficacy of specific immunotherapy to cat dander: a double‐blind placebo‐controlled trial
Authors: VARNEY V.A. , EDWARDS J. , TABBAH K. , BREWSTER H. , MAVROLEON G. , FREW A. J.
Published: April 2006

Objectives
To assess the efficacy of specific immunotherapy with standardized cat dander extract, using objective endpoints and simulated ‘natural’ exposure to cats.

Design
Double‐blind, randomized, placebo‐controlled study carried out at a UK Allergy research clinic.

Subjects
Twenty‐eight patients with moderate to severe allergic rhinoconjunctivitis with asthma due to cat allergy. Subjects were stratified for cat sensitivity, cat ownership and asthma, and the groups were well matched for all relevant parameters.

Main outcome measures
Symptom scores and peak flow rate during and after exposure to cats in a cat‐room. Skin tests and conjunctival provocation thresholds.

Results
The actively treated group showed a marked reduction in symptoms during the cat exposure (mean score 61.6–17.1; P < 0.001) with no change in the placebo group (64.7 vs 62.1). The active group also showed a reduced peak flow response to cat exposure (mean fall of 85L/min pretreatment, 29L/min after treatment, P < 0.005) as well as reductions in conjunctival provocation sensitivity, skin sensitivity to cat extract and skin sensitivity to house dust mite (D. pteronyssinus). Skin reactivity to histamine and codeine were unaltered. No significant adverse reactions were encountered.

Conclusions
Specific immunotherapy seems to be an effective treatment for cat allergy. Allergy to cats is common and often poorly controlled on conventional pharmacotherapy. Although cat allergy has not traditionally been considered as a valid indication for immunotherapy in the UK, it should now be considered as a legitimate treatment, especially for those who are unable to avoid exposure.
Skin test and crossreactivity studies with Euroglyphus maynei and Dermatophagoides pteronyssinus
Authors: KEMP S. F. , LOCKEY R. F. , FFRNÁNDFZ‐CALDAS E. , ARLIAN L. G.
Published: April 2006

Background
The prevalence of sensitization to Euroglyphus maynei (E. maynei) in the United States has not been reported previously.

Objectives
To determine: (l) the prevalence of skin‐test reactivity in allergic subjects to E. maynei compared to D. pteronyssinus, D. farinae, and B. tropicalis and (2) the allergenic crossreactivity between D. pteronyssinus and E. maynei.

Methods
Skin testing with extracts of B. tropicalis and E. maynei (1:50 w/v) and standardized D. pteronyssinus and D. farinae extracts (1:50 w/v; 10000 AU/mL) provided data on 250 subjects (87 males and 163 females) aged 9–77 years (mean age, 39.8 years) with possible allergic respiratory diseases. RAST inhibition assays were used to study crossreactivity between D. pteronyssinus and E. maynei.

Results
One hundred (40%) of 250 subjects had insignificant or no allergic diseases. Of the 150 allergic subjects (53 males, 97 females), 101 (67.3%) had a positive test (a percutaneous test with a weal diameter ≥ 3 mm larger than the saline control) to at least one mite species; 60.7%, 60.0%, 28.7%, and 52.0% reacted to D. farinae, D. pteronyssinus, B. tropicalis, and E. maynei, respectively; 40(26.7%) reacted to the four mite species. Positive tests to D. farinae, D. pteronyssinus, B. tropicalis, or E. maynei alone occurred in six (4.0%), four (2.7%), two (1.3%), and 0%, respectively. D. pteronyssinus and E. maynei showed moderately high crossreactivity in RAST inhibition assays.

Conclusion
There is a high rate of skin‐test reactivity to E. maynei in Florida. Moderately high crossreactivity exists between E. maynei and D. pteronyssinus.
Quantification in mass units of Bet v 1, the main allergen of Betula verrucosa pollen, by a monoclonal antibody based‐ELISA
Authors: RAMÍREZ J. , CARPIZO J. A. , IPSEN H. , CARREIRA J. , LOMBARDERO M.
Published: April 2006

Background
Fagales pollens are considered among the main agents responsible for allergic diseases in many countries of the northern hemisphere and single major allergens have been shown to be responsible for these responses.

Objective
To develop a solid phase immunoassay for the quantification of Bet v I, the main allergen from Betula verrucosa (birch), and to assess its suitability for quantitating the equivalent major allergen in other Fagales species as well.

Methods
The assay is based on the use of two different anti‐Bet v 1 monoclonal antibodies which were immobilized on the solid phase and. as a primary standard, affinity purified Bet v 1, the protein content of which was determined by amino acid analysis.

Results
The ELISA proved to measure less than 0.2 ng/mL of Bet v 1 with a practical range of 0.4–40 ng/mL and could be suitable lo quantify the equivalent major allergen in other Fagales species such as Corylus avellana (hazel), Carpinus betulus (horbeam) and Alnus glutinosa (alder). The method was compared witb quantitative electrophoresis and rocket immuno‐electrophoresis for the determination of the allergen content in several Betula verrucosa extracts, and a very good quantitative correlation was found. Likewise, the Bet V 1 content exhibited a good correlation (r = 0.87; P < 0.005) with the allergenic potency values obtained by RAST inhibition.

Conclusions
The results indicate that the Bet v 1‐assay could be useful for standardization purposes in Fagales pollen extracts intended for clinical use.
Effect of terfenadine on TNFα release from peripheral blood mononuclear cells during cow's milk allergy
Authors: BENLOUNES N. , DUPONT C. , CANDALH C. , BLATON M.‐A. , BLOOM M. , HEYMAN M.
Published: April 2006

BackgroundIn infants with cow's milk allergy and intestinal symptotns, peripheral blood mononuclear cells stimulatedin vitrowith cow's milk proteins, secrete large amounts of the proinflammatory cytokine TNFα thus altering intestinal barrier capacity. Terfenadine, an antihistaminic drug, inhibits the release of several inflammatory mediators, including histamine, prostaglandins and leukotrienes.

ObjectivesTo test the potential ability of terfenadine to inhibit TNFα secretion by mononuclear cells from infants with cow's milk allergy.

MethodsMononuclear cells from infants allergic to cow's milk proteins were stimulatedin vitrofor 6 days by a mixture of milk proteins (β‐lactoglobulin, α‐lactalbumin and casein) with or without terfenadine (0.1 –1 μM) and culture supernatants were assayed for TNFα by enzyme immunoassay. The effect of culture supernatants on intestinal barrier capacity was evaluated by measuring the electrical resistance (index of integrity) of filter‐grown HT29–19 A intestinal cells in Ussing chambers.

ResultsDuring active cow's milk allergy, mononuclear cells stimulated with cow's milk proteins secreted large amounts of TNFα which significantly reduced the electrical resistance of HT29–19 A intestinal cells. There was a dose‐dependent decrease in TNFα secretion in the presence of terfenadine, with a maximal inhibition of 62% of this secretion at 1 μM. Accordingly, terfenadine‐treated mononuclear cells supernatants did not alter the electrical resistance of intestinal HT29. 19 A cells.

ConclusionThese results indicate that in infants with intestinal dysfunction due to cow's milk allergy, terfenadine is a potent inhibitor of the TNFα secretion induced by sensitizing milk protein antigens. This inhibition prevents the degradation of intestinal function as measured in an intestinal cell line,in vitro.