bluuebunny/crossref_metadata_2025 huggingface dataset:
Glutaraldehyde: an occupational hazard in the hospital setting
Authors: Di Stefano F. , Siriruttanapruk S. , McCoach J. , Sherwood Burge P.
Published: March 2003

Background: We report a series of 24 health‐care workers with respiratory symptoms suggestive of occupational asthma due to glutaraldehyde exposure.

Methods: The history of asthmatic symptoms was investigated with peak expiratory flow rate (PEFR) monitoring, and in eight of the subjects, the specific bronchial provocation test (SBPT) was applied as reference standard for diagnosis of occupational asthma. Levels of glutaraldehyde were monitored in the challenge chamber during the SBPT. Work environmental levels of glutaraldehyde were measured from air samples collected at least once during the PEFR monitoring of endoscopy and theatre nurses. Specific IgE antibodies to glutaraldehyde were measured with a series of glutaraldehyde modified proteins.

Results: In the eight workers who underwent SBPT, the diagnosis of occupational asthma was confirmed by a positive reaction (late and dual reaction in five and in three subjects, respectively). The mean level of glutaraldehyde observed during the challenge tests was 0.075 mg/m3 (range 0.065–0.084 mg/m3). In 13 out of the 16 remaining workers, the serial PEFR monitoring showed a work‐related effect. In three workers, there was no physiological confirmation of occupational asthma. Levels of glutaraldehyde from the air samples collected in the workplace were as follows: personal short‐term samples (mean 0.208 mg/m3; median 0.14 mg/m3; range 0.06–0.84 mg/m3), personal long‐term samples (mean 0.071 mg/m3; median 0.07 mg/m3; range 0.003–0.28 mg/m3). Measurements of specific IgE antibodies to glutaraldehyde‐modified proteins were positive in seven patients (29.1%) according to a cutoff value of 0.88% RAST binding. The presence of atopy to common environmental allergens and smoking was not associated with specific IgE positivity (P>0.05; Fisher's exact test).

Conclusions: Our report indicates the importance of glutaraldehyde as an occupational hazard among exposed health‐care workers. Intervention in the workplace, training of personnel handling this chemical, and accurate health surveillance may reduce the risk of developing occupational asthma due to glutaraldehyde.
Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma
Authors: Kato M. , Nakashima I. , Kato M. , Nozaki Y. , Yoshimoto T. , Tamada Y. , Kageyama M. , Yamashita T. , Kurimoto F.
Published: March 2003

Background: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy‐inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis‐regulating molecules.

Methods: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme‐linked immunosorbent assay.

Results: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase.

Conclusions: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis‐linked step.
Cutaneous responses to substance P and calcitonin gene‐related peptide in chronic urticaria: the effect of cetirizine and dimethindene
Authors: Borici‐mazi R , Kouridakis S , Kontou‐fili K
Published: March 2003

Background: Neuropeptides appear to participate in the pathogenesis of chronic urticaria. The purpose of this study was to investigate the cutaneous responses to substance P (SP) and calcitonin gene‐related peptide (CGRP) in delayed pressure urticaria patients (DPUpt) and chronic idiopathic urticaria patients (CIUpt) compared to healthy adults (HA), and also to evaluate the effect of H1‐antagonists on these responses.

Methods: Wheal (W) and flare (F) reactions to intradermally (ID) injected SP, CGRP, histamine (H), and diluent controls were evaluated in nine CIUpt, nine DPUpt, and nine HA at 3, 7, 15, 30, 60, and 120 min after injection. Maximal W and F, area under curve (AUC), and time of W and F disappearance were calculated at baseline and 4 h after a single dose of 20 mg cetirizine (Ce), 4 mg dimethindene (Di), or placebo (P), in a double‐blind, placebo‐controlled (DBPC), crossover, randomized study.

Results: CIUpt exhibited enhanced and longer lasting W reactions to SP and CGRP (AUC: P<0.05) than HA; SP‐ and CGRP‐induced F (at maximal concentration) were larger and longer lasting in CIUpt than in HA (P<0.003 and P=0.004, respectively). In the DPU group, SP‐induced W and F responses were intermediate in magnitude compared to CIUpt and HA. In HA, SP‐induced flares were significantly suppressed only by Ce (P<0.020), while both Ce and Di affected SP‐induced W and F in the two patient groups (P<0.05). CGRP‐induced flare inhibition by the two H1‐antagonists was also greater in the urticaria patient groups than in HA.

Conclusions: CIUpt and, to a lesser extent, DPUpt showed enhanced SP‐ and CGRP‐induced W and F reactions. CGRP elicited an immediate W and F response, followed by prolonged erythema. H1‐antagonists partially affected W and F reactions to SP and only the F response induced by CGRP; this effect was more pronounced in the urticaria patient groups than in HA. Overall, W and F cutaneous responses to SP were suppressed to a greater extent by Ce than Di.
Immunologic significance of respirable atmospheric starch granules containing major birch allergen Bet v 1
Authors: Schäppi GF , Taylor PE , Staff IA , Rolland JM , Suphioglu C
Published: March 2003

Background: Birch‐pollen allergens are an important cause of early spring hay fever and allergic asthma. Recently, we reported a mechanism for the release of respirable allergenic particles from birch pollen containing the major allergen Bet v 1. In this study, we aimed to assess the immunologic significance of the released Bet v 1‐containing starch granules in the environment.

Methods: A two‐site monoclonal antibody‐based assay (ELISA) was employed to quantitate Bet v 1 in high‐volume air sampler filter extracts, and immunogold‐labelling was used on sections of these extracts to localize Bet v 1. Immunoblot analyses were performed with pooled sera from patients sensitive to birch pollen.

Results: Atmospheric starch granules contained Bet v 1, and the concentration increased upon light rainfall. Sera from patients allergic to birch allergens recognized extracts from isolated starch granules.

Conclusions: The clinical implications of these findings are that starch granules released from birch pollen are potentially able to trigger allergic asthmatic reactions to Bet v 1, since the allergen occurs in respirable particles. Thus, clinicians can advise asthma patients to remain indoors on days of light rainfall during the birch‐pollen season to avoid high levels of allergen exposure.
Nasal reactivity to capsaicin in patients with seasonal allergic rhinitis during and after the pollen season
Authors: Kowalski Ml , Dietrich‐miłobędzki A , Majkowska‐wojciechowska B , Jarzębska M
Published: March 2003

Background: We aimed to study the participation of neurogenic mechanisms in nasal allergic inflammation by assessing the effect of neurogenic stimulation on the secretory and cellular responses of nasal mucosa in patients with allergic rhinitis.

Methods: A group of patients suffering from seasonal allergic rhinitis was challenged intranasally with incremental doses of capsaicin (0.3, 3, 12 μg) during and after the pollen season. Clinical symptoms after provocations were monitored, and unilateral nasal lavages were obtained. The nasal lavage fluid (NAL) was assayed for concentration of total protein, albumin, lactoferrin, and number of leukocytes, following by differential count.

Results: Capsaicin challenge during the pollen season produced greater congestion (P<0.01) and rhinorrhea (P<0.05) than after the season. The intensity of burning sensation (pain) was similar on both occasions. Capsaicin failed to increase albumin content in NAL both during and after the season. Total protein was increased only after the highest dose of capsaicin (P<0.03) after the season. The number of eosinophils in basal lavages was higher during the season. During the season, the total number of leukocytes at least doubled in 7/12 patients and the percentage of eosinophils increased in 6/12 patients after the capsaicin challenge.

Conclusions: Our study demonstrated that during the symptomatic period the nasal mucosa of allergic patients is more susceptible to neurogenic stimulation, showing enhanced secretory and inflammatory (cellular) responses.
Long‐term treatment with allergoid immunotherapy with Parietaria. Clinical and immunologic effects in a randomized, controlled trial
Authors: Ariano R , Kroon AM , Augeri G , Canonica and GW , Passalacqua G
Published: March 2003

Background: Specific immunotherapy (SIT) is a valuable treatment for respiratory allergy, and the use of chemically modified allergens (allergoids) has improved its safety, as testified by several studies. We evaluated the effects of a SIT course with an allergoid extract of Parietaria pollen in a double‐blind, placebo‐controlled trial.

Methods: The study was double‐blind in the first year; then it was prolonged up to 3 years with all patients on active treatment. Clinical effectiveness, safety, skin reactivity, systemic immunologic parameters, and subjective assessment were evaluated. We also had available a self‐evaluation recorded in a follow‐up visit 4 years after the discontinuation of SIT.

Results: A significant reduction of the symptoms plus drug intake scores during the pollen seasons was observed in the patients receiving active SIT. The placebo patients, after switching to active SIT, also showed significant clinical improvement. The clinical efficacy persisted during years 2 and 3 of treatment. After year 1, the actively treated patients reported a significant subjective improvement (frequency of symptoms, P=0.001; duration of symptoms, P=0.024; physical performance, P=0.043) compared with the placebo group. The self‐evaluation by visual analog scale showed that all patients maintained a significant clinical improvement up to 4 years after discontinuing SIT (year 1: active=+31.6%, placebo=−15.7%; year 7: active=+35.8%, placebo=+31.3%). The systemic immunologic changes after active SIT paralleled those described elsewhere (IgE decreased from 22 to 9 and from 21 to 8 IU/ml; IgG4 increased from 43 to 87 and from 18 to 60 IU/ml). A significant decrease in skin reactivity to three different allergen concentrations was observed at year 3 compared with pretreatment values (P<0.05).

Conclusions: The investigational SIT with Parietaria appeared to be effective and safe; a 3‐year course of treatment achieved a long‐lasting efficacy.
The influence of female sex hormones on nasal reactivity in seasonal allergic rhinitis
Authors: Stübner Up , Berger Ue , Toth J , Marks B , Horak F , Gruber D , Huber J
Published: March 2003

Background: This study aimed to investigate whether the hormone peaks of estrogen and progesterone could influence the extent of the allergic reaction in grass‐pollen‐allergic women.

Methods: Twenty‐three allergic women with seasonal allergic rhinitis due to grass pollen were included in this trial. Twelve were taking oral contraceptives (OC) (control group), and 11 were taking no pill (target group). The subjects were challenged with grass pollen by nasal provocation test around day 14 of their menstrual cycle (ovulation day) and again at the end of the cycle (day 27). The primary criteria were the subjective nasal symptoms rhinorrhea, nasal blockage, itching, and sneezing. A further criterion was the objectively measured nasal mucosal swelling, assessed by active anterior rhinomanometry. All criteria were evaluated before and 15 min after provocation, and the hormone status was determined on each investigation day.

Results: Comparisons of symptoms between the groups resulted in P values of >0.05 for all symptoms at both visits except the symptom blocked nose, which was significantly lower (P=0.03) in the patients with OC intake at visit 2, and the symptom sneezing, which showed a significantly (P=0.02) higher increase in patients taking OC at the end of the cycle. The flow decrease reached a greater extent in the target group than in the controls.

Conclusions: These results indicate a correlation of the hormonal situation and the nasal allergic reactivity. OC intake led to an intensifying of neurogenic symptoms near the end of pill intake, a result which could be due to a protective effect of the endogenous progesterone, in contrast to the orally administered hormones.
Role of tachykinins in asthma
Authors: Joos G. F. , Germonpre P. R. , Pauwels R. A.
Published: March 2003

The sensory neuropeptides substance P (SP) and neurokinin A (NKA) are localized to sensory airway nerves, from which they can be released by a variety of stimuli, including allergen, ozone, or inflammatory mediators. Sensory nerves containing these peptides are relatively scarce in human airways, but it is becoming increasingly evident that inflammatory cells such as eosinophils, macrophages, lymphocytes, and dendritic cells can produce the tachykinins SP and NKA. Moreover, immune stimuli can boost the production and secretion of SP and NKA. SP and NKA have potent effects on bronchomotor tone, airway secretions, and bronchial circulation (vasodilation and microvascular leakage) and on inflammatory and immune cells. Following their release, tachykinins are degraded by neutral endopeptidase (NEP) and angiotensin‐converting enzyme. The airway effects of the tachykinins are largely mediated by tachykinin NK1 and NK2 receptors. Tachykinins contract smooth muscle mainly by interaction with NK2 receptors, while the vascular and proinflammatory effects are mediated by the NK1 receptor. In view of their potent effects on the airways, tachykinins have been put forward as possible mediators of asthma, and tachykinin receptor antagonists are a potential new class of antiasthmatic medication.
Allergenicity of major cow's milk and peanut proteins determined by IgE and IgG immunoblotting
Authors: Szabó I. , Eigenmann P.A.
Published: March 2003

Background: Specific IgG antibodies are frequently observed in food‐allergic patients. However, the allergen‐fraction specificity of IgG antibodies in relation to IgE antibodies is not well defined. Our aim was to determine the IgE and IgG antibody profile to major cow's milk and peanut antigen fractions in food‐allergic patients and tolerant individuals.

Methods: Sera were collected from 10 patients allergic to cow's milk and 10 patients allergic to peanuts, as well as from 20 control subjects. Cow's milk and peanut proteins were migrated on SDS–PAGE and immunoblotted for IgE, IgG, and IgG4 antibodies. Food‐specific IgE concentrations were measured by CAP System FEIA™, and IgG and IgG4 concentrations by ELISA.

Results:In food‐allergic children, similar fraction‐specific IgE, IgG, and IgG4 antibody‐binding profiles to the major cow's milk or peanut antigens were found. In nonallergics, the presence of fraction‐specific IgG antibodies was mostly dependent on regular ingestion of the food. The presence of specific antibody on immunoblots correlated with their quantitative measurement. The mean value for specific IgE in cow's milk‐allergic patients was 450±1326 IU/ml, and 337±423 IU/ml in peanut allergic patients. Specific IgG antibody values in milk‐allergic patients were not different (median OD 1.5, range 0.3–2.3) from controls (median OD 1, range 0.2–1.8). However, in peanut‐allergic patients, IgG concentrations were significantly higher than in controls (OD 1.2 [0.5–1.3] vs 0.5 [0.3–0.7]; P<0.01).

Conclusions: Similar fraction‐specific IgE and IgG antibody profiles in allergic individuals suggest a common switching trigger involving both isotypes. Intrinsic allergenicity might explain identical IgG antibody fraction specificity in nonallergics and in allergics. The presence of IgG antibodies in nonallergics was related to regular ingestion of the food.
Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students
Authors: Wantke F. , Focke M. , Hemmer W. , Bracun R. , Wolf‐Abdolvahab S. , Götz M. , Jarisch R. , Götz M. , Tschabitscher M. , Gann M. , Tappler P.
Published: March 2003

Background: The sensitizing potency of formaldehyde and phenol during anatomy dissecting was investigated. The objective was to determine whether exposure induces specific IgE or IgG against formaldehyde‐albumin or phenol‐albumin.

Methods: In 27 medical students, specific IgE against formaldehyde‐albumin by RAST plus ELISA and specific lgE against phenol‐albumin by ELISA were assessed. In addition, specific IgG against formaldehyde‐albumin was assessed in 23 students. Symptoms before and during dissecting were assessed, and indoor formaldehyde and phenol were measured.

Results: Mean indoor formaldehyde was 0.265±0.07 mg/m3, and mean indoor phenol was 4.65±2.96 mg/m3. Specific IgE/IgG against formaldehyde‐albumin was not found at the beginning. Four students developed specific IgE against formaldehyde‐albumin (RAST classes of ≥2.0), and all four also had specific IgE in the ELISA, but IgG against formaldehyde‐albumin was not found. Specific IgE against phenol‐albumin was not seen. Itch and paresthesia of the hands (PP<0.00001), dizziness (P<0.008), burning eyes (P<0.01), headache, sneezing, epistaxis, gingival bleeding, oral or pharyngeal itch, and shortness of breath were experienced.

Conclusion: Formaldehyde exposure during dissecting may induce specific IgE, but not IgG, against formaldehyde‐albumin. Sensitization did not correlate with symptoms.
Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis
Authors: Skov M. , Koch C. , Reimert C. M. , Poulsen L. K.
Published: March 2003

Background: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF.

Methods: Accumulated data from a 5‐year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non‐ABPA group (n=35). Patients in both groups were colonized with Aspergillus fumigatus, but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n=177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non‐ABPA group.

Results: The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P=0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P<0.05), SPT positivity to Af. (P<0.02), and Af. precipitins (P<0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in‐house RAST). The CAP level was one to two classes higher than the ML level; however, the results were comparable (r=0.66, P<0.005). IgE to Af. measured by CAP was the test which offered the highest positive predictive value (PPV) and negative predictive value (NPV). Optimal diagnostic cutoff levels for the diagnosis of ABPA were determined: class 2 for HR to Af., 200 kU/l for total IgE, and 3.5 (titer) for precipitating antibodies to Af., and class 2 for IgE to Af. (by CAP System).

Conclusions: Unspecific atopy markers were of limited value for the diagnosis of ABPA. Patients with ABPA do not seem to be more atopic to other aeroallergens than non‐ABPA patients. The most valid parameters for the diagnosis of ABPA in CF are SPT to Af., IgE to Af. in combination with precipitating antibodies to Af., and/or total IgE.
Detection and treatment of early asthma
Authors: Metso T. , Kilpiö K. , Björkstén F. , Kiviranta K. , Haahtela T.
Published: March 2003

Background: We sought answers to two questions:

1) how can mild, early asthma best be detected?

2) how should it be treated and the treatment effect monitored?

Methods: Eighty adult patients with early, mostly mild asthma and 30 control subjects were examined by lung‐function and biochemical tests. Patients were randomly assigned to two treatment groups. One group was treated with an inhaled steroid (budesonide) for 6 weeks, and the other first with an inhaled β2‐agonist (terbutaline) for 6 weeks and then with an inhaled steroid for 2 weeks.

Results: Treatment with budesonide was effective: symptom scores, PEF, blood eosinophils, and sputum ECP values all improved. Terbutaline was ineffective by these criteria. For the detection of early asthma and for the following treatment effects, sputum and serum ECP assays are useful supplements to lung‐function tests.

Conclusions: Treatment of early, mild asthma with an inhaled steroid is effective and worthwhile. Detection of the disease remains a problem, as both lung‐function and biochemical tests have low sensitivities.
Evidence of very delayed clinical reactions to cow's milk in cow's milk‐intolerant patients
Authors: Montalto G. , Custro N. , Notarbartlo A. , Carroccio A. , Cavataio F. , D'amico D. , Alabrese L. , Iacono G.
Published: March 2003

Background:In patients with cow's milk protein intolerance (CMPI), delayed clinical reactions to cow's milk (CM) ingestion may be misdiagnosed if the clinical symptoms are not “classical” and there is a long time lapse between ingestion of CM and the clinical reaction. The aim was to evaluate the clinical outcome of CMPI in a cohort of CM‐intolerant children, with particular attention to the occurrence of clinical manifestations beyond 72 h after CM challenge.

Methods:Eighty‐six consecutive patients (44 boys, 42 girls) with new CMPI diagnoses were enrolled; median age at diagnosis was 4 months. Patients were followed up for a mean period of 40 months. In all patients, CMPI diagnosis was made on the observation of symptoms, their disappearance after elimination diet, and their reappearance on double‐blind CM challenge. At CMPI diagnosis, immunologic tests to demonstrate IgE‐mediated hypersensitivity were performed. After 12 months of CM‐free diet, CM tolerance was re‐evaluated with a CM challenge continued at home for up to 30 days, according to a double‐blind, placebo‐controlled method. Patients who did not achieve CM tolerance continued a CM‐free diet and subsequently underwent yearly CM challenge.

Results:The percentages of CMPI patients who became CM‐tolerant after 1, 2, and 3 years of CM‐free diet were 30%, 54.5%, and 70%, respectively. At the end of the follow‐up period, 26/86 subjects showed persistent CMPI; these patients had a higher percentage of positivity of total serum IgE (P<0.05), RAST (P<0.01), and cutaneous prick tests for CM antigens (P<0.001) than all the others. At CMPI diagnosis, all patients had a clinical reaction within 72 h from the beginning of the CM challenge; at the subsequent “cure” challenges, we observed patients who first reacted to CM more than 72 h after ingestion. In total, 10 out of 86 patients showed “very delayed reactions”; in these patients, the mean time between the beginning of CM challenge and the onset of a clinical symptom was 13.3 days (range 4–26 days). The number of “very late reactors” increased from the first to the third of the “cure” CM challenges, performed at yearly intervals. The “very delayed” CMPI manifestations in these subjects were constipation (five cases), wheezing (two cases), dermatitis plus constipation (two cases), and dermatitis alone (one case); in 6/10 patients, the symptoms observed at the “cure challenge” were different from those at CMPI onset.

Conclusions:Very delayed clinical reactions to reintroduction of CM in the diet can occur in CMPI patients; thus, accurate follow‐up and frequent outpatient observation in patients with a long history of CMPI are probably more useful and safer than prolonged CM challenge.
Comparison of serum specific IgE antibodies to staphylococcal enterotoxins between atopic children with and without atopic dermatitis
Authors: Lin Y. T. , Yang Y. H. , Hwang Y. W. , Tsai M. J. , Tsao P. N. , Chiang B. L. , Shau W. Y. , Wang L. F.
Published: March 2003

Background: The skin of patients with atopic dermatitis (AD) exhibits a striking susceptibility to colonization and infection by Staphylococcus aureus. The exotoxins secreted by S. aureus can act as superantigens and classic allergens, inducing the production of functionally relevant specific IgE antibodies. The aim of this study was to compare the levels and positive rates of serum staphylococcal enterotoxin A (SEA)‐ and staphylococcal enterotoxin B (SEB)‐specific IgE between atopic children with and without AD.

Methods: Sixty children with AD, 55 children with respiratory allergy without AD, and 24 nonatopic healthy children were studied. The levels and positive rates of serum SEA‐ and SEB‐specific IgE were compared among three groups. The correlation between the levels or positive rates of serum SEA/SEB‐specific IgE and the severity of AD or the presence of previous skin infections was studied.

Results: The children with AD had significantly higher levels and positive rates of serum SEA‐ and SEB‐specific IgE than the atopic children without AD (P<0.001) and the nonatopic children (P<0.001). There was no significant difference in the levels and positive rates of serum SEA‐ and SEB‐specific IgE between the atopic children without AD and the nonatopic children. With or without adjustment for the potential confounding effect of total serum IgE levels, the levels and positive rates of serum SEA‐ and SEB‐specific IgE were significantly correlated with severity of AD (P<0.005), but they were not significantly different between AD children with and without previous skin infections.

Conclusions: SEA and SEB may contribute to chronic inflammation and exacerbation of AD through the IgE‐mediated immune response.
IL‐12 regulates bone marrow eosinophilia and airway eotaxin levels induced by airway allergen exposure
Authors: Zhao Lin‐ling , Lindén Anders , Sjöstrand Margareta , Cui Zhi‐hua , Lötvall Jan , Jordana Manel
Published: March 2003

Background: Airway allergen exposure causes local eosinophilic cell infiltration. This cellular inflammatory response is likely to involve the release of eosinophils from peripheral storage pools, and possibly also regeneration of eosinophils in the bone marrow. IL‐12 is an inhibitory cytokine in allergic inflammation, shown to reduce eosinophilic cell infiltration. The aim of the present study was to determine whether airway allergen exposure increases bone marrow eosinophil production, and, if so, whether IL‐12 modulates this effect.

Methods: Ovalbumin‐sensitized C57BL/6 mice and IL‐12 knockout (KO) mice were exposed to allergen via the airway route, and the inflammatory cell response was evaluated in bronchoalveolar lavage fluid, blood, and bone marrow.

Results: Allergen instillation intranasally produced a dose‐dependent inflammatory response in the lower airways of sensitized mice. This inflammatory response was dominated by eosinophils, but there were also increases of both lymphocytes and neutrophils. Sensitization and airway allergen exposure also increased the IL‐5‐dependent growth of bone marrow cells in vitro. The enhanced bone marrow responsiveness in vitro was paralleled by an increased number of bone marrow eosinophils in vivo. After sensitization and repeated allergen exposure, IL‐12 KO mice showed higher eosinophil levels in both BAL and bone marrow than parallel wild‐type control mice. Furthermore, BAL‐eotaxin levels were increased in IL‐12 KO mice as opposed to parallel wild‐type controls after allergen exposure.

Conclusions: Airway allergen exposure induced systemic immunologic responses, including increased eosinophil numbers in both airways and bone marrow, and also enhanced IL‐5 responsiveness in bone marrow cells. IL‐12 may regulate airway eosinophilia at both the level of eosinophilopoiesis and the level of local recruitment of eosinophils into the airways.
Influence of total IgE and seasonal increase of eosinophil cationic protein on bronchial hyperreactivity in asthmatic grass‐sensitized farmers
Authors: Di Gioacchino M. , Cavallucci E. , Di Stefano F. , Verna N. , Ramondo S. , Ciuffreda S. , Riccioni G. , Boscolo P.
Published: March 2003

Background: This study correlates biomarkers of atopy (serum total and specific IgE) and inflammation (serum eosinophil cationic protein) with bronchial hyperreactivity assessed after the complete end of pollination, in a group of farmers suffering from grass‐allergic asthma.

Methods: A total of 28 asthmatic farmers, with allergy to grass pollen, reporting persistent asthma symptoms after grass pollination, were enrolled. An accurate allergologic screening excluded other sensitizations. Analysis of total and grass‐specific IgE and eosinophil cationic protein was carried out before (March) and during (May) the following spring. After the complete end of pollination, bronchial hyperreactivity was assessed.

Results: Symptoms (cough, wheezing) persisted during the autumn for a mean period of 41 days (range 13–69). Total IgE was moderately high and grass‐specific IgE ranged from 9.25 to 41.12 kU/l without significant differences before and during spring. On the contrary, serum ECP levels significantly increased during the pollination period. PD20 methacholine evaluated after the end of grass pollination was negatively significantly correlated with levels of total IgE (r=−0.73; P<0.01) and the increase (from March to May) of serum ECP (r=−0.75; P<0.01). However, PD20 methacholine did not correlate with grass‐specific IgE and serum ECP absolute values of both March and May. A positive correlation was found between number of postseasonal days with symptoms and both spring increase of serum ECP (r=0.75; P=0.04) and levels of total IgE (r=0.76; P<0.01). The number of postseasonal days with symptoms inversely correlated with postseason PD20 methacholine (r=−0.76; P<0.01).

Conclusions: The study demonstrates that in grass‐sensitized farmers with asthmatic symptoms persisting for several weeks after grass pollination has ceased, the degree of airways hyperreactivity and the duration of postseasonal symptoms are directly related to the spring increase of ECP levels, as well as to the level of total IgE in serum. This allows us to identify two candidate biomarkers for the risk of developing prolonged asthma symptoms, and for the effective monitoring of anti‐inflammatory treatment and allergen‐specific immunotherapy.
A comparison of the anti‐inflammatory properties of intranasal corticosteroids and antihistamines in allergic rhinitis
Authors: Howarth. P. H.
Published: March 2003

Allergic rhinitis manifests itself clinically due to the local release of mediators from activated cells within the nasal mucosa. Treatment strategies aim either to reduce the effects of these mediators on the sensory neural and vascular end organs, or to reduce the tissue accumulation of the activated cells that generate them. Corticosteroids intervene at a number of steps in the inflammatory pathway, and, by reducing the release of cytokines and chemokines, inhibit cell recruitment and activation. These effects are evident both in vivo and in vitro. While antihistamines also have some anti‐inflammatory effects in vitro, these require higher concentrations than with corticosteroids and are not consistently reproduced in vivo. In addition, although antihistamines and corticosteroids might appear to have complementary mechanisms of action, clinical trials suggest that their co‐administration does not confer any additional long‐term benefits compared with that achieved with corticosteroids alone. Topical corticosteroids are therefore the preferred anti‐inflammatory therapy for persistent allergic rhinitis.
Analysis of epsilon germline transcripts and IL‐4 mRNA expression in the adenoids suggests local IgE switching
Authors: Åström K. , Papatziamos G. , Magnusson C. G. M. , Hemlin C. , Scheynius A. , Ploeg I. van der
Published: March 2003

Background: We have previously observed more frequent occurrence of IgE+ and FcεRI+ cells in adenoids of atopic than nonatopic children. To investigate the hypothesis that the adenoids are involved in IgE production, we analyzed the levels of ε germline (εGL), IL‐4, and IFN‐γ transcripts in the adenoids in relation to atopy and presence of ear disease.

Methods: Adenoidectomy was performed on 19 atopic and 18 nonatopic children (median age 5 years, range 2–12 years) suffering from otitis media with effusion (OME) (n=16) or obstructive adenoids hyperplasia (AH) (n=21). The levels of εGL transcripts, IL‐4, and IFN‐γ mRNA were analyzed by competitive reverse transcriptase‐PCR.

Results:εGL transcript levels in the adenoids were found to be dependent on IL‐4 mRNA expression (P<0.01) and serum IgE levels (P<0.05) (R2=0.32, n=37). IL‐4 mRNA expression was associated with εGL transcript levels (rs=0.32, P=0.05, n=37), especially among patients with AH (rs=0.53, P=0.01, n=21). No significant differences in IL‐4 and IFN‐γ mRNA levels were observed between the groups.

Conclusions: This study supports an IL‐4‐induced class switch to IgE production in the adenoids that might be of importance for inflammatory reactions in the upper respiratory tract.
Other anti‐inflammatory uses of intranasal corticosteroids in upper respiratory inflammatory diseases
Authors: Scadding G. K.
Published: March 2003

Topical corticosteroids are an effective treatment for nasal polyposis and other conditions associated with rhinitis. There is evidence that asthma, otitis media with effusion, and acute sinusitis may all benefit from such therapy. Fluticasone propionate (FP) drops have been shown to reduce polyp size, and to improve nasal inspiratory flow, while avoiding the side‐effects of, for example, topical betamethasone therapy. In small children with allergic rhinitis, fluticasone propionate aqueous nasal spray (FPANS) has been shown to be significantly more effective than ketotifen in relieving night and daytime symptoms, and nasal blockage. There is also preliminary evidence of efficacy in obstructive sleep apnoea and acute sinusitis. The advent of FP, with its low propensity to cause systemic side‐effects, makes it possible to use topical corticosteroid therapy safely for prolonged periods to treat many inflammatory diseases of the upper respiratory tract.
Epidemiology of contact allergy in adults
Authors: Schäfer T. , Böhler E. , Ruhdorfer S. , Weigl L. , Wessner D. , Filipiak B. , Wichmann H. E. , Ring J.
Published: March 2003

Background: We aimed to determine the prevalence of contact sensitization in the general population and to investigate associations with important sociodemographic and medical characteristics.

Methods: Within a population‐based nested, case‐control study in Germany, we performed patch tests with 25 standard allergens in 1141 adults (50.4% female, age median 50 years). Additional information was obtained by a dermatologic examination, a standardized interview, and blood analysis.

Results: At least one positive reaction was exhibited by 40.0% of the subjects, with reactions most frequently observed to fragrance mix (15.9%), nickel (13.1%), thimerosal (4.7%), and balsam of Peru (3.8%). Women were sensitized more often than men (50.2%vs 29.9%, OR 2.36, CI 1.84–3.03), and this was also significant for fragrance mix, nickel, turpentine, cobalt chloride, and thimerosal. Contact sensitization was more frequent in subjects who reported adverse skin reactions (53.8% vs. 32.6%; OR 2.41, CI 1.85–3.14), and this was particularly true for sensitization to nickel (45.5%vs 8.8%, OR 8.64, CI 5.67–13.17) and fragrance mix (29.0%vs 14.0%, OR 2.51, CI 1.60–3.91) and the corresponding intolerance of fashion jewelry and fragrances. Contact sensitization decreased with increasing degree of occupational training (unskilled 45.9%, apprenticeship 40.1%, technical college 40.4%, and school of engineering 12.5%; P=0.023; trend test P=0.042). Significant associations of contact sensitization and presence of allergen‐specific IgE antibodies, atopic eczema, or psoriasis were not observed. Frequency estimates for the general adult population based on these findings were 28.0% for overall contact sensitization and 11.4% for fragrance mix, 9.9% for nickel, and 3.2% for thimerosal.

Conclusions: It is concluded that contact allergy is influenced by sociodemographic parameters and plays an important role in the general population.
Cysteinyl‐leukotriene release test (CAST) in the diagnosis of immediate drug reactions
Authors: Lebel B. , Messaad D. , Kvedariene V. , Rongier M. , Bousquet J. , Demoly P.
Published: March 2003

Background: The diagnosis of allergic reactions to drugs is difficult. Most skin tests are not standardized, and in vitro tests are needed to avoid provocation tests. Cross‐linking of IgE on basophils is known to cause the release of both cysteinyl leukotriene (Cys‐LT) and histamine. We aimed to evaluate the diagnostic utility (sensitivity, specificity, and efficiency) of measurement of sulfidoleukotrienes in drug allergy.

Methods: We performed a prospective study in 55 patients with proven immediate adverse reactions to drugs (30 to β‐lactams, six to acetaminophen, and 19 to aspirin) and 64 drug‐exposed nonallergic controls. Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Cys‐LT release was determined after drug‐allergen stimulation by the cellular antigen stimulation test (CAST®) technique. Histamine release was also assessed on the same samples by enzyme immunoassay. Spontaneous and anti‐FcεRIα‐induced mediator release was also studied in all subjects. Sensitivity, specificity, and efficiency were calculated.

Results: Net Cys‐LT release was over the maximal threshold given by the manufacturer in 19/55 patients and in 9/64 controls. Net histamine release was over 5% of total histamine content in 28/55 patients and 34/64 controls. The efficiency of both tests was low.

Conclusions: Thus, in most cases, the in vitro Cys‐LT test has little or no diagnostic utility and is not superior to histamine release.
Fexofenadine reduces nasal congestion in perennial allergic rhinitis
Authors: Ciprandi G. , Cosentino C. , Milanese M. , Mondino C. , Canonica G. W.
Published: March 2003

Background: Nasal congestion is the predominant symptom in perennial allergic rhinitis (PAR), and it seems to be mainly related to the late‐phase inflammatory events. The present pilot study aimed to evaluate the therapeutic effect exerted by fexofenadine in patients with PAR due to mite allergy.

Methods: This study was a parallel, double‐blind, randomized, three‐arm (1:1:1), placebo‐controlled study. Thirty‐one subjects with PAR were enrolled and received double‐blind medication: fexofenadine 120 or 180 mg, or placebo, once a day for 28 days.

Results: The total symptom score was reduced by fexofenadine (both dosages) at V2 (P=0.007), whereas placebo did not modify it. Nasal congestion decreased after 1 week of treatment with fexofenadine 120 (P=0.027) and 180 (P=0.01), but not with placebo (P=NS). At V3, fexofenadine (both dosages) significantly reduced nasal congestion (P=0.011 and P=0.007, respectively), by placebo did not show any significant effect.

Conclusions: This pilot study represents the first evidence of the efficacy of fexofenadine in PAR, and also the control of the nasal congestion. We suggest performing larger trials to confirm these preliminary findings.
Do hepatitis B virus carriers develop atopic diseases?
Authors: Kocabas C. N.
Published: March 2003

The prevalence of allergic disorders, such as asthma, hay fever, and atopic dermatitis, has increased dramatically over the past few decades. Although the important inherited component in these diseases is well established, the role of environmental factors in relation to allergic disorders has become increasingly topical in the last decade. Immunologic data show that different infections can either promote atopy (as in respiratory syncytial virus infections) or inhibit it (as in measles, hepatitis A, and tuberculosis). Although there are 400 million hepatitis B virus (HBV) carriers around the world, and asymptomatic HBV carriers with a high level of virus replication are characterized by Th2‐type immune reactions, the relationship between HBV carriers and atopic disorders has not been studied.
The role of patient training in the management of seasonal rhinitis and asthma: clinical implications
Authors: Gani F. , Pozzi E. , Crivellaro M. A. , Senna G. , Landi M. , Lombardi C. , Canonica G. W. , Passalacqua G.
Published: March 2003

Background: Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first‐choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms.

Methods: One hundred and one patients (M/F=62/39, age range 12–62 years) with pollen‐induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n=30) with drug therapy alone, B (n=35) with drug therapy plus training on the use of nasal spray, and C (n=36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season.

Results: The rate of noncompliance/dropout was highest in the untrained patients (P=0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P=0.02) and less albuterol use (P=0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P=0.02).

Conclusions: Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs.
Allergenic cross‐reactivity between the nematode Anisakis simplex and the dust mites Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, and Dermatophagoides pteronyssinus
Authors: Johansson E. , Aponno M. , Lundberg M. , Van Hage‐Hamsten M.
Published: March 2003

Background: The nematode Anisakis simplex is a common parasite on fish and other seafood. It is considered to be a food allergen and to induce IgE‐mediated reactions. Allergenic cross‐reactivity between A. simplex and other nematodes has been reported, as has cross‐reactivity with arthropods: red mosquito larvae and German cockroach. We have here studied the allergenic relationship between A. simplex and four different dust‐mite species.

Methods: Serum samples collected from 69 farmers allergic to dust mites were analyzed for IgE to A. simplex by CAP FEIA. Allergenic cross‐reactivity between A. simplex and dust mites was studied in two of the sera by CAP FEIA and immunoblotting inhibition.

Results: We found that 14/69 farmers had detectable levels of IgE antibodies to A. simplex. The IgE response in CAP FEIA to A. simplex was inhibited to various degrees in the two studied sera by extracts of the dust mites Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, and Dermatophagoides pteronyssinus. In the reverse inhibition experiment, extract of A. simplex inhibited the response in both sera to A. siro and T. putrescentiae, but not to L. destructor. The IgE binding to D. pteronyssinus was inhibited in one of the two sera. In blotting inhibition experiments, the IgE binding to several allergens in A. simplex was inhibited by each of the four mite extracts, especially by A. siro and T. putrescentiae, which completely inhibited the IgE binding to several allergens.

Conclusions: The results show allergenic cross‐reactivity between several allergens in A. simplex and four dust‐mite species. The clinical significance of this cross‐reactivity remains to be evaluated.
Nasal and exhaled nitric oxide in response to occupational latex exposure
Authors: Tan K. , Bruce C. , Birkhead A. , Thomas P. S.
Published: March 2003

Background: Latex sensitivity is an increasing problem among health‐care workers. Allergic responses are associated with changes in nitric oxide (NO) generation and the changes secondary to latex have not been described.

Methods: A total of 22 subjects comprising equal numbers of control volunteers and subjects with self‐reported latex sensitivity were recruited to undergo latex skin prick testing. Symptom scores, exhaled nitric oxide (eNO), and nasal nitric oxide (nNO) were studied 1) before and after a controlled latex challenge (n=16), and 2) at the beginning and end of the working week, during exposure to latex (n=18).

Results: Latex challenge caused a significant fall in nNO levels in latex‐sensitive subjects, compared to normal control subjects (P=0.04). eNO levels also decreased in the latex‐sensitive subjects after latex challenge, but to a lesser degree. There were no significant differences between the beginning and end of the working week in terms of eNO or nNO in either group, although symptom scores showed a nonsignificant increase in latex‐sensitive subjects.

Conclusions: Fall in nasal NO after latex challenge is associated with reported symptomatic latex sensitivity, and this corresponds to latex skin prick test positivity. Neither nNO nor eNO showed a clear relationship to routine workplace exposure.
IL4‐R1 (5q31–q33) and FcεRI‐βca (11q13) markers and atopy: a case/control study in a Spanish population
Authors: Torres‐Galván M. , Quiralte J. , Pestano J. J. , Ortega N. , Blanco C. , Castillo R. , Carrillo T. , Pérez‐Aciego P. , Sánchez‐García F.
Published: March 2003

Background: Rhinoconjunctivitis and bronchial asthma are atopic diseases with a high prevalence in the Canary Islands (Spain). Given that the most prevalent allergen is the house‐dust mite Dermatophagoides pteronyssinus, early detection of genetically susceptible subjects would allow the application of preventive measures. The objective was to investigate the possible association of IL4‐R1 (chromosome 5q31–q33) and FcεRI‐βca (chromosome 11q13) markers with the atopic disease in our population.

Methods: We performed a case/control study in which patients were recruited on the basis of diagnosis of rhinoconjunctivitis and/or bronchial asthma, and positive skin prick test to D. pteronyssinus. Analysis of IL4‐R1 and FcεRI‐βca microsatellites was carried out by PCR and electrophoresis in acrylamide gels.

Results: We have not found evidence of association between IL4‐R1 and FcεRI‐βca markers and atopic disease in our population. In addition, these markers have shown a high percentage of homozygosis.

Conclusions: IL4‐R1 and FcεRI‐βca markers have not proved to be useful genetic markers for linkage or association studies in our population.