bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term repeatability of the skin prick test is high when supported by history or allergen‐sensitivity tests: a prospective clinical study
Authors: Bodtger U. , Jacobsen C. R. , Poulsen L. K. , Malling H.‐J.
Published: December 2004

Background: Long‐term reproducibility of the skin‐prick test (SPT) has been questioned. The aim of the study was to investigate the clinical relevance of SPT changes.

Methods: SPT to 10 common inhalation allergens was performed annually from 1999 to 2001 in 25 nonsensitized and 21 sensitized subjects. An SPT was positive when ≥3 mm, and repeatable if either persistently positive or negative. Clinical sensitivity to birch pollen was used as model for inhalation allergy, and was investigated at inclusion and at study termination by challenge tests, intradermal test, titrated SPT and IgE measurements. Birch pollen symptoms were confirmed in diaries.

Results: The repeatability of a positive SPT was 67%, increasing significantly to 100% when supported by the history. When not supported by history, the presence of specific IgE was significantly associated with a repeatable SPT. Allergen sensitivity was significantly lower in subjects loosing SPT positivity. The repeatability of a negative test was 95%, decreasing significantly to 87% by the presence of other sensitization. Development of a positive SPT was clinically relevant. Elevation of SPT cut‐off point did not enhance repeatability.

Conclusion: SPT changes are clinically relevant. Further studies using other allergens are needed. Long‐term repeatability of SPT is high in the presence of a supportive history.
Animal models of allergic and inflammatory conjunctivitis
Authors: Groneberg D. A. , Bielory L. , Fischer A. , Bonini S. , Wahn U.
Published: December 2004

Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small number of allergens such as ovalbumin, ragweed pollen or major cat allergens and consecutive challenge. Different animal species have been used so far. Starting with guinea‐pig models of allergic conjunctivitis to assess pharmacological aspects, new models including rats and mice have been developed which mimic major features of ocular allergy. The presently preferred species for the investigation of the immunological basis of the disease is represented by murine models of allergic conjunctivitis. In the future, combined ocular, nasal and aerosolic challenges with allergens may provide a model of allergy that encompasses simultaneously the target organs eye, nose and airways with conjunctivitis, rhinitis and asthma.
Spontaneous TH1 cytokine production by intraepithelial but not circulating T cells in infants with or without food allergies
Authors: Pérez‐Machado M. A. , Ashwood P. , Torrente F. , Salvestrini C. , Sim R. , Thomson M. A. , Walker‐Smith J. A. , Murch S. H.
Published: December 2004

Background:  It has been established that the maintenance of immunological tolerance to dietary antigen and the intestinal flora (oral tolerance) is an actively‐maintained process dependent upon mucosal lymphocyte populations. Early life exposures appear critical in the development of such tolerance. However little is known about the activation status of mucosal lymphocytes in human infancy and childhood.

Patients and methods:  We have performed flow cytometric analysis for cell lineage and cytokine‐production status in peripheral blood and duodenal intraepithelial lymphocytes taken during endoscopy from 20 children [median age 2.9 ± 0.6 years (median ± SE)] in whom investigation found no intestinal abnormalities (histologically normal controls) and 30 children (median age 1.6 ± 0.4 years) with confirmed allergy to cow's milk and other dietary antigens.

Results:  Regardless of clinical status, spontaneous production of cytokines was low or undetectable in peripheral blood cells. By contrast, intraepithelial CD4 and CD8 cells isolated from the small intestine were often activated, with 5% or more showing spontaneous production of TH1 type [interleukin‐2, interferon (IFN)‐γ] cytokines in both normal controls and food‐allergic children. Stimulation in vitro strongly induced cytokine production in peripheral blood but not intraepithelial lymphocytes. Immunohistochemistry showed similar density of IFN‐γ+ intraepithelial lymphocytes in controls and allergic children.

Conclusions:  Duodenal intraepithelial lymphocytes in human infants show a state of increased spontaneous activation compared with peripheral blood lymphocytes, and show no significant impairment of TH1 responses in food allergic children.
Sensory testing of recipes masking peanut or hazelnut for double‐blind placebo‐controlled food challenges
Authors: Ronteltap A. , Van Schaik J. , Wensing M. , Rynja F. J. , Knulst A. C. , De Vries J. H. M.
Published: December 2004

Background:  In a double‐blind placebo‐controlled food challenge (DBPCFC), it is necessary that recipes comprising the allergen cannot be distinguished from placebo.

Aims of the study:  We investigated whether the method of paired comparisons, a sensory difference test, could be used to test the suitability of recipes for a DBPCFC.

Methods:  We used two recipes, each with three concentrations of peanut or hazelnut flour. The recipe for peanut consisted of mashed potatoes with 2.7, 8.9, or 26.8 mg of peanut flour, and the recipe for hazelnut of oatmeal porridge with 74, 247, or 742 mg of hazelnut flour. Corresponding amounts of protein in the provided 15 g portions of each recipe were 0.7, 2.3, and 6.8 mg for peanut, and 11.6, 39, and 117 mg for hazelnut, respectively. Recipes were offered together with a placebo, and evaluated on sensory features by 81 healthy volunteers.

Results:  The sensory test was easy to perform. Volunteers were not able to detect peanut flour in mashed potatoes, but they recognized hazelnut flour in oatmeal porridge on visual features.

Conclusions:  Sensory testing by means of the method of paired comparisons is a useful method to evaluate masking of foods for DBPCFC.
Disease perception and social behaviour in persistent rhinitis: a comparison between patients with allergic and nonallergic rhinitis
Authors: Rydén O. , Andersson B. , Andersson M.
Published: December 2004

Background:  Although the understanding of the pathophysiology and pharmacology of rhinitis has increased within recent years, few studies have examined the impact of rhinitis on patients’ behaviour.

Aim:  To compare perennial allergic rhinitis (PAR) and perennial nonallergic rhinitis (PNR) in terms of patients’ perception of their disease and its psychosocial concomitants.

Methods:  Thirty‐one PAR patients and 32 PNR patients responded to a standard symptom list and were interviewed in‐depth regarding their complaints and the impact of rhinitis on their daily lives.

Results:  PAR and PNR patients reported similar somatic and psychosocial complaints. In both disease groups the adverse effects of rhinitis were reported to be substantially limiting, particularly in social contacts, the impact appearing to be more severe in the women.

Conclusion:  Rhinitis has a severe impact on the daily lives of patients, women reporting more severe psychosocial effects. Disease perception and social adjustment appear to not depend appreciably on whether or not an objective diagnosis of rhinitis can be established.
Risk factors for asthma among children in Maputo (Mozambique)
Authors: Mavale‐Manuel S. , Alexandre F. , Duarte N. , Albuquerque O. , Scheinmann P. , Poisson‐Salomon A. S. , de Blic J.
Published: December 2004

Background:  Few studies have looked at risk factors for asthma in African children. We aimed to identify the risk factors associated with childhood asthma in Maputo (Mozambique).

Methods:  This case–control study included 199 age‐matched children (100 asthmatic and 99 nonasthmatic) who attended Maputo Central Hospital between January 1999 and July 2000. We collected information concerning their familial history of atopy, birth weight, environment and breast‐feeding. Detailed information about morbidity and treatment was obtained for each asthmatic child.

Results:  The children were aged between 18 months and 8 years; 60% were male. The asthmatic children were hospitalized more frequently than the nonasthmatic children (P < 0.0001). Most of the asthmatic children lived in the urban area of Maputo [odd ratio (OR) = 6.73, CI = 3.1–14.0, P < 0.0001], had a parental history of asthma (OR = 26.8, CI = 10.8–68.2, P < 0.0001) or rhinitis (OR = 4, CI = 1.2–13.3, P = 0.005), had at least parent who smoked and were weaned earlier than the nonasthmatic children (OR = 2.4, CI = 1.3–4.4, P < 0.001).

Conclusion:  Childhood asthma was strongly associated with a family history of asthma and rhinitis, the place of residence, having smokers as parents and early weaning from maternal breast milk. These results highlight the need to reassess the management of asthmatic children in Maputo.
Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo‐controlled study1
Authors: Arvidsson M. B. , Löwhagen O. , Rak S.
Published: December 2004

Background:  Few placebo‐controlled studies have examined the effect of allergen specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this placebo‐controlled study we have investigated the effect of 1 year of SIT with standardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients.

Methods:  Nineteen patients with a history of birch‐pollen‐induced seasonal symptoms from upper and lower airways, positive skin prick test and in vitro specific immunoglobulin E to birch pollen extract were included. Allergen and methacholine bronchial challenges were performed and blood samples obtained for analyses of total eosinophil count and eosinophil cationic protein (ECP) in serum, before and after 1 year of immunotherapy treatment.

Results:  All patients developed early and 16 of 19 both early and late phase asthmatic reactions. A significant increase in allergen dose was required to evoke early asthmatic reaction in the immunotherapy group (P < 0.01) after 1 year of treatment. The difference between the groups was significant (P < 0.01). Also the size of late asthmatic reaction was significantly reduced in the SIT group compared with placebo treated patients (P < 0.01). Twenty‐four hours after allergen challenge methacholine sensitivity, number of total eosinophils and ECP increased significantly in the placebo (P < 0.02, P < 0.05 and P < 0.05 respectively), but not in the SIT group.

Conclusion:  Allergen SIT with standardized birch pollen extract decreased early and late asthmatic responses following bronchial challenge in pollen allergic patients, thus confirming anti‐inflammatory effect of the treatment.
Characterization of the protective and therapeutic efficiency of a DNA vaccine encoding the major birch pollen allergen Bet v 1a
Authors: Hartl A. , Hochreiter R. , Stepanoska T. , Ferreira F. , Thalhamer J.
Published: December 2004

Background:  An estimated 100 million individuals suffer from birch pollen allergy. More than 95% of birch pollen‐allergic subjects react with the major birch pollen allergen Bet v 1a, and almost 60% of them are sensitized exclusively to this allergen.

Objective:  DNA immunization using the Bet v 1a gene was evaluated with respect to its prophylactic and therapeutic efficacy.

Methods:  A DNA vaccine containing the entire Bet v 1a cDNA under the control of a CMV‐promoter was constructed. In order to estimate the protective efficiency, animals received three injections of this vaccine prior to sensitization with recombinant Bet v 1a. Vice versa, in a therapeutic approach, sensitization was followed by treatment with the DNA vaccine.

Results:  The Bet v 1a DNA vaccine induced strong Bet v 1‐specific antibody responses with a Th1‐biased response type. Animals which received the DNA vaccine were protected against a following allergic sensitization with Bet v 1a. The protective effect was characterized by suppression of Bet v 1‐specific immunoglobulin (Ig)E production, lack of basophil activation and enhanced interferon (IFN)‐γ expression. In a therapeutic situation, treatment of sensitized animals with DNA vaccines decreased IgE production, IgE‐mediated basophil release and drastically reduced anaphylactic activity as measured by passive cutaneous anaphylaxis assays. Concerning the cellular immune response, DNA immunization induced a sustaining and dominant shift from a Th2 type response towards a balanced Th1/Th2 type response as indicated by increased IFN‐γ but unchanged IL‐5 levels in lymphoproliferation assays.

Conclusion:  The results demonstrate the allergen‐specific protective and therapeutic efficacy of a DNA vaccine encoding the clinically highly relevant allergen Bet v 1a indicating the suitability of this concept for the treatment of allergic diseases.
The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies
Authors: Novak N. , Allam J.‐P. , Betten H. , Haberstok J. , Bieber T.
Published: December 2004

It has been repeatedly demonstrated that allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DC). The ability of allergens to cause allergic inflammation is contingent upon the presence of an immunological milieu and microenvironment that either privileges Th2 responses or prohibits these reactions by the induction of contraregulatory anti‐inflammatory activities of the immune system. In the light of recent developments it appears that DC have to manage two opposing tasks: on the one hand they can favor pro‐inflammatory reactions and actively induce a T‐cell response, yet on the other hand they serve an important function as ‘silencers’ in the immune system by sending out anti‐inflammatory, tolerance inducing signals. This unique capacity of DC has opened several exciting possibilities for a role of DC in both – accelerating and slowing down allergic reactions. It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity.
Infectious and uterus related complications during pregnancy and development of atopic and nonatopic asthma in children
Authors: Calvani M. , Alessandri C. , Sopo S. Miceli , Panetta V. , Tripodi S. , Torre A. , Pingitore G. , Frediani T. , Volterrani A. ,   the Lazio Association of Pediatric Allergology (APAL) Study Group
Published: December 2004

Background:  It has been suggested that environmental factors early in life, particularly related to hygiene and infections, seem to be involved in the increase of asthma and allergic disease observed recently in developed countries. The possible effect of these factors also in utero have yet to be completely clarified. The aim of this study was to investigate the association between infective and uterus related complications during pregnancy, as well as related drug factors, with atopic and nonatopic asthma in children.

Methods:  This was a case‐controlled study enrolling 338 children with asthma and 467 controls, who had never suffered from wheeze or asthma. Fever episodes, flu episodes, threatened abortions and related drug factors were retrospectively assessed by parental report via a standardized questionnaire. Atopy was determined by skin‐prick tests to 10 prevalent allergens at the time of examination.

Results:  Flu episodes during pregnancy were significantly associated with development of asthma in children [adjusted odds ratio (aOR) 1.91; 95% confidence interval (95% CI) 1.1–3.2], mainly with nonatopic asthma. Fever episodes showed similar results (aOR 2.16; 95% CI 1.2–3.9), but were associated with both atopic and nonatopic asthma. The effect seems mainly due to flu and fever episodes contracted in the third trimester. Exposure to isoxsuprine was significantly associated with asthma (aOR 1.54; 95% CI 1.08–2.19) while threatened abortions were more frequent in the asthma group than in controls, although the difference was statistically significant only when such events occurred in the second trimester (aOR 2.06; 95% CI 1.07–3.94). Both threatened abortions and exposure to isoxsuprine were associated only with nonatopic asthma.

Conclusions:  This study confirms that prenatal infective complications may contribute to the development of asthma in children and show a possible role for a new risk factor for asthma, that is exposure to isoxsuprine. Therefore, larger prospective studies, capable of separating atopic and nonatopic asthma, would serve to confirm these results and to explain the possible mechanism through which these factors may act.
Comparison of wheat and rye flour skin prick test solutions for diagnosis of baker's asthma
Authors: Sander I. , Merget R. , Degens P. O. , Goldscheid N. , Brüning T. , Raulf‐Heimsoth M.
Published: December 2004

Background:  Skin prick tests (SPTs) play an important role in the diagnosis of baker's asthma and in the investigation of sensitization frequencies in field studies. It was the aim of our study to compare different SPT solutions for wheat and rye flour sensitization and to assess the validity of test results.

Methods:  Skin prick tests with wheat and rye flour were performed in parallel with extracts from different companies and compared with the results of bronchial challenge tests with both flours (69 rye flour and 51 wheat flour challenge tests). Additionally, specific immunoglobulin E (sIgE) to wheat and rye flour were tested. SPT solutions were analysed for protein content and by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE).

Results:  Skin prick test solutions for diagnosis of wheat and rye flour sensitization from three companies differed in protein concentrations and composition with the consequence of widely differing SPT results. Sensitivity of SPTs in comparison with allergen‐specific bronchial challenge as a gold standard was between 40 and 67%, specificity was between 86 and 100%, the positive predictive value (PPV) ranged from 81 to 100% and the negative predictive value (NPV) from 44 to 70%. These numbers were only marginally affected by using a combination of challenge test result and sIgE value as a more specific gold standard.

Conclusion:  Improvement and standardization of SPT extracts for wheat and rye flour is highly recommended.
Occupational exposure of Brazilian neonatal intensive care workers to latex antigens
Authors: Lopes R. A. M. , Benatti M. C. C. , Zollner R. L.
Published: December 2004

Background:  Frequent exposure to latex causes various reactions such as respiratory symptoms and anaphylactic shock. In these cases, proteins found in natural latex are responsible for the serious systemic antilatex‐mediated immediate hypersensitive reactions.

Methods:  Cross‐sectional descriptive survey focusing on 96 Brazilian health care workers (HCW) in the neonatal intensive care unit at CAISM, State University of Campinas UNICAMP, Brazil. All subjects were interviewed, donated blood samples for the latex‐specific immunoglobulin E measurement and underwent the skin prick test (SPT) with an antigen extracted from latex gloves.

Results:  The prevalence of latex positive SPT was 8%. There were eight SPT positive and only one serologic test was in agreement with the SPT. Overall, there was evidence of an association between the latex SPT and reported eczema (P = 0.01); food allergy (P = 0.009) with pineapple (P = 0.01).

Conclusions:  These results suggest that the identification of reactions of immediate hypersensitivity mediated by antilatex antibodies in HCW should be encouraged to prevent occupational exposure to latex products.
Montelukast 10 mg improves nasal function and nasal response to aspirin in ASA‐sensitive asthmatics: a controlled study vs placebo
Authors: Micheletto C. , Tognella S. , Visconti M. , Pomari C. , Trevisan F. , Dal Negro R. W.
Published: December 2004

Aspirin‐induced asthma (AIA) is a clinical syndrome characterized by acute airway reaction to aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDS). The most recent etiological hypothesises is that an overexpression of the enzyme LTC4 synthase occurs in AIA, with the consequent production of sulfidopeptide leukotrienes (LTs).

Aim:  Aim of the present study was to assess the effect of Montelukast, a selective cys‐LT receptor antagonist, on nasal function, nasal reactivity to ASA and blood markers of eosinophilic inflammation in mild‐to‐moderate AIA.

Material and methods:  Thirty‐six nonsmoker subjects with AIA (17 males, 22–52 years) performed a nasal provocation test (NPT) with lysine‐aspirin (L‐ASA) in baseline and after a 4‐week Montelukast 10 mg or placebo treatment. Nasal function was assessed by the acoustic rhinomanometry, and they also performed a lung function test (forced expiratory volume in 1 s), and a blood sample for the eosinophil count and the eosinophil cationic protein (ECP) plasma measurements. After both treatments, all subjects repeated the NPT, the lung function, and the ECP and the eosinophil blood count.

Statistical analysis:  t‐Test was used to compare mean values ± SD between groups, and P < 0.05 was assumed as the level for statistical significance.

Results:  Airway patency was never affected by the NPT with L‐ASA. In baseline, NPT with L‐ASA precipitated a nasal reaction in all subjects, with a substantial increase in nasal resistance (calculated resistance [REQ]; from 0.89 ± 0.18 to 2.2 ± 0.17 cmH2O/l/min in group M, P < 0.001; and from 0.91 ± 0.48 to 2.3 ± 0.21 cmH2O/l/min in group P, P < 0.001); and a significant reduction in total nasal volume in at least one nostril (volume [VOL]; from 11.1 ± 3.2 to 8.1 ± 4.1 cm3 in the group M, P < 0.001, and from 12.3 ± 4.1 to 7.9 ± 4.5 cm3 in the group P, P < 0.001). The nasal reaction to L‐ASA remained unchanged following placebo, but it was completely minimized following a 4‐week treatment with Montelukast. Also nasal function, the nasal symptom score, and the markers of eosinophilic inflammation proved significantly affected and improved by the active drug only.

Conclusions:  Montelukast 10 mg daily for 4 weeks, but not placebo, improves nasal function and nasal response to Aspirin substantially in ASA‐sensitive asthmatics.
Lack of association of HLA class I genes and TNF α‐308 polymorphism in toluene diisocyanate‐induced asthma
Authors: Beghé B. , Padoan M. , Moss C. T. , Barton S. J. , Holloway J. W. , Holgate S. T. , Howell W. M. , Mapp C. E.
Published: December 2004

Background:  Toluene diisocyanate (TDI)‐induced asthma is a common cause of occupational asthma and it affects 5–15% of the exposed population suggesting an underlying genetic susceptibility.

Methods:  To investigate the role of genetic factors in the development of TDI‐induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)‐α A‐308G polymorphism in 142 patients with TDI‐induced asthma and in 50 asymptomatic exposed subjects.

Results:  Neither the distribution of HLA class I antigens nor the distribution of TNF‐α A‐308G polymorphism was different between patients with TDI‐induced asthma and asymptomatic exposed subjects.

Conclusions:  These results suggest that HLA class I antigens and TNF‐α A‐308G are not associated with susceptibility or resistance to the development of TDI‐induced asthma.
No effect of montelukast on asthma‐like symptoms in elite ice hockey players
Authors: Helenius I. , Lumme A. , Öunap J. , Obase Y. , Rytilä P. , Sarna S. , Alaranta A. , Remes V. , Haahtela T.
Published: December 2004

Background:  Controlled clinical trials on the effects of leukotriene antagonists on asthma‐like symptoms, bronchial hyperresponsiveness and airway inflammation have not been performed in elite athletes.

Methods:  In 2001, we examined 88 of 102 (86%) players from three junior, national league ice hockey teams in Helsinki. Athletes were included in the intervention if they reported at least two exercise‐induced bronchial symptoms (wheeze, cough, shortness of breath) weekly during the previous month on a previously validated respiratory‐symptom questionnaire. Sixteen male ice hockey players fulfilled the study criteria. A double‐blind, randomized, cross‐over, placebo‐controlled study included 4‐week active treatment (10 mg oral montelukast, bedtime), 1‐week washout period, and 4‐week placebo treatment. Before entering the study, all patients were clinically examined, skin prick tested, filled in a respiratory symptom questionnaire, performed a spirometry and a histamine challenge test, and gave induced sputum samples. Exhaled NO was measured. These measures were repeated after both treatment periods. During the treatment the athletes kept daily diary on lower respiratory tract symptoms on a scale from 0 (no symptoms) to 10 (most severe symptoms), morning peak expiratory flow (PEF), training amount, and use of study medication. Primary end‐point was daily lower respiratory tract symptom score.

Results:  Montelukast had no effect on daily lower respiratory symptom scores, spirometry parameters [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, PEF], bronchial hyperresponsiveness, sputum eosinophil or neutrophil cell counts, exhaled NO measurements, or morning PEF. Nine subjects were atopic in skin prick test, but their results did not differ from the nonatopic subjects.

Conclusion:  A leukotriene antagonist, montelukast, was of no benefit in the treatment of asthma‐like symptoms, increased bronchial hyperresponsiveness or a mixed type of eosinophilic and neutrophilic airway inflammation in highly‐trained ice hockey players.
Diagnosis of asthma and permitted use of inhaled β2‐agonists in athletes
Authors: Bonini S. , Brusasco V. , Carlsen K.‐H. , Delgado L. , Giacco S. D. , Haahtela T. , Rasi G. , van Cauwenberge P. B.
Published: December 2004

The prevalence of asthma and bronchial hyperreactivity has been reported to be higher in athletes than in the general population. This has also been related to reported asthma in order to obtain permitted use of β2‐agonists, whose assumption in athletes is ruled by anti‐doping regulations. The paper addresses the issue whether the recently established and evaluated rules of the International Olympic Committee on tests and procedures for diagnosis of asthma in athletes and permitted use of β2‐agonists are consistent with an adequate diagnosis and management of asthma according to international guidelines.
Can we prevent allergy?
Authors: Gore C. , Custovic A.
Published: December 2004

Allergic conditions continue to increase steeply. The last two decades have seen many prevention trials, studying the effect of dietary and environmental interventions. These trials have yielded invaluable information about the atopic march and also highlighted the need for a clear and commonly used nomenclature as well as a need for better outcome measures. This review discusses primary and secondary prevention studies and their results.
Improvements in simulated real‐world relevant performance for patients with seasonal allergic rhinitis: impact of desloratadine
Authors: Satish U. , Streufert S. , Dewan M. , Voort S. Vande
Published: December 2004

Background:  Seasonal allergic rhinitis (SAR) diminishes task performance and decreases quality of life. Antihistamines are frequently used to treat the symptoms of SAR. First generation antihistamines often have their own detrimental effects upon human functioning while second generation antihistamines appear to have fewer or no undesirable side‐effects.

Objective:  This study evaluated the impact of desloratadine on simulated real‐world performance demands in individuals suffering from SAR.

Methods:  This was a randomized, double‐blind, cross‐over study where asymptomatic participants were treated with placebo and symptomatic participants were treated with desloratadine or placebo. They then participated in a real‐world equivalent task performance simulation that assessed information processing capacity at multiple levels of task difficulty ranging from easy to difficult decision‐making tasks.

Results:  Desloratadine either completely restored performance to the level of the asymptomatic placebo control or improved performance in six of the nine performance categories, where it had been diminished by the presence of SAR.

Conclusions:  These findings suggest that treatment with desloratadine has considerable beneficial effects on work place performance when individuals suffer from SAR.
Cloning and expression of a major allergen from Cupressus arizonica pollen, Cup a 3, a PR‐5 protein expressed under polluted environment
Authors: Cortegano I. , Civantos E. , Aceituno E. , Del Moral A. , López E. , Lombardero M. , Del Pozo V. , Lahoz C.
Published: December 2004

Background:  This paper describes the cloning and expression of the Cupressus arizonica pollen protein Cup a 3. In addition, we present its modulation under polluted environmental conditions. Species of the Cupressaceae family are important because of their high sensitization prevalence.

Methods:  Cup a 3 cloning is based on the sequence of the homologous protein Jun a 3. Cup a 3 was expressed with good yield in the methylotropic yeast Pichia pastoris.

Results:  Recombinant Cup a 3 (rCup a 3) contains 199 amino acids, 10 potential phosphorylation sites and no glycosylation sites. By immunoblot 63% of cypress allergic patients had specific immunoglobulin E antibodies against rCup a 3 (n = 104). This major allergen is homologous to members of the pathogenesis‐related proteins (PR‐5 group) and contributes to the overall allergenicity of C. arizonica pollen. Our results show that the increased expression of Cup a 3 is dependent on the pollution in the area where the pollen has been collected, being higher under polluted conditions.

Conclusions:  Cup a 3 is a PR‐5 protein derived from C. arizonica pollen. The expression of the protein under polluted conditions has a direct incidence on the pollen allergenicity, as has been demonstrated by skin tests and Radioallergosorbent test inhibition.
Matrix metalloproteinases MMP‐7, MMP‐9 and their tissue inhibitor TIMP‐1: expression in chronic sinusitis vs nasal polyposis
Authors: Watelet J. B. , Bachert C. , Claeys C. , Van Cauwenberge P.
Published: December 2004

Background:  Nasal polyps (NP) are characterized by pseudocyst formation, whereas the mucosa in chronic sinusitis (CS) only shows a limited oedema. Matrix metalloproteinases (MMPs) are a family of endopeptidases able to degrade the extracellular matrix. Differences in histological features between CS and NP might be related to the respective expression of MMPs and their tissue inhibitors (TIMPs).

Objective:  The aim of this study was to investigate MMP‐7, MMP‐9 and TIMP‐1 proteins in NP and CS in comparison with normal mucosa.

Methods:  Nasal samples, obtained from controls (n = 10), from NP (n = 8) and from CS (n = 10), were analysed by immunohistochemistry and enzyme‐linked immunosorbent assay (ELISA).

Results:  In NP, compared with controls, staining for MMP‐9 and MMP‐7 appeared in blood vessels. Matrix metalloproteinase‐9‐positive inflammatory cells could be detected in increased numbers in pseudocyst formations. Concentrations of MMP‐9 protein was found significantly increased in both CS and NP compared with controls, while MMP‐7 was significantly increased in NP compared with controls and CS. Tissue inhibitors of metalloproteinase‐1 protein was significantly increased in CS and NP when compared with controls.

Conclusions:  Chronic sinusitis and NP show different pattern of MMP‐7/‐9 and TIMP‐1 expression. We suggest that this difference in regulation of enzymes is related to the respective tissue remodelling observed in both diseases.
Influence of a multidisciplinary paediatric allergy clinic on parental knowledge and rate of subsequent allergic reactions
Authors: Kapoor S. , Roberts G. , Bynoe Y. , Gaughan M. , Habibi P. , Lack G.
Published: December 2004

Background:  Studies have demonstrated that families of children with food allergy have significant deficiencies in their knowledge of how to avoid allergen exposure and how to manage allergic reactions. This study aims to assess the impact of a multidisciplinary paediatric allergy clinic consultation on parental knowledge of food allergy and to determine the rate of subsequent allergic reactions.

Methods:  Sixty‐two subjects (<17 years) referred with food allergy were prospectively enrolled. Parental knowledge was assessed by questionnaire and EpiPen trainer. Families saw a paediatric allergist, clinical nurse specialist and dietician. Knowledge was reassessed after 3 months and rate of allergic reactions after 1 year.

Results:  After one visit to the paediatric allergy clinic, there was a significant improvement in parental knowledge of allergen avoidance (26.9%, P < 0.001), managing allergic reactions (185.4%, P < 0.0001) and EpiPen usage (83.3%, P < 0.001). Additionally, there was a significant reduction in allergic reactions (P < 0.001). Children with egg, milk or multiple food allergies were more likely to suffer subsequent reactions.

Conclusions:  A single visit to a multidisciplinary allergy clinic considerably improves families’ abilities to manage allergic reactions to foods with an accompanying reduction in allergic reactions. Young children with egg, milk or multiple food allergies were at greatest risk of further reactions.
Is the increase in allergic asthma associated with an inborn Th1 maturation or with an environmental Th1 trigger defect?
Authors: Wjst M.
Published: December 2004

The main reason for the asthma epidemic in industrialized countries is unknown. While childhood mortality from acute respiratory infection is still high in developing countries where asthma prevalence is low, there might be a suppressed natural selection in industrialized countries with a high asthma prevalence. Children with an inborn Th1 maturation defect might survive by better health care and antibiotic use at the cost of higher asthma and allergy rates. Another distinct group of children maybe represented by those having an environmental Th1 trigger deficit where the immune systems is not being sufficiently exposed in early life. Both, a Th1 maturation and a Th1 trigger defect may contribute to a dual Th1 allergy theory.
Identification of serine protease as a major allergen of Curvularia lunata
Authors: Gupta R. , Sharma V. , Sridhara S. , Singh B. P. , Arora N.
Published: December 2004

Background:  Several proteins from Curvularia lunata have been identified as important fungal allergens. It will be worthwhile to study the functional aspects of these allergens. The present study aimed at purifying a major allergen and determining its biological function.

Methods:  Concanavalin A and Superdex 75 were used to purify Cur l 1 major allergen from C. lunata. Cur l 1 activity was determined qualitatively and quantitatively. Serine protease inhibitors and specific substrate was used to determine the biological function of the protein.

Results:  Concanavalin A‐bound fraction showed five allergenic proteins, which on Superdex G‐75 purification gave a homogenous Cur l 1 protein. Cur l 1 showed IgE reactivity with 80% of the C. lunata hypersensitive patient's sera indicating it to be a major allergen. It showed protease activity on different substrates. Cur l 1's amino terminal sequence, GLTQKSAPWGLGADTIVAVELDSY, showed homology with the alkaline serine protease precursor. Phenylmethylsulfonylfluoride, pefabloc, aprotinin and leupeptin inhibited 70–80% enzymatic activity of Cur l 1 and no inhibition was observed with ethylenediaminetetraacetic acid (EDTA). A dose‐dependent hydrolysis of Nα‐benzoyl‐l‐arginine ethyl ester‐hydrochloride, a specific serine protease substrate was obtained with Cur l 1.

Conclusion:  A major glycoprotein allergen Cur l 1 was purified to homogeneity from C. lunata. Amino terminal sequence and biochemical assays identified it as a serine protease.
Monosodium benzoate hypersensitivity in subjects with persistent rhinitis
Authors: Pacor M. L. , Di Lorenzo G. , Martinelli N. , Mansueto P. , Rini G. B. , Corrocher R.
Published: December 2004

Background:  Very few data are available from the literature on whether nonatopic subjects affected by persistent rhinitis may show the appearance of objective symptoms of rhinitis after the ingestion of food additives such as tartrazine (E102), erythrosine (E127), monosodium benzoate (E211), p‐hydroxybenzoate (E218), sodium metabisulphite (E223), and monosodium glutamate (E620). It is still unclear whether the ingestion of food additive may cause, as well, a consensual reduction of nasal peak inspiratory flow (NPIFR). Therefore, we used a double‐blind placebo‐controlled (DBPC) study to evaluate this hypothesis.

Patients and methods:  Two hundred and twenty‐six consecutive patients (76 males and 150 females) aged 12–60 years (mean age 40.2 ± 16.3 years). After 1 month of an additive‐free diet regimen, an open challenge was carried out (food additive‐rich diet for 2 weeks). After this period, challenges were administered in a DBPC manner using the above‐mentioned substances under investigation.

Results:  Twenty of 226 subjects (8.8%) reported an improvement of the symptoms of rhinitis after additive‐free diet. More precisely, six of 226 (2.6%) were symptom‐free and 14 of 226 (6.2%) showed an improvement in their symptoms after an additive‐free diet. As far as the results for DBPC are concerned, 20 challenges with monosodium benzoate induced both objective (i.e. sneezing and rhinorrhoea) and subjective symptoms (nasal blockage and nasal itching) of rhinitis with reduction of NPIFR ≥20%, 45 challenges induced subjective symptoms of rhinitis (i.e. nasal blockage and nasal itching), without reduction of NPIFR ≥20% of the basal value, two with tartrazine, seven with erythrosine, 19 with monosodium benzoate, three with p‐hydroxybenzoate, six with sodium metabisulphite, and eight with monosodium glutamate, respectively.

Conclusions:  The observation that nonatopic persistent rhinitis may be caused by the frequent, probably daily, ingestion of small doses of a nontolerated substance is intriguing and suggests that at least some patients with ‘chronic vasomotor rhinitis’ may be intolerant to a particular food additive. Therefore, food additives can be considered triggers or aggravating factors, rather than aetiological factors.
The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract
Authors: Straumann A. , Simon H.‐U.
Published: December 2004

Eosinophils and the gastrointestinal tract interact in an intimate and enigmatic relationship. Under healthy conditions, the presence of eosinophils is limited almost exclusively to the digestive tract mucosa where they exert several effector and immunoregulatory functions. While their precise function in the gastrointestinal tract is not completely understood, it is likely that, together with different T cell subsets, eosinophils are involved in maintaining the immunologic homeostastis across the mucosal barrier under resting conditions. Eosinophils also play a role in several inflammatory conditions, such as intestinal infections, hypersensitivity reactions, primary eosinophilic inflammations and several other chronic intestinal disorders. Depending on the responsible trigger, their effects may be beneficial or detrimental. Here, we discuss the available information regarding the physiological and pathological functions of eosinophils within the gastrointestinal tract.
Monitoring the allergic inflammation
Authors: Venge P.
Published: December 2004

Individual symptoms of allergy such as asthma, dermatitis, rhinitis have many different underlying mechanisms. The detailed characterization of the inflammatory mechanisms underlying symptom development in the individual patient is important in order to optimally control treatment. Measurement of eosinophil cationic protein (ECP) in sputum or blood and eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) in urine may be used to read the involvement of the eosinophil granulocyte in the process. An important information as eosinophil dominated processes seem to be particularly sensitive to corticosteroid treatment. The possibilities to measure the involvement of other inflammatory cells exist today, but are only used to a small extent. The dream would be that every patient with an inflammatory disease is characterized with respect to the profile of involving cells and mediators. Such information would provide us with a unique understanding of the underlying mechanisms of the development of disease symptoms and the possibilities of treating these.
Clinical efficacy of sublingual and subcutaneous birch pollen allergen‐specific immunotherapy: a randomized, placebo‐controlled, double‐blind, double‐dummy study
Authors: Khinchi M. S. , Poulsen L. K. , Carat F. , André C. , Hansen A. B. , Malling H.‐J.
Published: December 2004

Background:  Both sublingual allergen‐specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.

Objective:  To investigate the clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with placebo and to evaluate the relative clinical efficacy in relation to systemic side‐effects.

Methods:  A 3‐year randomized, placebo‐controlled, double‐blind, double‐dummy study including 71 adult birch pollen hay fever patients treated for two consecutive years after a baseline year. Allocation to treatment groups was based on disease severity in the baseline season, gender and age.

Results:  Clinical efficacy was estimated in 58 patients completing the first treatment year by subtracting baseline data and by calculating the ratio first treatment season vs baseline. SLIT diminished the median disease severity to one‐half and SCIT to one‐third of placebo treatment. No statistical significant difference between the two groups was observed. Both for symptoms and medication scores actively treated patients showed statistically significant and clinical relevant efficacy compared with placebo. SLIT treatment only resulted in local mild side‐effects, while SCIT resulted in few serious systemic side‐effects.

Conclusion:  Based on the limited number of patients the clinical efficacy of SLIT was not statistically different from SCIT, and both treatments are clinically effective compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The lack of significant difference between the two treatments does not indicate equivalent efficacy, but to detect minor differences necessitates investigation of larger groups. Due to the advantageous safety profile SLIT may be favored.
The role of climate on the geographic variability of asthma, allergic rhinitis and respiratory symptoms: results from the Italian study of asthma in young adults
Authors: Zanolin M. E. , Pattaro C. , Corsico A. , Bugiani M. , Carrozzi L. , Casali L. , Dallari R. , Ferrari M. , Marinoni A. , Migliore E. , Olivieri M. , Pirina P. , Verlato G. , Villani S. , de Marco R. ,   ISAYA Study Group
Published: December 2004

Background:  Variations in the prevalence of respiratory symptoms according to geo‐climatic factors could provide important clues to the knowledge of the aetiology of asthma.

Methods:  Geo‐climatic variations in the prevalence of current asthma, allergic rhinitis and chronic cough, and phlegm were assessed on a random sample of 18 873 subjects (response rate = 72.7%) from different climatic regions of Italy. An ecological analysis, supported by robust statistical methods, was employed to investigate potential trends.

Results:  The prevalence of all symptoms was significantly heterogeneous throughout the peninsula. Only asthma‐like symptoms showed a north–south trend: the prevalence increased at a decreasing latitude [odds ratio (OR) varies from 0.92 to 0.96, P < 0.05], at a decreasing distance from the sea (OR: 0.90–0.93 for 30 km distance, P < 0.05), at higher annual mean temperatures (OR: 1.11–1.14, P < 0.05) and at smaller annual temperature ranges (OR: 0.94–0.95, P < 0.05). Of the geo‐climatic variables considered, temperature range had the greatest influence on most asthma‐like symptoms. No association was found between geo‐climatic variables and allergic rhinitis or chronic cough and phlegm.

Conclusions:  Asthma prevalence seems to be significantly affected by climate as asthma‐like symptoms were more common in central‐southern Italy, with a Mediterranean climate, than in areas with a continental climate (northern Italy).
Management of allergic rhinitis: a common part of practice in primary care clinics
Authors: Wang D.‐Y. , Chan A. , Smith J. D.
Published: December 2004

Background:  Allergic rhinitis (AR) is an extremely common disease worldwide and one of the top‐ten reasons for a visit to primary care clinics. This study aimed to investigate the understanding of current guidelines and concepts of management for AR among general practitioners (GPs) in Singapore.

Methods:  A postal questionnaire was designed to survey the dispensing practice and understanding of current guidelines in the management of AR among Singapore GPs.

Results:  Two hundred GPs completed the questionnaire. AR was estimated to be 10–40% of total patient visits in 50% of the primary care clinics surveyed. There was no significant difference in diagnosis and management of AR among GPs practicing solo, as a group or in polyclinics. The use of allergy tests (skin or in vitro tests) was <50%. Most physicians understood correctly the efficacy, side‐effects, and cost effectiveness of first and newer generation H1‐antihistamines and nasal glucocorticosteroids. However, first generation H1‐antihistamines and oral/nasal decongestants are commonly used to reduce the cost of medication and to achieve quick relief from nasal obstruction.

Conclusion:  Management of allergic rhinitis is common in primary care clinics. Quick symptomatic relief with low‐cost medications is a major concern for GPs in the management of AR, as it will affect a patient's compliance and perception of efficacy. However, inappropriate use of decongestants and other nonevidence‐based therapies should not be recommended. Implementing the current evidence‐based international guidelines for AR needs to be improved.