bluuebunny/crossref_metadata_2025 huggingface dataset:
Measles infection, measles vaccination and the effect of birth order in the aetiology of hay fever
Authors: Lewis  , Britton
Published: March 2003

Background

It has recently been suggested that measles infection may reduce the risk of atopy.

Objective

To study the independent effect of measles infection and measles vaccination on the occurrence of hay fever in a British national birth cohort.

Methods

In over 6000 children born in 1970, details of immunizations and childhood diseases were collected by parental interviews at ages 5, 10 and 16 years, and hay fever within the past year at age 16 years.

Results

In univariate analysis, hay fever was less common in those contracting measles infection than in those not infected (OR 0.86, 95% CI 0.76–0.96), and more common in those given measles vaccination than in those not vaccinated (OR 1.16, 95% CI 1.03–1.31). However, these effects were strongly confounded by birth order, which was closely associated with the likelihood of receiving measles vaccination and with the risk of hay fever. A strong interaction between the effects of measles vaccination and infection, and birth order was found, such that in those with many older sibling contacts, hay fever was significantly and independently reduced in relation to both measles infection and measles vaccination relative to those who were neither infected nor vaccinated.

Conclusions

Both measles infection and measles vaccination in childhood appear to reduce the risk of hay fever in children with multiple older sibling contacts. Differential exposure or response to the measles virus may explain the effect of birth order on the occurrence of allergic disease.
Histamine – a major role in allergy?
Authors: Bachert
Published: March 2003

Since its discovery in 1911, histamine has been recognized as a major mediator in allergic reactions and diseases, and today antihistamines remain important agents in the treatment of these conditions. In addition to its known effects on glands, vessels and sensory nerves, recent data have provided further evidence of histamine’s proinflammatory actions, which appear to be mediated mainly by H1 receptors. Thus, findings indicate that histamine is a crucial mediator in both the early and late‐phase reactions of an allergic response, playing important roles in cytokine release and in the adhesion process. Histamine has been shown to increase the adhesion of leucocytes to the endothelium and to stimulate production of IL‐6 and IL‐8 by endothelial cells. It also increases TNFα‐induced IL‐6 production and expression of adhesion molecules. These effects can be inhibited by H1 receptor antagonists. First‐generation antihistamines, though moderately effective, showed poor selectivity and caused sedation, due to their penetration of the blood–brain barrier, and other troublesome side‐effects. Second‐generation antihistamines such as ebastine have increased potency due to greater selectivity for histamine receptors, and improved tolerability due to lack of penetration of the blood–brain barrier. Recent studies have shown ebastine 10 mg daily to be effective, safe and well tolerated in the treatment of seasonal allergic rhinitis (SAR), with a rapid onset of action, symptom relief comparable to that seen with topical azelastine or oral loratadine 10 mg o.d., cetirizine 10 mg o.d. or terfenadine 60 mg b.i.d., and no significant side‐effects. Ebastine therefore offers a new option in the treatment of seasonal allergic rhinitis.
Role of tachykinin NK1 and NK2 receptors in allergen‐induced early and late asthmatic reactions, airway hyperresponsiveness, and airway inflammation in conscious, unrestrained guinea pigs
Authors: Schuiling M. , Zuidhof A. B. , Zaagsma J. , Meurs H.
Published: March 2003

Using a guinea pig model of allergic asthma, we investigated the effects of the inhaled, highly selective nonpeptide tachykinin NK1 and NK2 receptor antagonists SR 140333 and SR 48968, respectively, on allergen‐induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR) after these reactions, and infiltration of inflammatory cells in the airways. Both SR 140333 (100 nM, 3 min) and SR 48968 (100 nM, 3 min) had no effect on the severity of the EAR, while the NK2 receptor antagonist SR 48968, but not the NK1 receptor antagonist SR 140333, caused significant inhibition of the LAR. SR 140333 significantly reduced the allergen‐induced AHR to histamine, both after the EAR and the LAR. By contrast, SR 48968 did not affect the AHR after the EAR, but significantly attenuated the AHR after the LAR. Bronchoalveolar lavage studies performed after the LAR indicated that SR 140333 caused significant inhibition of allergen‐induced infiltration of eosinophils, neutrophils and lymphocytes, while SR 48968 attenuated the infiltration of neutrophils and lymphocytes, but not of eosinophils. Both NK receptor antagonists tended to reduce the accumulation of ciliated epithelial cells in the airways. These results indicate that NK1 and NK2 receptors are importantly, but differentially, involved in the development of allergen‐induced airways obstruction, AHR and infiltration of inflammatory cells in the airways. Therefore, both NK1 and NK2 receptor antagonists, or dual NK1 and NK2 antagonists, could be useful in the treatment of allergic asthma.
The bronchial epithelium as a key regulator of airway inflammation and remodelling in asthma
Authors: Holgate S. T. , Lackie P. M. , Davies D. E. , Roche W. R. , Walls A. F.
Published: March 2003

While asthma is an inflammatory disorder of the airways involving mediator release from mast cells and eosinophils and orchestrated by T cells, inflammation alone is insufficient to explain the chronic nature of the disease and its progression. Evidence is presented that the epithelium is fundamentally disordered in chronic asthma manifest by increased fragility, and an altered phenotype to one that secretes mucus, mediators, cytokines, chemokines and growth factors. Epithelial injury is mediated by exogenous factors such as air pollutants, viruses and allergens as well as by endogenous factors including the release of proteolytic enzymes from mast cells (tryptase, chymase) and eosinophils (MMP‐9). Following injury, the normal epithelium should respond with increased proliferation driven by ligands acting on epidermal growth factor (EGF) receptors or through transactivation of the receptor. The epithelial response to these stimuli in asthma appears to be impaired despite upregulation of CD44 capable of enhancing presentation of EGF ligands to epidermal growth factor receptors (EGFR). Because the epithelium is ‘held’ in this repair phenotype, it becomes a continuous source of proinflammatory products as well as growth factors that drive airway wall remodelling.
Effect of specific immunotherapy with house dust mite extract on the bronchial responsiveness of paediatric asthma patients
Authors: Gruber  , Eber  , Mileder  , Modl  , Weinhandl  , Zach
Published: March 2003

Background and objective

Allergic asthma is common in children, and house dust mite (HDM) is an important source of perennial allergens. Bronchial hyperresponsiveness is a functional hallmark of asthma. Specific immunotherapy (SIT) with HDM extracts were shown to decrease symptoms, but its effect on bronchial responsiveness, as measured by non‐pharmacological challenges, has not been evaluated.

Methods

Twenty‐six paediatric asthma patients allergic to HDM participated in this study. Fourteen patients received SIT with a HDM extract (Alavac, Bencard) for 2 years, and 12 served as controls. Bronchial responsiveness was assessed non‐pharmacologically by cold dry air challenge (CACh) before and 3, 6, 12 and 24 months after SIT, and 12 months after termination of SIT.

Results

After 24 months, the SIT group showed a statistically significant reduction of the mean CACh‐induced changes of both forced expiratory volume in one second (−21.8 ± 2.7% vs −13.7 ± 2.4%; P = 0.03) and maximal expiratory flow at 25% remaining vital capacity (−48.9 ± 4.9% vs −27.9 ± 6.2%; P = 0.01). In contrast, no significant changes of bronchial responsiveness were observed in the control group. In the SIT group more patients lost their bronchial hyperresponsiveness than in the control group (6/14 vs 1/12; P < 0.05). One year after terminating SIT, the treatment group showed a tendency towards returning bronchial hyperresponsiveness.

Conclusion

These results demonstrate that during 2 years of SIT there was a reduction of bronchial hyperresponsiveness in HDM‐allergic paediatric asthma patients.
A role for the hepatobiliary system in IgE‐mediated intestinal inflammation in the rat
Authors: Collins  , Leach  , Payne A. Mitchell  , Dai  , Jackson
Published: March 2003

Background

For many years the central focus of research into gastrointestinal hypersensitivity reactions has been the mast cell population of the intestinal lamina propria. Since bile is known to deliver immunological mediators to the gastrointestinal tract, the possibility arises that extra‐intestinal populations of mast cells may also contribute to IgE‐mediated intestinal damage.

Objectives

To characterize hepatic mast cells in the rat and to investigate the role of the hepatobiliary system in a model of IgE‐mediated reactivity to dietary antigen.

Methods

Wistar rats were passively sensitized with monoclonal antidinitrophenyl (DNP) IgE antibodies, and were later challenged orogastrically with DNP‐HSA. Additional animals were sensitized, then bile duct‐cannulated prior to antigen challenge. At various time points, liver and intestinal samples were collected for histological examination, and bile was collected and assayed for histamine and TNFα.

Results

Hepatic mast cells display a mucosal mast cell‐like phenotype, and are closely associated with the vessels of the portal triads. Orogastric antigen challenge led to a rapid and significant decline (P < 0.0001) in detectable mast cells as a result of anaphylactic degranulation. The median number of granulated mast cells associated with each portal triad in liver sections declined from six per portal triad to one per portal triad post‐antigen challenge. After 15 min, biliary histamine concentrations rose above background levels (P < 0.01). TNFα was also detectable in the majority (4/6) of bile samples within 15 min of challenge. Histological examination of the gastrointestinal mucosa revealed disruption to the villous epithelium ranging from oedematous changes to gross destruction. Such damage was not seen in animals in which bile had been externally drained.

Conclusion

The data indicate that biliary products are major contributors to the gastrointestinal damage arising from IgE‐mediated hypersensitivity reactions in the rat, and such hypersensitivity reactions may involve a population of mast cells which reside in the liver.
Comparison of cytokine secretion profiles provoked in mice by glutaraldehyde and formaldehyde
Authors: DEARMAN  , BASKETTER  , EVANS  , KIMBER
Published: March 2003

Background

Glutaraldehyde and formaldehyde are commonly used sterilizing agents that are known skin sensitizers. There is some controversy, however, regarding their capacity to cause respiratory allergy. The authors have demonstrated previously that topical exposure of mice to chemical contact allergens such as 2,4‐dinitrochlorobenzene (DNCB) or respiratory allergens such as trimellitic anhydride (TMA) induces characteristic cytokine secretion profiles consistent with the selective activation of T helper 1 (TH1)‐ and TH2‐type cells, respectively.

Objective

To investigate the quality of immune response provoked following topical exposure of mice to these materials.

Methods

BALB/c strain mice were exposed topically to 50% formaldehyde or to various concentrations of glutaraldehyde in acetone. Control animals were treated concurrently with the reference contact allergen DNCB (1% in acetone:olive oil [AOO]) or with the reference respiratory sensitizer TMA (10% in AOO). Thirteen days after the initiation of exposure, draining lymph node cells (LNCs) were cultured for 12–120 h and cytokine content of supernatants analysed by cytokine‐specific enzyme‐linked immunosorbent assay.

Results

DNCB‐α and formaldehyde‐activated LNCs produced high levels of the TH1‐type cytokine interferon γ, but little of the TH2‐type products interleukins 4 and 10. TMA‐ and glutaraldehyde‐stimulated LNCs displayed the converse TH2‐type pattern of cytokine expression.

Conclusions

These data are consistent with glutaraldehyde, but not formaldehyde, having significant potential to cause allergic sensitization of the respiratory tract.
Norm values for eosinophil cationic protein in nasal secretions: influence of specimen collection
Authors: Klimek  , Rasp
Published: March 2003

Background

Eosinophil granulocytes play an important role in allergic inflammation of the nasal mucosa. Eosinophil cationic protein (ECP) is a specific eosinophil granule protein released upon activation of these cells. ECP concentration in nasal secretions has been demonstrated to be a good marker for the activity of eosinophilic nasal mucosal inflammation. The clinical use of such a marker requires defined values which are regarded as pathological or within normal range. In analyses of nasal secretion samples, the sampling method has an important influence on the data obtained.

Objective

We investigated ECP levels in nasal secretions (NS) of healthy volunteers obtained by seven different methods of sample collection to define norm values and to evaluate the clinical use of the different methods.

Methods

A total of 839 healthy individuals were evaluated using blowing the nose (Bl: n = 82), suction (Suc: n = 69), Okuda microsuction technique (MSuc: n = 93), absorbent cotton wool samplers (CWS: n = 156), rubber‐foam samplers (RFS: n = 193), nasal lavage (Lav: n = 112) and nasal spray washing (NSW: n = 134).

Results

Missing values occurred in more than 60% in Bl, Suc and MSuc, so that no norm range was defined for these methods. Norm range for ECP in NS was 5–46 ng/mL for CWS, 7–41 ng/mL for RFS, 4–51 ng/mL for NSW, and 3–31 ng/mL for Lav.

Conclusions

When comparing seven different methods used in this study to collect nasal secretions and determine ECP levels, the method based upon absorption or nasal washing was the best.
Sequence polymorphism of the group 1 allergen of Bermuda grass pollen
Authors: CHANG  , PENG  , LEE  , CHEN  , CHUA  , TSAI  , CHI  , HAN
Published: March 2003

Background

Cyn d 1, the major allergen of Bermuda grass pollen, consists of a number of isoforms.

Objective

To examine the extent of sequence variation of Cyn d 1 isoforms at the molecular level.

Methods

A Bermuda grass pollen λZAP II cDNA expression library was immunoscreened with anti‐Cyn d 1 monoclonal antibodies. The reactive clones were isolated, subcloned into Escherichia coli, and sequenced. Some of them were expressed in the yeast Pichia pastoris to obtain recombinant Cyn d 1 proteins.

Results

Ten cDNA clones were obtained, all these clones encode the full length of Cyn d 1 protein. Their deduced mature proteins can be grouped into: the long ones with 246 amino acids, and the short ones with 244 amino acids. The last two amino acids (AG) of the long Cyn d 1 are deleted in the short Cyn d 1. The remaining amino acid sequences share more than 98% identity; a total of nine amino acid variations were observed. Two recombinant Cyn d 1 proteins (rCyn d 3–2 and rCyn d 5–4) with three amino acid substitutions showed differential IgE‐binding profiles.

Conclusion

The present study extended our understanding of the primary structure of isoforms of Cyn d 1.
Antibiotic use in early childhood and the development of asthma
Authors: WICKENS  , PEARCE  , CRANE  , BEASLEY
Published: March 2003

Background and objective:

Recent investigations have focused on the role of infections in infancy in promoting or protecting against the subsequent development of asthma. A related hypothesis concerns the possible role of medical responses to infections, including the widespread use of antibiotics. We chose children at Rudolf Steiner schools to test this latter hypothesis because a significant proportion of parents rejects the use of conventional treatments, including antibiotics.

Methods

Seventy‐five per cent (n = 456) of parents of children aged 5–10 years attending Rudolf Steiner schools throughout New Zealand completed questionnaires which included questions on the use of antibiotics and a history of asthma and wheeze in their children.

Results

After controlling for potential confounders, antibiotic use was significantly associated with having a history of asthma (OR = 2.74, 95% CI: 1.10–6.85) or wheeze (OR = 1.86, 95% CI: 1.06–3.26) but not with current wheeze (OR = 1.08, 95% CI: 0.54–2‐16). The adjusted odds ratio for asthma was 4.05 (95% CI: 1.55–10.59) if antibiotics were used in the first year of life and 1.64 (95% CI: 0.60–4.46) if antibiotics had been used only after the first year of life when compared with children who had never used antibiotics. The number of courses of antibiotics during the first year of life was also associated with increased odds ratios for asthma: 2.27 (95% CI: 1.14–4.51) for one to two courses and 4.02 (95% CI: 1.57–10.31) for three or more courses when compared with no antibiotic use in the first year of life. Although not significant, the association of antibiotics and hay fever (OR = 1.99 [95% CI: 0.93–4.26]) was of a similar strength to the association of antibiotics with a history of wheeze. Antibiotics were not significantly associated with eczema (OR = 1.23 [95% CI: 0.71–2.13]).

Conclusion

Antibiotic use in infancy may be associated with an increased risk of developing asthma. Further study is required to determine the reasons for this association.
Inverse correlation of domestic exposure to Dermatophagoides pteronyssinus antigen patch test reactivity in patients with atopic dermatitis
Authors: GUTGESELL  , SEUBERT  , JUNGHANS  , NEUMANN CH.
Published: March 2003

Background

In recent years considerable interest in the pathogenetic role of aeroallergens exacerbating atopic dermatitis (AD) has emerged. The ‘atopy patch test’ with aeroallergens was introduced by Platts‐Mills et al. as an experimental model and as a diagnostic tool. However, its relevance for the clinical manifestation of AD is still not clear.

Objective

We asked whether there is a relationship between the individual antigen exposure to the major allergen of Dermatophagoides pteronyssinus (Der p 1) and the immunological markers of sensitization to Der p 1 or the clinical severity of AD.

Methods

We investigated 92 patients with moderate to severe AD. For clinical evaluation the SCORAD severity score was used. Patch tests were performed with purified Der p 1. Specific IgE was measured by a commercial assay. Der p 1 exposure was quantified in a sample of the patient's mattress dust by using a commercial ELISA.

Results

No correlation between SCORAD, Der p 1 exposure and RAST could be established. However, there was an unexpected significant inverse correlation between the quantity of mite antigen in the mattress dust and patch test reactivity. Patients with a high antigen load (> 25 μg/g) mostly had a negative patch test. Also, when Der p 1 was correlated to the mattress area (m2) in this group all patch tests were negative. A possible explanation could be that continuous exposure of the skin to house dust mite allergen Der p 1 may induce a down‐regulation of the skin immune system of patients with AD.

Conclusion

Although the mechanism of this phenomenon is presently unknown, our study shows that a positive allergen patch test alone should not be an indication to undertake allergen exclusion measures in AD patients.
The intestinal microflora in allergic Estonian and Swedish 2‐year‐old children
Authors: Björkstén  , Naaber  , Sepp  , Mikelsaar
Published: March 2003

Background

The prevalence of allergic diseases seems to have increased particularly over the past 35–40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1‐ and TH2‐like immunity.

Aims

To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy.

Methods

From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2‐year‐old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10−2–10−9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count.

Results

The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro‐organisms (P < 0.05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0.05) and bacteroides lower (P < 0.05) than in the nonallergic children.

Conclusions

Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.
Association studies on β2‐adrenoceptor polymorphisms and enhanced IgE responsiveness in an atopic population
Authors: DEICHMANN  , SCHMIDT  , HEINZMANN  , KRUSE  , FORSTER  , KUEHR
Published: March 2003

The β2 adrenergic receptor 2 represents a cell surface receptor responsible for the binding of endogenous catecholamines and their exogenously administered agonists and antagonists, mediating their effects to the interior of the cell. On the basis of these functions, the observed association of two of its polymorphisms, Gly16 and Gln27, with nocturnal‐ and steroid‐dependent asthma has been discussed. It has recently been suggested that Gln27 contributes to IgE variability in families with asthma.

The aim of this study was to investigate possible influences of the polymorphisms Arg16Gly and Glu27Gln on IgE levels in families recruited through an atopic index case without regard to the presence of clinical symptoms.

We employed linkage analysis in affected sibpairs characterized by elevated total IgE concentrations or sensitization to common inhalant allergens. Furthermore, we tested 258 children for association of any of the polymorphisms with enhanced IgE responsiveness.

We could find neither linkage at the locus 5q31 nor significant association of the polymorphisms with elevated total IgE concentrations or specific sensitization.

We conclude from our data that the polymorphisms Gln27Glu and Arg16Gly of the β2‐adrenergic receptor do not play a significant role in the pathogenesis of enhanced IgE responsiveness in an atopic population in general.
On early sensitization to allergens and development of respiratory symptoms
Authors: SHERRILL  , STEIN  , KURZIUS‐SPENCER  , MARTINEZ
Published: March 2003

Background

Various studies have suggested that a sequence of events occurring in childhood may affect the development of asthma in susceptible individuals. We have investigated whether early childhood sensitization to aeroallergens is an important risk factor in the later development of asthma symptoms.

Objective and methods

In this study we examine this issue in children enrolled in the Tucson epidemiology study of obstructive airways disease, who had at least two allergen skin tests, one before and one after 8 years of age. Respiratory symptom data were available from 12 survey questionnaires, spanning a period of 20 years. During the first, sixth, seventh and eleventh surveys, skin tests were performed with commercially available allergens.

Conclusion

As compared with children who were sensitized after 8 years of age, children over 8 years who were sensitized to any allergen before age 8 years were significantly more likely to report shortness of breath with wheeze (SOBWZ), wheeze apart from colds or wheeze most days (OR = 4.1 SOBWZ; OR = 3.88 WZ apart from colds; and OR = 2.83 WZ most days). Children who were sensitized after 8 years were no more likely to have the symptoms described above than children who were never found to be sensitized. Based on these results we conclude that early allergic sensitization is a significant risk factor for later development of wheezy symptoms, where as late sensitization is not.
Prevalence and residential determinants of fungi within homes in Melbourne, Australia
Authors: Dharmage  , Bailey  , Raven  , Mitakakis  , Thien  , Forbes  , Guest  , Abramson  , Walters
Published: March 2003

Background

Recent epidemiological studies suggest that the adverse respiratory health effects caused by the inhalation of fungal propagules are substantial. Knowledge of the prevalence and environmental determinants of indoor fungal levels is essential in designing effective avoidance measures.

Aim

To investigate the prevalence of fungi and the influence of residential characteristics on levels of fungi within homes in Melbourne, Australia.

Methods

Floor dust and air samples were collected from bedrooms in 485 houses over 1 year. The dust was analysed for ergosterol, a marker of cumulative fungal biomass exposure. Total and genera‐specific fungal propagules were identified in air samples. Details of the relevant residential characteristics were documented using a questionnaire. Independent predictors (P < 0.05) of ergosterol and total fungal propagules were identified by multiple linear regression.

Results

Fifty‐five percent of the houses had viable fungal propagules exceeding 500 CFU/m3. Cladosporium and Penicillium were identified as the most prevalent and abundant fungal genera in indoor air. The median ergosterol level in bedroom floor was 3.8 μg/g of dust. Multivariate analysis showed that total fungal propagules in indoor air were lower in bedrooms with a ceiling fan, without visible mould, and those that were more frequently vacuumed, had a solid fuel fire, had windows closed at the time of the sampling or lacked pets. The presence of more than one cat had the greatest effect on total fungal propagules. Ergosterol levels were significantly lower in homes without old fitted carpets, visible mould or pets and those with frequent airing and regular use of an extractor fan in the kitchen. Old wall‐to‐wall carpets had the greatest effect on ergosterol.

Conclusions

High indoor fungal exposures were associated with infrequent ventilation or vacuuming, presence of pets, visible mould and old carpets.
Debilitating beliefs, emotional distress and quality of life in patients given immunotherapy for insect sting allergy
Authors: Confino‐Cohen R. , Melamed S. , Goldberg A.
Published: March 2003

Background

Patients who receive immunotherapy for systemic reaction to insect stings are told that once they reach maintenance dose they are almost 100% protected against future systemic reactions. However, we have observed that some patients continued to perceive themselves as highly debilitated by the allergy, and this perception had a significant impact on their quality of life.

Objective

To validate this clinical observation and to explore possible reasons for such an undesired psychological reaction.

Methods

The study group consisted of 97 patients who regularly attended an allergy outpatient clinic for venom immunotherapy, and who had been under medical surveillance for up to 8 years. They completed a questionnaire measuring debilitating beliefs, preoccupation with the systemic reaction event, emotional distress, perceived restriction by allergy, and perceived quality of life. We also recorded the duration of immunotherapy, physician‐graded severity of the systemic reaction and the frequency at which immunotherapy was administered. The reference group consisted of patients who had not reached maintenance dose and were still at risk of recurrent systemic reactions.

Results

As many as one‐third of the patients held self‐imposed debilitating beliefs, were preoccupied with the systemic reaction event, perceived a moderate to severe impairment in their quality of life, and manifested symptoms of emotional distress. These psychological responses did not correlate with the immunotherapy dosage that had been reached. Patients who reached a full maintenance dose were doing no better psychologically than those in the reference group. Moreover, the length of time on immunotherapy did not result in attenuation of the psychological responses.

Conclusion

This study demonstrates for the first time, the long‐lasting psychological impact of a threatening systemic reaction. It suggests a need for intervention aimed at dispelling patients' unfounded and persisting debilitating beliefs.
Neutrophil activation following TDI bronchial challenges to the airway secretion from subjects with TDI‐induced asthma
Authors: Park  , Jung  , Kim  , Nahm  , Kang
Published: March 2003

Background

The immunopathological mechanism for occupational asthma induced by toluene diisocyanate (TDI) remains to be further clarified. There have been few reports suggesting involvement of neutrophils in inducing bronchoconstriction after TDI inhalation.

Objectives

To further understand the role of neutrophils in the pathogenesis of TDI‐induced asthma.

Materials and methods

Eight TDI‐induced asthmatic subjects were classified as group I, and five exposed workers who had complained of work‐related symptoms and worked in the same workplace, but showed negative bronchial challenges were enrolled as controls (group II). Serum neutrophil chemotactic activity during TDI bronchial challenge test was measured by the Boyden chamber method. Induced sputum was collected before and after the TDI bronchial challenge test. The myeloperoxidase (MPO) and interleukin (IL) ‐8 levels in the sputum were measured using RIA and ELISA.

Result

Serum neutrophil chemotactic activity significantly increased at 10 min (P = 0.01), then decreased at 60 min (P = 0.02) and remained unchanged for up to 420 min (P = 0.07) in group I subjects, while no significant changes were found in group II subjects (P > 0.05). MPO and IL‐8 were abundantly present in the sputum of all the TDI‐induced asthmatic subjects and they increased significantly at 420 min after the bronchial challenges (P = 0.02, P = 0.03, respectively), while no significant changes were noted in group II subjects (P > 0.05).

Conclusion

These findings support the view that activated neutrophils may contribute to bronchoconstriction induced by TDI which may be associated with IL‐8 release.
Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity
Authors: Taglialatela M. , Castaldo P. , Pannaccione A. , Giorgio G. , Genovese A. , Marone G. , Annunziato L.
Published: March 2003

Despite the enormous success of second generation antihistamines, in the mid‐1980s, about 10 years after their introduction in the market, several reports appeared in the literature indicating the rare occurrence of a form of polymorphic ventricular dysrhythmia, the ‘torsade de pointes’, after the administration of astemizole or terfenadine. This cardiac side‐effect has been interpreted as a consequence of the interference of these drugs with cardiac K+ channels involved in action potential repolarization, and in particular with the IKr component of the cardiac repolarizing current. As the K+ channels encoded by the human ether‐a‐gogo‐related gene (HERG) seem to represent the molecular basis of IKr, this cardiac K+ channel was soon recognized as a primary target for second generation antihistamine‐induced proarrhythmic effects. In fact, both terfenadine and astemizole have been shown to block HERG K+ channels in a concentration range similar to that found in the plasma of subjects with cardiotoxic manifestations. However, no correlation can be found between the ability to prolong the cardiac action potential duration and the H1‐antagonistic activity by several antihistamines, suggesting that HERG blockade and cardiotoxic potential are not class properties of second generation antihistamines. In fact, other molecules such as cetirizine, loratadine, acrivastine, and fexofenadine seem to lack both cardiotoxic potential and HERG‐blocking ability at therapeutically relevant concentrations. The marked heterogeneity displayed by second generation antihistamines in their ability to prolong the cardiac action potential duration and to block HERG K+ channels might be of considerable therapeutical significance for those patients at risk of developing cardiac dysrhythmias and in need of therapy with H1‐receptor blockers; it also emphasizes the importance of an evaluation of the possible blockade of HERG K+ channels during the early developmental phases of novel compounds belonging to this therapeutical class.
A review of the cardiac systemic side‐effects of antihistamines: ebastine
Authors: Moss A. J. , Chaikin P. , Garcia J. D. , Gillen M. , Roberts D. J. , Morganroth J.
Published: March 2003

The cardiac safety of ebastine, a long‐acting, non‐sedating antihistamine, has been thoroughly assessed in phase I–III clinical studies. Ebastine alone at the recommended doses of 10 mg and 20 mg has no clinically relevant effect on QTc interval in adults and in special patient populations (elderly, children or subjects with hepatic or renal impairment). Ebastine administered at 60 and 100 mg/day (3–5 times the maximum recommended dose) for 1 week had statistically significantly smaller effects (3.7 and 10.3 msec, respectively) on the QTc interval than terfenadine (18 msec) at three times the recommended dose (360 mg/day). The mean QTc interval prolongation observed with ebastine 100 mg/day was small and not clinically meaningful, although the results were statistically significant vs. placebo. The effect of ebastine 60 mg/day was not statistically different from placebo. Steady‐state drug interaction studies demonstrated that the co‐administration of ebastine 20 mg with ketoconazole or erythromycin produced significant increases in systemic exposure for ebastine, which were accompanied by small increases in QTc (approximately 10 msec above ketoconazole or erythromycin alone). Results from individual studies suggest that, when coadministered with ketoconazole, ebastine produces similar changes in QTc interval measurements compared to loratadine and cetirizine. Pooled data from clinical efficacy trials of ebastine 1–30 mg/day administered for 2–3 weeks showed no clinically relevant cardiac effects as assessed by serial electrocardiographs and Holter monitoring. The overall cardiac safety profile based on currently available information suggests that ebastine, like loratadine and cetirizine, has a lower potential for causing adverse cardiovascular effects than terfenadine.
The role of mast cells and basophils in inflammation
Authors: Holgate
Published: March 2003

Mast cells are positioned in the asthmatic airways so that they are able to respond to the inhaled environment. During active disease, the cells are primed to secrete an array of preformed and newly generated inflammatory mediators including histamine, neutral proteases and heparin sulphate, prostaglandins and cysteinyl leukotrienes as well as an array of cytokines and chemokines that are involved in leucocyte recruitment and activation. These cells are a potent source of mediators in both allergen‐ and exercise‐induced asthma and possibly in asthma provoked by other stimuli such as adenosine and inhaled air pollutants. The important role played by mast cells in maintaining airway dysfunction in asthma is underpinned by the efficacy of mediator inhibitors, such as those interfering with the release or action of the leukotrienes, agents that inhibit mast cell activation such as sodium cromoglycate and the recently studied E‐20 humanized monoclonal antibody that binds to and removes IgE. The recent discovery of novel inhibitory pathways involving inhibitory motifs (ITIMS) on critical cell surface signalling molecules has opened up new possibilities for preventing mast cell activation. Future research will focus on more effective ways for inhibiting the mast cell's contribution to asthma and understanding what role this unique cell has in the pathogenesis of airway wall remodelling.
Development and validation of the Mini Rhinoconjunctivitis Quality of Life Questionnaire
Authors: Juniper  , Thompson  , Ferrie  , Roberts
Published: March 2003

Background

The 28‐item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) has strong measurement properties but for large clinical trials, surveys and practice monitoring, where high efficiency is important, a shorter questionnaire is needed.

Objective

To develop and validate an abbreviated version of the RQLQ.

Methods

Using five RQLQ databases, items with high item–item correlations were combined and then the highest scoring items were selected for the MiniRQLQ (14 questions). There are five domains: activity limitations (standardized), practical problems and nose symptoms, eye symptoms and other symptoms. The MiniRQLQ, which is self‐administered, was tested in a 5‐week observational study in 100 adults with symptomatic rhinoconjunctivitis. Patients completed the MiniRQLQ, the RQLQ, and other measures of health status at baseline, 1 and 5 weeks.

Results

In patients whose rhinoconjunctivitis was stable between clinic visits, reliability (reproducibility and ability to discriminate between patients of different impairment) was very acceptable for the MiniRQLQ (ICC = 0.93) but not quite as good as for the RQLQ (ICC = 0.97). Responsiveness to change in clinical status was better with the MiniRQLQ than the RQLQ (P = 0.044). Construct validity (correlation with other indices of health status) was strong for both the MiniRQLQ and the RQLQ. Concordance between the two instruments was high (ICC = 0.87).

Conclusions

The MiniRQLQ has strong measurement properties and measures the same construct as the original RQLQ. The choice of questionnaire should depend on the task at hand.
Infant feeding patterns affect the subsequent immunological features in cow's milk allergy
Authors: Saarinen  , Savilahti
Published: March 2003

Background

The first exposure to food antigens provokes an immune reaction in an infant, its type depending on the quantity and frequency of doses and the age at introduction, and also being influenced by genetic factors. Most infants develop tolerance to food antigens, but in a small minority they provoke adverse symptoms.

Objective

To study the effects of breast and formula feeding and other environmental and genetic factors on the subsequent type of cow's milk allergy classified by the presence or absence of immunoglobulin (Ig) E antibodies to cow's milk.

Methods

A cohort of 6209 infants was followed prospectively from birth for symptoms of cow's milk allergy. The infant‐feeding regimen was recorded at the maternity hospital and at home. At a mean age of 6.7 months, a total of 118 infants (1.9%) reacted adversely to a challenge with cow's milk. Before the challenge, the response to a skin‐prick test with cow's milk and serum IgE cow's milk antibodies was measured.

Results

At challenge, 75 (64%) infants showed IgE‐positive reactions to cow's milk, their most common symptom being acute‐onset urticaria. Significant risk factors for the presence of IgE cow's milk antibodies in allergic infants were long breast‐feeding (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.6–9.8), exposure to cow's milk at the maternity hospital (OR 3.5, 95% CI 1.2–10.1) and breast‐feeding during the first 2 months at home either exclusively (OR 5.1, 95% CI 1.6–16.4) or combined with infrequent exposure to small amounts of cow's milk (OR 5.7, 95% CI 1.5–21.6). Fifty infants had their first adverse symptoms during exclusive breast‐feeding, and 32 infants were sensitized during exclusive breast‐feeding. Most of the infants in both cases were IgE‐positive: 37 and 23, respectively.

Conclusions

In infants who are prone to developing cow's milk allergy, prolonged breast‐feeding exclusively or combined with infrequent exposure to small amounts of cow's milk during the first 2 months of life induces development of IgE‐mediated response to cow's milk.
HLA DPB1*0201 allele is negatively associated with immunoglobulin E responsiveness specific for house dust mite allergens in Taiwan
Authors: Hu  , Hsu  , Lin  , Hsieh  , Chua
Published: March 2003

Background

House dust mite (HDM) Dermatophagoides pteronyssinus is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p 1, Der p 2 and Der p 5) to detect allergen‐specific immunoglobulin (Ig) E responsiveness among a large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM.

Objective

This study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, D. pteronyssinus.

Methods

Two hundred and forty‐eight subjects were selected for HLA association study. Plasma HDM allergen (Der p 1, Der p 2, Der p 5) ‐specific IgE and Der p 2‐specific IgG antibodies were detected by ELISA, while HLA class II ‐DRB1, ‐DQA1, ‐DQB1, ‐DPB1 genetic polymorphism was determined by polymerase chain reaction/sequence‐specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergen‐specific IgE and IgG antibodies were performed.

Results

There was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM‐specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p 5‐specific IgE responsiveness. However, we found that HLA‐DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p 5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p 1 and Der p 5. There was a strong negative association between the HLA‐DPB1*0201 allele with IgE responsiveness to Der p 1 (OR: 0.30, P ≤ 0.0001, P ≤ 0.0007, Pc ≤ 0.010).

Conclusion

We clearly observed the association between HLA DPB1 alleles and specific IgE responsiveness to HDM major allergens. The molecular mechanism of HLA‐DPB1*0201 involvement in protecting subjects from HDM‐specific IgE responsiveness awaits further investigation.
Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker
Authors: Broeckaert  , Bernard
Published: March 2003

Clara cell protein (CC16) is a 15.8‐kDa homodimeric protein secreted in large amounts in airways by the non‐ciliated bronchiolar Clara cells. This protein increasingly appears to protect the respiratory tract against oxidative stress and inflammation. In vitro, CC16 has been shown to modulate the production and/or the activity of various mediators of the inflammatory response including PLA2, interferon‐γ and tumour necrosis factor‐α. CC16 has also been found to inhibit fibroblast migration or to bind various endogenous or exogenous substances such as polychlorobiphenyls (PCBs). This protective role is confirmed by studies on transgenic mice, showing that CC16 deficiency is associated with an increased susceptibility of the lung to viral infections and oxidative stress. In humans, a polymorphism of the CC16 gene, localized to a region linked to airway diseases, has recently been discovered in association with an increased risk of developing childhood asthma. Finally, CC16 also presents a major interest as a peripheral marker for assessing the integrity of the lung epithelium. The determination of CC16 in serum is a new non‐invasive test to detect Clara cell damage or an increased epithelial permeability in various acute and chronic lung disorders.
Effects of luteolin, quercetin and baicalein on immunoglobulin E‐mediated mediator release from human cultured mast cells
Authors: Kimata  , Shichijo  , Miura  , Serizawa  , Inagaki  , Nagai
Published: March 2003

Background

Flavonoids have a variety of activities including anti‐allergic activities, and are known to inhibit histamine release from human basophils and murine mast cells.

Objective

The effects of luteolin, a flavone, on the immunoglobulin (Ig) E‐mediated allergic mediator release from human cultured mast cells (HCMCs) were investigated and compared with those of baicalein and quercetin.

Methods

HCMCs were sensitized with IgE, and then treated with flavonoids before challenge with antihuman IgE. The amount of released mediators was determined as was mobilization of intracellular Ca2+ concentration, protein kinase C (PKC) translocation and phosphorylation of intracellular proteins were detected after anti‐IgE stimulation.

Results

Luteolin, baicalein and quercetin inhibited the release of histamine, leukotrienes (LTs), prostaglandin D2 (PGD2), and granulocyte macrophage‐colony stimulating factor (GM‐CSF) from HCMC in a concentration‐dependent manner. Additionally, the three flavonoids inhibited A23187‐induced histamine release. As concerns Ca2+ signalling, luteolin and quercetin inhibited Ca2+ influx strongly, although baicalein did slightly. With regard to PKC signalling, luteolin and quercetin inhibited PKC translocation and PKC activity strongly, although baicalein did slightly. The suppression of Ca2+ and PKC signallings might contribute to the inhibition of mediator release. The activation of extracellular signal‐regulated kinases (ERKs) and c‐Jun NH2‐terminal kinase (JNK), that were activated just before the release of LTs and PGD2 and GM‐CSF mRNA expression in IgE‐mediated signal transduction events, were clearly suppressed by luteolin and quercetin. In contrast, the flavonoids did not affect the activation of p38 mitogen‐activated protein kinase (p38 MAPK) pathway.

Conclusion

These results indicate that luteolin is a potent inhibitor of human mast cell activation through the inhibition of Ca2+ influx and PKC activation.