bluuebunny/crossref_metadata_2025 huggingface dataset:
Fel d 1 and Can f 1 in settled dust and airborne Fel d 1 in allergen avoidance day‐care centres for atopic children in relation to number of pet‐owners, ventilation and general cleaning
Authors: WICKMAN  , EGMAR  , EMENIUS  , ALMQVIST  , BERGLIND  , LARSSON  , VAN HAGE‐HAMSTEN
Published: March 2003

Background

Special day‐care centres for atopic children have been established in Sweden. Objective To study concentrations of cat (Fel d 1) and dog (Can f 1) allergens in settled dust and airborne cat allergen in day‐care centres in relation to pet ownership among children and staff, ventilation and general cleaning. Methods Twelve allergen avoidanceday‐care centres and 22 conventional day‐care centres were included in the study. Settled dust was collected and analysed with ELISA. Airborne cat allergen levels were measured in eight allergen avoidance and seven conventional centres with a personal air sampler and analysed with an amplified ELISA. Air change rate per hour (ACH) was measured. A questionnaire which focused on keeping of cat and dog among staff and children and frequency of general cleaning was used. Results In the allergen avoidance day‐care centres neither children nor staff reported ownership of cats or dogs, compared with 21/22 of the conventional centres in which children and staff kept furred animals. Fel d 1 and Can f 1 were found in settled dust in all day‐care centres. In the allergen avoidance compared with the conventional centres the concentrations of Fel d 1 and Can f 1 were lower, Fel d 1: median 0.64 μg/g vs 5.45 μg/g and Can f 1: 0.39 μg/g vs 2.51, both P < 0.001, and airborne Fel d 1 was also lower in the allergen avoidance centres compared with the control centres, 1.51 ng/m3 vs 15.8 ng/m3, P = 0.002. A correlation was found between airborne and settled Fel d 1, rs = 0.75, P < 0.001. Furthermore, a correlation was found between increased ACH and decreased levels of Fel d 1 in the air in the day‐care centres with no cat‐owners, rs = – 0.86, P = 0.007. No relation was found between levels of cat or dog allergen and amount of general cleaning. Conclusion Not keeping pets seems to reduce children’s exposure to pet‐allergen in their ‘working environment’. Additionally, appropriate ventilation seems to reduce Fel d 1 in the air in day‐care centres.
Mast cell tryptase as a mediator of hyperresponsiveness in human isolated bronchi
Authors: BERGER  , COMPTON  , MOLIMARD  , WALLS  , N'GUYEN  , MARTHAN  , TUNON‐DE‐LARA
Published: March 2003

Background

Although the role of mediators and cytokines produced by mast cells is well established in asthmatic bronchial inflammation, the contribution of mast cell‐derived proteases to the development of hyperresponsiveness remains unclear. There have been reports indicating that tryptase alters the mechanical activity of animal airway smooth muscle or spontaneously sensitized human isolated airways.

Objective

The aim of this study was to analyse the effect of purified mast cell tryptase on non‐sensitized human isolated bronchi.

Methods

Both central and peripheral bronchi, dissected from lung specimens obtained at thoracotomy, were studied in terms of both mechanical activity i.e. isometric contraction in response to a variety of agonists and distribution of inflammatory cells i.e. immunohistochemistry.

Results

In both proximal and distal bronchi, the reactivity to histamine was significantly increased by a previous incubation in the presence of 1 μg/mL of tryptase (increase in maximal force, ΔFmax was 12.1 ± 3.8%, and 8.8 ± 3.1%, respectively). This effect of tryptase on histamine‐induced contraction was completely abrogated in the presence of the protease inhibitor benzamidine (100 μmol/L). Histological examination of specimens exposed to tryptase demonstrated an increase in mast cell number within the subepithelial tissue whereas mast cell numbers in the epithelial layer concomittently decreased.

Conclusion

These results indicate that human mast cell tryptase alters the contractile response of non‐sensitized human isolated bronchi and that this alteration is accompanied by a change in the mast cell distribution within the airway wall.
Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo‐oxygenase‐2 in cultured human mast cells
Authors: Obata  , Nagakura  , Masaki  , Maekawa  , Yamashita
Published: March 2003

Background

Eicosapentaenoic acid (EPA) is catalysed by cyclo‐oxygenase (COX), as is arachidonic acid, and is a competitive inhibitor of arachidonate metabolism.

Objectives

We examined the effect of EPA on prostaglandin (PG) D2 generation in the cultured human mast cells with IgE‐anti‐IgE challenge incubation.

Methods

Cultured human mast cells were incubated with EPA (1 μmol/L) for 20 h, then challenged with anti‐IgE incubation after treatment with IgE. At the same time, COX inhibitors were tested to identify COX‐1 and COX‐2 activity. PGD2 synthetic activity was also assayed in a cell‐free homogenate of cultured mast cells with COX inhibitors and EPA. Histamine in the culture medium and in cells was assayed with the HPLC‐fluorescent method. PGD2 and PGD3 were assayed with gas chromatography‐mass spectrometry and the stable isotope dilution method.

Results

Although EPA incubation did not affect histamine release by cultured human mast cells in response to IgE‐anti‐IgE challenge incubation, it did decrease PGD2 generation by inhibiting the COX‐2 pathway. In contrast, in the cell‐free homogenate of cultured human mast cells, EPA inhibited both COX‐1 and COX‐2 activities.

Conclusion

Pre‐incubation with EPA primarily affects the COX‐2 pathway in cultured human mast cells and reduces PGD2 generation in response to IgE‐anti‐IgE challenge incubation. These findings suggest that COX‐1 and COX‐2 have different substrate flow systems in mast cells. They also suggest that endogenous EPA diet supplementation would reduce PGD2 production and could serve as an anti‐inflammatory substrate in human mast cells.
Genetic linkage of HLA–class II locus to mite‐specific IgE immune responsiveness
Authors: Stephan  , Kuehr  , Seibt  , Saueressig  , Zingsem  , Dinh  , Moseler  , Wahn  , Deichmann
Published: March 2003

Background

IgE response to common inhalant allergens seems to be the major determinant of the development of atopic rhinitis and asthma but it has been difficult to demonstrate genetic control of the IgE response.

Objective

To investigate genetic linkage between specific IgE reactions to purified aero‐allergens (grass, birch, cat, mite) and the HLA–class II locus.

Methods

DNA‐based HLA–class II typing was performed for determination of DRB1, DQB1 and DPB1 alleles. Linkage was studied by the affected sibpair method and the extended transmission disequilibrium test in 100 children from 40 nuclear families selected from a homogeneous population in south‐western Germany.

Results

Significant linkage of mite‐specific IgE response to HLA–DPB (P = 0.00001), HLA–DRB (0.02) and HLA–DQB (P = 0.001) was revealed by sibpair analysis of MHC class II alleles and confirmed by the extended transmission disequilibrium test for HLA–DRB (P = 0.01) and HLA–DPB (P = 0.04). No consistent significant linkage between the HLA–class II locus and IgE response to grass pollen, birch pollen, and cat dander could be demonstrated.

Conclusion

The findings are consistent with the existence of one or more genes in the HLA–class II region modifying the IgE immune response to common environmental allergens.
Peels of Rosaceae fruits have a higher allergenicity than pulps
Authors: Fernández‐Rivas  , Cuevas
Published: March 2003

Background

It is not uncommon that patients allergic to fruits such as apple, pear, and peach, refer adverse reactions after the ingestion of the whole fruit, but subsequently tolerate the pulp.

Objective

This study aimed to compare the allergenicity of peels and pulps of apple, peach, and pear in 33 patients allergic to these fruits.

Methods

Clinical reactivity to the ingestion of whole fruit (peel + pulp) and pulp was established by medical history. Peels and pulps were tested separately in skin prick tests (SPTs), histamine release tests (HRTs) and RASTs. Cross‐allergenicity between peel and pulp of apple and peach was studied by RAST inhibition.

Results

Adverse reactions appeared more frequently and were more severe when the whole fruit was eaten. More than 40% of patients allergic to apple and pear tolerated the ingestion of the pulp of these fruits, and reactions were only elicited by the intake of the whole fruit. Peels induced higher SPTs, HRTs and RASTs than pulps. An important cross‐allergenicity was found between the peel and pulp of apple and peach, although the amount of the shared allergenic epitopes seemed to be higher in peels.

Conclusion

Our results suggest that peels of Rosaceae fruits such as apple, peach, and pear, have a higher allergenicity than pulps, which is clinically relevant. This aspect should be considered in the evaluation of patients allergic to Rosaceae fruits, and in the production of diagnostic materials.
Submucous turbinectomy decreases not only nasal stiffness but also sneezing and rhinorrhea in patients with perennial allergic rhinitis
Authors: Mori  , Fujieda  , Igarashi  , Fan  , Saito
Published: March 2003

Background

Turbinate surgery, in which mucous epithelium is resected, has often been used for patients with perennial allergic rhinitis, since the mucous epithelium is the principal site for immunoglobulin (Ig)E‐mediated allergic reactions and chronic inflammation.

Objective

To assess the effect of submucous turbinectomy on allergic rhinitis.

Methods

Sixty patients with severe perennial allergic rhinitis underwent submucous turbinectomy and were followed‐up for 1 year. Nasal symptoms were evaluated with a standard symptom score. Rhinometry was used to evaluate nasal congestion, and nasal provocation testsin vivowere performed to evaluate allergic reactions. In 16 cases, biopsies from the nose were also available for immunohistochemical analysis. These examinations were performed before and after submucous turbinectomy.

Results

The mean total nasal symptom score (7.2 ± 1.7, mean ± sdbefore surgery) was significantly reduced after surgery (1.2 ± 1.4,P < 0.0001), and the effect of the surgery on nasal symptoms continued for at least 12 months (1.9 ± 1.8,P < 0.0001). Submucous turbinectomy reduced both nasal discharge and sneezing, as well as nasal stiffness. Histopathological examination following surgery revealed that the lamina propria was occupied by fibrous tissues, and that the number of vessels, nasal glands, eosinophils and infiltrating IgE+cells decreased in the turbinate. There were no significant differences in the levels of either house dust mite‐specific or non‐specific IgE in the serum between before and after surgery.

Conclusion

Submucous turbinectomy preserving the ciliary epithelium is a powerful strategy for improving nasal symptoms induced by allergic reaction via the reduction in the number of allergy‐related cells in the nose.
Exhaled monoxides in asymptomatic atopic subjects
Authors: Horváth  , Barnes
Published: March 2003

Background

Atopy is a genetically determined condition and some atopic people develop airway hyperresponsiveness and sometimes asthma later in life. Since airway inflammation may be present before the onset of clinical symptoms of asthma, early and noninvasive detection of inflammation would be useful in atopic subjects. Mediators produced by activated inflammatory cells may lead to induction of inducible nitric oxide synthase producing nitric oxide (NO) and inducible heme oxygenase releasing carbon monoxide (CO) in the airways. Both monoxides are present in exhaled air and their levels are elevated in asthma reflecting airway inflammation.

Objective

We have measured exhaled NO and CO levels in atopic and nonatopic healthy non‐smoking subjects to determine whether inflammation is present in the airways.

Methods

Exhaled NO was measured by a chemiluminescence analyser and exhaled CO electrochemically and NO in asymptomatic atopic and age‐matched nonatopic normal subjects.

Results

Exhaled NO and CO levels were both significantly elevated in 15 atopic subjects compared with 40 nonatopic individuals (means ± sem: 18.3 ± 3.0 p.p.b. vs 6.3 ± 0.3 p.p.b., P < 0.0001 and 4.7 ± 0.3 p.p.m. vs 2.8 ± 0.2 p.p.m., P = 0.0005, respectively).

Conclusion

Increase in exhaled monoxide levels may be an early and noninvasive marker of airway inflammation in asymptomatic atopic subjects.
Association of FcεR1‐β polymorphisms with asthma and associated traits in Australian asthmatic families
Authors: Palmer  , Rye  , Gibson  , Moffatt  , Goldblatt  , Burton  , Cookson  , Lesouëf
Published: March 2003

Background

Asthma is a genetically complex disease, and is characterized by elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts and increased airway responsiveness. Polymorphisms in the β subunit of the high affinity receptor for IgE (FcεR1‐β) have been previously associated with these phenotypes and with an increased risk of asthma.

Objective

To investigate the association of all known bi‐allelic polymorphisms in FcεR1‐β to asthma and quantitative traits associated with asthma in a selected sample of Australian asthmatic children and their nuclear families.

Methods

Australian Caucasian nuclear families (n = 134 subjects) were recruited on the basis of a child proband with current, severe, symptomatic asthma. The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts and the dose–response slope of the forced expiratory volume in 1 s to histamine provocation.

Results

Neither the Leu181 nor the E237G mutations were detected in this population. Allele B of RsaI intron 2 (RsaI_in2*B) was significantly associated with physician‐diagnosed asthma (ever) (P = 0.002). Alleles of both the RsaI_in2 and RsaI exon 7 (RsaI_ex7) polymorphisms were significantly associated with loge total serum IgE levels and the combined RAST index. RsaI_ex7 was also associated with loge blood eosinophil counts. These associations were independent of age, sex and familial correlations.

Conclusion

This study supports a role for the FcεR1‐β gene or a nearby gene in the pathogenesis of asthma.
Are anaphylactic reactions to snake bites immunoglobulin E‐mediated?
Authors: Reimers  , Weber  , Müller
Published: March 2003

Background

Bites by poisonous European snakes of the genus Vipera lead to local tissue damage and systemic symptoms such as generalized oedema, hypotension, gastrointestinal symptoms, haemolysis and renal dysfunction. Not rarely anaphylactic symptoms like urticaria, localized angioedema and asthma are observed.

Objective

To look for snake venom‐specific immunoglobulin (Ig) E antibodies in patients with a history of bites by European vipers and for cross‐reactions with Hymenoptera venoms, that have a similar composition.

Method

Ten patients with a history of bites by Vipera aspis or Vipera berus were investigated. Three patients had been bitten only once, and two of these had developed only local reactions. Four reported previous allergic reactions to Hymenoptera stings. All patients, 10 Hymenoptera venom‐allergic and five nonallergic individuals who served as controls underwent i.c. skin test endpoint titration with snake (V. aspis, V. berus) and Hymenoptera venoms (honey bee, Vespula spp.) and were investigated for specific serum IgE antibodies to the same venoms.

Results

Seven of the eight patients with systemic snake bite reactions had both positive skin tests and serum IgE antibodies to snake venoms, while these tests were negative in the two patients with only local reactions to snake bites and all controls. Seven of the eight patients with systemic snake bite reaction also had positive skin tests and specific IgE with one or both Hymenoptera venoms. By RAST‐inhibition with sera of four patients with high IgE to both Vipera and Hymenoptera venoms, partial cross‐reactivity could be demonstrated in one.

Conclusions

Anaphylactic reactions following snake bites may be IgE‐mediated, especially in patients with repeated bites.
Positive atopy patch test reactions to Pityrosporumorbiculare in atopic dermatitis patients
Authors: Tengvall Linder  , Johansson  , Scheynius  , Wahlgren
Published: March 2003

Background

Pityrosporum
orbiculare, although a part of our normal cutaneous microflora, can cause skin infections and induce specific immunoglobulin (Ig) E antibodies in atopic dermatitis patients. P. orbiculare is therefore considered to be one of the trigger factors for atopic dermatitis.

Objective

To investigate if P. orbiculare can induce an eczematous reaction in atopic dermatitis patients, seborrhoeic dermatitis patients and healthy controls.

Methods

Fifteen atopic dermatitis patients, eight seborrhoeic dermatitis patients and eight healthy controls were patch tested with extract of P. orbiculare on non‐lesional, tape‐stripped skin of the back. NaCl was used as a negative control. The patch tests were evaluated after 24, 48 and 72 h. Skin biopsies were taken from P. orbiculare patch test sites at 24 h and 72 h, from NaCl patch test sites at 72 h, from non‐lesional skin and, in the atopic dermatitis patients, also from lesional skin. The skin biopsies were investigated with immunohistochemical techniques. P. orbiculare‐specific IgE in serum was analysed with RAST.

Results

Specific IgE to P. orbiculare was found in serum from 13/15 atopic dermatitis patients and in eight of them a positive patch test reaction to P. orbiculare was observed, with a maximal reaction at 48 h. Significantly higher serum levels of P. orbiculare‐specific IgE were detected in patch test‐positive compared with patch test‐negative atopic dermatitis patients (P < 0.01). The seborrhoeic dermatitis patients and healthy controls were RAST and patch test‐negative for P. orbiculare. In the patch test‐positive atopic dermatitis patients an infiltration of CD4+ T cells and eosinophils was observed at the P. orbiculare patch test sites together with an upregulation of ICAM‐1 and HLA‐DR expression.

Conclusions

P. orbiculare can induce an eczematous reaction in sensitized atopic dermatitis patients and may be an important trigger factor in these patients. The P. orbiculare patch test can be of diagnostic value in this subgroup of atopic dermatitis patients.
Investigation of the anti‐allergic activity of azelastine on the immediate and late‐phase reactions to allergens and histamine using telethermography
Authors: De Weck  , Derer  , Bähre
Published: March 2003

Background

Due to the interest in azelastine's diverse modes of action, this study investigated its effects on immediate and late‐phase cutaneous allergic reactions using visual methods and telethermography.

Objective

The aim of the study was to investigate the effect of azelastine on the immediate and late‐phase skin reactions using both planimetric evaluation of weal and erythema and a telethermographic technique.

Methods

The study was a double‐blind crossover study; medication consisted of one tablet per day for 7 days of either placebo or azelastine 4 mg. Eight allergic patients were assessed on five occasions: prior to treatment, at the end of the first 7‐day treatment, after a 21‐day washout period, following the second 7‐day treatment period and finally following a 2–6 week washout period. Skin prick tests with timothy grass and intradermal tests with Alternaria allergens were performed on the patients' back. In addition, patients were tested with intradermal histamine as a positive control.

Surfaces of weal, erythema and infiltration were calculated using computerized planimetry at 0, 20, 40 and 60 min, and 3, 6 and 8 h. Thermographic images were recorded and the thermographic area and the increase in average temperature (ΔT) were calculated.

Results

The coefficient of variation within baseline reactions ranged from 3 to 32% for weal and erythema and from 5 to 25% for thermographically recorded reactions. The stronger the reaction, the more constant the baseline was. Treatment with azelastine (4 mg/os once daily) inhibited immediate reactions to allergens by 65% (range 55–74) and to histamine by 68% (range 47–82). The late‐phase reactions to allergens were less well defined and showed larger individual differences in the degree of inhibition caused by azelastine, they were inhibited by 49% (range 32–67). Late‐phase reactions to histamine were less intense and could only be detected with thermography; only thermographic units showed a decrease (26%) in response to azelastine.

Conclusion

This study has confirmed azelastine's histamine‐blocking activity. In addition, the late‐phase results suggest that azelastine has anti‐inflammatory activity. The reproducibility and sensitivity of the thermographic results confirm the usefulness of this technique in immunopharmacology.
O‐glycans as a source of cross‐reactivity in determinations of human serum antibodies to Anisakis simplex antigens
Authors: Lorenzo  , Romarís  , Iglesias  , Audícana  , Alonso  , Leiro  , Ubeira
Published: March 2003

Background

Anisakis simplex is a seafood‐borne parasite that may both infect humans and cause allergy. Serodiagnosis of anisakiasis and allergy caused by this nematode is difficult since most Anisakis antigens show cross‐reactivity problems.

Objective

To analyse the possible role of sugar epitopes contained in Anisakis simplex antigens as causes of false‐positive results in serodiagnostic assays.

Methods

The antigens UA2R and UA3R recognized by two anti‐Anisakis monoclonal antibodies were used in this study. Capture ELISA techniques were used to compare the reactivities with native or O‐deglycosylated antigens of sera from Anisakis‐free children (most of them infected by several other parasites) and from Anisakis allergy patients. O‐deglycosylation was done by mild alkali treatment with NaOH. SDS‐PAGE and immunoblotting were used to characterize the effects of NaOH or N‐glycanase F treatment on UA3R.

Results

Native UA2R was recognized by IgG1 and IgM antibodies in the sera of both Anisakis‐free subjects and allergy patients. Native UA3R was recognized by most sera from allergy patients (92% considering immunoglobulin (Ig) G1, 100% considering IgE), but also by a significant proportion of sera from Anisakis‐free subjects (36% considering IgG1, 14% considering IgE). O‐deglycosylation of UA3R greatly improved specificity: none of the sera from Anisakis‐free patients showed either IgG1 or IgE reactivity with O‐deglycosylated UA3R, while the proportion of sera from allergy patients showing IgE reactivity with this antigen was practically unaffected. O‐deglycosylation of UA2R did not improve the specificity of assays using this antigen. Our results also show that the protein core of glycoproteins may be altered by even very mild alkali treatment, depending on the nature of the protein.

Conclusion

Native glycoproteins of A. simplex should not be used for diagnostic purposes. O‐deglycosylated UA3R seems to be an excellent candidate for use as target antigen in the serodiagnosis of anisakiasis and A. simplex allergy.
Early BCG vaccination and reduction in atopy in Guinea‐Bissau
Authors: Aaby  , Shaheen  , Heyes  , Goudiaby  , Hall  , Shiell  , Jensen  , Marchant
Published: March 2003

Background

It has been proposed that certain viral and bacterial infections in early childhood may prevent allergic sensitization, by inducing Th1‐type immune responses. This has led to speculation that mycobacterial vaccines might, through their Th1‐stimulating properties, also protect against atopy.

Objective

To investigate whether the prevalence of atopy is lower in children who have been vaccinated with BCG in infancy than in children who have not been vaccinated.

Methods

We measured skin test reactivity to three allergens (Dermatophagoides pteronyssinus, D. farinaeand cockroach) in 400 children, aged 3–14 years, as part of a follow‐up study to examine the immune sequelae of measles in an urban area of Bissau, the capital of Guinea‐Bissau in west Africa. Information on childhood vaccinations, including BCG in infancy, was available from child records. Of these children, 271 had been vaccinated with BCG (according to records) and 53 had not been vaccinated (no record and no BCG scar). Atopy was defined in two ways, according to the presence of any allergen reaction ≥ 2 mm and any reaction ≥ 3 mm.

Results

Of the children who had received BCG vaccine, 57 (21%) were atopic (any reaction ≥ 2 mm), compared with 21 (40%) of the unvaccinated children [odds ratio, after controlling for potential confounding factors, 0.19 (95% CI 0.06–0.59)]. When atopy was defined using the 3‐mm criterion, the reduction in atopy associated with BCG was greater the earlier the age at vaccination, and the largest reduction was seen in children vaccinated in the first week of life.

Conclusion

BCG vaccination given early in infancy may prevent the development of atopy in African children.
Eosinophils are a feature of upper and lower airway pathology in non‐atopic asthma, irrespective of the presence of rhinitis
Authors: Gaga  , Lambrou  , Papageorgiou  , Koulouris  , Kosmas  , Fragakis  , Sofios  , Rasidakis  , Jordanoglou
Published: March 2003

Background

Asthma and rhinitis often co‐exist and there are data to suggest that they may be two ends of the same disease spectrum. Immunohistochemical studies have shown that eosinophilia in the airways is a feature of rhinitic patients without asthma.

Objective

The aim of our study was to examine whether cellular infiltration exists in the nasal mucosa of asthmatics even in the absence of symptoms and signs of rhinitis.

Methods

Nasal mucosa biopsies were taken from 27 non‐atopic subjects and comprised nine asthmatic rhinitic patients (AR), eight asthmatic non‐rhinitic patients (ANR) and 10 healthy control subjects (N). Bronchial mucosa biopsies were also taken simultaneously from some of the patients (n = 10) to determine whether there was an association between cellular infiltration in the nose and the lungs. The alkaline phosphatase‐anti‐alkaline phosphatase (APAAP) method was used on 6 μm thick cryostat sections using monoclonal antibodies against T cells (CD4, CD8), eosinophils (EG2) and mast cells (mast cell tryptase). Slides were counted blind and results expressed as cells per field.

Results

The results showed that eosinophil counts were higher in both asthma groups compared with control nasal biopsies (median values AR 8.3, ANR 9.2, N 2.1 cells per field, P < 0.01). Furthermore, there was a significant correlation between eosinophil cell counts in the nose and the airways (r = 0.851 P < 0.001). No differences in eosinophil numbers were detected between the two groups of asthmatics. Also, no differences were noted for any other cell type (i.e. CD4, CD8, tryptase) among the three study groups.

Conclusions

These results show that eosinophil infiltration was present in the nasal mucosa of asthmatic patients even in the absence of rhinitis, and add further support to the hypothesis that asthma and rhinitis are clinical expressions of the same disease entity.
Effect of pranlukast on bronchial inflammation in patients with asthma
Authors: Yoshida  , Ishizaki  , Shoji  , Onuma  , Nakagawa  , Nakabayashi  , Akahori  , Hasegawa  , Amayasu
Published: March 2003

Background

Pranlukast (8‐[p‐(4‐phenylbutyloxy) benzol] amino‐2‐[tetrazol‐5‐yl]‐4‐oxo‐4H‐1‐benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, has been reported to exhibit not only antileukotrine activity but also pharmacological activity including antieosinophilic effects.

Objective

This study was designed to investigate whether the antiasthmatic activity of pranlukast is associated with a reduction in eosinophilic inflammation.

Methods

A double‐blind, randomized, crossover design was used. Subjects received 225 mg of pranlukast or placebo orally twice daily for 4 weeks and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine in 32 adult patients with mild or moderate bronchial asthma; those who were in stable clinical condition were allocated to this study. Blood and sputum samples were taken the morning of the methacholine provocation test. Eosinophil counts and measurement of eosinophilic cationic protein (ECP) were performed.

Results

After the 4 weeks of treatment with pranlukast, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. Furthermore, values of PC20‐methacholine significantly improved in the treatment with pranlukast.

Conclusion

Our results suggest that pranlukast has an anti‐inflammatory effect on bronchial eosinophilic infiltration. This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of bronchial asthma.
Preliminary criteria for the definition of allergic rhinitis: a systematic evaluation of clinical parameters in a disease cohort (I)
Authors: Ng  , Warlow  , Chrishanthan  , Ellis  , Walls
Published: March 2003

Background

The aim of this study is to formulate criteria for the definition of allergic rhinitis. Other studies have sought to develop scoring systems to categorize the severity of allergic rhinitis symptoms but it was never used for the formulation of diagnostic criteria. These other scoring systems were arbitrarily chosen and were not derived by any statistical analysis. To date, a study of this kind has not been performed.

Objective

The hypothesis of this study is that it is possible to formulate criteria for the definition of allergic rhinitis. This is the first study to systematically examine and evaluate the relative importance of symptoms, signs and investigative tests in allergic rhinitis. We sought to statistically rank, from the most to the least important, the multiplicity of symptoms, signs and test results.

Methods

Forty‐seven allergic rhinitis and 23 normal subjects were evaluated with a detailed questionnaire and history, physical examination, serum total immunoglobulin E, skin prick tests and serum enzyme allergosorbent tests (EAST).

Results

Statistical ranking of variables indicated rhinitis symptoms (nasal, ocular and oronasal) were the most commonly occurring, followed by a history of allergen provocation, then serum total IgE, positive skin prick tests and positive EAST's to house dust mite, perennial rye and bermuda/couch grass. Throat symptoms ranked even lower whilst EAST's to cat epithelia, plantain and cockroach were the least important. Not all symptoms, signs and tests evaluated proved to be statistically significant when compared to a control group; this included symtoms and signs which had been considered historically to be traditionally associated with allergic rhinitis, e.g. sore throat and bleeding nose.

Conclusion

In performing statistical analyses, we were able to rank from most to least important, the multiplicity of symptoms signs and test results. The most important symptoms and signs were identified for the first time, even though some of these were not included in our original selection criteria for defining the disease cohort i.e. sniffing, postnasal drip, oedematous nasal mucosa, impaired sense of smell, mouth breathing, itchy nose and many of the specific provocation factors.
Socioeconomic status is a risk factor for allergy in parents but not in their children
Authors: Bergmann R. L. , Edenharter G. , Bergmann K. E. , Lau S. , Wahn U. ,   THE MULTICENTER ALLERGY STUDY RESEARCH GROUP
Published: March 2003

Background

Allergic diseases are more prevalent in affluent countries, which has been attributed to life‐style factors. Life‐style habits may also differ between socioeconomic (SES) classes. The objective of this paper therefore was to evaluate if SES had an impact on the development of atopic disorders.

Methods

A total of 1314 German children were followed‐up in an observational birth cohort study to 6 years of age. Parents filled in questionnaires, and had multi‐allergen screening tests for sensitization. Indoor allergen concentrations were determined by ELISA. Children were examined regularly up to 6 years, specific serum IgE values were determined by CAP‐Rast‐Feia.

Results

The risk of aeroallergen sensitization (odds ratio 1.76; 95% CI 1.30–2.37), and the lifetime prevalence of hay fever (2.36; 1.76–3.17), and asthma (1.74; 1.08–2.80), but not of atopic dermatitis (AD: 0.90; 0.54–1.51) was elevated in parents of high compared to low SES. With high SES the risk of smoking in pregnancy (0.35; 0.23–0.51), in the home (0.31; 0.21–0.46), pet ownership (0.37; 0.26–0.55), high mite (0.42; 0.25–0.74), and high cat (0.38; 0.18–0.82) allergen concentration in house dust was reduced, but elevated for breastfeeding over more than 6 months (4.67; 2.9–7.48). In children, even after controlling for other risk factors, only the risk of AD from 3 to 6 years (2.42; 1.42–4.14) was elevated in families with high SES, but not of AD in infancy or of any other atopic disorder.

Conclusions

While parents of high SES have a higher prevalence of inhalative allergies, their favourable life‐style prevents the development of atopic disorders in their children, except for AD beyond infancy.
Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children
Authors: Sporik R. , Hill D. J. , Hosking C. S.
Published: March 2003

Background

The specificity of allergen skin prick testing to diagnose clinically relevant food allergy is controversial.

Objectives

To determine the specificity of the allergen weal diameter to correctly identify children who react on formal open food challenges.

Methods

Over a 9‐year period children referred to a tertiary allergy clinic for the evaluation of suspected food allergy were prospectively studied. Allergen skin prick testing to cow milk, egg white and peanut extracts (Dome‐Hollister‐Stier, Spokane, WA, USA) was undertaken using a lancet technique. All children underwent open food challenges to the relevant food(s) in a hospital clinic. Challenges were classified as positive, if objective signs were seen; negative, if the child could tolerate normal quantities of the food, daily, for one week; or inconclusive if none of the former criteria were met.

Results

Five hundred and fifty‐five challenges were undertaken in 467 children: 339 challenges to cow milk, 121 to egg, and 95 to peanut. Fifty‐five percentage of challenges were positive, 37% negative, and 8% inconclusive. For each food it was possible to identify a skin weal diameter at, and above, which negative reactions did not occur: cow milk, 8 mm; egg, 7 mm; peanut, 8 mm. In contrast, positive reactions could occur with a skin wheal diameter of 0 mm.

Conclusions

In this high risk referral population it was possible to define skin weal diameters to egg, milk and peanut above which open oral food challenges were positive (100% specificity). By utilizing these measurements the need for formal food challenges can be reduced.
Molecular cloning of major allergen from Cupressus arizonica pollen: Cup a 1
Authors: Aceituno E. , Del Pozo V. , Mínguez A. , Arrieta I. , Cortegano I. , Cárdaba B. , Gallardo S. , Rojo M. , Palomino P. , Lahoz C.
Published: March 2003

The family Cupressaceae is a relevant source of allergens that causes winter respiratory allergies. Cloning and sequencing the major antigen of Cupressus arizonica is important for a better diagnosis and treatment of sensitized patients.

To obtain a full‐length complementary DNA for Cup a 1, the major allergen of Cupressus arizonica pollen. It was cloned and sequenced and the recombinant protein was expressed.

Messenger RNA from Cupressus arizonica pollen was obtained and the Cup a 1 sequence was established using a 3′‐RACE system and primers based on the N‐terminal amino acid sequence. Recombinant Cup a 1 was cloned in pBluescript and expressed in a glycosylated form in rabbit reticulocytes. The cDNA was subcloned in pGEX‐5X‐1 and expressed in Escherichia coli as a fusion protein with GST.

Recombinant Cup a 1 is highly homologous with the major allergens of mountain cedar (Jun a 1), Japanese cypress (Cha o 1) and Japanese cedar (Cry j 1). Cup a 1 contains three potential N‐glycosylation sites that are different from those found in Jun a 1 and Cry j 1. The cloned protein contains a pectate lyase active site identical to those of Cry j 1 and Jun a 1. The IgE from patients' sera recognizes recombinant Cup a 1, and this reactivity is higher with the glycosylated protein.

Cup a 1 has been cloned and sequenced. As expected, the high degree of homology with Cha o 1, Jun a 1 and Cry j 1 explains the cross‐reactivity of conifer pollens. Different IgE reactivity with the glycosylated and non‐glycosylated protein suggests the importance of carbohydrate moieties in the IgE binding site.
Association between a C+33T polymorphism in the IL‐4 promoter region and total serum IgE levels
Authors: Suzuki I. , Hizawa N. , Yamaguchi E. , Kawakami Y.
Published: March 2003

Susceptibility to asthma and other atopic diseases is known to be associated with elevated total IgE levels. Several investigators have linked the interleukin‐4 (IL‐4) gene and nearby markers located on chromosome 5q to elevated total IgE levels. A single nucleotide polymorphism in the IL‐4 gene promoter region (C+33T) has recently been identified.

As part of an effort to identify genetic variants contributing to the susceptibility to elevated total serum IgE levels, an association analysis of a newly identified promoter polymorphism (C+33T) with total serum IgE levels was conducted.

The study was conducted using 240 Japanese subjects (120 asthmatics and 120 healthy controls). The IL‐4 C+33T polymorphism was genotyped by PCR‐restriction fragment length polymorphism analysis. The frequency of the T allele was 0.675 in asthmatic subjects and 0.671 in healthy controls. An anova model adjusted for age, sex and disease status suggested a genetic association of C+33T polymorphism with elevated total serum IgE levels (P < 0.05).

The data suggest that IL‐4 promoter C+33T polymorphism may be one of the genetic polymorphisms that explain genetic linkage or association between elevated total serum IgE levels and markers on chromosome 5q.
Peanut challenge: a retrospective study of 140 patients
Authors: Pucar F. , Kagan R. , Lim H. , Clarke A.E.
Published: March 2003

Background Accurate diagnosis of peanut allergy is essential given that it is a lifelong and potentially fatal food allergy. Diagnosis relies on patient history, prick skin test (PST), and in many situations, food challenge. More information is required on the safety of food challenge and the informational value of a PST.

Objectives Primary: to assess the safety of peanut challenges. Secondary: to estimate the sensitivity, specificity, and the positive and negative predictive values of PST to peanut performed in those who underwent a peanut challenge.

Methods A retrospective study of peanut challenges performed at a tertiary care paediatric hospital allergy clinic between January 1994 and November 1998.

Results Of the 140 peanut challenges performed on 140 patients, 18 were positive. The most frequent adverse clinical effects of positive peanut challenges were: urticaria, oropharyngeal irritation, rhinitis, vomiting and abdominal pain. Among the 18 patients who had a positive result, 10 required medical treatment (antihistamines, ± epinephrine, ± salbutamol) to control the allergic reaction. The sensitivity, specificity, and the positive and negative predictive values of PST to peanut in this group of children undergoing a peanut challenge were 100%, 62.3%, 28.1% and 100%, respectively.

Conclusions Given the poor positive predictive value and specificity of PST, a peanut challenge is usually required to diagnose peanut allergy with certainty when the PST is positive. In cases of a clear history of anaphylaxis to peanut and a positive PST, challenges are unwarranted. When the history is strongly suggestive and the PST is borderline positive, i.e. 3 or 4 mm, peanut challenge is generally necessary to confirm the diagnosis. Given the excellent negative predictive value and sensitivity of PST, a blinded peanut challenge is usually unnecessary in the context of a negative PST except for patients with a history strongly suggestive of immediate hypersensitivity. These patients should be individually assessed for the need to undergo a blinded challenge. The peanut challenge is a useful and safe diagnostic tool when performed by qualified personnel under appropriate conditions.
Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment
Authors: Greiff L. , Petersen H. , Mattsson E. , Andersson M. , Erjefält J. S. , Linden M. , Svensson C. , Persson C. G. A.
Published: March 2003

Background Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (α2‐macroglobulin) and eosinophil cationic protein (ECP) are also examined.

Methods Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges.

Results At baseline nasal lavage fluid levels of eotaxin correlated to levels of α2‐macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05).

Conclusions Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti‐eosinophilic actions of topical glucocorticosteroids.
The release of histamine is associated with the inactivation of mast cell chymase during immediate allergic wheal reaction in the skin
Authors: Saarinen J. V. , Harvima R. J. , Naukkarinen A. , Horsmanheimo M. , Harvima I. T.
Published: March 2003

Background Chymase released by mast cells can participate in the immediate allergic wheal. However, chymase may be susceptible to inactivation by protease inhibitors during degranulation.

Objective To study the inactivation of chymase and the release of histamine in the immediate allergic wheal reaction.

Methods Ten sensitive atopic subjects were prick‐tested with the cow dander allergen, and skin biopsies were taken from the control skin and from the challenge site at 30 and 120 min. Tryptase (Tact) and chymase (Cact) activities in mast cells were measured enzyme‐histochemically. Sequential double‐staining was used to demonstrate the activity and immunoreactivity (Cprot) of chymase in the same mast cell as well as α1‐proteinase inhibitor (α1‐PI) and α1‐antichymotrypsin (α1‐AC) in Tact+ cells. Skin microdialysis was used to monitor histamine release after the allergen challenge for up to 120 min

Results The numbers of Tact+ and Cact+ cells were already maximally decreased at 30 min by 37 ± 17% and 61 ± 31%, respectively (mean ± SD, P < 0.0001). At the same time the Cact+/Cprot+ ratio decreased from 82 ± 15% to 43 ± 16% (P < 0.0001). The cumulative histamine release at 30 min correlated negatively with the Cact+/Tact+ (P = 0.047) and Cact+/Cprot+ (P = 0.024) ratios, but positively with the decrease in the number of Cact+ cells (P = 0.024). These data indicate that the higher the histamine release the lower the chymase activity. Also the number of Tact+ cells in the control skin correlated positively with the cumulative histamine release at 120 min (P = 0.043). In the control skin, 95 ± 6% and 76 ± 8% of the Tact+ cells displayed α1‐AC and α1‐PI, respectively.

Conclusion In addition to extensive degranulation of mast cells, chymase is also rapidly inactivated after the allergen challenge, possibly by pre‐existing chymase inhibitors in the mast cells. This inactivation is associated with the release of histamine.
Allergen‐induced basophil activation: CD63 cell expression detected by flow cytometry in patients allergic to Dermatophagoides pteronyssinus and Lolium perenne
Authors: Sanz M. L. , Sánchez G. , Gamboa P. M. , Vila L. , Uasuf C. , Chazot M. , Diéguez I. , De Weck A. L.
Published: March 2003

Background In this study, we determined by flow cytometry the percentage of basophils activated after in vitro stimulation by allergens and expressing the CD63 marker. The diagnostic reliability of the technique was assessed as well as its correlation with other in vitro diagnostic parameters.

Methods Fifty‐three patients suffering from asthma and/or allergic rhinitis following sensitization to Dermatophagoides pteronyssinus and 51 patients sensitized to Lolium perenne were investigated. Twenty‐four atopic patients not sensitive to these allergens and 38 healthy subjects were also selected as controls. The basophil activation test determines the percentage of basophils which express CD63 as an activation marker, by means of flow cytometry, after in vitro stimulation with allergen, using double labelling with monoclonal antibody anti‐CD63–PE and anti‐IgE–FITC.

Results No differences in basal values (non‐activated control) were found between sensitized patients, atopic controls and healthy controls. On the other hand, sensitized patients showed a significantly higher percentage of activated basophils after stimulation by allergens in vitro than both control groups (P < 0.001). We found a significant correlation between skin tests and basophil activation tests (r = 0.72, P < 0.001). We also found a positive and significant correlation between basophil activation tests and histamine release tests (r = 0.80, P < 0.001), allergen‐specific sulphidoleukotriene production (r = 0.7, P < 0.001) and the occurrence of serum allergen‐specific IgE (r = 0.71, P < 0.001).

Conclusion The basophil activation test is a highly reliable technique in the diagnosis of allergy to inhalant allergens. The sensitivity of the basophil activation test was 93.3%, and its specificity 98.4%, when using a cut‐off point of 15% activated basophils as positive result.