bluuebunny/crossref_metadata_2025 huggingface dataset:
Asthma, atopy and Chlamydia pneumoniae antibodies in adults
Authors: VON HERTZEN  , TÖYRYLÄ  , GIMISHANOV  , BLOIGU  , LEINONEN  , SAIKKU  , HAAHTELA
Published: March 2003

Background

Factors involved in the development of inflammation and asthma in nonatopic subjects have remained largely obscure, although there is some evidence to suggest that certain infections may play a role.

Objective

We investigated the association between serological evidence of Chlamydia pneumoniae infection and asthma in adults, and the possible modifying effect of the patients' atopic status on this association.

Methods

Four hundred and thirty consecutive patients who attended the hospital between 1992 and 1993 with symptoms suggestive of asthma, rhinitis or allergy were enrolled. Diagnostic procedures including lung function measurements and skin‐prick tests were performed in all patients. The patients with established asthma (n = 332) were divided into those with recent asthma (n = 224, onset 1985 onward) and longstanding asthma (n = 108, onset before 1985). The controls (n = 98) comprised all subjects who did not meet the criteria of asthma. Serum immunoglobulin (Ig)G, IgA and IgM antibodies to C. pneumoniae were measured by the microimmunofluorescence test.

Results

In women, the prevalences of elevated IgG (a titre of ≥ 128) and IgA (≥ 32) antibody levels and the age‐adjusted geometric mean titres (GMT) of IgG and IgA antibodies were invariably highest among subjects with nonatopic longstanding asthma. Elevated IgG titres in women occurred in 11% of controls, in 28% of nonatopic recent onset asthmatics, and in 43% of asthmatics with nonatopic longstanding disease; for men the respective figures were 33, 50 and 64%. Logistic regression analysis controlling for age, sex and smoking showed that asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae (odds ratio 3.3, 1.6–6.8 for longstanding asthma, 2.3, 1.2–4.4 for recent asthma, and among women only 4.2, 1.6–10.9 for longstanding asthma, and 3.0, 1.3–7.2 for recent asthma). When the atopics and nonatopics were analysed separately, an even stronger relationship in the nonatopics was obtained for longstanding asthma (6.0,2.1–17.1). In contrast, the relationship between atopic asthma, either recent or longstanding, and elevated IgG titres was not significant, indicating that asthma per se does not predispose to C. pneumoniae infection.

Conclusions

Asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae, and this association was strongest for nonatopic longstanding asthma.
Characterization of allergens from Penicillium oxalicum and P. notatum by immunoblotting and N‐terminal amino acid sequence analysis
Authors: SHEN  , LIN  , TAM  , WANG  , TZEAN  , HUANG  , HAN
Published: March 2003

Background

Penicillium species are important causative agents of extrinsic bronchial asthma. However, little is known about the allergens of these ubiquitous fungal species. Objective    The object was to analyse the composition, the allergenic cross‐reactivity and the N‐terminal sequences of allergens from two prevalent airborne Penicillium species, P. oxalicum and P. notatum.

Methods

The allergenic composition and the immunoglobulin (Ig)E cross‐reactivity were analysed by immunoblot and immunoblot inhibition, respectively, using sera from asthmatic patients. The N‐terminal amino acid sequences of major allergens were determined by Edman degradation. Allergens identified were also characterized by immunoblotting using monoclonal antibody (MoAb) PCM39 against the alkaline serine proteinase major allergen of P. citrinum.

Results

Among the 70 asthmatic sera tested, 18 (26%) and 17 (24%) had IgE immunoblot reactivity towards components of P. oxalicum and P. notatum, respectively. Major allergens (> 80% frequency of IgE‐binding) from both species are the 34 and 30 kDa proteins of P. oxalicum and the 34 and 32 kDa proteins of P. notatum. IgE cross‐reactivity among these major allergens and the 33 kDa major allergen of P. citrinum can be detected by immunoblot inhibition studies. The N‐terminal amino acid sequences of the 34 kDa allergen of P. oxalicum and of the 32 and the 28 kDa allergens of P. notatum share homology with sequences of the vacuolar serine proteinase from Aspergillus fumigatus. The N‐terminal amino acid sequence of the 34 kDa allergen of P. notatum shows sequence homology with that of alkaline serine proteinase from P. citrinum. Results obtained from immunoblotting showed that MoAb PCM39 reacted with the 34, 30 and 16 kDa IgE‐binding components of P. oxalicum, and with the 34, 32 and 28 kDa IgE‐binding components of P. notatum.

Conclusions

Results obtained suggest that the 34 kDa major allergen of P. oxalicum may be a vacuolar serine proteinase. The 34 and the 32 kDa major allergens of P. notatum may be the alkaline and the vacuolar serine proteinases of P. notatum, respectively. The 30 and 16 kDa IgE‐binding components of P. oxalicum and the 28 kDa IgE‐binding component of P. notatum may be breakdown products of the 34 and the 32 kDa major vacuolar serine proteinase allergens of P. oxalicum and P. notatum, respectively.
Interleukin‐5 immunoreactivity and mRNA expression in gut mucosa from patients with food allergy
Authors: VANDEZANDE L. M. , WALLAERT B. , DESREUMAUX P. , TSICOPOULOS A. , LAMBLIN C. , TONNEL A. B. , JANIN A.
Published: March 2003

Background and aims

Eosinophils, mast cells and T lymphocytes are important cells in the allergic inflammatory process. These cells produce and are regulated by cytokines such as interleukin‐3 (IL‐3), interleukin‐5 (IL‐5) and granulocyte macrophage‐colony stimulating factor (GM‐CSF). We initiated this study to evaluate pathological abnormalities and to detect IL‐5 in the duodenal mucosa from patients with food allergy.

Methods

Endoscopy duodenal biopsy specimens were obtained from seven food‐allergic patients, six atopic healthy controls and six nonatopic healthy controls. IL‐5 protein was evaluated by immunohistochemistry. Electron microscopy as well as double immunofluorescent staining were used to identify the labelled cells and to localize IL‐5. IL‐5 mRNA expression was evaluated by qualitative polymerase chain reaction.

Results

A significantly increased number of lymphocytes, mast cells and eosinophils was detected in the lamina propria in food‐allergic patients and, in lower number, in atopic controls. Immunostaining for IL‐5 was markedly positive in food‐allergic patients, slightly increased in atopic controls and negative in nonatopic controls. Ultrastructurally, in food‐allergic patients and in atopic controls, IL‐5 was localized in eosinophil granules, in the matrix of intact granules and at the periphery of altered granules. Double immunofluorescent staining was performed in food‐allergic patients and showed that 86.7% of IL‐5+ cells were eosinophils, and that IL‐5 was expressed by 24% of eosinophils. IL‐5 mRNA was expressed in food‐allergic patients but was not detected in atopic and nonatopic controls.

Conclusion

Activated eosinophils are involved in gut atopic reactions occurring in food allergy and are probably in part upregulated by their own local production of IL‐5.
Polymorphisms in the β2‐adrenoreceptor gene are associated with decreased airway responsiveness
Authors: Ramsay  , Hayden  , Tiller  , Burton  , Goldblatt  , Lesouef
Published: March 2003

Background

There are a number of candidate genes thought to play a role in the development of asthma. Polymorphisms at amino acid positions 16 (arginine to glycine) and 27 (glutamine to glutamic acid) of the β2‐adrenoreceptor (B2AR) gene are known to be functionally relevant and have been associated with more severe forms of asthma, nocturnal asthma and decreased airway responsiveness in asthmatic subjects.

Objective

To determine if these polymorphisms contribute to the development of asthma by investigating the associations between the polymorphisms at amino acid positions 16 and 27 of the B2AR gene and asthma‐related parameters in a large, phenotypically well‐characterized population which was unselected for asthma.

Methods

Subjects (n = 332) were characterized using physiological assessments, immuno‐logical data and information obtained from questionnaire. PCR was used to generate a 229 base pair fragment spanning the mutations of interest. Genotype was determined using allele‐specific oligonucleotide hybridization and confirmed in 10% of the samples by direct sequencing. Multivariate analysis of the association between genotype and phenotype was then undertaken.

Results

Homozygotes for Glu27 were significantly less responsive to histamine than Gln27 homozygotes. In addition, Arg16 homozygotes were more likely to ‘wheeze during a cold’, in comparison with Gly16 homozygotes. However, there was no association between either polymorphism and physician‐diagnosed asthma, eczema, skin reactivity to common allergens or total and specific serum IgE levels. The two polymorphisms were found to be in significant linkage disequilibrium.

Conclusion

The polymorphism at position 27 was associated with decreased airway responsiveness in the study population and the polymorphism at position 16 was associated with increased wheeze during respiratory infection, but neither was associated with physician‐diagnosed asthma or any of the other variables considered.
Cetirizine counter‐regulates interleukin‐8 release from human epithelial cells (A549)
Authors: Arnold R. , Rihoux J.‐P. , König W.
Published: March 2003

Background

Cetirizine, a H1‐receptor antagonist, exerts besides its well‐known anti‐allergic potential an array of anti‐inflammatory activities. In particular epithelial cells activated in the presence of cetirizine showed a reduced ICAM‐1 cell surface expression and a diminished release of sICAM‐1.

Objective

We wondered whether cetirizine might influence the release of interleukin‐8 (IL‐8) from human epithelial cells activated with agonists distinct from histamine.

Methods

We used the human lung epithelial cell line A549 for our in vitro studies. IL‐8 release was determined by IL‐8 enzyme immunoassay, the intracellular staining for IL‐8 and NF‐kB was analysed by FACS analysis and IL‐8 mRNA steady state level was studied by Northern blot analysis. Confluent epithelial cell monolayer were pre‐incubated with cetirizine (0.01 −1.0 μmol/L) for 30 min and afterwards activated with pro‐inflammatory cytokines (TNF‐α IL‐1β, IL‐6, IFN‐γ) or different agonists (PMA, NaF, respiratory syncytial virus [RSV]) for 24 h.

Results

Epithelial cells stimulated with TNF‐α IL‐1β, PMA and RSV, respectively, showed a significantly increased release of IL‐8. Pre‐incubation with cetirizine diminished the IL‐8 release from cells activated with TNF‐α or PMA in a significant manner. The reduced IL‐8 release coincided with a diminished percentage of cells expressing IL‐8. Northern blot analysis revealed a reduced steady state level of IL‐8 mRNA in cells pretreated with cetirizine and stimulated with TNF‐α. Furthermore, a decreased amount of accessible DNA‐binding sites of the nuclear factor kappa B (NF‐kB) was determined by FACS analysis.

Conclusions

These results suggest that cetirizine reduced the release of IL‐8 from A549 cells stimulated with PMA and TNF‐α, respectively, by lowering IL‐8 gene expression. Therefore, cetirizine might exert anti‐inflammatory effects beyond its H1‐receptor antagonistic activity in the course of inflammatory respiratory tract disorders such as bronchial asthma and allergic rhinitis.
QT interval monitoring during clinical studies with mizolastine, a new H1 antihistamine
Authors: Delauche‐Cavallier M. C. , Chaufour S. , Guérault E. , Lacroux A. , Murrieta M. , Wajman A.
Published: March 2003

Background

Some H1 antihistamines are at risk for rare but severe dysrhythmias due to an effect on the ventricular repolarization.

Objective

To present an overview of the QT interval monitoring performed during the clinical development of mizolastine, a new selective second‐generation H1 antihistamine.

Methods

The ECGs database analysis of clinical studies conducted in volunteers and patients is summarized and focused on the results of reported studies and studies specifically designed for the assessment of the effect of mizolastine on cardiac repolarization, through the QT interval measurements. Mizolastine was orally administered up to 75 mg single dose and 40 mg repeated dose in healthy volunteers (i.e. 7.5 and 4 times the recommended dose, respectively) and at a dose of 10 or 15 mg in patients.

Results

In healthy volunteers, no increased incidence of QTc values >440 msec or ΔQTc ≥40 msec were recorded compared to placebo. No dose‐related increase in QTc interval was observed. The ECG parameters were not modified by the co‐administration of mizolastine with digoxin, diltiazem and erythromycin, when compared to the effect of each co‐administered drug alone. In patients, the mean QTc interval changes from baseline did not significantly differ from placebo. In comparative studies vs. loratadine a similar incidence of out of range values was observed with mizolastine and loratadine.

Conclusion

ECG monitoring of volunteers and patients included in clinical studies conducted with mizolastine showed no significant effect of mizolastine on cardiac repolarization.
Bronchoprotective effects of atrial natriuretic peptide against propranolol‐induced bronchoconstriction after allergic reaction in guinea pigs
Authors: Mizuguchi  , Myo  , Fujimura
Published: March 2003

Objective

To study the effects of intravenous atrial natriuretic peptide (ANP) on antigen‐induced bronchoconstriction, propranolol‐induced bronchoconstriction (PIB) after antigen challenge, and histamine‐induced bronchoconstriction in guinea pigs.

Methods

Allergic bronchoconstriction was evoked by inhalation of ovalbumin (OA) and PIB was caused when 10 mg/mL of propranolol was inhaled 20 min after OA challenge in passively sensitized and artificially ventilated guinea pigs. 25, 50, 100 and 200 μg/mL of histamine were inhaled for 20 s at 5‐min intervals in non‐sensitized guinea pigs.

Results

Pretreatment with ANP in doses of 0.1 and 1.0 nmol/kginjected intravenously 15 min after antigen challenge reduced PIB in a dose‐dependent manner, and 5 min before antigen challenge significantly attenuated PIB but not antigen‐induced bronchoconstriction. Intravenous ANP significantly reduced bronchial responses to increasing concentrations of inhaled histamine in a dose‐dependent manner.

Conclusion

These results suggest that ANP possesses protective effects against propranolol‐induced and histamine‐induced bronchoconstriction, albeit by a non‐specific mechanism in guinea pig in vivo.
Allergic sensitization and clinical reactions to latex, food and pollen in adult patients
Authors: Levy  , Mounedji  , Noirot  , Leynadier
Published: March 2003

Background

Many latex‐allergic patients are sensitized to one or more foods. Patients allergic to tree and/or grass pollens are also often sensitized to plant‐derived foods. Atopy, defined in most studies as sensitivity to an aeroallergen, is a risk factor for latex allergy. The relative importance of pollen sensitivity, a sign of atopy, as a risk factor for food allergy in latex‐allergic patients has not, however, been examined.

Objective

To investigate the relationship between pollen sensitivity and sensitivity to food in latex‐allergic patients.

Methods

Forty‐four latex‐allergic patients (Groups 1 and 2), 24 of whom were also allergic to tree and/or grass pollen (Group 1) and 25 pollinosis patients who were not allergic to latex (Group 3) were studied. We obtained a history of reactions to food and skin tested them with 12 fresh‐frozen fruits.

Results

All 12 foods induced a skin test reaction in at least one patient in each of the three Groups. There were, however, twice as many positive skin test reactions to food in patients with pollinosis, whether or not they were allergic to latex, as there were in patients allergic to latex but not to pollen. Latex‐allergic patients were most likely to have a positive skin test and a history of a reaction to avocado or banana whereas patients with pollinosis only were most likely to have a positive skin test and a history of a reaction to apple, peach or celery.

Conclusions

These results suggest that concomitant allergy to pollen is an important risk factor in determining which plant‐derived foods sensitize latex‐allergic patients.
Evidence to suggest that the phosphodiesterase 4 isoenzyme is present and involved in the proliferation of umbilical cord blood mononuclear cells
Authors: Banner  , Dimitriou  , Kinali  , Page  , Greenough
Published: March 2003

Background

The type 4 phosphodiesterase (PDE) isoenzyme is the main isoenzyme of PDE involved in the control of adult mononuclear cell proliferation.

Objective

To establish whether PDE isoenzymes are present in umbilical cord blood mononuclear cells by the use of selective PDE inhibitors, and to identify which PDE isoenzymes are involved in controlling the proliferation of cord blood mononuclear cells.

Methods

Cord blood was obtained from normal deliveries and mononuclear cells isolated as described previously [ 1] with some modifications. Mononuclear cells were then stimulated to proliferate with phytohaemagglutinin (PHA) (2 μg/mL) in the presence of selective PDE inhibitors. Proliferation was measured by [3H]‐thymidine incorporation.

Results

The type 4 PDE inhibitors (CDP840, rolipram and RO 20‐1724), and the mixed PDE3/4 inhibitor, zardaverine, produced a concentration‐related inhibition of PHA‐stimulated cord blood mononuclear cell proliferation (P < 0.05,
anova). The non‐selective PDE inhibitor, theophylline, also produced a concentration‐related inhibition of proliferation (P < 0.05,
anova). In contrast, the PDE1 inhibitor, vinpocetine, the PDE3 inhibitor, siguazodan, and the PDE5 inhibitor, zaprinast, were unable to inhibit cord blood mononuclear cell proliferation.

Conclusion

PDE4 is present in umbilical cord mononuclear cells and is involved in the control of cord blood mononuclear cell proliferation.
Sensitization to inhaled antigen by intratracheal instillation of dendritic cells
Authors: Lambrecht  , Peleman  , Bullock  , Pauwels
Published: March 2003

Background

Airway dendritic cells (DCs) capture and present inhaled antigen. It is not known whether antigen presentation by DCs in the airways is sufficient to induce sensitization to inhaled antigen in vivo.

Methods

Rats were immunized by intratracheal instillation of ovalbumin (OVA) ‐pulsed bone marrow‐derived DCs or macrophages and exposed 10 days later to a 30‐min aerosol of OVA on 3 consecutive days. Total and differential cell counts and flow cytometry on bronchoalveolar lavage (BAL) fluid, airway histology and serum OVA‐immunoglobulin (Ig) E levels were analysed 24 h after the last exposure.

Results

As few as 2 × 104 OVA‐DC induced sensitization to inhaled OVA. The secondary response to OVA‐aerosol consisted of an antigen‐specific increase in the number of bronchoalveolar mononuclear cells, activated CD4‐positive αβ‐TCR T lymphocytes, neutrophils and few eosinophils. Peribronchial and perivascular mononuclear cell infiltrates were seen on histological analysis. There was no production of systemic OVA‐IgE. Bone marrow‐derived macrophages did not induce sensitization.

Conclusion

Delivering antigen to the respiratory tract via professional antigen‐presenting DCs sensitizes for a secondary response to inhaled antigen leading to airway inflammation. This model will prove very useful for studying the early events of sensitization to inhaled antigen using the respiratory route.
A randomized trial of dehumidification in the control of house dust mite
Authors: Hyndman  , Vickers  , Htut  , Maunder  , Peock  , Higenbottam
Published: March 2003

Background

House dust mites (HDM) are sensitive to humidity. Few studies have adequately examined the potential of dehumidification in reducing HDM numbers.

Objective

The study examined the effect of portable domestic dehumidifiers, and a behavioural programme to reduce humidity, on HDM counts and HDM allergen levels.

Methods

A randomized controlled trial was undertaken. A total of 76 homes were allocated to three groups that received a portable domestic dehumidifier, a behavioural programme, or no intervention. Humidity, temperature, HDM counts (trap and vacuum samples), HDM allergen, and other details of the home environment were measured on four occasions over a period of 1 year. Interventions and measurements were concerned predominantly with one bedroom.

Results

There was a reduction in relative humidity in the dehumidifier group, but not the behavioural group. A decline in HDM trap counts was observed for all three groups. Change scores did not indicate that the dehumidifier group had a greater decline than the other groups. A secondary analysis examining presence or absence of HDM showed a shift from households having HDM at baseline to households not having HDM in the final round for some trap measures. Change score analysis indicated that this shift was greater in the dehumidifier group compared with other groups. The dehumidifier group did not show a greater decline in HDM allergen than that seen in the other two groups.

Conclusion

Neither the dehumidifier nor the behavioural intervention had a major effect on HDM counts or allergen levels. However, the study did have a number of limitations relating to size, timing of intervention, and running of the dehumidifiers. The secondary data analysis may indicate some effect of dehumidification, but clearly this effect was small. There is a need for more information on the effects of reducing ambient humidity on the distribution of HDM within their habitats.
Localization of a major allergen, Der p 2, in the gut and faecal pellets of Dermatophagoides pteronyssinus
Authors: Park  , Lee  , Lee  , Ree  , Kim  , Hong  , Yong
Published: March 2003

Background

The house dust mite Dermatophagoides ptronyssinus is one of the most significant indoor sensitizing agents of allergy. Allergen localization may indicate the importance of secreted materials, faeces, and nonexcreted mite body components as allergen sources.

Objective

This study attempted to localize the sites and concentrations of Der p 2 in the cryostat sections of D. pteronyssinus using antirecombinant Der p 2 monoclonal antibody.

Methods

Male and female mites and mite faeces collected separately from both sexes were used. Live mites were embedded and serial cryostat sections for light microscopy were performed. Anti‐recombinant Der p 2 monoclonal antibody previously produced by the authors was used. For immunoprobing, mite cryostat sections were incubated in the following antibody‐containing solutions: monoclonal antibody against Der p 2 was initially applied to the sections and fluorescent isothiocyanate conjugated antimouse immunoglobulin G was reacted as the secondary antibody. The faecal pellets were treated the same as described above.

Results

Immunofluorescent probing of cryostat sections with the monoclonal antibody showed labelling of the gut lining, gut contents and defecated faecal pellets. No other internal organs were identified as positively labelled.

Conclusion

This study suggested that a major allergen, Der p 2, found in the house dust mite D. pteronyssinus is derived from the digestive tract and concentrated in the faeces.
Regulation of cyclooxygenase‐1 and ‐2 expression in human nasal mucosa. Effects of cytokines and dexamethasone
Authors: Fernández‐Morata  , Mullol  , Fuentes  , Pujols  , Roca‐Ferrer  , Pérez  , Xaubet  , Picado
Published: March 2003

Background

Cyclooxygenase (COX) converts arachidonic acid in prostanoids. COX exists in two isoforms, COX‐1 is the constitutive whereas COX‐2 is the inducible isoform. The regulation of COX‐1 and COX‐2 expression in nasal mucosa has not been previously reported.

Aim

We studied expression and regulation by cytokines and corticosteroids of COX‐1 and COX‐2 in human nasal mucosa. Cultured human nasal explants from patients undergoing corrective nasal mucosal resection were examined for COX‐1 and COX‐2 expression by semiquantitative competitive PCR and Western blot.

Methods

Explants were incubated with pro‐(IFNγ, IL‐1β, and TNF‐α) and anti(IL‐10) inflammatory cytokines and dexamethasone. The mechanisms which regulate COX‐2 mRNA expression were studied using inhibitors of translation (Actinomycin D) and transcription (Cicloheximide).

Results

The baseline expression of COX‐2 mRNA was higher than COX‐1 mRNA. Once in culture, there was a slight spontaneous up‐regulation of COX‐1 and a strong COX‐2 mRNA and protein up‐regulation. The incubation of nasal explants with pro‐inflammatory cytokines increased the expression of COX‐2 mRNA and protein, from 1 to 24 h of incubation in a dose‐related manner. The regulation of these effects occurred at both transcriptional and post‐transcriptional levels. Dexamethasone and IL‐10 abrogated cytokine‐induced COX‐2 mRNA and protein expression. Pro‐inflammatory cytokines, dexamethasone and IL‐10 had no effect on COX‐1 mRNA expression.

Conclusions

As prostanoids have important regulatory effects on the immunologically mediated inflammatory responses, our findings throw some light on the mechanisms that regulate the enzymes which produce these metabolites in the human airway.
Cytokine responses to Der p 1 and Der p 7: house dust mite allergens with different IgE‐binding activities
Authors: Hales  , Shen  , Thomas
Published: March 2003

Background

There is very limited information comparing T‐cell responses to different house dust mite (HDM) allergens even though T cells are essential in the initiation and regulation of immunoglobulin (Ig) E synthesis and eosinophilia.

Objective

To compare the level of T‐cell proliferation and cytokine production to the group 1 and group 7 HDM allergens which are known to have different IgE‐binding capabilities.

Methods

Freshly isolated peripheral blood mononuclear cells (PBMC) from HDM‐allergic and HDM‐nonallergic donors were stimulated with the group 1 and group 7 allergens of Dermatophagoides pteronyssinus and the level of proliferation as well as IL‐5 and IFNγ production were measured.

Results

The proliferative and IL‐5 production to the group 1 and group 7 allergens were equivalent despite the group 7 allergen's lower frequency of IgE‐binding. However more IFNγ was produced to Der p 7 than to Der p 1, particularly for the nonallergic donors. As expected IL‐5 production was much higher for PBMC from the allergic donors than for cells from nonallergics; however, there was no difference in the level of T‐cell proliferation between the donor groups.

Conclusion

The relative importance of the individual HDM allergens is normally determined by measuring the frequency of IgE‐binding to the allergen in sera from an allergic population. The equivalent increased IL‐5 response of PBMC from allergic people to the group 1 and group 7 allergens despite the different IgE‐inducing activity indicates that these allergens may be equally capable of contributing to an asthmatic response by inducing eosinophilia.
Expression of platelet‐derived endothelial cell growth factor and vascularity in the nasal mucosa from allergic rhinitis
Authors: Mori S. , Fujieda S. , Sunaga H. , Fox S. B. , Saito H.
Published: March 2003

Background

Angiogenesis plays critical roles in various pathological mechanisms. It has been hypothesized that the vascularity in allergic nasal mucosa is different from that in normal mucosa, and that changes in the vascular network contributes the pathogenesis of allergic rhinitis.

Objective

To determine whether hypervascularity and overexpression of the platelet‐derived endothelial cell growth factor (PD‐ECGF), an angiogenic factor, are found in allergic nasal mucosa and whether these two factors are associated with the allergic reaction.

Methods

We investigated the expression of PD‐ECGF and counted microvessels in 51 nasal mucosae (30 samples from patients with allergic rhinitis and 21 samples as control from normal subjects) using an immunohistochemical technique.

Results

PD‐ECGF expression in allergic nasal mucosae was significantly higher than that in control mucosae at the interstitium of the lamina propria (P = 0.0024) and nasal gland (P = 0.024). PD‐ECGF positive areas were coincident with areas of high vascularity in the sections. The microvessel count in the lamina propria of allergic mucosae was higher than that of control mucosae (P = 0.050). Regarding the correlation with various clinical factors, the total nasal symptom score was significantly associated with both the PD‐ECGF expression in the interstitium of the lamina propria (P < 0.05) and in the nasal gland (P < 0.005), as well as with the number of vessels (P < 0.05).

Conclusion

PD‐ECGF and hypervascularity in the nasal mucosa may be involved in the pathogenesis of allergic rhinitis.
Airway inflammation in a murine model of chronic asthma: evidence for a local humoral immune response
Authors: Kumar R. K. , Temelkovski J. , Mcneil H. P. , Hunter N.
Published: March 2003

Background

Asthma is an acute‐on‐chronic inflammatory disease of the airways characterized by recruitment of eosinophils into the epithelial layer, chronic inflammation in the lamina propria, as well as variable accumulation of mast cells in the airway wall. The role of local production of allergen‐specific immunoglobulins in triggering mast cell‐mediated asthmatic inflammation is unknown.

Methods

We used a chronic inhalational exposure model of asthma in ovalbumin‐sensitized BALB/c mice to examine the phenotype of immunoglobulin‐secreting cells and mast cells in the airway wall. In parallel, we assayed ovalbumin‐specific IgG and total IgE in the plasma of these animals.

Results

In sensitized mice exposed to aerosolized ovalbumin for 6 weeks, aggregates of chronic inflammatory cells consisted of a majority of plasmacytoid cells, including numerous IgG‐synthesizing cells, which were significantly increased in sensitized animals compared to controls. IgA‐synthesizing cells were also present, but were not increased in the sensitized exposed mice. Immunoglobulins in the cytoplasm of the plasma cells were demonstrated to be antigen‐specific. No IgM‐or IgE‐synthesizing cells were observed, although levels of total IgE in the plasma were significantly increased. There was no recruitment of mast cells of either the mucosal or the connective tissue phenotype into the lamina propria or the epithelium.

Conclusion

In this experimental model of chronic asthma, the pattern of inflammation in the airway wall is consistent with development of a local IgG‐mediated humoral immune response. However, there is no evidence of local production of IgE or recruitment of mast cells.
Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid
Authors: Pullerits T. , LindÉn A. , Praks L. , Cardell L. O. , LÖtvall J.
Published: March 2003

Background

Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils.

Objective

We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression.

Methods

Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 μg/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season.

Results

Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo‐treated (P = 0.04; n = 9) but not in beclomethasone‐treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo‐treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season.

Conclusion

Expression of eotaxin in nasal mucosa of grass‐pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.
Immunological and molecular characterization of the major allergens from lilac and privet pollens overproduced in Pichia pastoris
Authors: González E. , Villalba M. , Rodríguez R.
Published: March 2003

The main allergens from privet and lilac pollens, Lig v 1 and Syr v 1, are proteins homologous to Ole e 1 and have been shown to be involved in cross‐reactivity.

To overproduce the correctly folded Lig v 1 and Syr v 1 allergens and to study their immunological properties in comparison with those of their natural counterparts.

The yeast Pichia pastoris was used as an expression system to produce these recombinant allergens. The proteins were isolated by ion‐exchange and size‐exclusion chromatographies. Amino acid quantifying, Edman degradation, mass spectrometry and circular dichroism were carried out to obtain molecular properties of the recombinant proteins. Anti‐Ole e 1 monoclonal and polyclonal antibodies, as well as sera from patients allergic to olive pollen, were used in immunoblotting and ELISA for immunological characterization.

Recombinant Lig v 1 and Syr v 1 were secreted at high yield to the extracellular medium of the yeast. The purified proteins displayed the native conformation, as deduced from their spectroscopic properties and binding ability to an IgG monoclonal antibody. The recombinant allergens behaved similarly to their natural counterparts when they were analysed against Ole e 1‐specific antibodies. IgE and IgG binding properties of lilac and privet allergens to olive allergic sera and Ole e 1‐specific antibodies indicated that these molecules share common B‐cell epitopes with Ole e 1.

P. pastoris yeast is an appropriate system for the efficient production of Ole e 1‐like allergens, which could be used as analogous allergens and predictors of clinical sensitization.
Effect of a specific cysteinyl leukotriene‐receptor 1‐antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells
Authors: Virchow Jr J. C. , Faehndrich S. , Nassenstein C. , Bock S. , Matthys H. , Luttmann W.
Published: March 2003

Background Leukotrienes have been implicated in the selective infiltration of eosinophils into the bronchial mucosa in asthma.

Objective We studied whether eosinophil transmigration through cultured human umbilical vein endothelial cells (HUVECs) can be blocked by a specific cysteinyl LT1‐receptor‐antagonist.

Methods Unstimulated and stimulated eosinophils from patients with asthma and normal controls were subjected to confluent human umbilical vein endothelial cell (HUVEC) monolayers separating the upper and lower chamber of Transwell™‐culture plates. Unstimulated eosinophils or cells pre‐incubated in the presence of the eosinophil activating cytokines GM‐CSF or IL‐13 were placed in the upper chambers while PAF, a potent chemoattractant factor for eosinophils, was added to the lower chamber. Migration of eosinophils was quantified by a β‐glucuronidase assay.

Results The assumption that eosinophils express CysLT1 (cysteinyl‐leukotriene 1)‐receptors was based on our demonstration of mRNA‐expression for the CysLT‐1‐receptor by polymerase chain reaction on purified eosinophils. The chemotactic response to PAF was significantly reduced when eosinophils were pre‐incubated with montelukast for 15 min. When eosinophils were pre‐incubated with GM‐CSF and/or IL‐13, the migratory response to PAF was also significantly reduced by montelukast.

Conclusion From these data we conclude that the specific cysteinyl LT1‐receptor antagonist montelukast can inhibit PAF‐induced eosinophil transmigration through cultured HUVEC monolayers.
Fusarium solani major allergen peptide IV‐1 binds IgE but does not release histamine
Authors: Verma J. , Sridhara S. , Singh B. P. , Pasha S. , Gangal S. V. , Arora N.
Published: March 2003

Background Fusarium solani (FS) is an important allergen source afflicting 4% of the nasobronchial allergy patients. Fus s I3596*, a 65 kDa major glycoprotein allergen of FS reacts with 95% fungus sensitive patients.

Objectives To purify and characterize a potent peptide from Fus s I3596* which may be useful for therapeutic purposes.

Methods The 65 kDa protein was sequentially cleaved with trypsin and cyanogen bromide (CNBr). The cleaved products were purified on reverse phase high performance liquid chromatography (rpHPLC) column and functionally characterized by in vitro and in vivo methods for its IgE binding and histamine release.

Results The protein on cleavage showed 11 peaks (I to XI). Of these, peaks I, III, IV and V were highly allergenic as determined by IgE ELISA. These peaks were further purified and peptide IV‐1 was most potent in comparison to other peptides by ELISA‐inhibition. This peptide showed IgE binding but could not evoke intradermal response in Fusarium‐sensitive patients. Heparinized blood challenged with peptide IV‐1 does not release histamine. Preincubation of heparinized blood with peptide IV‐1 and challenging with crude extract blocked histamine release in a dose dependent manner.

Conclusion Peptide IV‐1 binds to IgE but does not release histamine, demonstrating its potential use in therapy of Fusarium‐allergic patients.
IgE‐dependent release of myeloperoxidase by neutrophils from allergic patients
Authors: Monteseirín J. , Bonilla I. , Camacho M. J. , Conde J. , Sobrino F.
Published: March 2003

Background The three forms of IgE receptor: the heterotrimeric high‐affinity receptor for IgE (FcεRI), the low‐affinity receptor for IgE (FcεRII/CD23) and the Mac‐2/IgE‐binding protein (εBP), have previously been found on human neutrophils. We have previously shown that specific allergens are able to activate functional responses by neutrophils from allergic patients sensitized to those allergens. Neutrophils are present in the sites of allergic inflammation. The primary (azurophilic) granules of neutrophils contain a variety of enzymes that might potentiate inflammation, such as myeloperoxidase (MPO). It is not known whether specific allergens are able to elicit MPO release by neutrophils from allergic patients.

Methods Neutrophils were challenged in vitro with the specific allergen that produced clinical symptoms in asthmatic patients. Also, the cells were challenged with allergens that the patients were not sensitive to. Neutrophils from normal subjects were also challenged with allergens.

Results The in vitro challenge of neutrophils with allergens that the patients were sensitive to elicited a release of MPO by these cells. The in vitro activation of neutrophils was highly allergen‐specific, in such a way that allergens other than those accounting for clinical symptoms did not evoke MPO release, and allergens were ineffective on neutrophils from healthy donors.

Conclusion An IgE‐dependent mechanism might promote MPO release by neutrophils at allergic sites.
In vivo airway eosinophil accumulation induced by polymyxin‐B reduces bronchial responsiveness in guinea pigs
Authors: Ishiura Y. , Fujimura M. , Myou S. , Nobata K. , Liu Q. , Yamamori C. , Amemiya T.
Published: March 2003

Background Chronic desquamative eosinophilic bronchitis and bronchial hyperresponsiveness have been considered essential for bronchial asthma. However, it has not been studied whether airway eosinophils enhance or inhibit bronchial responsiveness in vivo.

Objective This study was conducted to elucidate the influence of airway eosinophil accumulation on bronchial responsiveness in vivo.

Materials and methods Guinea pigs were transnasally treated with 75 µg/kg of polymyxin‐B or vehicle twice a week for a total of 3 weeks. Guinea pigs were surgically cannulated and artificially ventilated 24 h after the last administration of polymyxin‐B or vehicle. Ten minutes after the installation of artificial ventilation, ascending doses of methacholine, acetylcholine or histamine were inhaled for 20 s at intervals of 5 min. Subsequent study was conducted 20 min after treatment of 60 mg/kg of indomethacin in the same manner. Final study was conducted in naive guinea pigs after single inhalation of 75 µg/mL of polymyxin B.

Results The proportion of eosinophils in bronchoalveolar lavage fluid significantly increased in guinea pigs treated with polymyxin‐B compared with vehicle. Bronchial responsiveness to inhaled methacholine, acetylcholine and histamine was significantly decreased by the polymyxin‐B treatment. This protective effect induced by polymyxin B was abolished by pretreatment of indomethacin. A significant increase in bronchial responsiveness was observed after a single inhalation of polymyxin B.

Conclusion These results suggest that in vivo airway eosinophils may reduce non‐specific bronchial responsiveness through inhibitory or bronchoprotective prostanoids.
IgE binding components in Tetranychus urticae and Panonychus ulmi‐derived crude extracts and their cross‐reactivity with domestic mites
Authors: Kim Y.‐K. , Oh S.‐Y. , Jung J.‐W. , Min K.‐U. , Kim Y.‐Y. , Cho S.‐H.
Published: March 2003

Background Recent investigation has revealed that spider mites such as Tetranychus urticae and Panonychus ulmi are important allergens in the development of occupational asthma among apple farmers.

Objective To evaluate IgE binding components in T. urticae and P. ulmi‐derived crude extracts and their cross‐reactivity with Panonychus citri, Tyrophagus putrescentiae and Dermatophagoides pteronyssinus in apple cultivating farmers.

Methods Thirty‐one apple farmers with positive skin responses to T. urticae or P. ulmi were randomly recruited, and specific IgE levels in their sera were measured using ELISA. Cross‐reactivity was evaluated by ELISA inhibition. IgE binding components were evaluated by IgE immunoblotting.

Results A total of 11 IgE binding components in T. urticae and 10 in P. ulmi were found. Among them, the 17 kDa, 27 kDa, 33 kDa, 37 kDa, 41 kDa, 56 kDa, and 75 kDa allergens in T. urticae, and the 33 kDa, 41 kDa, and 51 kDa allergens in P. ulmi were identified as dominant allergens. T. urticae‐specific IgE binding was completely inhibited by 100 μg/mL of T. urticae (99.7%), but only partially inhibited by P. citri (83.0%), P. ulmi (71.6%), T. putrescentiae (69.7%), and D. pternonyssinus (60.1%). P. ulmi‐specific IgE binding was completely inhibited by additions of P. citri (92.3%) and P. ulmi (91.2%), but only partially inhibited by the addition of T. urticae (61.5%), T. putrescentiae (57.7%), and D. pteronyssinus (54.4%).

Conclusion There were seven dominant allergens found in T. urticae and three in P. ulmi. T. urticae‐ and P. ulmi‐specific IgE bindings were partially inhibited by crude extracts derived from D. pteronyssinus and T. putrescentiae.
Ambient ozone exposure is associated with eosinophil activation in healthy children
Authors: Frischer T. , Studnicka M. , Halmerbauer G. , Horak Jr F. , Gartner C. , Tauber E. , Koller D. Y.
Published: March 2003

Background Eosinophil activation is characteristic for allergic airways disease. However, eosinophilic airways inflammation has also been observed subsequent to ambient ozone exposure.

Methods For a population sample of 877 children living at nine sites with different ozone exposure we measured urinary eosinophil protein X (U‐EPX) as a marker of eosinophil activation. U‐EPX was determined from a single spot urine sample during autumn 1997. Children were participants in a longitudinal study of ozone effects on lung function.

Results The 5–95% percentiles of ozone exposure (30‐day mean before test) were 11.8–51.5 p.p.b. (mean: 31.6 ppb). U‐EPX was measured by radioimmunoassay and expressed as ratio to urinary creatinine (µg EPX/mmol creatinine). Log transformation was performed to achieve a normal distribution. LogU‐EPX was associated with gender, a diagnosis of asthma and atopy (skin test sensitivity to any of seven aeroallergens). LogU‐EPX increased with ozone exposure for all children. The medians of LogU‐EPX according to the first–fourth quartiles of ozone exposure were: 1.82, 1.88, 1.95 and 2.03. For 172 non‐asthmatic children who had spent the whole summer at their site corresponding figures were 1.57, 1.78, 2.07 and 2.13. In a multivariate model with logU‐EPX being the dependent variable and adjusted for gender, site and atopy, ozone was found to be significant (estimate: 0.007 µg/mmol creatinine per ppb ozone; SE:0.02; P < 0.001).

Conclusion Our observation supports the hypothesis that ozone in healthy children is associated with eosinophil inflammation, most likely in the airways.
Concomitant allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis: a review of an uncommon association*
Authors: Shah A. , Panchal N. , Agarwal A. K.
Published: March 2003

Background Although thought to have common immunopathological processes, concomitant occurrence of allergic bronchopulmonary aspergillosis (ABPA) and allergic Aspergillus sinusitis (AAS) appears to be rarely reported as to date only five detailed case reports are available.

Objective To present a review of seven cases of concomitant ABPA and AAS, three of whom were earlier reported for their unusual presentations.

Methods Patients with ABPA with nasal symptoms were evaluated radiologically. Consent was taken for antral wash and/or Caldwell‐Luc operation in those with radiological evidence of sinusitis and the material was sent for histopathological and mycological studies.

Results Of the 95 patients with ABPA, 22 had radiological evidence of sinusitis. Nine consented to surgery, seven of whom were diagnosed as concomitant AAS. Nasal symptoms preceded chest symptoms in two patients, vice versa in one and occurred simultaneously in four. Familial occurrence of ABPA, middle lobe syndrome and collapse with effusion along with an operated aspergilloma were seen in one patient each. Transient pulmonary infiltrates and central bronchiectasis were seen in all patients. Computed tomography of the paranasal sinuses, carried out in six patients, revealed mucosal thickening with hyperdense lesions, without any bony erosion or destruction. All patients had positive skin tests, positive precipitin study and raised total and specific IgE. Allergic mucin was seen in all patients, fungal hyphae in five, and culture grew Aspergillus spp. in four. All patients responded favourably to oral prednisolone.

Conclusion Concomitant occurrence of ABPA and AAS seems to be infrequently recognized. Since asthma and sinusitis are often seen by two different specialities, the occurrence of AAS in ABPA and ABPA in AAS may easily be overlooked.