bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory neuropeptides induce histamine release from bronchoalveolar lavage cells in both nonasthmatic coughers and cough variant asthmatics
Authors: Forsythe  , Mcgarvey  , Heaney  , Macmahon  , Ennis
Published: March 2003

Background

Sensory neuropeptides have been suggested to play a role in the pathogenesis of a number of respiratory diseases including asthma and chronic non‐productive cough.

Objectives

To investigate the action of sensory neuropeptides on airway mast cells obtained by bronchoalveolar lavage (BAL).

Methods

BAL was performed on 23 nonasthmatic patients with cough (NAC), 11 patients with cough variant asthma (CVA) and 10 nonatopic controls. Washed lavage cells were stimulated (20 min, 37 °C) with calcitonin gene‐related peptide (CGRP), neurokinin A (NKA) and substance P (25 and 50 μmol/L).

Results

The neuropeptides tested induced histamine release in all groups studied. Only CGRP (50 μmol/L) induced significantly more histamine release from both NAC and CVA patients compared with control subjects (P = 0.038 and 0.045, respectively).

Conclusion

Regardless of aetiology, mast cells from patients with chronic cough appear to have an increased responsiveness to CGRP compared with controls. The results of the present study suggest that the role of CGRP in chronic cough should be further investigated.
Functional effects of the inhibition of the cysteine protease activity of the major house dust mite allergen Der p 1 by a novel peptide‐based inhibitor
Authors: John  , Rusznak  , Ramjee  , Lamont  , Abrahamson  , Hewitt
Published: March 2003

Background

The house dust mite (HDM) Dermatophagoides pteronyssinus is an important source of allergens, which can cause allergic conditions. The cysteine protease activity of Der p 1 may enhance the potency of this major mite allergen through cleavage of CD23 and CD25 from the surface of immune cells, IgE independent mast cell activation, increases in epithelial cell permeability and inactivation of an endogenous serine protease inhibitor. Inhibition of the enzymatic activity of Der p 1 may therefore be of therapeutic benefit.

Objective

To examine the activity of PTL11028, a newly developed Der p 1 inhibitor, in a range of assays that directly or indirectly measure Der p 1 protease activity and to compare its activity to endogenous cysteine protease inhibitors.

Methods

The proteolytic activities of purified Der p 1 or HDM extract and inhibitory properties of PTL11028 were examined through cleavage of an artificial peptidyl substrate, cleavage of CD23 from human B cells and permeability studies on primary human bronchial epithelial cells.

Results

PTL11028 is a highly potent and specific Der p 1 inhibitor, being effective against both purified protease and Der p 1 within HDM extract. PTL11028 can completely inhibit Der p 1‐mediated CD23 cleavage from human B cells and also reduces HDM‐induced human bronchial epithelial cell permeability by 50%. Der p 1 is potently inhibited by cystatin A and to a lesser extent by cystatins C and E/M.

Conclusion

PTL11028 is a highly potent and selective irreversible inhibitor of the cysteine protease activity of Der p 1, an activity that may be modulated in vivo by some human cystatins. PTL11028 prevents the Der p 1‐mediated cleavage of CD23 from human B cells and significantly reduces HDM‐induced permeabilization of the epithelial barrier. PTL11028 is an important tool to examine the biological effects of Der p 1 in a range of in vitro and in vivo model systems.
Validation of the ISAAC video questionnaire (AVQ3.0) in adolescents from a mixed ethnic background
Authors: Gibson  , Henry  , Shah  , Toneguzzi  , Francis  , Norzila  , Davies
Published: March 2003

Background

The International Study of Asthma and Allergies in Childhood (ISAAC) has developed an international version of the asthma video questionnaire (AVQ3.0) to measure asthma prevalence. This questionnaire has not been validated in adolescents from a mixed ethnic background.

Objective

The aims of this study were to compare the video questionnaire with a written questionnaire in the detection of airway hyperresponsiveness to hypertonic saline in a population of adolescents from a mixed ethnic background, and to establish the repeatability and psychometric properties of the asthma video questionnaire.

Methods

The study was conducted in four secondary schools in Sydney, an area with a high proportion of people from a non‐English speaking background. Four hundred and seventy‐five students from schools 1 and 2 completed the video questionnaire and a subgroup of these students (n = 170) completed the written questionnaire and a hypertonic saline inhalation challenge. Reproducibility of the questionnaire was evaluated by administering the questionnaire to a subsample of students 2 weeks later. The psychometric properties of the video questionnaire were examined in 852 students at two other schools (schools 3 and 4).

Results

One hundred and sixty‐nine students aged 13.5 (sd 1.3) years completed both written and video questionnaires, and the hypertonic saline challenge. The students had widely different cultural backgrounds including Asian, South Pacific, Middle Eastern, European and African countries. There was good agreement between the questionnaires for wheeze (kappa 0.42). Questions on the video questionnaire concerning wheezing had good sensitivity (90%) and specificity (68%) for airway hyperresponsiveness to hypertonic saline. The video questionnaire was reproducible (kappa 0.82), had good internal consistency (Cronbach's alpha 0.81) and each question pertained to a single construct explaining 58% of the variance in total score.

Conclusion

This study has validated the international version of the ISAAC video questionnaire against airway hyperresponsiveness to hypertonic saline in adolescents from a mixed ethnic background, and identified that the questionnaire has good psychometric properties. The ISAAC video has proved to be a valuable tool for the assessment of asthma prevalence in populations of ethnic diversity.
Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin E antibodies and identification of an allergenic determinant
Authors: Pham  , Weiner  , Reisner  , Baldo
Published: March 2003

Background

There are many reports of allergic reactions, including anaphylaxis, following exposure to chlorhexidine. Reactions may occur via contact with the skin and mucous membranes or from catheters treated with the antibacterial agent. Apart from implicating chlorguanide in immunoglobulin (Ig) E antibody‐binding studies on serum from an anaphylactic patient, little work has been done on the molecular basis of recognition of the agent in sensitive subjects.

Objectives

The molecular basis of IgE‐binding to chlorhexidine was closely examined with the view of defining its fine structural recognition features by antibodies from a subject who experienced anaphylaxis following contact with the antiseptic.

Methods

Tryptase determinations, different drug‐solid phases, immunoassays and quantitative hapten inhibition studies with chlorhexidine and selected structural analogues were employed together with serum from the anaphylactic patient. Results were analysed to define the complete drug allergenic determinant and to identify the important structural features complementary to the IgE antibody combining sites.

Results

The subject's serum tryptase levels sampled after the reaction were elevated and employment of a chlorhexidine‐EA Sepharose solid phase showed the presence of serum IgE antibodies to the drug. Lack of inhibition by 4‐chlorophenol and other selected substituted phenyl compounds showed that the terminal groups at each end of the chlorhexidine molecule, alone, did not account for antibody recognition of the antibacterial agent. Although chlorguanide and alexidine, the structures of which each comprise part of the chlorhexidine molecule, showed significant inhibition of the binding of IgE antibodies to chlorhexidine, neither compound was as potent an inhibitor as chlorhexidine itself. Two molecules of chlorguanide make up the symmetrical molecule of chlorhexidine while the interior structure of alexidine (that is excluding the terminal 2‐ethylhexyl groups) is identical to part of the chlorhexidine molecule.

Conclusions

Taken together, for this patient, these results lead to the conclusion that the whole chlorhexidine molecule is complementary to the IgE antibody combining sites and that the 4‐chlorophenol, biguanide and hexamethylene structures together comprise the allergenic determinant. Hence, like one of the trimethoprim determinants identified, but unlike most drug allergenic determinants identified so far, the chlorhexidine allergenic determinant identified here encompasses the entire molecule.
The association of sensitization to inhalant allergens with allergy symptoms: the influence of bronchial hyperresponsiveness and blood eosinophil count
Authors: Kerkhof M. , Schouten J. P. , De Monchy J. G. R.
Published: March 2003

Background

We investigated whether the association of allergy symptoms with sensitization to inhalant allergens depends on bronchial hyperresponsiveness, blood eosinophil count, or the degree and nature of sensitization.

Methods

Data on asthma and rhino‐conjunctivitis symptoms were obtained from 1904 subjects from a random sample of the Dutch population, aged 20–70 years by the ECRHS questionnaire. Total IgE and specific IgE to four inhalant allergens were measured using CAP System. Bronchial hyperresponsiveness (BHR) was defined as PD20≤ 2 mg methacholine and ‘high eosinophil count’ as an eosinophil count in the highest quartile.

Results

Forty‐three percent of the subjects with specific IgE to inhalant allergens was asymptomatic. These subjects had a lower degree of sensitization than symptomatic sensitized subjects and had ‘normal’ prevalences of BHR and ‘high eosinophil count’. Logistic regression showed that the presence of BHR increased the risk of having symptoms for subjects who were sensitized to indoor allergens. Low levels of specific IgE to indoor allergens were only associated with symptoms when BHR was present. Sensitization to outdoor allergens was associated with symptoms at all levels of specific IgE, independently of BHR or eosinophils.

Conclusion

Our epidemiological data suggest that whether low levels of specific IgE to indoor allergens lead to allergic symptoms is probably determined by the concurrent existence of inflammation of the airways.
Intranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo‐controlled study
Authors: Gerth Van Wijk R. , Terreehorst I. T. , Mulder P. G. H. , Garrelds I. M. , Blom H. M. , Popering S.
Published: March 2003

In a recent placebo‐controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non‐allergic non‐infectious rhinitis. In this study the therapeutic effect lasted more than 9 months. This effect was not based on modulation of inflammation.

To evaluate the effect of repeated application of capsaicin to patients with a nasal allergy to house dust mites (HDM), using the same treatment protocol as recently introduced in the treatment of non‐allergic patients.

Twenty‐six patients with rhinitis, 15 females and 11 males (range: 20–46 years; mean 30.5), allergic to HDM were treated with either capsaicin or placebo in a double‐blind, placebo‐controlled, parallel group design. Nasal reactivity to HDM expressed as nasal symptoms, albumin and leukotriene levels in nasal lavage fluid and responsiveness to histamine, assessed as symptoms before and 6 weeks after treatment, were used to compare both treatment groups. In addition, visual analogue scales and rhinitis quality of life (RQL) assessment before, 6 weeks after and 3 months after treatment were used as outcome variables.

No significant effect of capsaicin on nasal challenge tests with HDM (nasal symptoms, albumin and leukotriene levels), on VAS or RQL outcome 6 weeks or 3 month's after treatment, was demonstrated. Capsaicin did have a small effect on the area of the curve (AUC) of histamine dose response curves (P = 0.03).

Desensitization with capsaicin in doses sufficient to control symptoms in patients with severe non‐allergic rhinitis is lacking therapeutic effect in perennial allergic rhinitis.
The lymphoproliferative response to enzymatically digested gelatin in subjects with gelatin hypersensitivity
Authors: Kumagai T. , Nakayama T. , Kamada M. , Igarashi C. , Yuri K. , Furukawa H. , Wagatuma K. , Tsutsumi H. , Chiba S. , Kojima H. , Saito A. , Okui T. , Yano S.
Published: March 2003

Background

This study was designed to evaluate the immunogenic characteristics of enzymatically digested gelatin, ‘FreAlagin’, employing the lymphoproliferative response in subjects with gelatin hypersensitivity. Our purpose was to assess the response of primed lymphocytes to the newly developed FreAlagin and compare it to the response to conventional gelatin.

Methods

A gelatin‐specific lymphocyte proliferation test (LPT) was performed in 110 children with adverse reactions to gelatin‐containing vaccines, who showed positive gelatin‐specific cell‐mediated immunity and were thus diagnosed as having gelatin hypersensitivity. Gelatin‐specific IgE was measured in all subjects. The antigenic activity of FreAlagin to lymphocytes was compared with that of conventional bovine gelatin. Positive and negative control specimens were obtained from the patients with anaphylaxis and from subjects inoculated with gelatin‐free vaccine who showed no adverse reactions in order to establish the fluorometric ELISA system to determine IgE antibody to gelatin and LPT.

Results

The lymphocyte activity against FreAlagin was much less than that to Wako gelatin and more than half of the subjects who reacted positively to Wako gelatin had a negative LPT to FreAlagin. Although 47% of the subjects had positive LPTs to FreAlagin, all but two still had lower SIs to FreAlagin compared with Wako gelatin.

Conclusion

We conclude that the antigenic activity of FreAlagin as measured by the cell‐mediated immune response is significantly less than that of conventional bovine gelatin. However, it is still necessary to perform clinical trials to show a reduced or absent clinical reactivity to FreAlagin in sensitized patients to conventional gelatin.
Differential mediator release from basophils of allergic and non‐allergic asthmatic patients after stimulation with anti‐IgE and C5a
Authors: Abrahamsen O. , Haas H. , Schreiber J. , Schlaak M.
Published: March 2003

The differentiation between allergic and non‐allergic asthma is a common and important challenge for the clinician. Until now, no in vitro diagnostic characteristics have been described to distinguish between these types.

To examine the diagnostic value of a basophil stimulation test, we compared anti‐IgE‐ and C5a‐induced mediator release from peripheral blood leucocytes in different types of bronchial asthma.

Peripheral blood leucocytes (PBL) from 10 aspirin‐sensitive asthmatics (ASA), 12 non‐allergic asthmatics without aspirin intolerance (NAA), seven allergic asthmatics (AA), and nine healthy controls were prepared by dextran sedimentation. After priming with interleukin‐3 (IL‐3) PBL were stimulated with anti‐IgE and C5a, and the release of histamine (HR) and sulfidoleukotrienes (LTR) in the supernatant was compared. Additionally, purified leucocyte fractions were studied to determine the cellular source of mediator release.

Upon stimulation with anti‐IgE LTR was slightly, but not significantly, lower in ASA and NAA compared to AA and controls. In contrast, C5a‐triggered LTR was significantly higher in ASA (14.4 ± 12.88 pg/105 cells) and NAA (22.9 ± 22.61 pg/105 cells) than in AA (9.6 ± 3.29 pg/105 cells) and controls (7.5 ± 7.19 pg/105 cells) (P < 0.05). This difference between ASA and NAA vs. AA and controls was even more pronounced when determining the quotient C5a‐/anti‐IgE‐induced LTR (P < 0.001). At an optimal cut‐off point of 1.0, calculated by relative operating characteristics (ROC) analysis, the positive predictive value for a donor to belong to ASA or NAA was 0.94. No significant differences could be found in HR between the asthmatic patient groups and healthy controls in either condition. As cellular source of LTR and HR the basophil could be determined.

Determination of anti‐IgE‐ and C5a‐induced LTR from basophils allows us to discriminate between allergic and non‐allergic asthmatic patients. For diagnostic purposes the quotient C5a‐/anti‐IgE‐induced LTR is more significant than considering a single parameter. ASA cannot be distinguished from NAA.
The NK‐2 receptor antagonist SR 48968C does not improve adenosine hyperresponsiveness and airway obstruction in allergic asthma
Authors: Kraan J. , Vink‐Klooster H. , Postma D. S.
Published: March 2003

When stimulated, excitatory nonadrenergic noncholinergic (e‐NANC) nerves locally release tachykinins like Neurokinin (NK) A and Substance P, causing neurogenic inflammation and airway obstruction via activation of specific NK‐1 and NK‐2 receptors. The recently developed nonpeptide NK‐2 receptor antagonist SR 48968C has a high affinity for the NK‐2 receptor, and is a strong and selective antagonist of NK‐2 receptor mediated airway obstruction.

In a placebo‐controlled cross‐over study, we investigated the effect of SR 48968C, administrated orally once‐daily in a dosage of 100 mg during 9 days, on airway responsiveness to adenosine 5′‐monophosphate (AMP) in 12 allergic asthmatic patients. Furthermore, we assessed its effect on airway obstruction, by measuring FEV1 on the first and last day of each treatment period and by peak flow registration at home throughout the study period.

SR 48968C had no significant effect on PC20AMP or on FEV1 measured on day 1 and 9, and morning and evening peakflow measured at home on day 2–8. Thus, although SR 48968C was administrated in a dosage that might cause a demonstrable blocking effect on airway NK‐2 receptors in asthma, it did not have a significant bronchodilatory or bronchoprotective effect against adenosine hyperresponsiveness in this study. Further studies are needed to assess the value of SR 48968C and other NK receptor antagonists in the treatment of asthma
Pharmacokinetics of an allergen and a monomeric allergoid for oromucosal immunotherapy in allergic volunteers
Authors: Bagnasco M. , Passalacqua G. , Villa G. , Augeri C. , Flamigni G. , Borini E. , Falagiani P. , Mistrello G. , Canonica G.W. , Mariani G.
Published: March 2003

Little is known about the pharmacokinetics of allergens for local immunotherapy. Thus, we studied the pharmacokinetics in allergic volunteers of a commercial allergenic vaccine in orosoluble tablets (LAIS®, Lofarma S.p.A).

The carbamylated monomeric allergoid derived from Parietaria judaica major allergen (Par j 1), characterized by maintenance of the original molecular size, and the native allergen, were radiolabelled with 123I, then incorporated into the commercial soluble tablets and administered to allergic subjects. Early sequential and late static scintigraphic acquisitions were performed, and plasma radioactivity was measured at different time intervals.

No difference in local pharmacokinetics was observed between the allergen and the allergoid: part of the tracer was retained in the mouth for at least 2 h after swallowing. No direct absorption through the oral mucosa could be detected, as plasma radioactivity increased only after swallowing and peaked at 2 h. However, the plasma peak attained with the allergoid in tablets was significantly higher with respect to the native allergen. Finally, some undegraded allergoid, but not the allergen, could be constantly detected in the bloodstream at plasma peak.

The results showed a similar behaviour of the allergoid and the allergen in tablets as far as their local kinetics are concerned, whereas plasma peak was higher with the allergoid than with the allergen. Therefore we conclude that the chemical modification of the allergen may affect its pharmacokinetics, by making it less susceptible to enzymatic degradation.
Allergen‐induced bronchial inflammation is associated with decreased levels of surfactant proteins A and D in a murine model of asthma
Authors: Wang J. Y. , Shieh C. C. , Yu C. K. , Lei H. Y.
Published: March 2003

Background Increasing evidence suggests that pulmonary surfactant protein A (SP‐A) and D (SP‐D) participate in the lung defence against pathogens. However, the role of surfactant proteins in the pathogenesis of allergen‐induced airway inflammation has not been elucidated. In this study we examined the levels and distributions of SP‐A and SP‐D in a dust mite (Dermatophagoides pteronyssinus, Der p) allergen‐induced murine model of asthma.

Methods The concentration of SP‐A and SP‐D in the bronchoalveolar lavage fluid (BALF) and the distribution of surfactant proteins in the lung were assayed by ELISA and immunohistochemistry methods, respectively. The effect of surfactant proteins on allergen‐induced pulmonary lymphocyte proliferation was also studied.

Results We demonstrated that there were marked reductions of SP‐A and SP‐D levels in the BALF of Der p‐sensitized BALB/c mice at 48–72 h after allergen challenge (AC). Both purified SP‐A and SP‐D were able to suppress, in a dose dependent manner, Der p‐stimulated intrapulmonary lymphocyte proliferation of naïve mice with saline or allergen challenge, or of Der p‐sensitized mice with saline challenge. On the contrary, this suppressive effect was mild (< 9%) on lymphocytes from sensitized mice after AC.

Conclusion These results indicated the involvement of pulmonary surfactant proteins in the allergic bronchial inflammation of sensitized mice.
Serum eosinophil cationic protein levels measured during exacerbation of asthma: characteristics of patients with low titres
Authors: Matsumoto H. , Niimi A. , Minakuchi M. , Izumi T.
Published: March 2003

Background Serum eosinophil cationic protein (ECP) levels reflect ongoing eosinophilic airway inflammation and are used as a marker for asthma activity. ECP levels, however, may not be elevated in some asthmatic patients, even when they are symptomatic.

Objective To clarify the characteristics of patients with ‘low’ ECP titres despite asthma exacerbation.

Methods Serum ECP levels were measured in 113 asthmatic patients during exacerbation. Patients were divided into two groups according to ECP titre: a high ECP group (H; ECP ≥ 16.0 µg/L) and a low ECP group (L; ECP <16.0 µg/L). Twenty‐two patients who had recently received systemic steroids were excluded and the clinical features of the remaining patients in H (n = 54) and L (n = 37 were compared.

Results Gender, atopic or smoking status, disease severity, inhaled steroid or theophylline usage, peak expiratory flow (% personal best) and forced expiratory volume in 1 s (FEV1) (% predicted) did not significantly differ between the two groups. Patients in L were significantly older and had longer disease duration and lower serum IgE levels than those in H. Multivariate analysis combining age, disease duration and IgE levels showed that age and disease duration were independently associated with ECP level. Airway wall thickness, assessed in a subset of patients using computed tomography, was significantly larger in L.

Conclusion Serum ECP levels in asthmatic patients may not be elevated during exacerbation and thus may not be a useful marker in patients who are older, have longer disease duration or possibly have thicker airway walls. Mechanisms other than eosinophilic inflammation, such as airway remodelling, may be involved in asthma exacerbation in these patients.
Cloning and expression of Aspergillus fumigatus allergen Asp f 16 mediating both humoral and cell‐mediated immunity in allergic bronchopulmonary aspergillosis (ABPA)
Authors: Banerjee B. , Kurup V. P. , Greenberger P. A. , Johnson B. D. , Fink J. N.
Published: March 2003

Background Aspergillus fumigatus, a ubiquitous fungus, is responsible for a number of lung disorders in atopic and non‐atopic individuals. Standardized, pure, and relevant allergens are desirable for reliable immunodiagnosis of the disease and to understand the structural and functional properties of these allergens and the role they play in causing ABPA.

Objective Molecular cloning and characterization of a relevant allergen from A. fumigatus cDNA library.

Materials and methods A cDNA library was constructed from 96 h old mycelium of A. fumigatus using λ ZAP expression vector. A novel gene encoding an A. fumigatus allergen was identified by screening the library with sera from ABPA patients. The gene was cloned and the allergen over‐expressed in Escherichia coli. This recombinant allergen, Asp f 16, was evaluated in ELISA and Western blots using sera from patients and normal subjects and peripheral blood mononuclear cells (PBMC) for antigen‐induced stimulation.

Results Seventy percent of the patients with ABPA demonstrated high levels of serum IgE antibodies to Asp f 16, a 43‐kDa protein, whereas patients with allergic asthma, Aspergillus skin test‐positive asthmatics without clinical evidence of ABPA, and normal controls failed to show Asp f 16‐specific IgE binding by ELISA. The deduced amino acid sequences of Asp f 16 showed extensive sequence homology to 30.6‐kDa Asp f 9 at the N‐terminal region of the protein. PBMC from the majority of patients with ABPA exhibited significant proliferation with the recombinant Asp f 16 allergen.

Conclusion Specific humoral and cell‐mediated immune responses of Af‐sensitized patients against Asp f 16 suggest its usefulness in the immunodiagnosis of hypersensitivity diseases due to Af and understanding the pathophysiology of ABPA.
Influenza virus A stimulates expression of eotaxin by nasal epithelial cells
Authors: Kawaguchi M. , Kokubu F. , Kuga H. , Tomita T. , Matsukura S. , Suzaki H. , Huang S.‐K. , Adachi M.
Published: March 2003

Background Respiratory virus is one of the most common causes of airway inflammation, but its pathogenic mechanisms are not well understood. Eotaxin is a potent eosinophil chemoattractant and is a selective agonist for C‐C chemokine receptor 3 (CCR3). Although it has recently been demonstrated that epithelial cells express eotaxin, both in vivo and in vitro, there are few data concerning the expression in viral infection.

Objects We hypothesized that eotaxin may play an important role in attracting inflammatory cells into the airway after viral infection and analysed whether viral infection induces eotaxin in nasal epithelial cells in vitro.

Methods Nasal epithelial cells obtained from polypectomy for nasal polyp were infected with influenza virus A (subtype H3N2). The cells and supernatants were collected 8, 24 and 48 h after infection. Eotaxin mRNA was analysed by RT‐PCR. Eotaxin concentration in the supernatants was analysed by enzyme‐linked immunosorbent assay. We also examined a blocking assay to analyse the intervention of pro‐inflammatory cytokines, TNF‐α and IL‐1β in eotaxin production induced by influenza virus.

Results The results showed that eotaxin was expressed constitutively in uninfected cells, but was up‐regulated for both mRNA and protein levels in infected cells. Blocking experiments using anti‐TNF‐α and anti‐IL‐1β antibodies showed no effects of these agents on the level of eotaxin. In addition, UV‐inactivated virus did not enhance the expression of eotaxin.

Conclusions These results suggest that influenza virus A infection in nasal epithelial cells stimulates the expression of eotaxin, and may play an important role in the pathogenesis of airway inflammation by inducing eotaxin.
Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six‐year follow‐up study.
Authors: Pajno G. B. , Barberio G. , De Luca FR. , Morabito L. , Parmiani S.
Published: March 2003

Background Specific immunotherapy (SIT) is a recognized way of treating IgE‐mediated respiratory diseases. The clinical outcome is usually better in allergic children than in adults.

Objective To increase our knowledge of the ability of SIT to prevent the onset of new sensitizations in monosensitized subjects, so far poorly documented.

Methods 134 children (age range 5–8 years), who had intermittent asthma with or without rhinitis, with single sensitization to mite allergen (skin prick test and serum‐specific IgE), were enrolled. SIT was proposed to all the children's parents, but was accepted by only 75 of them (SIT Group). The remaining 63 children were treated with medication only, and were considered the Control Group. Injective SIT with mite mix was administered to the SIT Group during the first three years and all patients were followed for a total of 6 years. All patients were checked for allergic sensitization(s) by skin prick test and serum‐specific IgE every year until the end of the follow‐up period.

Results Both groups were comparable in terms of age, sex and disease characteristics. 123 children completed the follow‐up study. At the end of the study, 52 out of 69 children (75.4%) in the SIT Group showed no new sensitization, compared to 18 out of 54 children (33.3%) in the Control Group (P < 0.0002). Parietaria, Gramineae and Olea were the most common allergens responsible for the new sensitization(s).

Conclusions According to our data, SIT may prevent the onset of new sensitizations in children with respiratory symptoms monosensitized to house dust mite (HDM).
Efficacy of leukotriene receptor antagonist in chronic urticaria. A double‐blind, placebo‐controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid
Authors: Pacor M. L. , Di Lorenzo G. , Corrocher R.
Published: March 2003

Background The cause and pathogenesis of chronic urticaria are still poorly understood. IgE‐independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H1‐receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double‐blind, placebo‐controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives.

Patients and methods A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3‐day run‐in. The assessment of the efficacy was based on scores of daily urticaria symptoms.

Results MT significantly increased the percentage of symptom‐free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P < 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P < 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P < 0.001, and 20 days, P < 0.001, respectively). Finally, a low incidence of adverse events was observed in this study.

Conclusion The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.
Heterogeneity of IgE epitopes of vinyl sulphone reactive dye: human serum albumin that react with IgE
Authors: Park J. W. , Kang D. B. , Choi S. Y. , Kim C. W. , Kim K. S. , Hong C.‐S.
Published: March 2003

Background Vinyl sulphone reactive dye (vRD), which consists of vinyl sulphone reactive groups and a chromogen, can elicit IgE‐mediated occupational asthma (OA) by haptenation. Human serum albumin (HSA) is known as the most reliable carrier protein for the vRD, the IgE epitopes of vRD‐HSA are not well characterized. In this study we evaluated the epitope of vRD‐HAS‐specific IgE.

Methods Two vRD (Remazole Black‐GR and Remazole Orange‐3R), Procion Red‐MX‐5B, which has a dichlorotriazine reactive group, and vinyl sulphone (VS), were haptenated to HSA, respectively. vRD‐HSA was denatured by heat or mercaptoethanol treatment and the allergenicities of denatured and non‐denatured vRD‐HSA were compared by ELISA and IgE immunoblotting using the sera of six vRD‐OA patients. vRD‐HSA‐specific, Procion Red‐MX‐5B (pRD)‐HSA‐specific and VS‐HAS‐specific IgE were also measured with ELISA and the cross‐reactivity between them was evaluated with ELISA inhibition.

Results Denaturation of vRD‐HSA by heat affected its allergenicity markedly in five of six sera of RD‐OA. When vRD was conjugated to the pre‐heated HSA, its allergenicity also disappeared or was markedly attenuated compared with the vRD‐HSA in five of six sera. Mercaptoethanol treatment markedly affected the allergenicity of the RD‐HSA in all six RD‐OA sera. Immunoblotting from non‐denatured PAGE showed strong IgE affinity to vRD‐HSA but immunoblotting from denatured SDS PAGE did not show IgE affinity. Among six RD‐OA patients, five and four patients had pRD‐HSA‐specific and VS‐HSA‐specific IgE, respectively. However, the vRD‐HSA‐specific IgE was neither inhibited by pRD‐HSA nor VS‐HSA

Conclusion We considered that the conformational structure of HSA would be critical for the IgE epitopes during the haptenation process and both of the chromogen and reactive groups of the vRD would contribute to the formation of IgE epitope. Our results also confirmed the heterogeneity of IgE epitopes in the RD‐HSA complex.
PHA‐induced IL‐12Rβ2 mRNA expression in atopic and non‐atopic children
Authors: Janefjord C. K. , Jenmalm M. C.
Published: March 2003

Background IL‐12 is a strong inducer of Th1 responses. Stimulation via the CD2 receptor increases IFN‐γ production and enhances the responsiveness of activated T‐cells to IL‐12, possibly due to an up‐regulation of the signal transducing β2 chain of the IL‐12 receptor (IL‐12Rβ2). Atopic children have a reduced Th1‐like immunity and a reduced CD2 expression. Our hypothesis is that atopic individuals have a reduced function of the CD2 pathway, causing reduced responsiveness to IL‐12 and decreased IFN‐γ production.

Objective The aim was to study the mRNA expression of the IL‐12Rβ2 chain, after stimulation via the CD2 pathway in peripheral blood mononuclear cells (PBMC), of atopic and non‐atopic children, and to investigate correlations to the production of Th1 and Th2 cytokines.

Materials and methods The study included 23 skin prick test positive, and 9 non‐sensitized, 12‐year‐old children. PBMC were stimulated for 24 h with phytohemagglutinin (PHA) (2 µg/mL), which stimulates T cells through the CD2 pathway. Expression of IL‐12Rβ2 mRNA was analysed by quantitative real time PCR and the cytokine production was detected with ELISA.

Results Atopic and non‐atopic children had similar baseline expression of IL‐12Rβ2 mRNA, whereas PHA‐induced IL‐12Rβ2 mRNA expression was lower in atopic than in non‐atopic children. The PHA‐induced IL‐12Rβ2 mRNA expression correlated well with the PHA‐induced IFN‐γ production and with the IFN‐γ/IL‐4 ratio.

Conclusion PBMC from atopic children expressed less IL‐12Rβ2 mRNA than non‐atopic children after stimulation via the CD2 pathway (PHA). This may indicate a reduced capacity to respond to Th1‐inducing stimuli in atopic children.
Long‐term absence of sensitization to mepivacaine as assessed by a diagnostic protocol including patch testing
Authors: Astarita C. , Gargano D. , Romano C. , Cutajar M. , Manguso F. , Montanaro D. , Napolitano A. , Pezzuto F. , Lo Schiavo M. , Altucci P. , Abbate G.
Published: March 2003

BackgroundProspective assessment of non‐reactivity to local anaesthetics is a frequent reason for allergy consultation.

ObjectivesTo investigate the clinical profiles of subjects referred for allergy evaluation; to prospectively reduce the frequency of evaluation by assessing the persistence, during clinical use, of non‐reactivity to contaminant/additive‐free mepivacaine; and to determine the usefulness of a diagnostic protocol involving patch testing.

MethodsIn a prospective study, 198 consecutive patients underwent collection of clinical data, skin prick tests and patch tests using allergens/antigens relevant for the investigation, and an intradermal/subcutaneous challenge procedure using contaminant/additive‐free mepivacaine, as appropriate. Patients were followed up for 3 years for assessment of non‐reactivity persistence using the same diagnostic protocol.

ResultsOnly one‐third of the patients had a history of previous adverse local anaesthetic reactions. Absence of sensitization to contaminant/additive‐free mepivacaine persisted in all subjects completing the follow‐up. Controlled challenge with mepivacaine was negative in 196 patients with both negative specific skin prick tests and patch tests but it was eventful in two subjects with positive specific patch tests. A few subjects displayed positive skin prick tests and/or patch tests for latex and/or additives.

ConclusionsA few patients had a relevant history for potential local anaesthetic‐induced adverse reactions. Upon assessment of absence of sensitization and reactivity, contaminant/additive‐free mepivacaine could safely be given for as long as 3 years. The patch testing was shown to be useful and safe for prediction of challenge outcomes. True allergic reactions to contaminant/additive‐free mepivacaine were not observed in our patient series.
Increased HLA‐DR expression after exposure of human monocytic cells to air particulates
Authors: Don Porto Carero A. , Hoet P. H. M. , Nemery B. , Schoeters G.
Published: March 2003

Background The expression of HLA‐DR on the cell membrane of antigen‐presenting cells is of major importance for the induction of an allergic response in the airways. Environmental particulates are thought to play an important role in inducing or enhancing allergic sensitization, possibly by increasing the expression of HLA‐DR on the cell membrane of antigen‐presenting cells. In addition, these particulates may synergize with common sensitizing agents in inducing or enhancing HLA‐DR and thus antigen presentation.

Objective In this study, we investigated the potential of three particle types, namely carbon black, diesel exhaust particles and urban air particulates (0.1–1000 ng/cm2), to induce the expression of HLA‐DR on differentiated THP‐1 cells, taken as a model for alveolar macrophages. We also assessed the ‘adjuvant’ potential of the particles on interferon (IFN)‐γ, a known enhancer of HLA‐DR.

Results By themselves, the particles (0.1–1000 ng/cm2) were not able to induce HLA‐DR on the THP‐1 cells after an incubation of 48 h. However, even at very low concentrations, carbon black (from 1 ng/cm2 on) and diesel exhaust particles (from 0.1 ng/cm2 on), interacted with IFN‐γ (100 U/mL) to enhance HLA‐DR expression (up to 2.5‐fold increase).

Conclusion This finding may reflect in vitro one of the mechanisms by which pollutant particles exert an ‘adjuvant’ activity and may partially explain how exposure to particles can be related to the enhancement of allergic sensitization.
Elevated expression of interleukin‐9 mRNA in the bronchial mucosa of atopic asthmatics and allergen‐induced cutaneous late‐phase reaction: relationships to eosinophils, mast cells and T lymphocytes
Authors: Ying S. , Meng Q. , Kay A. B. , Robinson D. S.
Published: March 2003

Background Interleukin‐9 is a T cell‐derived Th2‐type cytokine that has been linked to airway hyper‐responsiveness, mucus hypersecretion and mast cell infiltration in animal models. We recently demonstrated the potential for IL‐9 to act in human eosinophil development and survival.

Objectives The aims of this study were: (i) to compare IL‐9 mRNA expression in bronchial biopsies between atopic asthmatics and normal controls, (ii) to investigate kinetic expression of IL‐9 mRNA in skin biopsies after allergen challenge; and (iii) to relate IL‐9 expression to infiltration of eosinophils, mast cell and T lymphocytes in local tissue.

Methods Bronchial biopsies were obtained from atopic asthmatics (n = 12) and normal non‐asthmatics (n = 12) at baseline. Skin biopsies were obtained from atopic subjects (n = 11) at 1, 3, 6, 24, 48 and 72 h after allergen challenge. Diluent challenge sites at 24 h were used as controls. IL‐9 mRNA was identified using the technique of in situ hybridization. The numbers of eosinophils, mast cells and T cells were evaluated by immunohistochemistry.

Results The numbers of IL‐9 mRNA+ cells present in the bronchial mucosa were significantly greater in atopic asthmatics than those in normal controls (P = 0.003). The numbers of eosinophils, but not mast cells, were also significantly higher in asthmatics (P < 0.005). The numbers of IL‐9 mRNA+ cells present in the airway of asthmatics significantly correlated with the numbers of eosinophils (r = 0.623, P = 0.03), but not mast cells or T cells. Compared with diluent challenge, the numbers of IL‐9 mRNA+ cells were significantly elevated at all allergen‐challenged sites in the skin, with maximal signals at 48 h (P < 0.005). At 72 h, the numbers of IL‐9 mRNA+ cells significantly correlated with the numbers of eosinophils (r = 0.707, P = 0.015).

Conclusion Elevated expression of IL‐9 in allergic inflammation may contribute to local eosinophil infiltration and survival in asthma and other allergic atopic diseases.
An interaction between the IL‐4Rα gene and infection is associated with atopic eczema in young children
Authors: Callard R. E. , Hamvas R. , Chatterton C. , Blanco C. , Pembrey M. , Jones R. , Sherriff A. , Henderson J. ,   the ALSPAC Study Team
Published: March 2003

Background A gain of function mutation (Q551‐ > R) in the IL‐4 receptor α‐chain (IL‐4Rα) has been found to be associated with atopy in some studies but not others. The different results may be explained by interactions between the IL‐4Rα polymorphism and environmental factors.

Objectives To identify interactions between the R551 mutation and environmental factors that are associated with atopy.

Methods DNA from the Children in Focus (CiF) cohort of the Avon Longitudinal Study of Parents and Children (ALSPAC) was genotyped by heteroduplex formation for the presence of the R551 polymorphism. The data were then analysed for associations with flexural eczema as an indicator of atopic eczema, skin prick tests to allergens and serum IgE levels, and for interactions with environmental factors.

Results A significant (P = 0.02) positive association was seen between the R551 polymorphism and flexural eczema in children up to 6 months of age who had not been given antibiotics, but not in children who had been given antibiotics. This association was maintained as a trend until 30 to 42 months of age but was no longer statistically significant. There was no significant association between the R551 polymorphism and positive skin prick tests or levels of serum IgE at 61 months of age, consistent with the effect of the R551 polymorphism being restricted to early life.

Conclusion There is an association between the R551 polymorphism and flexural eczema in children at 6 months of age who have not had infection requiring treatment with antibiotics. Restriction of the R551 association with eczema to children who have not had antibiotics lends support to the ‘hygiene hypothesis’, which states that exposure to infection in childhood can protect against allergic disease.
Expression and localization of the cysteinyl leukotriene 1 receptor in human nasal mucosa
Authors: Shirasaki H. , Kanaizumi E. , Watanabe K. , Matsui T. , Sato J. , Narita S. , Rautiainen M. , Himi T.
Published: March 2003

Background The cysteinyl leukotrienes (CysLT) are lipid mediators that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate that two classes of receptors, named CysLT1 and CysLT2 receptor, exist. The former is sensitive to the CysLT1 antagonist currently used to treat asthma and allergic rhinitis. Recently, the cDNA for human CysLT1 and CysLT2 receptor have been cloned, making it now possible to study the gene expression of CysLTs receptors.

Objective We have used reverse transcription and polymerase chain reaction (RT‐PCR) to study the gene expression of CysLT1 and CysLT2 receptor and in situ hybridization to determine the distribution of CysLT1 receptor mRNA in human nasal mucosa. In addition, the distribution of the CysLT1 receptor protein was studied by immunohistochemistry.

Methods Human turbinates were obtained after turbinectomy from six patients with nasal obstruction refractory to medical therapy. Total RNA was isolated from human nasal mucosa and both CysLT1 and CysLT2 receptor mRNA was detected in these tissues by using RT‐PCR. For in situ hybridization study of human nasal mucosa, we used biotin‐labelled oligonucleotides probes encoding human CysLT1 receptor cDNA. To identify the cells expressing the CysLT1 receptor protein, double immunostaining was performed by using anti‐CysLT1 receptor antibody and monoclonal antileucocyte antibodies.

Results RT‐PCR analysis of total nasal RNA demonstrated the expression of both CysLT1 receptor and CysLT2 receptor mRNA. In situ hybridization indicated high levels of CysLT1 receptor hybridization in blood vessels and the interstitial cells, but a sparse signal in airway epithelium and submucosal glands. The immunohistochemical studies revealed that anti‐CysLT1 receptor antibody labelled eosinophils, mast cells, macrophages, neutrophils and vascular endothelial cells in the nasal mucosa.

Conclusion The results may have an important clinical implication and also promote further investigation of the regulation of CysLT1 receptor in health and disease.