bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between − 308 tumour necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma
Authors: Li Kam Wa  , Mansur  , Britton  , Williams  , Pavord  , Richards  , Campbell  , Morton  , Holgate  , Morrison  
Published: March 2003

BackgroundTumour necrosis factor (TNF) is a pivotal cytokine in the inflammation underlying asthma. The TNF gene is located in the polymorphic HLA class 3 region on chromosome 6p. Several polymorphisms in this region have been described and associated with alteration of TNF secretion in vitro.ObjectiveIn this study we tested the hypothesis that two such polymorphisms, lymphotoxin α NcoI B*1 and − 308 TNF2 may be components of the genetic predisposition to asthma.MethodsFive hundred and fifty‐six random individuals were studied, comprising approximately equal numbers of asthmatic subjects, with or without atopy, and a nonatopic nonasthmatic control group. In addition, 355 subjects (172 asthmatics) from 60 multiplex families were typed at the LTα NcoI locus.ResultsThere was an association between allele two of the − 308 TNF polymorphism and bronchial hyperreactivity (OR 2.12, 95% CI 1.04–4.32, P = 0.036). However, there was no association with LTα NcoI alleles. To determine whether this was influenced by linkage disequilibrium within the MHC, 91 subjects with bronchial hyperreactivity and 85 control subjects were typed for class 2 and 3 alleles. Following identification of the extended TNF2 haplotype, we found no independent association of these alleles with BHR.ConclusionsWe conclude that the − 308 TNF2 promoter polymorphism may form a component of the genetic predisposition to BHR in asthma.
Means of increasing sensitivity of an in vitro diagnostic test for aspirin intolerance
Authors: May  , Weber  , Gall  , Kaufmann  , Zollner  
Published: March 2003

BackgroundPseudo‐allergic reactions caused by aspirin (acetyl salicylic acid; ASA) often resemble immediate‐type hypersensitivity reactions consisting of urticaria and angioedema or rhinoconjunctivitis, asthma and nasal polyps. In the last few years, a new in vitro assay based on determination of sulfidoleucotrienes from isolated leucocytes (cellular allergen stimulation test — CAST) has been introduced for type I allergies and pseudoallergic reactions. In ASA intolerance, there is only limited experience using this assay with — in some studies — only moderate sensitivity. Furthermore, the necessity to use freshly isolated leucocytes from untreated patients is inconvenient for routine settings.ObjectiveThe purpose of our study was to search for possibilities of increasing the sensitivity of the test and to use stored blood samples which would permit shipping, two requirements for the clinical suitability of this test.Patients and methodsLeucotriene release in response to ASA and other non‐steroidal anti‐inflammatory drugs (NSAIDs) was analysed in 38 ASA‐intolerant patients (predominantly airway‐related symptoms n = 22; predominantly cutaneous symptoms n = 16) and 50 controls. The diagnosis of ASA intolerance was established by history and placebo‐controlled oral challenge tests.ResultsUsing 24 h‐stored leucocytes obtained from 10 ASA‐intolerant patients and 10 healthy controls there were no significant differences of leucotriene release by resting, ionomycin‐, and anti FcεRIα‐stimulated leucocytes compared with freshly isolated leucocytes. Analysis of ASA + C5a‐mediated leucotriene release by stored blood samples in combination with indomethacin‐ and diclofenac‐mediated leucotriene release in ASA‐intolerant patients (n = 38) resulted in an increased sensitivity (from 50 to 72.7% in ASA‐intolerant patients with predominantly airway‐related symptoms and from 81 to 100% in ASA‐intolerant patients with predominantly skin symptoms) compared with assays in which only ASA + C5a‐mediated leucotriene release has been determined. Moreover, the specificity of the assay remained high (96.7% when analysing different NSAIDs compared with > 99% when analysing only ASA + C5a‐mediated leucotriene release).Conclusion In vitro stimulation with ASA + C5a leucocyte stimulation with other NSAIDs should be performed to achieve a higher sensitivity. This finding can be explained by the clinical observation of a high ratio of cross‐reactivities between the mentioned NSAIDs.
A retrospective study of the relationship between childhood asthma and respiratory infection during gestation
Authors: Hughes  , Jones  , Wright  , Dobbs  
Published: March 2003

BackgroundWheeze in children has been found to be associated with prior antepartum haemorrhage and raised levels of IgE in cord blood, and acute wheezing episodes are intimately linked with respiratory viral infections.ObjectiveTo assess the relationship between maternal presentation with respiratory tract infections in pregnancy and childhood asthma, taking into account factors which could affect presentation.MethodsThis was a case‐control study of 200 asthmatic children, 5–16‐year‐old, age‐matched with one control, having no recorded history of wheeze. Data on respiratory tract infections, maternal wheeze, atopy and smoking was collected from primary care records. Deprivation score was assessed according to small residential areas andsubjects were equally distributed between four general practices in Plymouth, UK.ResultsPresentation with respiratory tract infections during pregnancy was significantly associated with childhood asthma (OR 1.69, 95% confidence interval 1.05–2.77, P = 0.03). The association was marginally stronger for infections in the first trimester (OR 2.30, 95% CI 1.05–5.41, P = 0.04) and for those with cough during pregnancy (OR 2.24, 95% CI 1.23–4.22, P = 0.007). The associations remained significant after allowing for the effect of the independent variables (gender, maternal smoking, maternal wheeze, allergic rhinitis, eczema, asthma treatment in pregnancy and deprivation [Townsend] score), using multiple logistic regression analysis (ORs and 95% CIs 1.91, 1.14–3.22; 2.32, 1.01–5.34 and 2.29, 1.17–4.48, respectively). There was also an association between numbers of presentations with respiratory infections and childhood asthma (test for trend, P = 0.02).ConclusionsThis study has shown an association between presentation with respiratory infection during gestation and childhood asthma. The results were not affected by the other independent variable factors studied and therefore provide some evidence to support the theory that respiratory viruses may be implicated in the aetiology of asthma.
Allergen‐specific production of interferon‐γ by peripheral blood mononuclear cells and CD8 T cells in allergic disease and following immunotherapy
Authors: O'brien  , Xu  , Rolland  , Byron  , Thomas  
Published: March 2003

BackgroundCD8 T cells are important immunoregulatory cells in animal models of allergic disease, but their role in human allergic immune responses has not been defined. With the development of novel immunotherapeutic reagents, it is clearly important to ascertain whether CD8 T‐cell responses are altered following conventional allergen‐specific immunotherapy (SIT) and hence targets for future developments/strategies.ObjectiveTo study the allergen‐specific cytokine release of freshly isolated CD8 T cells from the blood of separate groups of house dust mite‐ (HDM) allergic patients, patients post‐SIT and control nonatopic donors.MethodsCD8 T cells were isolated by positive selection with immunomagnetic beads and cultured with the affinity purified major mite allergen Der p 1 or with different mitogens, using irradiated autologous peripheral blood mononuclear cells as antigen‐presenting cells (APCs). Supernatants were collected at a number of time points and assayed by ELISA for the cytokines interleukin (IL) ‐4, IL‐5 and interferon‐gamma (IFNγ).ResultsCD8 T cells stimulated with Der p 1 produced significant quantities of IFNγ with cells from HDM‐allergic subjects releasing considerably more IFNγ than cells from nonatopic subjects, an average of 804 ± 283 pg/mL of supernatant compared with 30.2 ± 18.8 pg/mL (P = 0.006). The cytokine was detected in cultures of 16/17 of the allergic subjects and 4/7 of the nonatopic. CD8 T cells from 6/10 patients who had received HDM‐SIT released IFNγ at an average of 363 ± 202 pg/mL, which was less than the allergic group but still higher than the nonatopic (P = 0.05). Equivalent levels of IFNγ were detected when the cells were stimulated with the mitogen PHA and this was the same in all groups. Reliable allergen‐specific release of significant quantities of IL‐4 or IL‐5 was not detected from CD8 T cells.ConclusionAllergen‐specific IFNγ is produced at far greater levels from CD8 T cells of HDM‐sensitive allergic patients than from nonatopic control individuals and this level is reduced following SIT.
Evaluation of treatment response in patients with seasonal allergic rhinitis using domiciliary nasal peak inspiratory flow
Authors: Wilson  , Dempsey  , Sims  , Coutie  , Paterson  , Lipworth  
Published: March 2003

BackgroundMeasurement of domiciliary nasal peak inspiratory flow rate (PIFR) may have a role in the objective assessment of treatment response in seasonal allergic rhinitis (SAR).ObjectiveWe wished to evaluate the relationship between domiciliary measurement of nasal PIFR and a variety of symptoms associated with rhinitis.MethodsThirty‐eight nonasthmatic patients, mean age (SEM) 30 years (1.4), with symptomatic SAR were evaluated in a placebo‐controlled, single‐blind, double‐dummy, three way parallel group study. Patients received oral cetirizine 10 mg once daily and were randomized to receive, in addition, either: (i) intranasal mometasone furoate 200 μg (n = 14); (ii) oral montelukast 10 mg (n = 11); or (iii) placebo (n = 13). All treatments were given once daily for 4 weeks and were preceded by a 1 week placebo period. Domiciliary diary cards were used to record morning (am) and evening (pm) domiciliary nasal PIFR and symptom (nasal, eye, throat) scores and impact on daily activity. A total daily symptom score was then calculated from the sum of these separate symptom scores.ResultsBaseline values for symptom scores and PIFR after placebo run‐in were not significantly different when comparing the three groups. After 4 weeks of active treatment, there were significant (P < 0.05) improvements in nasal symptoms, total daily symptoms and PIFR with all treatments, with there being no significant confounding effect of pollen count, when analysed as a covariate. There were significant (P < 0.01) correlations for nasal symptom scores vs PIFRam (r = − 0.51) and PIFRpm (r = − 0.56), and similarly for daily activity vs PIFRam (r = − 0.42) and PIFRpm (r = − 0.48).ConclusionsThese results suggest that domiciliary measurements of nasal peak flow correlate significantly with symptoms of seasonal allergic rhinitis and may therefore be a potentially useful objective short‐term marker of treatment response.
Skin and laboratory tests in amoxicillin‐ and penicillin‐induced morbilliform skin eruption
Authors: Schnyder  , Pichler  
Published: March 2003

BackgroundCutaneous amoxicillin‐ and penicillin‐mediated reactions can be classified as immediate and delayed‐type reactions. Immediate reactions are thought to involve IgE antibodies and have been studied extensively. In contrast only few data exist about delayed reactions such as morbilliform or maculopapular rash.ObjectiveTo assess the predictive value of immediate skin tests, skin‐patch tests, specific IgE and lymphocyte transformation tests with regard to the diagnosis of delayed skin eruptions.MethodsSkin and in vitro tests were performed in 18 subjects. Twelve subjects had penicillin‐ or amoxicillin‐induced morbilliform exanthema and six were controls without hypersensitivity reaction, tested before and after exposure.ResultsSpecific IgE to penicillin and immediate penicillin skin tests were negative in amoxicillin‐ or penicillin‐induced delayed skin eruptions. In contrast, skin‐patch testing and LTT were positive in 9/12 or 10/12, respectively, but negative in all six controls.ConclusionThese findings substantiate a T‐cell‐mediated immune pathomechanism in the majority of penicillin‐induced delayed skin reaction. Moreover, they underline the necessity to adapt the test procedures to underlying pathomechanisms and support the diagnostic value of skin‐patch testing and LTT in delayed cutaneous reactions to penicillins.
Identification of peptide motifs recognized by a human IgG autoanti‐IgE antibody using a phage display library
Authors: Shakib  , Hooi  , Smith  , Furmonaviciene  , Sewell  
Published: March 2003

BackgroundThe potential of murine monoclonal anti‐IgE antibodies as long‐term therapy for atopic diseases will have to rely, for the time being, on passive antibody administration. There is therefore considerable interest in developing a peptide‐based vaccine for active immunization to elicit long‐term protective anti‐IgE antibodies in the patient. It has been shown that some human IgG autoanti‐IgE antibodies have the ability to partially block the binding of IgE to Fc receptors such as FcεRI. Therefore, the epitopes recognized by such antibodies could have vaccine potential.ObjectiveTo determine the epitope specificity of one such human IgG anti‐IgE antibody.MethodsA 15‐mer phage‐peptide library was used to establish the epitope specificity of an IgG anti‐IgE antibody isolated from the serum of an asthma patient.ResultsThe SRPSP sequence, or part of it (i.e. RPS, RPSP, SPS or PSP), was present in all 18 phage‐peptides that have been sequenced. This common motif was found to be within the human ε chain sequence Ser341‐Thr355 near the N‐terminus of the Cε3 domain. According to the human Fcε model, the most accessible residues in this sequence are Arg342, Ile350, Arg351, Lys352 and Ser353.ConclusionsThe present data should provide the molecular basis for the rational design of a suitable peptide immunogen (vaccine) for boosting the production of protective autoanti‐IgE antibodies.
Topical glucocorticoids application induced an augmentation in the expression of IL‐1α while inhibiting the expression of IL‐10 in the epidermis in murine contact hypersensitivity
Authors: Igawa K. , Yokozeki H. , Miyazaki Y. , Minatohara K. , Satoh T. , Katayama I. , Nishioka K. 
Published: March 2003

The repeated application of glucocorticoids (GC) on the skin augmented the inflammatory response of both allergic and irritant contact dermatitis in our studies.In order to further clarify the mechanism of such an augmentation of contact hypersensitivity (CHS), we investigated the modulatory effects of cytokines in the epidermis after the administration of GC at challenged sites in CHS.Diflucortolone valerate was applied to BALB/c mice on alternate days for a total of nine times. On day 12, they were contact sensitized with dinitrofluorobenzene (DNFB). Next, on day 17, one day after the last application of GC, they were challenged with DNFB on the ear. The whole challenged ear lobes were removed after a hapten challenge and then were analysed by the RT‐PCR method or underwent an immunohistochemical analysis. To clarify the modulatory effects of cytokines in vivo, DNFB sensitized mice pre‐treated with GC were injected with rIL‐10, IL‐1 receptor antagonist (ra) and anti‐IL‐1α monoclonal antibody (mAb) and thereafter were challenged with DNFB.A RT‐PCR analysis has demonstrated IL‐10 mRNA to be detected in the challenged skin of non‐GC‐pretreated mice but not in that of GC‐pre‐treated mice after challenge. On the other hand, the expression of IL‐1α mRNA in the challenged skin of mice pretreated with GC was more strongly detected that that in mice without GC‐pretreatment. Furthermore, an immuno‐histochemical analysis in the challenge showed the expression of IL‐10 in the skin showed the expression of IL‐10 in the challenged epidermis of the non‐GC‐pretreated mice but not in the GC‐pretreated mice and IL‐1α was also strongly expressed in the epidermis of the GC‐pretreated mice. A subcutaneous injection of anti‐IL‐1α mAb or IL‐1 ra inhibited the augmented CHS reaction in the GC‐pretreated mice. A subcutaneous injection of rIL‐10 also inhibited the augmentation of the CHS reaction in the GC‐pretreated mice; however, no such inhibition was observed in the non‐GC‐pretreated mice.These results indicated that both an up‐regulation of IL‐1α production and the inhibition of the IL‐10 production in the epidermis at the challenged skin sites in the GC‐pretreated mice appear to play a critical role in the GC‐induced augmentation of murine CHS.
Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study
Authors: Purello‐D'Ambrosio F. , Gangemi S. , Merendino R. A. , Isola S. , Puccinelli P. , Parmiani S. , Ricciardi L. 
Published: March 2003

Background Specific immunotherapy is the only currently available allergen‐orientated treatment able to modify the natural history of respiratory allergic diseases. Safety and clinical efficacy of this treatment are well documented, but evidence about the ability to reduce new sensitizations is still poor.Objective We report a retrospective study conducted in order to assess the prevention of new sensitizations in monosensitized subjects treated with specific immunotherapy vs. monosensitized patients treated with anti‐allergic drugs.Methods 8396 monosensitized patients with respiratory symptoms were selected according to an open, retrospective design. Group A included 7182 patients submitted to specific immunotherapy (and anti‐allergic drugs when needed) for 4 years and then treated with drugs for at least 3 years. Group B included 1214 patients treated only with drugs for at least 7 years. All patients underwent prick test with a standard panel of allergens and total and specific IgE determination before and after 4 years of treatment and again 3 years later.Results Groups were well balanced. Polysensitized subjects were 23.75% in Group A and 68.03% in Group B after 4 years (P < 0.0001) and 26.95% and 76.77%, respectively, after 7 years (P < 0.0001). Asthmatic subjects were more prone to develop polysensitization in comparison to subjects suffering only from rhinitis (32.14% instead of 27.29% after 4 years, 36.5% instead of 31.33% after 7 years; P < 0.0001). Specific IgE decreased by 24.11% in Group A and increased by 23.87% in Group B (P < 0.0001). Total IgE decreased by 17.53% in Group A and increased by 13.71% in Group B (P < 0.0001).Conclusions Specific immunotherapy was observed retrospectively to reduce new sensitizations in monosensitized subjects suffering from respiratory allergic diseases.
Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma
Authors: Hoshino M. , Takahashi M. , Takai Y. , Sim J. , Aoike N. 
Published: March 2003

Background Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied.Objective We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients.Subjects and methods We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 µg/daily, or placebo, for 6 months in a double‐blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non‐asthmatic control subjects.Results There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP‐treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP‐treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = −0.49, P < 0.05) and airway responsiveness (rs = −0.36, P < 0.05).Conclusion These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.
A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma
Authors: Wilson A. M. , Dempsey O. J. , Sims E. J. , Lipworth B. J. 
Published: March 2003

Background Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy.Objective To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma.Patients and methods A single‐blind double‐dummy placebo‐controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 µg inhaled plus 200 µg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1‐week placebo run‐in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms.Results There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2–18.6) for placebo vs. budesonide, 2.9 (1.0–8.4) for placebo vs. montelukast, and 2.1 (1.1–4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms.Conclusion Once‐daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.