bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of cyclo‐oxygenases 1 and 2 proteins in upper respiratory mucosa
Authors: Demoly  , Crampette  , Lebel  , Campbell  , Mondain  , Bousquet
Published: March 2003

Background

Cyclo‐oxygenases 1 (Cox‐1) and 2 (Cox‐2) catalyse the conversion of arachidonic acid to prostaglandin endoperoxides, leading to the formation of prostaglandin and thromboxane mediators of inflammation. The involvement of these enzymes in inflammatory disorders such as sinusitis and nasal polyps is unknown although this may be relevant to their pathophysiology.

Methods

We studied Cox‐1 and Cox‐2 immunoreactivities in nasal polyp, maxillary sinus, and turbinate biopsies obtained from eight patients with chronic allergic rhinitis and sinusitis and/or nasal polyps, 15 patients with chronic non‐allergic rhinitis and sinusitis and/or nasal polyps and five control subjects (patients requiring nose surgery not related to sinusitis or nasal polyps).

Results

Both Cox‐1 and Cox‐2 were mainly expressed in the epithelium (basal, ciliated) and were found in 16/28 and 25/28 subjects for Cox‐1 and Cox‐2 respectively. We did not find any differences between the patient populations. There were no correlations between any of the clinical parameters studied nor the pathological patterns and the presence and characteristics of the Cox immunoreactivities.

Conclusion

Both cyclo‐oxygenase enzymes are expressed in normal human upper respiratory epithelium and are not upregulated in chronic sinusitis nor in nasal polyposis, possibly suggesting that Cox products do not have an important role as mediators of the chronic upper airway inflammation.
Serum eosinophil cationic protein as a marker of eosinophilic inflammation in asthma
Authors: Niimi A. , Amitani R. , Suzuki K. , Tanaka E. , Murayama T. , Kuze F.
Published: March 2003

Background

The serum level of eosinophil cationic protein (ECP) has been used as a clinical marker in asthma, on the assumption that it reflects ongoing eosinophilic inflammation of the airways. However, only a few studies have investigated this issue, using bronchial secretions but not tissue specimens.

Objective

To evaluate cross‐sectionally the correlation between serum ECP level or blood eosinophil count, and the degree of eosinophilia in bronchoalveolar lavage fluid (BALF) and bronchial biopsy tissue, and disease activity, in asthmatic patients.

Methods

Thirty‐three adults with symptomatic asthma and six healthy controls were studied. The blood eosinophil count, ECP levels in serum and BALF, percentage of eosinophils in BALF, number of eosinophils in bronchial tissue, pulmonary function, and methacholine bronchial responsiveness of these subjects were clarified. An asthma severity score and inhaled β2‐agonist requirement (puffs/day) were also assessed for the asthmatic patients.

Results

The asthmatic patients, compared with the controls, had more obstructive (as tested by %FEV1, FEV1/FVC, and FEF25–75%) and more responsive airways, and showed a significant increase in the number of eosinophils in the blood, BALF, and tissue, and in the serum ECP levels. The ECP levels in BALF were below the detection limit for most of the subjects in both groups examined. In the asthmatic patients, serum ECP level demonstrated correlations with the number or percentage of eosinophils in BALF and tissue, whereas the blood eosinophil count correlated only with the percentage of eosinophils in BALF. Serum ECP level correlated with all indices of disease activity examined; %FEV1, FEV1/FVC, FEF25–75% bronchial responsiveness, severity score and β2‐agonist usage, whereas the blood eosinophil count correlated only with %FEV1 and bronchial responsiveness.

Conclusion

The data suggest that serum ECP level reflects the intensity of eosinophilic airway inflammation, as well as the disease activity, and may be useful as an inflammatory marker in asthma.
Stability of Pityrosporum ovale allergens during storage
Authors: Lintu  , Savolainen  , Kalimo  , Terho
Published: March 2003

Background

Pityrosporum ovale is a common saprophyte on the skin capable to induce IgE antibody production in atopic dermatitis. Generally IgE response to P. ovale has been established with skin‐prick test, but the stability of P. ovale skin test allergens is not known.

Objective and methods

In this study we analysed the stability of identified allergens of P. ovale in skin test solutions during storage. The stability was checked with immunoblotting and densitometry after different time periods and at various temperatures.

Results

Coomassie Brilliant blue staining clearly showed, that proteins were preserved poorly at +20 °C in 50% glycerol. Even extracts stored at +4 °C during 6 and 12 months in 50% glycerol were degraded. Only extract stored at +4 °C for 1 month in 50% glycerol was guite well preserved. According to densitometry results the 9 kDa band was the most stable main protein allergen. The 20 kDa and expecially the 96 kDa bands were far more labile. The stability of low molecular allergens was in general better than the stability of high molecular weight allergens.

Conclusions

The stability of P. ovale extracts stored for more than 1 month was poor even when kept at +4 °C temperature. Reliability of negative skin prick results should be questioned when older extracts are used. In skin test negative cases, the sensitization should be evaluated also with the measurement of specific serum IgE antibodies to P. ovale.
Validation of a screening questionnaire for atopy with serum IgE tests in a population of pregnant Dutch women
Authors: Lakwijk  , Van Strien  , Doekes  , Brunekreef  , Gerritsen
Published: March 2003

Background

We have started a large birth cohort study in which pregnant women with and without atopy are differentially included. In view of the large number of subjects to be screened (12 000), a simple questionnaire was developed for the assessment of atopy in pregnant women.

Objective

The objective of our study was to evaluate the efficacy of a questionnaire using serum IgE tests.

Methods

During a antenatal visit to the midwife clinic, 175 expecting mothers completed a questionnaire and from each subject blood was obtained in which total and specific IgE against house dust mite, cat, dog, birch and grass was determined.

Results

When atopy was defined as the presence of a positive test for IgE against at least one allergen, seven questions from the questionnaire had a sensitivity and specificity of 55.0% and 88.7%, respectively. With the use of the questionnaire it was possible to select about 50% of the subjects with specific IgE to one or more common inhalant allergens. The positive predictive value of the screening questions was 71.7%. Taking total IgE into account did not change these results.

Conclusion

The screening questionnaire is an efficient tool for differential inclusion of subjects with and without atopy in epidemiological studies.
The significance of specific IgG4 antibodies to methyltetrahydrophthalic anhydride in occupationally exposed subjects
Authors: Yokota  , Yamaguchi  , Takeshita  , Morimoto
Published: March 2003

Background

A definitive role for allergen‐specific IgG4 as either an anaphylactic or a blocking antibody, or both, remains controversial.

Objective

A population of 148 workers from two condenser plants (A and B) using epoxy resin with methyltetrahydrophthalic anhydride (MTHPA) was studied to evaluate the significance of MTHPA‐specific IgG4 antibody.

Methods

The workers were evaluated through questionnaire and serological investigations.

Results

Ninety‐seven (66%) of the currently exposed workers had positive MTHPA‐specific IgE. IgE‐sensitized workers in each plant had significantly more eye and nose complaints than unsensitized workers (P < 0.03). As the result of multiple logistic analysis, specific IgE antibodies was the most important predictor of work‐related symptoms and its effect was greater than that of specific IgG4 (odds ratio 16.7 and 3.68, respectively). These indicate an IgE‐mediated mechanism in most cases of work‐related symptoms associated with MTHPA exposure. However, it cannot be denied that specific IgG4 is an anaphylactic antibody. Furthermore, IgE‐sensitized workers in these plants displayed work‐related symptoms despite the presence of specific IgG4. The frequency of positive specific IgG4 in continuously exposed workers was significantly (P < 0.02) higher in plant A than in plant B, reflecting the difference of the MTHPA levels between the two plants. In plant A, the frequency of positive specific IgG4 was significantly (P < 0.002) higher in continuously exposed workers than in intermittently exposed workers. Multiple regression analysis also confirmed that plant and exposure style contributed significantly (P < 0.01) to the determination of specific IgG4 levels.

Conclusion

These results suggest that work‐related eye and nasal symptoms are likely to be IgE‐mediated, and that specific IgG4 may reflect the intensity of MTHPA exposure and may not act as a blocking antibody.
Correlation between antigen‐specific IL‐2 response test and provocation test for egg allergy in atopic dermatitis
Authors: Noma  , Yoshizawa Izumi , Aoki  , Sugawara  , Odajima  , Kabasawa  , Matsui  , Yata  , Yamaguchi  , Mukouyama  , Baba
Published: March 2003

Background

The antigen‐specific interleukin‐2 response (AIR) test using lymphocytes is effective in searching for the antigen which causes allergic diseases and understanding their disease activity .

Objective and Methods

The correlation between the raw egg oral provocation test and egg white antigen‐specific interleukin‐2 (IL‐2) response test was investigated in 123 children with infantile atopic dermatitis and 13 children with bronchial asthma.

Results

Among the 83 who showed positive reactions to provocation, 75 also reacted positively to the AIR test (sensitivity, 90.4%), while among the 53 children who showed negative responses to antigen provocation, 45 produced negative responses to the AIR test (specificity, 84.9%). The specificity of egg white IgE RAST score and skin‐prick test are 88.7 and 81.3% which are comparable to that of the AIR test. However, their sensitivity was low (38.6 and 66.7%). In the patterns of symptom developed in the provocation AIR displayed late and delayed type allergic responses in addition to the immediate type which RAST reflected. The RAST‐negative group composed of 98 patients included 51 (52.0%) who exhibited positive reactions to the provocation test. Among these 44 responded positively to the AIR test (86.3%).

Conclusion

The AIR test is effective for screening egg white antigen as part of the tests for antigens responsible for allergic diseases and as a test to ascertain the relevant antigens, and that the conditions that could not be diagnosed by RAST can be detected by the AIR test.
Effects of birch pollen‐specific immunotherapy on apple allergy in birch pollen‐hypersensitive patients
Authors: Asero
Published: March 2003

Background

Most patients with birch pollen allergy report oral allergy symptoms after eating fresh apples and other vegetable foods. Major birch pollen and apple allergens, Bet v 1 and Mal d 1, are highly homologous; as a consequence, pollen‐specific immunotherapy (SIT) might be expected to improve apple hypersensitivity.

Objective

To evaluate the clinical and immunological effects of birch pollen SIT on oral allergy syndrome (OAS) induced by apples.

Methods

A prospective study carried out in 49 birch pollen‐sensitive patients with apple‐induced OAS who received injection immunotherapy for 12, 24, or 36 months. Twenty‐six patients not submitted to SIT and followed up for 12–48 months were used as controls. Both SPT and open oral challenges with fresh golden delicious apple were performed, as well as specific IgE measurements, before and after SIT.

Results

Forty‐one patients (84%) vs no control (0%) reported a significant reduction (50–95%) or a total disappearance (100%) of OAS symptoms after SIT (P < 0.001). Similar responses were observed in patients treated for 12, 24, or 36 months. SIT also induced a marked reduction in skin reactivity against fresh apple in 43 patients (88%). The effect of SIT was inversely related with baseline skin reactivity: 50% and 8% patients with a weakly or strongly positive baseline apple skin prick tests (SPT), respectively, did not report changes in OAS severity after SIT (P < 0.01). In contrast, baseline birch pollen‐specific or apple‐specific IgE antibodies levels did not influence SIT effectiveness on OAS. SIT induced a marked decrease in birch pollen‐specific IgE levels (P < 0.001), whereas apple‐specific IgE showed an unexpected variability (reduction in 21%, no change in 43%, increase in 38%). No control subject reported a reduction in OAS severity or showed a decrease in skin reactivity at follow‐up (P < 0.001).

Conclusions

SIT with birch pollen extracts effectively reduces clinical apple sensitivity and skin reactivity in most cases after only 1 year of treatment; these effects are not paralleled by a similar reduction in apple‐specific IgE. These findings suggest a decrease in activability of effector cells as the mechanism underlying clinical benefit.
Serum eosinophil cationic protein: distribution and reproducibility in a randomly selected sample of men living in rural Norfolk, UK
Authors: Marks  , Kjellerby  , Luczynska  , Burney
Published: March 2003

Background

It has been proposed that serum levels of eosinophil cationic protein (ECP) may be a clinically useful measure in allergic illness. The aim of this report is to describe the distribution and reproducibility of serum ECP levels in a population sample and to examine its relationship with other markers of disease.

Methods

The study was conducted in rural areas of Norfolk, UK in a random sample of men aged 20–44 years enriched with subjects drawn from general practice ‘asthma registers’. Asthma symptoms were assessed using the EC Respiratory Health Survey questionnaire. Atopy was measured by skin prick tests and serum IgE. Airway hyperresponsiveness (AHR) was tested by methacholine challenge test. Serum IgE and ECP was measured by fluoroimmunoassay using the Pharmacia CAP system. Reference equations were derived in subjects from the random sample who did not have symptoms of asthma, abnormal lung function or AHR. The relation of serum ECP with various clinical characteristics was examined in the whole study population. Reproducibility of serum ECP measurement was assessed in 57 subjects 4 weeks after the initial test.

Results

The study population comprised 311 from the random sample and 58 from the asthma sample. The reference equation for serum ECP for healthy men was log10 ECP = 1.3966 − [(age − 20) × 0.0057]. The estimated mean serum ECP for a 20‐year‐old man was 25 μg/L. Current smokers have higher serum ECP levels that non‐smokers (P = 0.014). ECP levels were not related to the skin prick test reactivity, serum IgE, a questionnaire‐based diagnosis of asthma, or impaired lung function (all P > 0.05). Levels were higher in subjects with AHR (P = 0.003) and those who reported wheeze (P = 0.017) but there was no clinically useful separation in ECP levels between subjects classified by these criteria. The test was moderately reproducible over a 4‐week period (intraclass correlation coefficient = 0.62).

Discussion

Serum ECP levels were higher in this rural English population than reported in a comparable population in Sweden. Serum ECP is a reproducible test but cross‐sectionally does not relate in any clinically useful way to markers of asthma. The meaning of between‐ subject differences in ECP levels requires further exploration.
The inflammatory nature of allergic disease
Authors: Durham
Published: March 2003

The allergic inflammatory response in allergic rhinitis has been studied extensively owing to the high frequency of the condition, the significant morbidity it causes and the accessibility of the nasal tissue. The allergic inflammatory response is characterized by IgE synthesis, IgE‐dependent mast cell activation and infiltration of the nasal mucosa by T lymphocytes and eosinophils. The immediate‐phase response is mediated by a range of inflammatory mediators (such as histamine, leukotrienes and prostaglandins), resulting in vasodilatation, oedema, mucus secretion, itching and sneezing. Individuals who experience a late‐phase response have further nasal symptoms 4–24 h after the initial challenge with allergen. Results of nasal biopsy studies indicate that the late‐phase allergic response involves T‐lymphocyte activation, production of TH2‐type cytokines and tissue eosinophilia. Corticosteroids potently inhibit T‐lymphocyte responses, and clinical studies in subjects with allergic rhinitis have demonstrated that they are extremely effective in blocking both early‐ and late‐phase allergic reactions. Topical aqueous triamcinolone acetonide nasal spray represents a novel formulation of a topical corticosteroid for the treatment of allergic rhinitis. Data from controlled clinical studies indicate that it is effective in treating seasonal and perennial disease, is well tolerated, does not suppress adrenocortical function, is odourless, and can be administered as a once‐daily dose.
Diesel exhaust particulates upregulate histamine receptor mRNA and increase histamine‐induced IL‐8 and GM‐CSF production in nasal epithelial cells and endothelial cells
Authors: TERADA  , HAMANO  , MAESAKO  , HIRUMA  , HOHKI  , SUZUKI  , ISHIKAWA  , KONNO
Published: March 2003

Background

Histamine is the most important chemical mediator in the pathogenesis of nasal allergy. Diesel exhaust particulates (DEPs) are common air pollutants from diesel engine‐powered car exhaust and cause chronic airway diseases. Recently we observed that the nasal reactivity to histamine was enhanced in diesel exhaust‐exposed guinea‐pigs. It was also revealed that epithelial cells and endothelial cells in the airway produce certain cytokines in response to histamine.

Objective

We examined the effects of DEP extract on the expression of histamine H1 receptor (H1R) mRNA in human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs), and on the production of IL‐8 and GM‐CSF induced by histamine.

Methods

HNECs and HMMECs were isolated from human nasal mucosa specimens. HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract. The change in the expression of H1R mRNA was then evaluated by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and the Southern blot analysis. To investigate the effects of DEP extract on the histamine‐induced cytokine production, HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract for 3–24 h. After three washes with PBS, they were then incubated with 10−6 mol/L histamine for 24 h. The amounts of IL‐8 and GM‐CSF in the culture media were measured by enzyme‐linked immunoabsorent assay.

Results

DEP extract increased the expression of H1R mRNA in both HNECs and HMMECs. The amount of IL‐8 and GM‐CSF, induced by histamine, was significantly higher in DEP extract pretreated HNECs and HMMECs than nontreated HNECs and HMMECs.

Conclusion

These results strongly suggest that DEP accelerates the inflammatory change by not only directly upregulating H1R expression but also increasing histamine‐induced IL‐8 and GM‐CSF production.
Association between body mass index and allergy in teenage girls in Taiwan
Authors: Huang  , Shiao  , Chou
Published: March 2003

Background

The prevalence of atopy and asthma is affected by age, sex and lifestyle factors. Obesity was reported to be a risk factor for asthmatic symptoms in children and adults.

Objective

To examine the relation between body mass index (BMI) and the prevalence of atopy, rhinitis, wheezing and bronchial responsiveness in adolescents.

Methods

BMI (kg/m2), skin‐prick test, bronchial hyperresponsiveness (BHR) to methacholine, and self‐reported rhinitis and airway symptoms were assessed in a cross‐sectional survey in 1459 eighth‐grade students (age 13.2 to 15.5, mean 13.6 years) of seven junior high schools in northern Taiwan.

Results

The prevalence of atopy was 42% in boys and 27% in girls. The study population was grouped into quintiles of BMI by sex. Girls in the highest BMI quintile had higher prevalence of atopy and rhinitis symptoms. Compared with the middle three quintiles, they had increased risk of atopy in multivariate analyses adjusted for area of living, sibling number, parent education level and family history of asthma (odds ratio = 1.77, 95% confidence interval = 1.15–2.73). Girls with the lowest BMI quintile had lower prevalence of BHR and wheezing. Compared with the middle three quintiles, they had reduced risk of BHR in multivariate analyses adjusted for area of living, atopy, family history of asthma, and baseline pulmonary function (odds ratio = 0.40, 95% confidence interval = 0.20–0.81). No association between BMI and atopy or BHR was seen in boys.

Conclusion

BMI was a significant predictor of atopy, allergic symptoms and BHR in teenage girls.
Lack of association of atopy/asthma and the interleukin‐4 receptor α gene in Japanese
Authors: Noguchi  , Shibasaki  , Arinami  , Takeda  , Yokouchi  , Kobayashi  , Imoto  , Nakahara  , Matsui  , Hamaguchi
Published: March 2003

Background

Susceptibility to the development of atopic diseases is known to involve genetic factors. Several investigators have reported the interleukin‐4 (IL‐4) receptor α gene to be involved in the development of atopy. Recent study has shown that the R allele of a polymorphism in the IL‐4 receptor α chain gene (Q576R) to be associated with atopy.

Objective

The objective of this study was to evaluate the possible role of the IL‐4 receptor α gene; in modulating allergic response and asthma in the Japanese population.

Methods

We conducted linkage analysis using microsatellite markers flanking the IL‐4 α receptor gene in 82 families ascertained through asthmatic children. The IL‐4 receptor Q576R polymorphism was also genotyped by PCR‐restriction fragment length polymorphism analysis.

Results

We did not find evidence for linkage of the asthma and atopy phenotypes with the markers D16S298 and D16S403 (P = 0.10 and P = 0.56, respectively, for the atopy phenotype and P = 0.17 and P = 0.60, respectively, for the asthma phenotype). The IL‐4 receptor R576 allele was not preferentially transmitted to atopy‐ or asthma‐affected children (χ2 = 1.67, P = 0.24 for atopy and χ2 = 0.91, P = 0.40 for asthma). In addition, the prevalence of the R576 allele among parents with and without atopy was similar, 20 of 81 (24.7%) parents with atopy and 22 of 77 (28.6%) parents without atopy.

Conclusion

Our findings indicate that the IL‐4 receptor α gene does not exert a substantial influence on the inheritance of atopy or asthma in this Japanese population.
Evaluation of the efficacy of a hospital‐based asthma education programme in patients of low socioeconomic status in Hong Kong
Authors: L CHOY  , TONG  , KO  , LI  , HO  , CHAN  , LEUNG  , LAI
Published: March 2003

Background

Good asthma control requires optimal medical treatment in conjunction with appropriate self‐management. In the West, the effectiveness of patient education on improving self‐management has been well documented. However, data amongst Asian populations are lacking. We performed a pilot study to evaluate the efficacy of a hospital based education programme aimed at improving self‐management skills and reducing morbidity in a Chinese population with low socioeconomic status and education level.

Methods

Our asthma education programme was a low‐cost programme conducted in essence by specialist respiratory nurses. Patients attending our asthma clinic were instructed during a two‐hour educational session on the pathophysiology of asthma, its potential triggers, the appropriate use of medications including proper inhaler techniques, and the self‐management of their disease. These instructions were reinforced by video sessions at subsequent outpatient clinic attendance when patients' inhaler and peak flow techniques were checked by the same nurses and their self‐management plan re‐examined by the attending physicians. Asthma knowledge, inhaler technique, FEV1 and peak expiratory flow (PEF), and patients' self‐rating of their asthma were determined at baseline, 6 months and 1 year after the intervention. Morbidity was assessed by the numbers of hospitalizations, unscheduled visits to family physicians and accident and emergency department attendance, courses of oral steroid used and days off work or school at baseline and 1 year.

Results

Two hundred and thirty patients were recruited for the study, 83% completing the entire assessment period. The group demonstrated significant improvements in lung function: the mean FEV1  ±  SD increased from 63.6  ±  20.6% of predicted values at baseline to 68.5  ±  22.3% at 6 months and 68.6  ±  22.8% at 1 year (P  <  0.05), and the mean PEF  ±  sd increased from 64.6  ±  23.0% of predicted values at baseline to 75.4  ±  27.0% at 6 months and 76.8  ±  24.5% at 1 year (P  <  0.001). There were also significant improvements in inhaler technique (P  <  0.01), asthma knowledge (P  <  0.001), patients' self‐rating of their asthma (P  <  0.05), and reductions in the numbers of hospitalizations (P  <  0.01), visits to family physicians (P  <  0.001) and accident and emergency department attendance (P  <  0.001) during the study period. Patients with moderate to severe asthma as defined by an FEV1 of < 80% of predicted values were most likely to benefit from the programme.

Conclusions

We conclude that patient education is likely to be an essential component in the holistic approach to the management of asthma even amongst Asian populations of low socioeconomic status and education level. Further studies using randomised controlled trials are necessary to consolidate our findings.
Head circumference at birth and maternal factors related to cord blood total IgE
Authors: Oryszczyn  , Annesi‐Maesano  , Campagna  , Sahuquillo  , Huel  , Kauffmann
Published: March 2003

Background

A recent study reported an association between a large head circumference at birth and adult total IgE. However, no study has yet looked at the relation between head circumference and cord blood IgE.

Objectives

To assess the relationship between child's cord blood total IgE and head circumference at birth taking parental allergy and smoking habits as well as placental calcifications into account.

Methods

Two samples of unselected newborns and their mothers with uncomplicated pregnancies were studied: 235 in study A with data on parental allergy and 99 in study B with data on placental calcifications.

Results

In both studies, cord blood IgE was significantly related to large head circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs ≥ 37 cm, respectively, P = 0.03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE significantly increased in mothers exposed to both active and passive smoking during pregnancy compared with other pregnant women. High cord blood IgE were associated with high maternal IgE (r = 0.38; P < 0.001). Multiple linear regression showed that large head circumference, maternal IgE and clinical manifestations of maternal, but not paternal, allergy were independently related to cord blood IgE (study A). Large head circumference and placental calcifications were independently related to a higher cord blood IgE level (study B).

Conclusions

Besides the role of genetic factors, results on the preferential role of maternal vs paternal allergy and associations to large head circumference and placental calcifications support the hypothesis of the role of environmental factors during pregnancy on the level of cord blood IgE.
Class I endochitinase containing a hevein domain is the causative allergen in latex‐associated avocado allergy
Authors: POSCH  , WHEELER  , CHEN  , FLAGGE  , DUNN  , PAPENFUSS  , RAULF‐HEIMSOTH  , BAUR
Published: March 2003

Background

In the medical literature immunoglobulin (Ig)E‐mediated sensitization to avocado is rarely reported. On the other hand, more than 50% of subjects having IgE‐mediated natural rubber latex allergy are sensitized to avocado fruit as demonstrated by skin‐prick testing and/or specific IgE measurements and about 10–20% report hypersensitivity reactions after ingesting avocado.

Objective

The underlying pathomechanism of latex‐associated avocado allergy is still unknown. The conserved hevein domain of the major latex allergen prohevein (Hev b 6.01) is a ubiquitous chitin‐binding protein structure that can be found in several plant proteins and may be responsible for the observed cross‐reactivity between latex and avocado fruit.

Methods

Chitin‐binding avocado proteins (CBAPs) were isolated by affinity‐chromatography and their IgE‐binding characteristics were studied by immunoblotting using the sera from 15 avocado‐sensitized latex patients. Inhibition experiments using isolated hevein and CBAPs as inhibitor solutions were performed to study the immunological cross‐reactivity between both protein species and to assess the role of the CBAPs as mediators in latex‐associated avocado allergy.

Results

In 80% of avocado‐sensitized subjects (n = 15), IgE antibodies directed against a 31‐kDa allergen were detected by immunoblotting. This IgE‐binding protein was identified by protein sequencing to be a class I endochitinase containing a hevein domain at the N‐terminus. Purified native and digested (using simulated gastric fluid) endochitinase were able to completely block all avocado‐specific IgE antibodies in six out of seven avocado patients.

Conclusions

Sensitization to endochitinase class I containing a hevein domain is the main underlying pathomechanism in latex‐mediated avocado allergy.
Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross‐sectional study
Authors: EYSINK  , DE JONG  , BINDELS  , SCHARP‐VAN DER LINDEN  , DE GROOT  , STAPEL  , AALBERSE
Published: March 2003

Background

Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE‐mediated allergy in initially nonatopic children.

Objective

To examine the cross‐sectional relation between IgG to foods (i.e. mixture of wheat and rice, mixture of soybean and peanut, egg white, cow’s milk, meat, orange and potato) and specific IgE to cat, dog, mite, milk and egg white in 1‐year‐old children.

Methods

All atopic children (n = 120; 58 with and 62 without eczema) and a random sample of the nonatopic children (n = 144) of the Bokaal study were tested on their IgG response to foods. The IgG results of the food assays were dichotomized high or low using the 66th centile as a cut‐off value.

Results

Atopic children more often had high IgG levels to foods than nonatopic children. IgG to egg white (OR = 7.50) and mixture of wheat and rice (OR = 4.79) were most strongly associated with positive specific IgE. In a stepwise logistic regression analysis egg white, mixture of wheat and rice, and orange were selected (OR = 3.76, OR = 2.43, and OR = 2.11, respectively). In children without eczema higher levels of IgG to foods were still significantly associated with atopy, which was most prominent for egg white, orange and cow’s milk.

Conclusion

An increased IgG antibody level to foods, especially to egg white, orange, and mixture of wheat and rice, indicates an increased risk of having IgE to cat, dog, mite, egg and/or milk allergens, even in the noneczematous group. Therefore, in another prospective study we are currently investigating the usefulness of IgG in early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing allergic diseases in the future.
Cytokine production and mRNA expression by conjunctival T‐cell lines in chronic allergic eye disease
Authors: Calder  , Jolly  , Hingorani  , Adamson  , Leonardi  , Secchi  , Buckley  , Lightman
Published: March 2003

Background

Activated CD4+ T cells, mast cells and eosinophils are the main cytokine‐producing cell‐types infiltrating the conjunctiva during chronic allergic eye diseases. Interactions between these cells are thought to play an important immunopathogenic role in these disorders (giant papillary conjunctivitis; vernal keratoconjunctivitis; atopic keratoconjunctivitis).

Objective

The objective was to compare the cytokine profiles of conjunctival T‐cell lines from patients with different forms of chronic allergic eye disease.

Methods

T cells were isolated from conjunctival biopsies and non‐specifically expanded into lines. The lines were immunophenotyped by flow cytometry. Cytokine production was quantified by immunoassays and more sensitive molecular techniques were used to investigate cytokine mRNA expression to identify the presence of interleukin (IL) ‐2, IL‐4 and interferon (IFN) ‐γ transcripts.

Results

Following four to six rounds of stimulation, the conjunctival T‐cell populations were CD3+ (> 93%), with variable levels of CD4 and CD8 expression. All were HLA‐DR+ (> 80%) with some HLA‐DQ expression. Conjunctival T‐cell lines from atopic keratoconjunctivitis produced selective increases in IFN‐γ, IL‐10 and IL‐13 (P < 0.01), those from vernal keratoconjunctivitis produced increased IL‐5 (P < 0.01) whereas T‐cell lines from giant papillary conjunctivitis produced only low levels of cytokines. IL‐4 was only detected at the mRNA level and was expressed in four out of five T‐cell lines in the vernal keratoconjunctivitis group. In contrast there was moderate to strong expression of IFN‐γ in five out of six T‐cell lines in atopic keratoconjunctivitis.

Conclusion

Different patterns of T‐cell cytokine profiles were observed for each disease, with low‐level, non‐polarized cytokine production in giant papillary conjunctivitis, a TH2‐like profile in vernal keratoconjunctivitis and a shift towards a TH1‐like profile in atopic keratoconjunctivitis.
Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects
Authors: Jang  , Choi  , Lee  , Seo  , Yang  , Park  , Lee  , Lee  , Park  , Park
Published: March 2003

Background and objective

The role of nitric oxide (NO) needs to be further clarified in allergic inflammation. This study was designed to investigate the relationships between NO metabolites and eosinophil count, eosinophil cationic protein (ECP), interleukin (IL)‐5 in induced sputum from asthmatics.

Methods

Hypertonic saline‐induced sputum was obtained in 25 asthmatic subjects, among which 13 patients were examined before and after anti‐asthmatic medications including steroid preparations. Ten normal subjects were enrolled as controls. Fresh expectorated sputum separated from saliva was treated with equal volume of dithiothreitol 0.1%, cytospined for cell count, and the supernatant was collected for biochemical assay. NO metabolites were assayed by using modified Griess reaction. ECP was measured by fluoroimmunoassay, and detected IL‐5 by a sandwich ELISA.

Results

Asthmatic subjects, compared with controls, had significantly higher concentration of NO metabolites (1035.4 ± 125.3 vs 557.2 ± 101.5 μmol/L, P < 0.01), higher percentage of eosinophils (25.6 ± 4.6 vs 1.7 ± 0.2%, P < 0.01), and higher levels of ECP (1117.8 ± 213.9 vs 154.6 ± 47.4 μg/L, P < 0.01) in the induced sputum. IL‐5 was detected more frequently in asthmatic subjects than in control subjects (11/25 [44%] vs 1/10 [10%], P < 0.05). According to asthma severity, moderate to severe asthmatic subjects (n = 18) had higher level of NO metabolites (1143.8 ± 156.3 vs 575.5 ± 89.5 μmol/L, P < 0.01), higher levels of ECP and IL‐5 (P < 0.01, respectively) in the induced sputum than in those of mild asthmatic subjects (n = 7). NO metabolites, the percentage of eosinophils, the levels of ECP, and IL‐5 were reduced following treatment with anti‐asthmatic drugs (P < 0.01, respectively). There were significant positive correlations between NO metabolites and percentage of eosinophils or ECP (r = 0.34, P < 0.05; r = 0.28, P < 0.05). Negative correlations were noted between FEV1, FEV1/FVC and proportion of eosinophils, ECP, or IL‐5 levels.

Conclusion

These findings confirmed that the level of NO metabolites was increased in the tracheobronchial secretion of asthmatic subjects and was paralleled with severity of asthma. Measurement of NO metabolites in induced sputum may be used for monitoring the degree of airway inflammation in asthmatics.
Elevated levels of soluble TNF receptors in bronchoalveolar lavage fluid in extrinsic allergic alveolitis
Authors: Dai  , Guzman  , Bauer  , Costabel
Published: March 2003

Background

Soluble TNF receptors (sTNFR1 and sTNFR2) are inhibitors of TNF and can block TNF bioactivity. TNF plays an important role in the development of extrinsic allergic alveolitis (EAA).

Objective

To evaluate whether sTNFR1 and sTNFR2 are locally increased in EAA.

Methods

We measured sTNFR1 and sTNFR2 in bronchoalveolar lavage fluid (BALF) and serum from nine EAA patients and 11 control subjects using an ELISA method.

Results

BALF sTNFR1 and sTNFR2 levels were 0.24 ± 0.04 ng/mL and 0.59 ± 0.16 ng/mL in EAA patients, and thus significantly elevated in comparison with the controls (0.13 ± 0.02 ng/mL and 0.08 ± 0.04 ng/mL, both P < 0.05). Serum sTNFR levels were not significantly different between the two groups. Both sTNFR1 and sTNFR2 concentrations in BALF correlated significantly with the lymphocyte percentage of BALF (r = 0.57 and 0.81, respectively).

Conclusion

The two alveolar sTNFRs, particularly sTNFR2, may be involved in the pathogenesis of EAA as counter‐regulators of TNF.
Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing
Authors: Shields  , Brown  , Stevenson  , Fitch  , Schock  , Turner  , Taylor  , Ennis
Published: March 2003

Background

Serum eosinophilic cationic protein (ECP) concentrations may be useful noninvasive markers of airways inflammation in atopic asthma. However, the usefulness of serum ECP measurement for the prediction of airways inflammation in children with a history of wheezing is unknown.

Objective

To determine the test accuracy of serum ECP and blood eosinophil percentage as noninvasive markers of eosinophilic airways inflammation.

Methods

Bronchoalveolar lavage (BAL) fluid and peripheral blood samples for eosinophil percentages and serum ECP were obtained from children undergoing elective surgery and who gave a history of wheezing in the previous year. Sensitivity, specificity and likelihood ratios (LH) and the area under the curve (AUC) for the receiver operator characteristic (ROC) curve were calculated for each blood marker for the prediction of airways inflammation defined by a BAL eosinophil percentage > 0.86. Data were analysed on the basis of how recently symptoms had occurred.

Results

Seventy‐seven children (median age 6.75 years) were studied. An AUC of 0.75 (log serum ECP concentration) and 0.76 (log blood eosinophil percentage) was obtained for predicting airways inflammation. A serum ECP > 13 μg/L yielded a LH of 4.4, whereas using a cutoff blood eosinophils > 4% yielded a LH of 1.9, for the prediction of elevated eosinophils in BAL. Serum ECP and eosinophil percentages in BAL and blood were lowest (not statistically significant) when last symptoms had occurred more than 12 weeks previously.

Conclusions

Serum ECP and blood eosinophil percentages are useful markers for predicting eosinophilic airways inflammation in wheezing children.
Grass pollen immunotherapy decreases the number of mast cells in the skin
Authors: Durham  , Varney  , Gaga  , Jacobson  , Varga  , Frew  , Kay
Published: March 2003

Background

Allergen injection immunotherapy is effective for summer hay fever and reduces cutaneous sensitivity to grass pollen.

Objective

We have addressed whether this effect of immunotherapy may be due to a decrease in mast cell numbers in the skin.

Methods

Total mast cells and mast cell subtypes in the dermis were measured by dual immunocytochemistry in 40 adult patients who had received either ‘active’ grass pollen immunotherapy or placebo injections for 9 months in a double‐blind clinical trial.

Results

Clinical improvement in hay fever was accompanied by a greater than 10‐fold reduction in the immediate cutaneous response to grass pollen (P = 0.0002) and a sevenfold decrease in mast cell numbers in the skin (P = 0.0001). The number of mast cells after immunotherapy correlated with the clinical response in terms of seasonal symptoms (r = 0.61, P = 0.001) and rescue medication use (r = 0.75, P = 0.0001). Specific double immunostaining showed that the majority of mast cells (greater than 60%) were tryptase/chymase‐positive (MCTC) and the remainder tryptase‐only (MCT) cells. Following immunotherapy both subtypes were equally reduced.

Conclusion

One mechanism by which immunotherapy may act is to reduce mast cell numbers with a consequent reduction in immediate allergic sensitivity.
Intracellular expression and serum levels of eosinophil peroxidase (EPO) and eosinophil cationic protein in asthmatic children
Authors: Krug  , Napp  , Enander  , Eklund  , Rieger  , Schauer
Published: March 2003

Background

Eosinophils are involved in the chronic inflammatory response in asthma and their basic proteins are thought to play a major pathophysiological role in this process. While serum levels of basic proteins have been used to monitor the ongoing allergic disease, little is known about the intracellular expression of these proteins in clinical situations.

Objective

The aim of the study was to determine the intracellular expression of eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) in asthmatic children and control subjects and relate it to serum levels of both proteins,lung function tests and immunoglobulin (Ig)E levels.

Methods

Serum ECP and EPO concentrations were determined by immunoassays in 13 asthmatic children (mean age: 9 ± 1 years, mean FEV1: 92 ± 10% predicted, geometric mean PC20 histamine 0.5 mg/mL) and 10 age‐matched, healthy control subjects. A flow cytometric single cell assay was employed to detect intracellular ECP and EPO in peripheral blood eosinophils.

Results

While serum concentrations of both ECP (asthma: median 15.0 μg/L [range 3.6–57.7] vs control: 5.9 μg/L [2.7–9.1]; P = 0.02) and EPO (22.9 μg/L [5.2–82.5] vs 7.2 μg/L [2.5–12.7]; P = 0.008) were significantly elevated in asthmatics, the intracellular expression of ECP and EPO (measured as mean fluorescence intensity) was decreased (EG1: 55.3 [17.7–120.8] vs 100.3 [46.5–264.4]; P = 0.01; EG2: 80.2 [24.1–135.3] vs 133.7 [32.1–244.9]; P = 0.04 and EPO: 49.7 [23.1–155.8] vs 94.9 [28.8–115.2]; P = 0.03). In asthmatics there was a significant correlation of FEV1 with intracellular ECP and of bronchial hyperresponsiveness with serum EPO and ECP. Furthermore, total IgE levels were positively correlated with serum EPO only.

Conclusion

We conclude that in asthmatics the intracellular content of ECP and EPO in peripheral eosinophils is reduced possibly due to degranulation. Epitope masking in activated eosinophils or a shift to early bone marrow‐derived progenitors with less granule proteins are further possible explanations.
Increased carbon monoxide in exhaled air of patients with seasonal allergic rhinitis
Authors: Monma  , Yamaya  , Sekizawa  , Ikeda  , Suzuki  , Kikuchi  , Takasaka  , Sasaki
Published: March 2003

Background

Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients. However, it is uncertain whether exhaled CO is increased in patients with allergic rhinitis.

Objective and methods

To study whether exhaled CO is increased in patients with allergic rhinitis, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 86 patients with seasonal allergic rhinitis during and out of the cedar pollen season.

Results

During the season, exhaled CO concentrations were 3.6 ± 0.3 p.p.m. and decreased to 1.2 ± 0.1 p.p.m. out of the season. The values of exhaled CO out of the season were similar to those in age‐matched non‐smoking healthy control subjects (1.2 ± 0.1 p.p.m.). Exhaled CO concentrations were significantly higher in patients with symptoms than in those without symptoms (P < 0.01). Exhaled CO concentrations in patients did not differ significantly among oral and nasal exhalation, and oral exhalation with an expiratory resistance (P > 0.20).

Conclusion

These findings suggest that allergic rhinitis increases the concentration of CO in exhaled air and increases in exhaled CO may be derived from lower airways.
Is antihistamine (H1‐receptor antagonist) therapy useful in clinical asthma?
Authors: Simons F. E. R.
Published: March 2003

Airway hyperresponsiveness to histamine is a hallmark of asthma, and histamine inhalation reproduces asthma symptoms. Plasma histamine concentrations are elevated during the early and late responses to inhaled allergens, and may also increase during spontaneous acute asthma episodes. Ordinary doses of currently available antihistamines (H1‐receptor antagonists) have minimal bronchodilator and bronchoprotective activity. In severe persistent asthma, H1 antagonists have no significant clinical effect. In moderate persistent asthma, clinical benefits of H1 antagonists are apparent, but may not be worth the potential risks of the higher‐than‐usual doses required. When mild seasonal asthma and allergic rhinitis coexist, however, relief of rhinitis symptoms with H1 antagonists administered in ordinary dose is associated with significant improvement in asthma symptoms.
Substrate preference profiles of proteases released by allergenic pollens
Authors: Widmer  , Hayes  , Whittaker  , Kumar
Published: March 2003

Background

Pollens are important triggers for allergic asthma and seasonal rhinitis. We have recently reported that proteases released by major allergenic pollens can injure airway epithelial cells in vitro. Disruption of epithelial integrity by proteases released following deposition of pollens on mucosal surfaces could promote sensitization and induce inflammation.

Objective

To compare protease activities released by allergenic pollens of various genera.

Methods

We used a rapid microassay which quantifies cleavage of dipeptide ester substrates to characterize the substrate preference profiles of serine proteases in diffusates of the pollens of perennial ryegrass (Lolium perenne), Kentucky blue grass (Poa pratensis), Bermuda grass (Cynodon dactylon), Western ragweed (Ambrosia spp.), white birch (Betula spp.) and Sydney golden wattle (Acacia longifolia).

Results

Comparison of the profiles revealed notable differences as well as similarities between serine protease activities released by these pollens. Diffusates of Kentucky blue grass pollen exhibited very high substrate preference for arginine and lysine. For other pollens, cleavage of the cysteine substrate was usually the most rapid and was associated with marked preference for leucine and methionine. There was considerable variation between these pollens in the rates of cleavage of the histidine substrate. In addition, we observed high rates of cleavage of arginine and lysine substrates by Acacia pollen diffusate.

Conclusion

At least two dominant patterns of substrate preference are identifiable in the mixtures of proteases released by hydrated pollens. Purification of the proteases responsible for these patterns of activity will facilitate investigation of their role in airway epithelial injury and allergic disease.