Biomedical subjects

T Frischer

Publications and source records attributed to T Frischer.

At least 19 recordsLinked to original sources

PubMed2004

Effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a multinational randomized, controlled birth-cohort study -- 24 months results of the Study of Prevention of Allergy in Children in Europe.

BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.

Allergens↗

PubMed2004

Long- and medium-term ozone effects on lung growth including a broad spectrum of exposure.

The effects of semi-annual and 3.5 yr mean ozone (O3) concentrations on children's forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were assessed over a study period of 3.5 yrs in 2,153 schoolchildren from 15 study sites in South Western Germany and Lower Austria. Spirometric parameters were assessed twice a year, and differences between consecutive measurements divided by days were considered as a measure of lung growth. Exposure was analysed in four classes, separately for winter and summer (semi-annual mean O3 concentrations 22-30, 30-38, 38-46, 46-54 parts per billion (ppb) in summer and 4-12, 12-20, 20-28, 28-36 ppb in winter). Regression methods for repeated measurements were used, and these revealed a significantly lower FVC (FEV1) increase estimated at -19.2 (-18.5) mL x 100 days(-1) for semi-annual mean O3 exposure in summer between 46 and 54 ppb compared to exposure between 22 and 30 ppb. However, in winter, the estimated difference in FVC (FEV1) was 16.4 (10.9) mL x 100 days(-1) between the semi-annual O3 class 28-36 ppb and the 4-12 ppb class. By means of linear regression the study found that there was no association between growth rates and mean summer O3 for FVC and FEV1 over a 3.5 yr period. The authors conclude that medium-term effects on schoolchildren's lung growth are possibly present, but are in the long-term not detectable for forced vital capacity and forced expiratory volume in one second over a 3.5 yr period due to partial reversibility.

Air Pollutants↗

PubMed2002

Prevention of sensitization to house dust mite by allergen avoidance in school age children: a randomized controlled study.

BACKGROUND: Sensitization to dust mites predisposes to asthma and allergic rhinitis, and prevention of this sensitization might reduce the rising prevalence of these disorders. OBJECTIVE: To test the effectiveness of dust mite avoidance measures on the development of sensitization to dust mites in children. METHODS: As part of a multicentre study (Study of Prevention of Allergy in Children of Europe), 242 children, aged 5-7 years, in three European countries (United Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127) and control group (n = 115). At randomization these children were required to have a family history of atopy and positive skin test to an aeroallergen but not to house dust mite. Children in the prophylactic group were provided with dust mite impermeable mattress covers and advice on environmental measures to reduce exposure to dust-mite allergen. Control group children were given non-specific advice. After 12 months a standardized questionnaire was completed and skin prick tests were performed. RESULTS: Ten children in the prophylactic group and 19 in the control group were lost to follow-up. Three of 117 (2.56%) children in the prophylactic group and nine of 96 (9.38%) in the control group developed sensitization to dust mites. Logistic regression analysis confirmed an independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95% confidence interval (CI): 0.03-0.79, P = 0.03). Fifteen children need to be treated to prevent sensitization in one child. CONCLUSION: Dust mite sensitization can be reduced in school age children with simple mite avoidance measures.

Air Pollution, Indoor↗

PubMed2002

Parental farming protects children against atopy: longitudinal evidence involving skin prick tests.

BACKGROUND: There is growing evidence that the development of allergic sensitization can be influenced by environmental co-factors. Studies showed that growing up on a farm can protect children against allergic sensitization. However, little is known whether this 'farming effect' can only be observed in early lifetime or whether it also plays a role in later childhood. OBJECTIVE: The aim of our study was to test whether a farming environment is negatively associated with a new occurrence of skin prick test (SPT) positivity in school children. As a secondary outcome we investigated whether children living on a farm lose their allergic sensitization more frequently than other children. METHODS: In a longitudinal design, 1150 elementary school children (mean age 7.8 years, SD 0.7) were recruited from nine different areas of Austria in 1994. A questionnaire and an SPT involving seven common aero-allergens were performed at study entry and at follow-up 3 years later. RESULTS: A total of 844 children, who underwent two SPTs, were included in the analyses; 15.1% of their families reported working on a farm. Adjusting for potential confounders (parental education, number of siblings, sex, family history of allergy), parental farming was inversely related to the prevalence and new occurrence of SPT positivity [no farming 12.2%, part-time farming 6%, full-time farming 2.2% incidence; odds ratio (OR) farming vs. non-farming 0.34, 95% confidence interval (CI) 0.12-0.98]. Furthermore, children living in a farming environment were more likely to lose their SPT positivity during follow-up (no farming 14.6%, part-time farming 50%, full-time farming 60% loss of sensitization; OR farming vs. non-farming 8.06; 95% CI 2.05-31.75). No difference in the pattern of sensitization to specific allergens could be observed between farming and non-farming children. CONCLUSION: A farming environment has a strong negative effect on the development of allergic sensitization. Furthermore, the study provides evidence that atopic children living on a farm lose their SPT positivity more frequently than children from non-farming environments.

Agriculture↗

PubMed2002

Predictors of lung function in infants at high risk of atopy: effect of allergen avoidance.

Children of atopic parents are recognised as being at higher risk of developing bronchial asthma, drawing the attention of prevention strategies towards this population. Due to recent advances, lung function abnormalities in asthmatic children may now be measured early in life. The aim ofthis investigation was to examine possible predictors of lung function development in a sub sample of high-risk infants who took part in an allergy avoidance study In 60 babies of atopic parents, measurements of upper airways inflammation were performed at 4 weeks of age, respiratory symptoms were assessed at 6 and 12 months of age, and lung function (Vmax, FRC) was measured at 18 months by the rapid thoracoabdominal compression technique. Twenty-eight babies were enrolled in an allergen avoidance program, and 32 recruited as controls. No significant differences were detected for V'max,FRC between the intervention group (mean 331 ml s(-1)) and the control group (359 ml s(-1)), P = 0.382. A multiple linear regression model could explain levels of V'max FRC by weight gain since birth (beta = -35.35 ml s(-1) kg(-1), P = 0.022) and by eosinophilic cationic protein (ECP) (beta = -0.95 ml s(-1) microl(-1), P = 0.044), but not by intervention. Lung function measured at the age of 18 months in high-risk children is associated with weight gain and nasal ECF.

Age Factors↗

PubMed2002

Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren.

The effects of particulate matter <10 microm in diameter (PM10) and other air pollutants on lung function were assessed in 975 schoolchildren, from eight communities in Lower Austria between 1994-1997. In each community, air pollution data were collected. Spirometry was performed twice a year. PM10 concentration (mean concentration between two subsequent lung-function measures in spring and autumn (summer interval) or between autumn and spring (winter interval)) showed a mean value of 17.36 microg x m(-3) in the summer interval and 21.03 microg m(-3) in the winter interval. A slower increase in the forced expiratory volume in one second (FEV1) and midexpiratory flow between 25 and 75% of the forced vital capacity (MEF25-75) with age in children exposed to higher summer PM10 was observed in the 3-yr study period. After adjusting for potential confounders (sex, atopy, passive smoking, initial height, height difference, site, initial lung function) an increase of summer PM10 by 10 microg x m(-3) was associated with a decrease in FEV1 growth of 84 mL x yr(-1) and 329 mL x s(-1) x yr(-1) for MEF25-75. Nitrogen dioxide and ozone also showed a negative effect on lung-function growth, confirming previous work. The authors concluded that long-term exposure to particulate matter <10 microm in diameter had a significant negative effect on lung-function proxy for the development of large (forced expiratory volume in one second) and small (midexpiratory flow between 25 and 75% of the forced vital capacity) airways, respectively, with strong evidence for a further effect of ozone and nitrogen dioxide on the development of forced vital capacity and forced expiratory volume in one second.

Air Pollutants↗

PubMed2001

Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children.

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. METHODS: We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. RESULTS: One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). CONCLUSIONS: At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.

Animals↗

PubMed2001

Ambient ozone exposure is associated with eosinophil activation in healthy children.

BACKGROUND: Eosinophil activation is characteristic for allergic airways disease. However, eosinophilic airways inflammation has also been observed subsequent to ambient ozone exposure. METHODS: For a population sample of 877 children living at nine sites with different ozone exposure we measured urinary eosinophil protein X (U-EPX) as a marker of eosinophil activation. U-EPX was determined from a single spot urine sample during autumn 1997. Children were participants in a longitudinal study of ozone effects on lung function. RESULTS: The 5-95% percentiles of ozone exposure (30-day mean before test) were 11.8-51.5 p.p.b. (mean: 31.6 ppb). U-EPX was measured by radioimmunoassay and expressed as ratio to urinary creatinine (microg EPX/mmol creatinine). Log transformation was performed to achieve a normal distribution. LogU-EPX was associated with gender, a diagnosis of asthma and atopy (skin test sensitivity to any of seven aeroallergens). LogU-EPX increased with ozone exposure for all children. The medians of LogU-EPX according to the first-fourth quartiles of ozone exposure were: 1.82, 1.88, 1.95 and 2.03. For 172 non-asthmatic children who had spent the whole summer at their site corresponding figures were 1.57, 1.78, 2.07 and 2.13. In a multivariate model with logU-EPX being the dependent variable and adjusted for gender, site and atopy, ozone was found to be significant (estimate: 0.007 microg/mmol creatinine per ppb ozone; SE:0.02; P < 0.001). CONCLUSION: Our observation supports the hypothesis that ozone in healthy children is associated with eosinophil inflammation, most likely in the airways.

Air Pollutants↗

PubMed2001

[Lung function reference data in school-age children].

UNLABELLED: The practical interpretation of lung function data depends to a very great extent on the quality of reference values. METHODS: From a population of n = 2615 schoolchildren between 6 and 12 years of age 15,404 lung function measurements were taken in accordance with commonly accepted guidelines. In the present study the validity of reference equations from the literature is examined with regard to our measured data. RESULTS: Employing linear regression analysis, the natural logarithm (ln) of forced vital capacity in ml (FVC) and expiratory volume in one second in ml (FEV1) were explained on the basis of the equation ln y = a + b* ln x (y = FVC, FEV1 (ml); x = height (cm)). Analyses were performed for girls (lnFVC = -4.8789 + 2.5504* lnheight, lnFEV1 = -4.3078 + 2.4070* lnheight) and boys (lnFVC = -4.5241 + 2.4917* lnheight, lnFEV1 = -3.7338 + 2.2985* lnheight), separately. Our coefficients correspond best to the literature dealing with a population of the same age group. On the other hand, for example, if reference values are derived from equations from the literature for the age group 6 to 18 years, they result at 6 years in an underestimation of the volume measured by us (FVC -150 ml) and at 12 years to an overestimation (FVC + 120 ml). CONCLUSIONS: The extent of the proven systematic deviations of the reference values from the measured values is of clinical and epidemiological relevance. To avoid misinterpretations, special reference values should be applied for preadolescents, at least with regard to FVC and FEV1.

Body Height↗

PubMed2001

Effects of beta-carotene supplementation for six months on clinical and laboratory parameters in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of nutrient antioxidant vitamins, especially of beta-carotene, which is thought to result from fat malabsorption and chronic pulmonary inflammation. The aim of this double blind, placebo controlled study was to investigate the effect of oral beta-carotene supplementation for six months on clinical parameters. METHODS: Twenty four patients with CF were randomised to receive beta-carotene 1 mg/kg/day (maximum 50 mg/day) for three months (high dose supplementation) and 10 mg/day for a further three months (low dose supplementation) or placebo. At monthly follow up visits the plasma beta-carotene concentration, total antioxidant capacity, malondialdehyde (MDA) as a marker of lipid peroxidation, and clinical parameters (Shwachmann-Kulczycki score, body mass index (BMI), height, and lung function (FEV(1))) were assessed. The number of pulmonary exacerbations requiring antibiotic treatment (in days) three months before and during the study were evaluated. RESULTS: The plasma concentration of beta-carotene increased significantly to the normal range during the three months of high dose supplementation (baseline 0.08 (0.04) micromol/l to 0.56 (0.38) micromol/l; p<0.001) but decreased to 0.32 (0.19) micromol/l in the period of low dose supplementation. Initially raised plasma levels of MDA fell to normal levels and the total antioxidant capacity showed a non-significant trend towards improvement during high dose supplementation. Antibiotic treatment decreased significantly in the supplementation group from 14.5 (14.9) days/patient during the three months before the study to 9.8 (10.3) days/patient during high dose supplementation (p=0.0368) and to 10.5 (9.9) days/patient during low dose supplementation, but increased in the placebo group. The Shwachmann-Kulczycki score, lung function, and BMI did not show any changes in either of the treatment groups. No adverse events were observed during the study period. CONCLUSION: Oral beta-carotene supplementation in a dose of 1 mg/kg/day only was effective in normalising the plasma concentration of beta-carotene and resulted in a decrease in pulmonary exacerbations. These data suggest that patients with CF may benefit clinically from supplementation with beta-carotene and further studies are warranted.

Adolescent↗

PubMed2001

Association of allergy-related symptoms with sensitisation to common allergens in an adult European population.

BACKGROUND: Atopy is an important risk factor for asthma and allergic diseases. However, the relationship between atopy and allergic symptoms is not fully understood, and may not be the same for different allergy related symptoms and in differing environmental conditions. OBJECTIVE: To study the differences in the association of allergy-related symptoms and atopy, in an adult population from five European countries. METHODS: A prospective, multi-national study was conducted. Centres included Isle of Wight (UK), Vienna (Austria), Freiburg (Germany), Athens (Greece), and Kaunas (Lithuania). We used five questions derived from the ISAAC (International Study of Asthma and Allergy in Children) and other validated questionnaire, to evaluate the presence of allergic symptoms in a selected adult population. Atopy was assessed by SPT or IgE measurement to 3 core allergens (dust mite, cat and grass pollen) in all centres and 1-2 additional allergens relevant to each area (parietaria, olive, birch pollen, tree pollen mix, dog). RESULTS: Of 3985 subjects, 2478 (62%) responded positively to one or more core ISAAC questions. Sensitisation rate was high in Austria and UK and relatively low in Greece. Dust mite and cat were important allergens for asthma, odds ratio (OR): 2.24, 95% confidence interval (CI): 1.63-3.08 and OR: 2.31, CI: 1.69-3.14, respectively. Grass pollen was strongly associated with hay fever in all centres (OR: 3.62 CI: 2.81-4.66) and with birch pollen in Austria (OR: 3.57, CI: 2.09-6.09) and with parietaria in Greece (4.61 (2.99-7.12). In the comparative analysis, using UK as a reference, Lithuanians had a 10-20-fold reduced risk of asthma and hay fever, but were twice more likely to report chronic itching. The risk of dust mite allergy was 3- and 10-fold lower in Lithuania and Greece, respectively, whereas the risk of cat and grass pollen allergy was one and half times higher in Austria. CONCLUSION: The risk of allergic symptoms and sensitisation and their association vary widely in different European countries.

Adolescent↗

PubMed2000

Familial cryptic translocation with del 4q34-->qter and dup 12pter-->p13 in sibs with tracheal stenosis: clinical, classical and molecular cytogenetic studies and CGH analyses from archival placental tissues evidencing tertiary trisomy 4 in one abortion specimen.

We report on two retarded half-sibs of different sex and seemingly normal karyotype who had the same syndrome of minor anomalies, heart defect and a distal tracheal stenosis, and who shared a healthy mother. These findings raised suspicions of a cryptic chromosome translocation. A translocation t(4;12)(q34;p13), balanced in the mother and unbalanced in the sibs with loss of terminal 4q and gain of terminal 12p regions, was verified by FISH using whole chromosome painting, subtelomeric and YAC probes. Clinical features could be explained by partial monosomy 4q and partial trisomy 12p. Tracheal stenosis was interpreted as a consequence of the same developmental disturbance leading to esophageal atresia and tracheo-esophageal fistula. It was attributed to the 4q deletion in which esophageal atresia as also respiratory difficulties and airway obstructions had been described. Paraffin-embedded placental tissues were available from three of the five abortions of the mother allowing DNA extraction and comparative genome hybridization (CGH). Two of the abortion specimens had the same der(4)t(4;12)(q34;p13) unbalanced translocation as identified in the sibs. In the third abortion specimen, suspicious of triploidy because of partial hydatidiform mole, CGH uncovered a tertiary trisomy 4 resulting from a 3:1 segregation of the translocation chromosomes and their homologs during maternal meiosis I. Differences in CGH results using DNA generated directly or after DOP-PCR were explained by DNA fragmentation in paraffin-embedded tissues and unequal amplification. Am. J. Med. Genet. 94:271-280, 2000.

Adult↗

PubMed2000

[The effect of inhalable dust particles (PN10) on lung function and respiratory symptoms of school children in Lower Austria].

The effect of PM10 (particulate matter less than 10 microns in diameter) on respiratory symptoms and lung function was evaluated in 881 children (aged 8 to 11 years) in 8 communities in Lower Austria. In each community, air pollution data (PM10, SO2, NO2, O3) were collected. The examination of each child included a questionnaire (spring 1996), and two lung function tests (autumn 1995, spring 1996). Statistically significant relationships were observed between PM10 levels (annual mean, 15.8-26.9 micrograms/m3) and parameters of lung function (adjusted for sex, height, atopy, passive smoking, altitude, temperature). A 10 micrograms/m3 increase in the last two weeks' mean PM10 in spring 1996 was associated with a 0.05% decrease in FVC, a 0.05% decrease in FEV1, a 0.15% decrease in MEF50, and a 0.13% decrease in MEF75-25. Furthermore, a 10 micrograms/m3 increase in last year's mean PM10 was associated with a 0.07% decrease in FVC. No association between the prevalence of respiratory symptoms and the last year's mean PM10-exposure was found. Our study demonstrates a small effect of low-level particulate air pollution on lung function of healthy school children.

Age Factors↗

PubMed2000

Eosinophil cationic protein and eosinophil protein X in the nasal lavage of children during the first 4 weeks of life. SPACE Collaborative Study Team.

Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) are well established as markers of eosinophil activation. We analyzed ECP and EPX concentrations in nasal lavage fluids (NALF) of 378 neonates during their first 4 weeks of life. Inclusion criteria were a positive history of parental allergy and a positive skin prick test or specific IgE (RAST class > or = 2) against at least one out of a panel of common aeroallergens in one or both parents. Twenty-four infants with no history of parental allergy were used as controls. A volume of 2 ml of 0.9% saline was instilled into each nostril and immediately recovered by a suction device. ECP and EPX were analyzed by radioimmunoassay. In 65 samples of three consecutive lavages, EPX was detected in nine samples (13.8%) in the control group, whereas it was detected in 197/360 samples (54.7%) in the study population. The corresponding figures for ECP were 17/65 (26.2%) in the control group and 173/365 (47.4%) in the study group. Both proteins showed a skewed distribution (median/5-95th percentiles for ECP: 0 microg/l [0-69.4] and EPX: 6.6 microg/l [0-73.2]). The differences between the control group and the study group were statistically significant, regardless of the allergic disease of the parents. In children of allergic parents, activation proteins of the eosinophil granulocyte are released on the nasal mucosal surface in about 50% of the studied population at the age of 4 weeks. This early onset of eosinophil activation in the nasal respiratory epithelium may reflect a genetic predisposition to allergy or early exposure to allergens.

Blood Proteins↗

PubMed2000

Urinary eosinophil protein X in children: the relationship to asthma and atopy and normal values.

BACKGROUND: In epidemiologic studies, it may be difficult to identify children with bronchial asthma. Since this is the most common chronic respiratory disease in childhood, and its prevalence is still increasing, reliable methods for identification of asthmatic children are required. This study evaluates the use of urinary eosinophil protein X (U-EPX) in epidemiologic studies in identifying atopic and asthmatic children. METHODS: U-EPX was measured in 877 Austrian schoolchildren. The skin prick test (SPT) was performed with eight common aeroallergens, and established questionnaires were used to assess respiratory symptoms. RESULTS: Of our cohort, 2.8% reported physician-diagnosed asthma, 5.1% reported wheezing within the last 12 months, and 24.1% were found to be atopic. In children with physician-diagnosed asthma, as well as in atopic children (positive SPT), median U-EPX levels were significantly higher than in healthy subjects (142.8 and 89.6 vs 63.9 microg/mmol creatinine, P<0.0001 and P<0.0001, respectively). In addition, perennial sensitization to inhalant allergens resulted in higher U-EPX levels than did seasonal sensitization. The odds ratio for U-EPX levels over the 90th percentile was significantly elevated for asthma, for wheezing, for nocturnal cough, and for breathlessness at exercise, as well as for seasonal and perennial sensitization. Pulmonary function was negatively related to U-EPX levels. CONCLUSIONS: Measurement of U-EPX, which can be obtained easily, may be helpful in diagnosing both asthma and atopy in children. However, there is a great overlap between controls and symptomatics, a fact which reduces the sensitivity of U-EPX in determination of the prevalence of asthma in epidemiologic studies.

Asthma↗

PubMed2000

Eosinophil-derived proteins in nasal lavage fluid of neonates of allergic parents and the development of respiratory symptoms during the first 6 months of life. Collaborative SPACE team. Study on the Prevention of Allergy in Children in Europe.

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. METHODS: We studied upper-airways inflammation by nasal lavage in a cohort of 397 infants within the first 4 weeks of life. They participated in an international multicenter study on the prevention of allergy in Europe (SPACE-Biomed II Program). A volume of 2 ml of prewarmed 0.9% saline was instilled into each nasal cavity and immediately re-collected by a suction device. The average recovery was 502 microl (SD: 311 microl). The concentrations of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were determined by RIA analysis. RESULTS: ECP was detectable (>2 microg/l) in 47% of samples (173/365) and EPX (>3 microg/l) in 54.7% (197/360). Children with a doctor's diagnosis of a wheezy bronchitis within the first 6 months of life (n = 40) had significantly higher ECP and EPX concentrations in the nasal lavage at 4 weeks of age (median ECP: 14 microg/l; 5-95th percentile: 0-122.4 microg/l) than children without such diagnosis (median ECP: 0 microg/l; 5-95th percentile: 0-86.6 microg/l; P<0.05). Corresponding figures for EPX were 12.14 microg/l (0-148.98 microg/l) vs 7.5 microg/l (0-81.46 microg/l; P<0.05). No associations between nasal ECP/EPX and the development of food allergy or eczema were observed. CONCLUSIONS: Increased nasal ECP and EPX in the first 4 weeks of life are associated with wheezing in 6-month-old infants at increased risk of atopic disease. We suggest that this might be related to a general tendency for a Th2 cytokine pattern in these young infants and subsequent trafficking of eosinophils into the nasal mucosa, or it might be a consequence of intrauterine allergen exposure.

Blood Proteins↗

PubMed2000

Culture conditions for the detection of allergen-specific T-cell reactivity in cord blood: influence of cell number.

Raised T-cell proliferation of cord blood mononuclear cells (CBMC) in response to various ingestant and inhalant allergens has been reported in newborns, suggesting a prenatal allergen contact. In general, for in vitro proliferation assays a concentration of 50 x 10(3) or 100 x 10(3) cells/well are used. The aim of this study was to analyze whether cell concentration influences T-cell reactivity in cord blood cells and to study differences of T-cell reactivity triggered by inhalant and ingestant allergens. CBMC from 51 neonates (34 females: 22 with and 29 without a family history of allergy, i.e. FH+ or FH-) were incubated with interleukin-2 (IL-2), beta-lactoglobulin (beta-LG), ovalbumin (OVA), house dust mite allergen Dermatophagoides pteronyssinus (Der p 1), and timothy grass allergen Phleum pratense (Ph1 p 1) for 7 days. The cell concentration ranged from 6.25 x 10(3) to 100 x 10(3) cells/well. Proliferation was assessed by incorporation of [3H]-thymidine and was expressed as counts per minute (c.p.m.). In unstimulated cells, a decreasing cell concentration paralleled a steep drop of background activity. In response to IL-2, a decreasing cell concentration led to a slow decrease of c.p.m. The corresponding mean stimulation indices (SI) were 9, 32, 77, 47, and 21 for 100 x 10(3), 50 x 10(3), 25 x 10(3), 12.5 x 10(3), and 6.25 x 10(3) cells/well, respectively. In addition, the highest number of positive proliferative responses to specific allergens were obscured at lower cell concentrations. For beta-LG, the maximal number of positive responses were obtained between 25 x 10(3) (n = 44) and 12.5 x 10(3) (n = 46) cells/well, for OVA at 25 x 10(3) (n = 3) cells/well, for Der p 1 at 50 x 10(3) (n = 5) cells/well, and for Ph1 p 1 between 25 x 10(3) and 12.5 x 10(3) (n = 5) cells/well. Positive proliferation in at least one of the tested assays was observed in 100% of samples in response to beta-LG, in 22% in response to Ph1 p 1, and in 14% in response to OVA and Der p 1. T-cell reactivity did not differ between samples of newborns with or without a family history of atopy. Therefore, sensitivity of T-cell proliferation measurement is highly influenced by background proliferation of unstimulated cells. Hence, proliferation assays with lower cell numbers unmask T-cell reactivity in response to ingestant and inhalant allergens. We suggest the use of concentrations of 12.5 x 10(3)-50 x 10(3) cells/well in proliferation experiments.

Allergens↗

PubMed2000

The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies.

The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV(1), an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.

Adult↗