EAACI/GA2LEN position paper: present status of the atopy patch test.

A number of scientific reports have been published on patch tests with protein allergens performed on patients with atopic eczema (AE). Evaluation of eczematous skin lesions with an atopy patch test (APT) can be used as a diagnostic tool in characterizing patients with aeroallergen- and food-triggered AE. Indications for testing with APT, choice of allergens (aeroallergens and foods), test materials and technique, including present knowledge on sensitivity and specificity, are reviewed on the basis of available literature. This position paper also points out the need for future research on the clinical use of the APT.

Comparison of two budesonide dry powder inhalers in the treatment of asthma in children.

The aim of this study was to compare the clinical efficacy, safety, and acceptability of budesonide inhaled from Easyhaler dry powder inhaler (DPI) (Giona Easyhaler, Orion Pharma, Finland) and from Turbuhaler DPI (Pulmicort Turbuhaler, AstraZeneca, Sweden) in the treatment of asthma in children. The 6-month, randomised, double-blind, double-dummy, parallel-group study was conducted in 229 completed, asthmatic children (5-10 years), who were symptomatic at study entry. For the first 2 months, children inhaled budesonide 2 x 200 microg b.i.d. (high-dose treatment period). Thereafter, the daily dose of inhaled budesonide was 2 x 100 microg for 4 months (low-dose treatment period). The study was carried out at 32 centers in Finland, Sweden, Norway, and Denmark. During the high-dose treatment period, the initially symptomatic patients improved in both treatment groups and the achieved control was maintained during the low-dose treatment period. An improvement was seen in the efficacy outcome parameters in the initially symptomatic patients in both treatment groups. Also, there were no differences in the number of asthma exacerbations between the treatments. The urinary free cortisol/creatinine (UCC) ratios were significantly lower in the Turbuhaler group compared to the Easyhaler group after the high-dose treatment period. In addition, there was a slight but statistically significant slower growth rate in the Turbuhaler group after the 6- month treatment period compared with the Easyhaler group. Pulmicort Turbuhaler and Giona Easyhaler are equally effective in the treatment of asthma in children aged 5-10 years old. Budesonide inhaled from Turbuhaler showed slightly greater systemic effects than budesonide inhaled from Easyhaler. The majority of children and parents preferred Easyhaler to Turbuhaler.

Diagnosis of food allergy in Finland: survey of pediatric practices.

Food-related symptoms are common in the first years of life, and food allergy should be diagnosed using an elimination challenge test. We surveyed Finnish hospital-based pediatricians using a self-completion questionnaire to ascertain the current clinical practice: 24 of the 25 pediatricians (representing 24 of 25 hospitals) so approached gave evaluable responses. Food allergies were diagnosed using a clinical elimination challenge test in patients with suspected allergy to cow's milk or cereals (wheat, rye, barley, oats). Of the 24 departments, four reported that they performed challenge in all patients before diagnosis was confirmed, and 14 performed challenge in most patients before diagnosis was confirmed. The duration of the challenge varied from 0.5 to 7 days (median 4 days). A 1-week challenge was used in eight hospitals. The double-blind placebo-controlled challenge was used in seven of the hospitals, and in none routinely. Altogether, 16 of the respondents agreed that there is a need to establish clinical guidelines for the diagnosis of food allergy. In conclusion, despite a long tradition of medical education on the subject of food allergy, practices vary for its diagnosis. There is therefore a requirement for appropriate clinical guidelines.

Altered cardiovascular autonomic regulation after salmeterol treatment in asthmatic children.

The effects of therapeutic 4 weeks' inhaled salmeterol treatment on the cardiovascular and respiratory autonomic nervous regulation was studied in 11 asthmatic children using inhaled corticosteroid medication. The study followed a randomized, double-blind, placebo-controlled cross-over design. The salmeterol dose was 50 micrograms twice daily. The 4-week salmeterol treatment increased baseline heart rate, low-frequency/high-frequency (LF/HF) variability ratio of R-R intervals, LF variability of systolic arterial pressure (SAP) and maximum tidal volume during the deep breathing test, as well as morning and evening peak expiratory flow (PEF) values. The 4-week salmeterol treatment decreased baseline HF variability of R-R intervals. As a response to the acute 600 micrograms of salbutamol, the changes in heart rate, HF variability of R-R intervals and diastolic blood pressure were significantly smaller after 4 weeks' salmeterol treatment. In conclusion, 4 weeks' therapeutic salmeterol treatment decreases basal cardiovagal reactivity, increases sympathetic dominance in the cardiovascular autonomic balance and improves pulmonary function. A tolerance develops in the cardiovascular response but not in the bronchodilatory response.

Serum eosinophil cationic protein in the evaluation of asthma severity in children.

To assess the sensitivity and specificity of serum eosinophil cationic protein (ECP) in the diagnosis of asthma and evaluation of asthma severity, we conducted a prospective study to compare parameters of asthma severity, peripheral blood eosinophilia, and serum ECP concentrations in 88 children presenting to a university hospital outpatient clinic with suspected (n=59) or recently diagnosed asthma (n=29). Serum ECP correlated significantly (r[s]=0.676, P = 0.0001) with peripheral eosinophil counts, but only weakly with asthma severity (r[s]=0.21, P=0.046). Serum ECP was significantly higher in atopic children (25+/-11 microg/l) than in nonatopic children (16+/-15 microg/l) (P=0.01). Bronchial hyperresponsiveness had no significant correlation (r[s]= -0.21, P=0.30) with serum ECP. Lung function test results had no (peak flow) or only a weak (FEV1) correlation with serum ECP. In distinguishing between children with and without asthma or in assessing asthma severity, serum ECP is not superior to the peripheral blood eosinophil count. The diagnostic sensitivity and specificity of ECP in serum for detecting symptomatically active asthma, evaluated against the cutoff level of ECP in serum of 16 mg/l, were 54% and 71%, respectively.

Altered cardiovascular autonomic regulation after 2-week inhaled salbutamol treatment in asthmatic children.

UNLABELLED: We studied the effects of therapeutic 2-week inhaled salbutamol treatment on the cardiovascular and respiratory autonomic nervous regulation in eight children with asthma. In this randomized, double-blind, placebo-controlled crossover study our test subjects inhaled 200 microg salbutamol or placebo thrice daily for 14 days. After the 14-day treatment we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline and the response to a single 600 microg salbutamol inhalation. The periodic variability components of R-R intervals (the time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis. Two-week salbutamol treatment increased baseline low frequency (LF) variability (P < 0.05) and low frequency/high frequency (LF/HF) variability ratio of R-R intervals (P < 0.05) when compared to the placebo treatment. As a response to the single salbutamol inhalation the increase in LF/HF ratio of R-R intervals was smaller after the 2-week salbutamol treatment (P < 0.01). No significant differences were found in the bronchodilatory response after the treatment period. CONCLUSION: Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. Because these effects were evident 18 h after cessation of the therapy they are likely to reflect the adaptation of organ responses to regular therapy or altered central autonomic regulation rather than direct drug effect. A slight tolerance developed in the sympathovagal cardiac response but not in the bronchodilatory response.

The acute effects of inhaled salbutamol on the beat-to-beat variability of heart rate and blood pressure assessed by spectral analysis.

AIMS: We wanted to study the effects of a 600 micrograms inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma. METHODS: In this randomized, double-blind, placebo-controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R-R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross-spectral analysis. RESULTS: Salbutamol significantly decreased the total and low frequency (LF) variability of R-R intervals as well as the high frequency (HF) variability of R-R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R-R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation. CONCLUSIONS: We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.

Cardiovascular autonomic regulation in asthmatic children evidenced by spectral analysis of heart rate and blood pressure variability.

The objective of the study was to investigate the features of cardiovascular and respiratory autonomic nervous regulation in asthmatic and control children. Cardiorespiratory reactivity was studied by continuous and non-invasive recording of the electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions and during a deep breathing test in 19 children with bronchial asthma and 10 healthy control children (age 8-11 years). The periodic variability components of R-R intervals (the time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. Nine asthmatic children without beta2-agonist medication had a lower respiratory rate and larger high frequency (HF) variability of SAP than the controls, and 10 asthmatic children with beta2-agonist medication had greater low-frequency (LF) variability of SAP and LF/HF ratio of R-R intervals, but their respiratory rate did not differ from the controls. No intergroup differences were found in the postural change of variables. Stable bronchial asthma appears to increase respiratory-induced alterations in systolic blood pressure in children. Beta2-agonist medication, on the other hand, increases sympathetic cardiovascular activity in children with asthma.

Whey hydrolysate compared with cow's milk-based formula for weaning at about 6 months of age in high allergy-risk infants: effects on atopic disease and sensitization.

Ninety-one high atopy-risk infants were prospectively followed up to 18 months of age with regard to the development of allergic/atopic manifestations and sensitization. They were randomized into one of two feeding groups, i.e., a hydrolyzed, ultrafiltered cow's milk whey formula, Profylac (n = 32), or an ordinary cow's milk formula (n = 39), for 12 months, started after exclusive breast-feeding for 0-9 (median 6.0) months. Lactating mothers avoided milk, egg, and fish, as did the infants up to 12 months of age. Twenty of the 91 infants were breast-fed exclusively for more than 9 months and regarded as a control group. All infants were followed-up by questionnaires, physical examinations, skin prick tests, and determination of serum total IgE and cow' milk-specific IgE. The frequency of allergic/atopic disease was similar in the three groups. However, all three infants who developed cow's milk allergy with skin symptoms belonged to the cow's milk formula group. The skin prick test with whey hydrolysate was negative in all, while with cow's milk it was positive in eight infants. Growth was similar in the three groups. The study comprises too few infants to allow us to make statistically based statements. However, the difficulties encountered and the limited effects obtained by the use of whey hydrolysate at weaning at about 6 months of age made us conclude that we can spare high atopy-risk families this extra burden.

High anti-IgE levels at birth are associated with a reduced allergy prevalence in infants at risk: a prospective study.

Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (> = 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350 AU/l than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms.

Recurrent wheezy bronchitis and viral respiratory infections.

Fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing. Of the 115 episodes of upper or lower respiratory tract symptoms, virus or Mycoplasma pneumoniae infection were diagnosed in 52 (45%). Thirty four of rhinoviruses. The patients had an average of 2.1 episodes of respiratory tract symptoms the total mean (SD) duration of which was 30 (2) days of the 92 days that followed. Wheezing occurred during 76 (66%) of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea. Wheezing started a mean (SD) of 43 (7) hours after the first symptoms of respiratory infection and persisted for 3.8 (4.2) days in patients in whom virus infection was diagnosed. The incidence of wheezing was not associated with IgE mediated atopy, with positive virological tests, or with fever during virus infection, but was associated with parental smoking and more than one sibling.

Seasonal variation of IgE synthesis in vitro by human peripheral blood mononuclear cells.

Seasonal variations in IgE antibody synthesis in vitro were studied in cultures of blood mononuclear cells (MNC) from 11 pollen allergic individuals. The IgE levels were significantly higher in two summer seasons than in the winter and spring between them. Net synthesis was confined to the summer in all but one of the patients. All the IgE in the cultures outside the pollen season represented preformed IgE which was present mainly (59%) in the monocyte fraction. Thus, preformed IgE seems to persist in monocytes at times when there is little de novo synthesis of IgE.

Immunodominant antigens of Streptococcus mutans in dental caries-resistant subjects.

Previously, we reported that dental caries-resistant subjects, who have significantly fewer Streptococcus mutans in whole saliva than caries-susceptible patients, have significantly higher levels of naturally occurring binding and neutralizing parotid salivary immunoglobulin A and serum immunoglobulin G antibodies to native S. mutans antigens than caries-susceptible patients. Recent animal studies indicated that the immunogenicity of swallowed S. mutans may be altered by either saliva-coating or stomach acid-denaturation. These results suggest a difference not only in the quantity of antibody to S. mutans, but also in the antigenic epitopes that caries-resistant subjects synthesize antibody to as compared with caries-susceptible patients. In the present report, sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting studies indicate that caries-resistant subjects produce salivary immunoglobulin A and serum immunoglobulin G antibodies to several different (molecular weight: 94, 80, 40, and 35 kilodaltons) as well as several similar (molecular weight: 67, 55, and 30 kilodaltons) S. mutans epitopes as compared to caries-susceptible patients. This provides additional confirmation for our previous binding and functional antibody studies, indicating that caries-resistant subjects synthesize antibodies of different specificities than caries-susceptible patients. This study supports the concept of immune regulation of dental caries by naturally occurring antibodies induced by swallowing S. mutans antigens in saliva.

Effects of smokeless tobacco on the ability of secretory component to bind to the IgA/J chain complex.

Previously, we reported that smokeless tobacco users have significantly higher levels of immunoglobulin A and J chain in whole saliva than non-tobacco users. Because there was no difference in levels of secretory component between the two groups, the proportion of secretory component/immunoglobulin A was significantly lower in users than non-users. There was no significant difference in antibody function. In the present study, we examined immunoglobulin A from whole saliva of users and non-users to determine the effect of smokeless tobacco on the ability of secretory component to bind to immunoglobulin A containing J chain. Whole saliva was passed over an affinity chromatography filter unit coupled with anti-alpha heavy chain-specific antibody followed by passage over a molecular sieve high-performance liquid chromatography column. Peaks were collected and examined for immunoglobulin A, J chain and secretory component by enzyme-linked immunosorbent assay. Saliva from users had three significantly larger peaks (3-4 fold) at 280 nm than non-users, confirming the presence of a higher concentration of immunoglobulin A in users. The secretory component/J chain and secretory component/immunoglobulin A ratios for the largest peak were significantly less in users. This indicates that smokeless tobacco has an effect on the ability of secretory component to bind to immunoglobulin A without a loss in antibody function. This may occur either prior to immunoglobulin A/J chain binding to secretory component receptors on secretory epithelial cells or internal to the epithelial cells. These studies provide further evidence for the role of secretory component in mucosal immunity.

Reproducibility of the skin prick test.

Reproducibility of the skin prick method of testing for allergy was studied in 20 subjects examined by four nurses. Hypodermic needles were used for pricking and the test panel included a histamine control, a diluent control, and nine allergens. The reproducibility of the method was best when the size of the weal reaction caused by an allergen was expressed as the geometric area of the weal. When the weal reaction was expressed as the ratio of the weal reaction caused by an allergen to that caused by histamine, the reproducibility of the method was decreased considerably. When the ratios were further classified into three class ratings, reproducibility was very low. The reduction in reproducibility was due to the low reproducibility of histamine reactions. According to these results, at least in epidemiological studies the weal reactions should be expressed as geometric areas. In clinical practice it might also be preferable to express prick test results as the diameters of the weals without adjusting them by histamine reactions.

Circulating immune complexes during immunotherapy in allergy to dog.

Circulating immune complexes (CIC) were determined from dog-allergic asthmatic children (n = 35) receiving immunotherapy with dog dander and hair extract. The results from CIC are expressed in SDU (standard deviation units) and presented as follows: pretreatment results (n = 20), rush results (n = 11), mid-schedule results (n = 20), maintenance results (n = 15) and the results of the placebo-treated group (n = 12). The results of the placebo-treated group (n = 12) and those of the untreated atopic (n = 12) and non-atopic (n = 14) were controls. CIC levels were analysed by means of KgB-ELISA (conglutinin binding enzyme linked immunosorbent assay), C1qB-ELISA (C1q-binding enzyme linked immunososrbent assay), RFb-ELISA (rheumatoid factor binding enzyme linked immunosorbent assay) and by PIPA (platelet 125J-labelled staphylococcal protein-A test). The CIC level determined by KgB-ELISA in dog-allergic asthmatic children was higher than that of the atopic controls (P less than 0.05) already before the onset of the hyposensitization. During conventional hyposensitization with dog dander and hair the CIC level remained the same as before treatment. On day 5 of rush hyposensitization the mean level of CIC showed no increase when compared with the pretreatment values. A statistically significant correlation (P less than 0.01) was observed between the dog dander and hair-specific IgG antibodies and the CIC level measured by KgB-ELISA during the maintenance period of conventional immunotherapy. The samples of sera to measure this correlation were collected before the injection of allergen and after 2 weeks of injection during maintenance treatment.(ABSTRACT TRUNCATED AT 250 WORDS)