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.

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.

Efficiency of different skin prick testing methods in the diagnosis of allergy to dog.

The study of 202 asthmatic children shows that prick testing with standardized dog allergen extract is very useful in the diagnosis of allergy to dog dander. A good correlation was demonstrated with clinical history, RAST and the provocation tests. The use of the histamine control system improves the specificity of the prick test when compared with the simple measuring of the mean wheal diameter. End-point titration of the skin prick reactivity did not further improve the specificity when compared with the histamine control system.

[Immediate sensitivity of asthmatic children to dog allergens]. / Unmittelbare Sensibilität der Asthmakinder gegen Allergum vom Hund.

The occurrence of dog hypersensitivity in 203 unselected asthmatic children was investigated by means of skin prick test, provocation test and RAST. The history of past and present exposure to dogs, symptoms in contact with dogs, and the effects of dog avoidance were recorded. The amount of dog dander antigens was measured from dust samples from 67 homes using counter-immunoelectrophoresis. A history of past or present dog hypersensitivity was obtained for 120 subjects (59%). The skin prick test was found to be a sensitive method for diagnosing dog hypersensitivity, when a standardized allergen extract was used. The results of the skin prick test correlated well with the provocation test (r = 0.832) and the RAST (r = 0.777). A positive (greater than or equal to ++) skin reaction was observed in 56% of the subjects, a positive (class greater than or equal to 1) RAST in 69%, and a positive provocation test with the same extract in 41% of the subjects. The occurrence of dog hypersensitivity was not significantly associated with past or present exposure to dog at home. However, the children who were exposed to a dog at home during early childhood developed dog hypersensitivity symptoms significantly earlier and had dog hypersensitivity slightly more often than the subjects with a later exposure or no exposure to dog. Significant amounts of dog dander antigens were found even in dust samples from homes where dogs had never been kept. The effect of dog avoidance on dog dander-specific IgE levels was studied from sera obtained from 24 subjects. Steadily high and even rising levels were observed in cases when a strict avoidance of dogs was reported by the patient. Dog saliva was found to be a more potent and more species-specific source of dog allergens, in comparison with a commercial dander extract, according to skin prick test and RAST inhibition studies.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Humoral and cell-mediated immune responses to dog dander and hair in asthmatic children.

Dog dander and hair (DDH) specific IgA and IgG antibodies from serum samples of 202 asthmatic children aged from 4 to 15 years were measured by enzyme-linked immunosorbent assay. The results were compared with clinical history, and with allergy tests (skin prick test, provocation test and RAST) using the same DDH extract. A blood sample for the in vitro lymphocyte stimulation test was obtained from 40 children, and a nasal secretion sample for analysis of the local DDH-specific IgA, IgG and IgE antibody levels was collected from 35 of them. In children of dog-keeping families, higher serum levels of DDH-specific antibodies, especially IgE antibodies, were observed if the dog had been in the home already during the first years of the child's life. The serum levels of DDH-specific antibodies, however, did not correlate with the degree of the present exposure to dogs. The serum levels of DDH-specific IgA and IgG antibodies did not correlate with each other, with the levels of specific or total IgE, or with the results of skin prick or provocation test. The serum levels of DDH-specific IgA were highest in children who were subjectively most sensitive to dogs. Nasal levels of DDH-specific IgE correlated positively with serum specific IgE levels. The correlation was weaker between nasal and serum titers of specific IgG, and not significant between nasal and serum IgA antibody levels. Specific IgE antibody levels were higher, while specific IgA and IgG antibody levels were lower, in nasal secretion from subjects with nasal symptoms on contact with dogs, when compared with subjects with other complaints (asthma, conjunctival or skin reactions). DDH-specific IgG levels correlated negatively with specific IgE level in the nasal secretion from subjects with a positive provocation test result, while the correlation was positive in subjects with a negative provocation test. The in vitro lymphocyte responses to DDH did not correlate with the results of allergy tests, or with the levels of DDH-specific antibodies in serum or in nasal secretion.

Skin prick test in the diagnosis of dog dander allergy: a comparison of different extracts with clinical history, provocation tests and RAST.

Skin prick tests (SPT) were carried out on 164 asthmatic children using dog dander allergen preparations (A, B1, B2 and D) from three manufacturers. Bronchial and/or conjunctival provocation tests with allergen A were performed on all patients, as well as the Phadebas RAST (allergen e5). There was a close agreement between the clinical history and the SPT with allergens A and D. The provocation tests and RAST gave results in good agreement with the SPT reactions to all allergens except B1. The overall agreement between the SPT reactions to the different allergens was good. However, significant differences were observed in the allergenic activity of the different preparations and between different batches from the same manufacturer (allergens B1 and B2).

Dog serum albumin as an allergen. IgE, IgG and lymphocyte responses in dog dander-sensitive asthmatic children.

To study the allergenicity of dog serum albumin (DSA) in dog-sensitive subjects, we investigated 203 asthmatic children by means of the skin prick test (SPT), the radioallergosorbent test (RAST) and the in vitro lymphocyte stimulation test. Significant SPT reactions to DSA were observed in only 9 out of 80 subjects with a significantly positive SPT reaction to dog dander and hair (DDH). Analogously, positive DSA RAST results were observed only in a minority of the cases with a positive DDH RAST. Significant SPT reactions to DSA were not observed in subjects with a negative clinical history of dog allergy, or in subjects with a negative reaction to DDH in the SPT or in the provocation test. DSA induced remarkable lymphocyte stimulation in only 1 subject, who also had a significant SPT reaction to DSA. DSA-specific serum IgG antibody titers measured by ELISA were not found to correlate with DSA SPT or DSA RAST.

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.

Cross-reactivity of cat and dog allergen extracts. RAST inhibition studies with special reference to the allergenic activity in saliva and urine.

The commercial cat and dog allergen extracts are traditionally prepared from pelt, fur or dander. However, there is increased evidence of the allergenicity of saliva and urine of the animals. We have investigated 25 asthmatic children with a positive cat and/or dog RAST result. All 20 subjects with a positive cat RAST gave a positive skin prick test result to cat saliva, cat urine and cat hair. Analogously, all 20 subjects with a positive dog RAST had a positive skin reaction to dog saliva, urine and dander. In RAST inhibition experiments with dog and cat allergen discs, dog saliva appeared to be at least as potent as a commercial dog dander and hair extract, while cat saliva was less potent than the respective commercial extract. Both dog and cat salivas were clearly more potent than the respective urine. Significant cross-reactivity was observed between cat hair and dog dander in the RAST inhibition, whereas saliva and urine were shown to be more species-specific. An experimental dog dander preparation had about the same specificity as, and even higher allergenic activity than, that of dog saliva or urine. Our results suggest that saliva actually may be the best source of cat and dog allergen preparations. The importance of urine warrants further investigation.

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.

Determination of theophylline in serum with the Seralyzer Aris reagent strip test evaluated.

We evaluated a new Seralyzer Aris reagent strip test (Ames Div., Miles Labs.) for the determination of theophylline in human serum. The method is based on the monoclonal enzyme immunoassay with dry reagent chemistry. The analysis is rapid and simple to perform: results are available only 5-10 min after receipt of the sample. Intra-assay precision (CV) was 2.2-3.3% (n = 15) for theophylline concentrations of 5-25 mg/L; interassay CV was 5.9% (n = 19) at 15 mg/L. The results (y) agreed well with those by liquid chromatography (x): r = 0.949 (p less than 0.001), and y = 0.967x + 0.214. We conclude the method is useful for rapid evaluation of theophylline concentrations in asthmatic patients.

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.

Immunotherapy in allergy to dog. Immunologic and clinical findings of a double-blind study.

Twenty-seven dog-allergic asthmatic children with no pets in the home were included in the study. The clinical trial was performed as a double-blind study using a commercial standardized aluminum hydroxide-bound dog dander and hair extract or histamine-placebo. The patients were randomized into the active treatment or the placebo group on the basis of the RAST (e5) and the provocation test with aqueous dog dander and hair extract. The good clinical response of immunotherapy with dog dander and hair extract has been reported earlier. The specific immunotherapy resulted in an increase in the serum level of antigen-specific IgG antibodies (P less than .01) and a decrease in the skin sensitivity to dog extract (P less than .001) in the active treatment group when compared with the placebo group. The treatment was well-tolerated. No systemic reactions occurred and local reactions were mild. The results show a good immunologic response with a standardized dog dander and hair extract. There were no major changes in the course of bronchial asthma in either group. After 1 year of immunotherapy the subjects had no symptoms on a dog-exposure of short duration. This must be carefully emphasized when considering the indications for immunotherapy.

A sandwich enzyme immunoassay for the detection of human IgG antibodies to dog allergens.

A double-sandwich enzyme immunoassay (DSEIA) was developed for the detection of human IgG antibodies to dog dander and hair (DH) allergens. Since DH allergens are immunogenic in rabbits, the gamma-globulin fraction of rabbit antiserum to DH (RGG-a-DH; 10 micrograms/ml) was used for coating of polystyrene microtiter plates. Dog allergens (1 microgram/ml of DH extract) were bound to RGG-a-DH. Binding of human IgG Ab to nonimmune RGG (10 micrograms/ml)--used as a background control--was substracted from the DH specific one and nonspecific binding was further eliminated by using 0.5% of normal rabbit serum in the dilution buffer. Sera were diluted 1:10 in this buffer. Specificity of the assay was shown by absorption experiments: protein A, anti-IgE discs (Phadebas PRIST) and dog or birch (e5, t3; Phadebas RAST) allergen discs were used to remove total and allergen specific IgG and IgE, respectively. The results were expressed as net absorbances or as a percentage of a reference serum. A significant correlation (r = 0.65, p less than 0.001) between IgG (DSEIA) and IgE (RAST) antibodies to dog allergens was observed in 40 untreated dog allergic subjects. The DSEIA was found to be more sensitive than conventional ELISA in detecting IgG Ab in 15 asthmatic children during hyposensitization: a significant rise was observed in 14 compared to 12 with ELISA, while no significant increases were observed in the placebo-treated group.

Leukocyte migration inhibition test in children with cow milk allergy.

The usefulness of the leukocyte migration inhibition factor (LIF) test to detect cow milk (CM) hypersensitivity was studied in 40 children with suspected allergy to CM. Hypersensitivity was carefully investigated by oral milk challenges, which gave a final confirmation of cow milk hypersensitivity in 12 subjects, and excluded it in the remaining 28 subjects. Leukocyte migration inhibition was measured using beta-lactoglobulin (BLG), alpha-lactalbumin (ALA), alpha-casein (ACA) and bovine serum albumin (BSA) as antigens. IgA and IgG antibodies to these antigens were measured by an enzyme-linked immunosorbent assay, and IgE antibodies to these antigens and to CM by radioallergosorbent test (RAST). Skin prick test with CM was performed in 38 subjects, and with BLG, ALA, ACA and BSA in 29 subjects. Leukocyte migration was more often inhibited by cow milk antigens in the CM challenge positive (CM+) subjects than in the challenge negative (CM-) subjects. Of the specific milk antigens, ALA was the most potent inhibitor, and gave a positive LIF test result in all CM+ subjects, and significantly (P less than 0.02) less often (15/24) in CM- subjects. Also in the skin prick test and RAST, ALA gave positive results more often than the other milk antigens. BLG, ACA and BSA had an inhibiting effect on leukocyte migration, but the difference between the CM+ and CM- subjects was not statistically significant. Two of the 12 CM+ subjects had no demonstrable IgE antibodies to CM proteins; both of them, however, had a positive LIF test with at least one of the CM antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

RAST in the diagnostic of dog dander allergy. A comparison between three allergen preparations using two variants of RAST.

The results of the skin, bronchial or conjunctival provocation tests and of the radioallergosorbent test (RAST) with dog dander and hair extract preparations from two different producers were compared. 202 asthmatic children were included in the study. The clinical tests, Al-RAST and paper RAST, were performed using only one allergen preparation (Hu073), while two allergen preparations (e2 and e5) were used in Phadebas RAST. A good correlation was generally found between the results of the clinical diagnostic tests, the clinical history and the results of RAST. Phadebas RAST e2 was the most specific but the least sensitive: it gave a class 0 result in 18% and class 3-4 in 34.5% of the subjects with a positive provocation test. The corresponding numbers for e5 RAST were 6.0% and 70.2%, respectively. Al-RAST was equally sensitive, but had lower specificity than Phadebas RAST e5. The correlation between Phadebas RAST e5 and paper RAST Hu 073 was excellent, which indicates a remarkable similarity between these allergen extracts. Using sensitive, immunochemically standardized Phadebas RAST e5 or Al-RAST methods, classes 0-1 can be regarded as negative, class 2 as doubtful and classes 3-4 as clinically positive results.