Asthma mortality rate in Swedish children and young adults 1973-88.

To investigate the asthma mortality rate in Sweden for the period 1973-88, we reviewed all death certificates for suspected death from asthma coded as 493 of the International Classification of Diseases (ICD)-8 and ICD-9 for the age group 1-24 years. Age-related mortality rates were calculated and compared with the results from a previous Swedish study of 1952-72. To identify factors contributing to death, we assessed hospital records. The mortality rate was 3.46 for the period 1973-88 and 3.31 for the earlier period, a net increase of 5%. This small overall increase includes a minor decrease in deaths for the age group 1-14 years and a rather pronounced increase for 15-24-year-old asthmatic patients. More deaths among "mild" asthmatic patients were found in the higher age group for 1986-8 than 1973-81. In younger children, asthma was more severe, and no difference was found between the two periods of the study. Asthma mortality is increasing in Sweden in adolescents and young adults, and there is a tendency to increasing mortality from less severe asthma not treated with anti-inflammatory drugs.

Peak expiratory flow rates in healthy Saudi Arabian children living in Riyadh.

The peak expiratory flow rate (PEFR) was measured in 457 healthy Saudi schoolchildren (235 boys and 222 girls) aged 6 to 16 years, living in Riyadh, using two simple and commercially available airflow meters, Wright peak flow meter and the mini-Wright peak flow meter. All measurements were obtained in the standing position and the best of three trials was recorded. Standing height and age were used as independent variables. The regression equations for PEFR were determined for boys and girls separately. The boys had higher values than the girls at all heights. The difference was not significant. Both boys and girls had lower PEFRs as compared with European children and American children of different racial origin (P < .0001). When age was added to height as the second independent variable the Saudi boys and girls had significantly lower PEFRs than Swedish and British children (P < .0001). One explanation for these differences may be that the Saudi children on the average are shorter and have lower body weights than, eg, American children. The PEFR did not differ when using the Wright peak flow meter or the mini-Wright peak flow meter. These findings will serve as an important basis for preparing charts for normal PEFR values for Saudi children.

Immunotherapy with cat- and dog-dander extracts. V. Effects of 3 years of treatment.

The effect of a 3-year course of cat or dog immunotherapy (IT) was evaluated in 32 patients with a history of asthma on exposure to cat or dog. Twenty-one subjects (14 children and seven adults) received cat IT and 11 subjects (six children and five adults) received dog IT. Bronchial challenges with allergen and histamine were performed once a year. Specific IgE, IgG1, and IgG4 were measured, and skin prick tests were done in connection with the challenges. Allergen sensitivity decreased significantly in both treated groups (p less than 0.001 and p less than 0.05 in the cat-allergen and dog-allergen treated groups, respectively). Bronchial hyperreactivity measured by the provocative concentration of histamine causing a 20% decrease in peak expiratory flow in the cat-allergen treated patients (p less than 0.001) but not in the dog-allergen treated patients. Skin sensitivity decreased in both groups (p less than 0.01 and p less than 0.05), whereas specific IgE increased initially but dropped to the pretreatment level during the second year. Specific IgG1 and IgG4 increased during the first and second year in the cat-allergen treated group (p less than 0.01 and p less than 0.001), whereas only IgG4 increased in the dog-allergen treated group (p less than 0.01). Five cat-allergen treated children and one of the adults who completed 3 years of therapy had mild systemic reactions. We conclude that cat IT ameliorated bronchial allergen sensitivity and bronchial hyperreactivity and resulted in an adequate antibody response. Dog IT was less efficacious but led to attenuation of bronchial allergen sensitivity.

Effects of maternal diet during late pregnancy and lactation on the development of IgE and egg- and milk-specific IgE and IgG antibodies in infants.

The IgE levels and food-allergen-specific IgE- and IgG-antibodies (Ab) to ovalbumin (OA), ovomucoid (OVO) and beta-lactoglobulin (BLG) were determined up to 18 months of age in 163 infants born to women who were atopic. A high (HIGH group) or a low (REDUCED group) intake of hen's egg and cow's milk by the mother during the third trimester gave no significant differences in the concentrations of IgE or in IgE-Ab (OVO, BLG) and IgG-Ab (OA, OVO, BLG). Similarly, a prolongation of the abstention diet to the early lactation period did not influence the immune response. The IgG-Ab levels to all three food allergens decreased significantly (P less than 0.001) in both study groups between birth and 2 months of age, but then increased significantly (P less than 0.001) between 6 and 18 months of age. The presence in serum of IgE-Ab to OVO (greater than or equal to 0.15 PRU/ml) was associated with significantly higher IgG-Ab levels to OVO at 6 months (P less than 0.001) and at 18 months (P less than 0.05). Infants with positive skin-prick tests (SPT) to OA and OVO showed higher IgG-Ab levels at 6 and 18 months of age than did infants with negative SPT reactions to the two egg allergens. This indicates a relation between the IgE- and IgG-Ab response and it also suggests that some individuals are 'high responders' to both types of immunoglobulin isotypes while others are 'low responders'.

Juvenile pemphigus vulgaris.

Pemphigus vulgaris is extremely rare in childhood. Only 35 cases of juvenile pemphigus vulgaris have been reported in the literature up until to now. During the pre-steroid era, the outcome of the disease was usually regarded as fatal. Today, the prognosis has improved because of the possibility of early diagnosis by immunofluorescent techniques, determination of antibodies against epidermal intercellular substance and early therapy with systemic steroids. A case of juvenile pemphigus vulgaris with a favourable outcome in a 13-year old girl is described.

Twelve hours' bronchodilating effect of inhaled formoterol in children with asthma: a double-blind cross-over study versus salbutamol.

Thirteen children, mean age 10.9 yr, with perennial asthma, were studied with respect to the duration of the bronchodilating effect of formoterol, a new long-acting beta 2 agonists for inhalation. The duration of action of formoterol metered dose aerosol (12 micrograms) was compared with salbutamol metered dose aerosol (200 micrograms) in a double-blind cross-over study. Formoterol was found to have significantly better bronchodilating effect 8 hr (P less than 0.01) and 12 hr (P less than 0.05) after inhalation of the drug. Formoterol (24 micrograms) was given single-blindly on the third trial day and showed a tendency towards a better bronchodilating effect (n.s.) than formoterol (12 micrograms). There was no difference between the treatments with regard to adverse reactions such as tremor, palpitations, raised heart rate or anxiety. Formoterol proved to be superior to salbutamol as a long-acting bronchodilator in children with bronchial asthma.

Asthma from childhood to adulthood--a follow-up study of 20 subjects with special reference to work capacity and pulmonary gas exchange.

Twenty men with a mean age of 24.9 years, who had moderate to severe asthma during childhood, underwent a follow-up examination of their physical fitness, working capacity, maximal oxygen uptake, and pulmonary function during and after physical work. Comparison was made with similar data obtained at the age of 10.9 years. The young men had a normal physical working capacity with a normal oxygen uptake of 3.65 +/- 0.56 L/min. The respiratory parameters and the arterial blood gases during work demonstrated values as in healthy individuals, and no differences between groups with mild and severe asthma during childhood were observed. The alveolar-arterial oxygen difference was normalized, compared to that at 10.9 years. Only a few subjects still had exercise-induced asthma with a postexercise fall of greater than 20% in FEV1 compared to childhood. The mean FEV1 values for the whole group after exercise were lowered and had not returned to the baseline level even after 20 minutes. Oxygen pressure (tension), arterial, measured during 20 minutes after work, demonstrated continuously decreasing values. This might reflect a persisting disturbance in the pulmonary ventilation perfusion relationship caused by the underlying asthma disease.

Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age--in-vivo results.

One hundred and sixty-two women with respiratory allergy to animal danders and/or pollens were randomly allocated to a diet consisting of either a very low ingestion of hens' egg and cows' milk or a daily ingestion of one hens' egg and about 11 of cows' milk during the last 3 months of pregnancy. One hundred and sixty-three infants were followed prospectively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly. No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy. The numbers of skin-prick tests positive to ovalbumin, ovomucoid, beta-lactoglobulin and cows' milk were likewise not influenced by differences in the maternal diet during late pregnancy. Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy.

Ipratropium bromide (Atrovent) in childhood asthma: a cumulative dose-response study.

Thirteen children with perennial bronchial asthma, with a mean age of 11.2 years, were studied concerning the bronchodilatory effect of ipratropium bromide in cumulative doses. All the children had reduced basal forced expiratory flow (FEV1) and bronchial reversibility of at least 20% after inhalation of salbutamol. The study had a double-blind design with a crossover technique. The inhaled dose of ipratropium bromide solution was increased stepwise from 25 micrograms to 500 micrograms and saline was used as the placebo. FEV1 was recorded 20, 40, and 60 minutes after inhalation of the test solution. At the lower ipratropium bromide dose levels no bronchodilatory effect was seen, but 60 minutes after the inhalation of 500 micrograms ipratropium bromide the increase in the FEV1 was significantly greater than that after placebo. Additional inhalation of salbutamol caused no further rise in FEV1. At the 500-micrograms level a fall in the heart rate was noted. No side effects occurred. We concluded that ipratropium bromide has bronchodilatory properties in childhood asthma when given in sufficiently high doses.

Immunotherapy with cat- and dog-dander extracts. IV. Effects of 2 years of treatment.

Thirty-five patients (20 children and 15 adults) with animal-dander asthma completed 2 years of immunotherapy with partly purified and standardized cat- or dog-danger extracts. The first year of the study was performed double-blind with a placebo-treated control group. These 15 patients were transferred to active treatment for a second year. All patients were followed by use of the skin prick test (SPT), allergen and histamine bronchial challenges, and tests for allergen-specific IgE, IgG1, and IgG4 levels. In the group treated with active extracts for 2 years (group A), the previously reported decrease in bronchial responsiveness to cat extract (p less than 0.001) and histamine (p less than 0.01) was even more pronounced after the second year. After 1 year of active treatment in the original placebo group (group B), a significant decrease in the bronchial responsiveness to cat extract was noted (p less than 0.001). The responsiveness to histamine was decreased only in the patients treated with cat-dander extracts (p less than 0.05). A significant decrease in the SPT (p less than 0.001) and an increase in the allergen-specific IgE (p less than 0.001) and IgG4 (p less than 0.001) was also noted in patients (group B) treated with cat-dander extracts. The side effects in the two groups (A and B) were negligible, except for some systemic side effects, especially among the children during the initial phase of immunotherapy. The symptoms were mild and responded promptly to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Penicillin allergy--a rare paediatric condition?

A total of 298 children with a history of adverse reactions in connection with oral penicillin treatment were investigated with a radioallergosorbent test for penicillin metabolites, the skin prick test, and oral challenge with penicillin V. No severe reactions were seen. In 30 (10%) of the subjects slight to moderate skin reactions were observed on the seventh to 10th day of the challenge period. Between one to four years after the oral challenge 222 children were reinvestigated by interview. One hundred and ten had been given treatment by penicillin and 103 (94%) of these children tolerated the new treatment well and without any adverse reactions. We conclude that the term 'penicillin allergy' is often misused. Such a diagnosis should be established by clinical investigation.

Asthma from childhood to adult age. A prospective study of twenty subjects with special reference to the clinical course and pulmonary function.

Twenty young men with a mean age 24.9 years, who had moderate to severe asthma during childhood, underwent a follow-up examination of their clinical status and pulmonary function. Comparison was made with data obtained at a mean age of 10.9 years. Eight of twenty showed a clinical improvement and 12 no change in their asthma. During childhood 12 of 20 boys had been on longterm ACTH or corticosteroid treatment. In the present study no one was given systemic steroid treatment. The static lung volumes (VC, TLC, FRC RV) were within normal limits for children and adults. In spite of clinical improvement, the expiratory flow rates (FEV1, FEV%) were still significantly reduced (p less than 0.005). Thus, the clinical improvement was not accompanied by a corresponding improvement in expiratory flow rates.

Immune response of the atopic woman and foetus: effects of high- and low-dose food allergen intake during late pregnancy.

The influence of the mother's consumption of cows' milk and hens' egg on the immune response (IgE, IgG) in the mother and foetus was studied in 165 pregnant women with atopical respiratory disease with an allergy to pollen and/or animal dander. The women were randomly allocated to four diets ranging from a diet free from hens' egg and cows' milk to a diet containing intake of one egg and one litre of milk daily during the third trimester. No significant differences in cord blood IgE levels were noted in spite of differences in maternal diet, and no specific IgE antibodies to ovalbumin, ovomucoid and betalatoglobulin were found in the cord blood. The mother's IgG antibody concentrations to ovalbumin, ovomucoid and betalactoglobulin were influenced by her diet, but cord blood IgG antibody levels to the selected food allergens were unaffected. The data presented on the IgE and IgG antibody levels to ovalbumin, ovomucoid and betalactoglobulin in cord blood suggest that changes in maternal diet during the last trimester of pregnancy in order to prevent atopic sensitization in utero are less likely to affect the foetus than previously supposed.

Working capacity and pulmonary gas exchange in children with exercise-induced asthma.

Sixteen children aged 10.1-14.3 years with a history of exercise-induced asthma (EIA) were evaluated as to their working capacity both during a maximal exercise test and during submaximal exercise. During submaximal exercise ventilation and alveolar gas exchange were measured. Working capacity was normal with respect to the oxygen uptake and to the maximal load. Arterial blood gases were normal before exercise but PaO2 decreased (p less than 0.01) during the submaximal exercise test. The values were, however, still within the normal limits in all but two of the children. The flow-volume data showed bronchial obstruction in the resting state, before exercise, with lower values of MEF50 and MEF25 (p less than 0.01) than in healthy children. Following exercise, 14 of the 16 children developed clinical symptoms of asthma with increased impairment of the flow-volume curves. Most of them recovered from asthmatic symptoms within 30 min. Flow-volume curves were found to be a sensitive measurement of bronchial obstruction during the symptom-free phase and during EIA although with larger individual variations than FEV1.

Ketotifen in pollen-induced asthma: a double blind placebo-controlled study.

Twenty-nine children with an average age of 10.5 years were studied with respect to the protective effect of ketotifen on pollen-induced bronchial asthma. All of them were sensitive to deciduous tree pollen, the diagnosis being verified by bronchial challenge. The children were stratified in matched pairs and randomly allocated to two treatment groups, placebo or ketotifen 1 mg twice daily. The study was double-blind and was performed during the whole of the deciduous tree pollen season. Daily pollen counts were made, allergic symptoms were noted, additional medication was given and the expiratory pulmonary flow was recorded. During the birch pollen peak the ketotifen group showed significantly fewer, and less severe asthma and rhinoconjunctivitis than the placebo group. The anti-asthmatic medication was also used significantly less than in the placebo group. Ketotifen appeared to have good protective properties in the treatment of pollen-induced asthma and rhinoconjunctivitis.

Immunotherapy with partially purified and standardized animal dander extracts. I. Clinical results from a double-blind study on patients with animal dander asthma.

Forty-one patients (21 adults and 20 children) with cat dander-or dog dander-induced asthma were selected for immunotherapy with standardized and partially purified cat- or dog-dander extracts by use of a double-blind protocol. Based on sex, age, clinical history, results of bronchial challenge, and crossed radioimmunoelectrophoresis studies, the patients were stratified in matched pairs, and the treatment alternatives were distributed randomly among the pairs. Twenty-two patients treated with allergen (15 with cat allergen and seven with dog allergen) and 17 patients receiving placebo therapy completed the first year of treatment. In the cat allergen-treated group, the bronchial sensitivity toward cat and histamine decreased (p less than 0.001 and p less than 0.05, respectively). Measured by bronchial challenge, the cat allergen-treated patients could tolerate 11 times more allergen at the end than at the start of the study, and they also demonstrated a tendency toward less pronounced symptoms after exposure to cat and dog allergens. No significant changes were observed in the dog allergen treated- or placebo-treated groups. The adverse effects in general were negligible except for some systemic side effects during rush hyposensitization, especially among the children, but these were mild and responded promptly to treatment.

Immunotherapy with cat- and dog-dander extracts. II. In vivo and in vitro immunologic effects observed in a 1-year double-blind placebo study.

The effects of immunotherapy on the skin prick test, allergen-specific IgE, and IgG in 39 patients (19 adults and 20 children), treated with partially purified cat- or dog-dander extracts or placebo for 1 year, were studied by use of a double-blind protocol. IgG levels were measured by three different assays: IgG RAST, IgG4 RAST, and Staph A IgG1, 2, and 4. The skin prick test reaction decreased continuously in the allergen-treated patients, the decrease being the first sign of an immunologic effect of the therapy. Allergen-specific IgE levels increased during the first 9 months in both children and adults. The RAST activity during the last 3 months continued to rise for the children, whereas it declined for the adults. IgG levels measured by all three methods demonstrated an increase in the allergen-treated patients and no increase in the placebo-treated patients. The children developed higher values on IgG RAST and IgG4 RAST than the adults. IgG RAST correlated negatively with IgE levels in the cat allergen-treated group. No correlation between skin prick test results, IgE levels, and IgG levels was found, nor was there any correlation between these parameters and the patients' own subjective evaluation or the allergen bronchial challenge test. In summary, the expected change in skin prick test reaction and allergen-specific IgE and IgG levels was found. The children tended to be more immunologically active than the adults.

Immunotherapy with cat- and dog-dander extracts. III. Allergen-specific immunoglobulin responses in a 1-year double-blind placebo study.

An investigation was made of the specific antibody response to individual antigens in 40 patients taking part in a double-blind placebo study of immunotherapy with cat- or dog-dander extracts. Antigen-specific IgE levels were measured by means of CRIE, and the results were expressed as scores. The patients demonstrated IgE specificities toward 1 to 5 antigens. Cat-dander antigens Nos. 4 (cat Ag 1) and 7, and dog antigens Nos. 6 and 13, produced the highest scores, but high IgE binding was also found for dog albumin. After 1 year of treatment, the IgE responses of the two treatment groups (allergen and placebo) were statistically indistinguishable from those before the start of treatment. There was a tendency toward a reduction in score for two of the dander antigens (cat Ag 1 and dog Ag No. 13), and no new IgE specificities appeared. Antigen-specific IgG levels were measured by means of CIE with patient serum incorporated in an intermediate gel, and the results were expressed as plus/minus precipitins. Only two patients had precipitating antibodies before the start of treatment (one against cat albumin and one against cat Ag 1). During the course of treatment, the production of antigen-specific IgGs was observed in 18/22 allergen- and 1/18 placebo-treated patients. For the cat allergen-treated group, the specificities were directed against cat antigens Nos. 2, 3 (cat albumin), 4 (cat Ag 1), and 7, and for the dog allergen-treated group, against dog antigens Nos. 2 (dog albumin), 13, and 20.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of ketotifen on bronchial hyperreactivity in childhood asthma.

Eighteen children with perennial bronchial asthma with an average age of 9.6 yr were studied with respect to the protective effect of ketotifen on bronchial hyperreactivity. All children included demonstrated bronchial reversibility after inhalation of salbutamol, and the methacholine challenge produced a decrease of the forced expiratory volume during the first second of at least 20% in the concentration interval of 0.25 mg/ml to 4.0 mg/ml. The study was double-blind with patients divided into two parallel groups treated for 12 wk with ketotifen or placebo. Methacholine provocation tests were performed every fourth week during this period. No differences between the challenges before and during the treatment period were found in either group, nor were any differences found between the ketotifen and placebo groups. Long-term treatment with ketotifen does not appear to alter the bronchial hyperreactivity in children with bronchial asthma.