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.

Population based study of risk factors for underdiagnosis of asthma in adolescence: Odense schoolchild study.

OBJECTIVE: To describe factors related to underdiagnosis of asthma in adolescence. DESIGN: Subgroup analysis in a population based cohort study. SETTING: Odense municipality, Denmark. SUBJECTS: 495 schoolchildren aged 12 to 15 years were selected from a cohort of 1369 children investigated 3 years earlier. Selection was done by randomisation (n = 292) and by a history indicating allergy or asthma-like symptoms in subject or family (n = 203). MAIN OUTCOME MEASURES: Undiagnosed asthma defined as coexistence of asthma-like symptoms and one or more obstructive airway abnormalities (low ratio of forced expiratory volume in 1 second to forced vital capacity, hyperresponsiveness to methacholine or exercise, or peak flow hypervariability) in the absence of physician diagnosed asthma. Risk factors (odds ratios) for underdiagnosis. RESULTS: Undiagnosed asthma comprised about one third of all asthma identified. Underdiagnosis was independently associated with low physical activity, high body mass, serious family problems, passive smoking, and the absence of rhinitis. Girls were overrepresented among undiagnosed patients with asthma (69%) and underrepresented among diagnosed patients (33%). Among the risk factors identified, low physical activity and problems in the family were independently associated with female sex. The major symptom among those undiagnosed was cough (58%), whereas wheezing (35%) or breathing trouble (50%) was reported less frequently than among those diagnosed. Less than one third of those undiagnosed had reported their symptoms to a doctor. CONCLUSIONS: Asthma, as defined by combined symptoms and test criteria, was seriously underdiagnosed among adolescents. Underdiagnosis was most prevalent among girls and was associated with a low tendency to report symptoms and with several independent risk factors that may help identification of previously undiagnosed asthmatic patients.

Reduced forced expiratory flow in schoolchildren with respiratory symptoms: the Odense Schoolchild Study.

In the present population-based study, spirometric lung function was assessed in symptomatic schoolchildren with and without asthma as compared to an asymptomatic reference group. The primary aim was to investigate if impaired lung function could be demonstrated in symptomatic schoolchildren, even in the absence of diagnosed asthma. Spirometry [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), 50% of forced expiratory flow (FEF 50%) and 75% of forced expiratory flow (FEF 75%)] and anthropometric measures (standing height, weight, skin fold thickness, and length and circumference of the upper arm) were obtained from 1369 8-10-year-old children (81.5% of the eligible population) during the school year 1985-86. In 1321 of those subjects (96.5% of those examined), a self-administered questionnaire was completed. Thirty-five children belonging to ethnic minorities were excluded, thus 1286 subjects were included for further analysis. Point prevalences concerning asthma and respiratory symptoms (wheeze, cough and shortness of breath) were obtained. Thirty-seven children reported asthma and one or more asthma-like symptoms (symptomatic asthmatics), whereas 40 children denied having asthma, although claiming one or more asthma-like symptoms (symptomatic non-asthmatics). In both symptomatic groups, FEF 50% and FEF 75% were reduced relative to the reference group, the deficit being larger in the symptomatic asthmatics. FEF 75% was found to be more reduced than FEF 50%. FEV1 and FVC did not differ significantly between groups. It is concluded that only half of the schoolchildren with respiratory symptoms usually associated with the presence of asthma actually reported having this disease. These results demonstrate the presence of reduced lung function in symptomatic, reportedly non-asthmatic, children, suggesting clinically important underdiagnosis of asthma. More severe impairment of lung function was found in known asthmatics, also implying some degree of undertreatment.

[Discrepancies between diagnosed asthma, asthma-like symptoms and a test for abnormal lung function]. / Manglende overensstemmelse mellem diagnosticeret asthma, asthmalignende symptomer og test for abnorm luftvejsfunktion.

For the diagnosis of asthma, it is neither clear to which degree various tests and symptoms identify the same subjects nor how these characteristics are best combined. We assessed the interrelationship between physician-diagnosed asthma, asthma-like symptoms and abnormal airway function in a population based sample of 495 12-15 year old schoolchildren. Participants filled in a questionnaire and underwent baseline spirometry (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. Most symptomatic subjects with any test positive were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). Although interest agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, between PEF and EXE and between FEV1% and PD15. However, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology, and the combined use of the two tests may be helpful as an epidemiological screening tool for asthma.

Interrelationships between diagnosed asthma, asthma-like symptoms, and abnormal airway behaviour in adolescence: the Odense Schoolchild Study.

BACKGROUND: The diagnosis of asthma is based on several characteristics including symptoms and suitable tests of airway lability. However, it is neither clear to what degree various tests and symptoms identify the same subjects, nor how these characteristics are best combined to diagnose asthma. The interrelationships between physician-diagnosed asthma, asthma-like symptoms, and abnormal airway function, as defined by four commonly used tests, have therefore been assessed. METHODS: A population based sample of 495 Danish schoolchildren aged 12-15 years, comprising 292 randomly selected subjects and 203 subjects considered at risk of having or developing asthma, was examined. Symptoms and background information were recorded by questionnaire. The test panel consisted of baseline forced expiratory volume in one second (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. RESULTS: The sensitivity for diagnosed asthma was highest for PD15 followed by PEF monitoring, whereas specificity for asthma or asthma-like symptoms was marginally higher with the other two tests. Most symptomatic subjects with any positive test were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). PEF variability was more susceptible to treatment with inhaled steroids than the PD15 index. Although inter-test agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, PEF and EXE, and FEV1% and PD15. CONCLUSIONS: The agreement between the four tests was weak. In particular, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology. The combined use of methacholine provocation testing and PEF monitoring may be helpful as an epidemiological screening tool for asthma.

Evaluation of peak expiratory flow variability in an adolescent population sample. The Odense Schoolchild Study.

The validity of peak expiratory flow (PEF) recordings and the sensitivity of PEF variability indices in asthma and asthma-like conditions were examined in an adolescent population. Recordings from 245 randomly selected subjects and from an additional 181 subjects reporting or considered at risk for developing asthma were analyzed. Subjects recorded PEF twice daily for 2 wk using Mini-Wright meters, completed a symptoms questionnaire, and were tested for airway responsiveness to methacholine. The first three recording days showed significant accumulation of lowest PEF values recorded (41%) and were excluded from further analysis. Among nine PEF variability indices, the Two-lowest%mean (the mean of the two lowest PEF values as a percentage of the period mean) had the best sensitivity for physician-diagnosed asthma (28%). The sensitivity of the methacholine dose-response slope (DRS) was 69%. Combining these indices, a sensitivity of 77% for diagnosed asthma was obtained. Among subjects with asthma-like symptoms but no diagnosis of asthma, 14% had increased Two-lowest%mean and the DRS was increased in 17%, but only 3% were identified by both tests. In conclusion, inhomogeneity of PEF data could be corrected by disregarding the first three recording days. PEF variability indices identified some diagnosed asthmatics, and particularly some symptomatic "nonasthmatics," not identified by the DRS, suggesting that the combined use of these indices might be helpful.

Sodium-potassium pump activity in white blood cells from children with an increased risk of developing hypertension--The Odense Schoolchild Study.

We have measured the capacity of the sodium-potassium pump, as assessed by 86rubidium uptake and the number of [3H]-ouabain binding sites on white blood cells, in children aged 9-11 years, partly cross-sectionally and partly longitudinally after a physical training programme. Children from a hypertensive subgroup comprising the upper 5% of the blood pressure distribution and children from a randomly selected normotensive subgroup were eligible for the study. In the cross-sectional study 40 children from the hypertensive subgroup and 40 children from the normotensive subgroup were evaluated. A significant increase in 86rubidium uptake was present in boys as compared to girls. After adjustment for differences in sexual maturation the observed significant difference disappeared. Important correlates of pump activity were height, plasma glucose, and physical fitness. In the training study 10 boys from the hypertensive subgroup and 10 boys from the normotensive subgroup were also evaluated after eight months of physical training. A significant fall in 86rubidium uptake was observed. No control group was examined and probably the changes reflect some effects of sexual maturation on cation handling of cells. These results indicate a significant effect of sexual maturation in capacity of sodium-potassium pump in children.

Blood pressure and cardiac structure in children with a parental history of hypertension: the Odense Schoolchild Study.

OBJECTIVE: To examine the relation between a parental history of hypertension and blood pressure and cardiac structure in children aged 8-10 years. DESIGN: Cross-sectional study of a sample of children drawn from a population survey of coronary risk factors in children. SETTING: Odense, Denmark. SUBJECTS: Sixty-nine children of hypertensive parents (5.2% of the eligible population). MAIN OUTCOME MEASURES: Physical fitness assessed by calculation of maximum oxygen uptake, blood pressure recorded by one blind observer and left ventricular structure determined by echocardiography. RESULTS: Children with a parental history of hypertension displayed a significant decrease in physical fitness and a significant increase in obesity and systolic and diastolic blood pressure compared with the rest of the population. After controlling for differences in body size and physical fitness, they also showed significantly higher levels of systolic and diastolic blood pressure. Apart from a significant increase in thickness of the interventricular septum during systole, no significant differences in echocardiographic measures or indices could be demonstrated between children with a parental history of hypertension and a normotensive control group. CONCLUSION: Our results indicate that a higher level of blood pressure in children with a parental history of hypertension is apparent before the age of 10 years.

Left ventricular hypertrophy in children from the upper five percent of the blood pressure distribution--the Odense Schoolchild Study.

Left ventricular structural dimensions were assessed by echocardiography in a group of 64 children aged 9-11 years with a mean blood pressure at or above the 95th percentile (HC-group) and in a group of 66 children randomly selected from the rest of the population (NC-group). Children in the HC-group were heavier, more obese, and less fit. Parental history of hypertension was more frequent in the HC-group. Calculated left ventricular mass (LVM), and LVM corrected for body surface area (LVMI), were significantly greater in the HC-group and in boys. Repeated echocardiographic examination in 57 of the children following 8 months of physical training revealed significant increases in posterior wall thickness and the posterior-wall-thickness-to-radius ratio. LVM increased significantly in the NC-group. Neither physical fitness nor change in physical fitness contributed independently to the variability in LVM following the training period. In children aged 9-11 years at increased risk of developing essential hypertension left ventricular hypertrophy is present.

A controlled study of eight months of physical training and reduction of blood pressure in children: the Odense schoolchild study.

OBJECTIVE: To examine the effect of physical training on physical fitness and blood pressure in children aged 9-11 years. DESIGN: Prospective randomised controlled intervention study of a sample of children drawn from a population survey of coronary risk factors in children. SETTING: Odense, Denmark. SUBJECTS: 69 children with mean blood pressure greater than or equal to 95th centile (hypertensive group) and 68 with mean blood pressure less than 95th centile (normotensive group), randomly selected from a population of 1369 children. INTERVENTION: 67 children were randomised to receive three extra lessons a week of an ordinary school physical education programme for eight months. MAIN OUTCOME MEASURES: Physical fitness assessed by calculation of maximum oxygen uptake and blood pressure recorded by one unblinded observer. RESULTS: After three months neither blood pressure nor physical fitness had changed significantly. After adjustment for values in weight, height, heart rate, and the variable in question before training physical fitness rose significantly at the end of eight months' training, by 3.7 mlO2/kg/min (95% confidence interval 2.2 to 5.3) in the normotensive training subgroup and by 2.1 mlO2/kg/min (0.1 to 4.2) in the hypertensive training subgroup compared with that in the controls. Systolic and diastolic blood pressures in the training subgroups fell significantly by 6.5 mm Hg (3.2 to 9.9) and 4.1 mm Hg (1.7 to 6.6) respectively in the normotensive group and by 4.9 mm Hg (0.7 to 9.2) and 3.8 mm Hg (0.9 to 6.6) respectively in the hypertensive group. CONCLUSIONS: Physical training lowers blood pressure and improves physical fitness in children and might have implications for an important non-pharmacological approach to primary prevention of essential hypertension.

Blood pressure and physical fitness in a population of children--the Odense Schoolchild Study.

This cross-sectional study examined the association between blood pressure and physical fitness in 1,369 children (81.5% of the eligible population) aged 8-10 years participating in the first phase of a primary intervention study with physical training. An inverse correlation between BP and physical fitness was demonstrated, and significant differences have been found between quartiles of distribution of physical fitness in girls with regard to systolic BP and in boys and girls with regard to diastolic BP respectively. Important determinants of physical fitness seemed to be dependent on confounding variables representing body mass index, height, heart rate and age. Our observations suggest that the contribution of confounding variables may explain the relationship between BP and physical fitness in childhood.

Blood pressure distribution in a school-age population aged 8-10 years: the Odense Schoolchild Study.

This paper describes the distribution of systolic and diastolic blood pressures in a homogeneous population of 1330 schoolchildren (81% of the eligible population) aged 8-10 years in Odense, Denmark. A single blood pressure measurement was made. No significant difference in mean blood pressure between the sexes could be demonstrated. A significant age-related increase in systolic blood pressure of 4.4 mmHg/year and in diastolic blood pressure of 3.4 mmHg/year was observed. Weight and the heart rate were important determinants of blood pressure level. Other positive determinants were age and triceps skinfold thickness. There was a significant association between diastolic blood pressure and sexual maturation, which seemed to depend on body weight.

Immunotherapy of tree pollen allergy with a modified alginate conjugated birch pollen extract compared to an aluminium adsorbed extract.

The safety and efficacy of two birch pollen extracts, one chemically conjugated to alginate (Anjuvac) the other adsorbed to aluminium hydroxide (Alutard), were investigated in an open multicentre comparative study of 63 birch pollen allergic patients. Both extracts decreased the nasal symptoms during the birch pollen season. The changes in specific IgE and IgG were much the same in both treatment groups. The adverse reactions recorded were mild in both groups, but more frequent in the Anjuvac group, probably because of a more aggressive dose schedule though there were twice as many asthmatics in the Anjuvac group. The two investigated allergen extracts were useful alternatives for immunotherapy.

Exercise testing in children as a diagnostic tool of future hypertension: the Odense Schoolchild Study.

Systolic blood pressure response and double product (systolic blood pressure x heart rate) response to a progressive maximal exercise test were evaluated in two groups of children aged 8 to 10 years. One group (normal children, n = 68) consisted of children randomly selected from a subset of the population with a resting blood pressure below the 95th percentile, and the other group (high blood pressure, n = 64) included children with a resting blood pressure at or above the 95th percentile. A rise in systolic blood pressure and in the double product was observed during the ergometric performance in both boys and girls in the normal group, and a similar response was observed in the high blood pressure group. These results suggest that the blood pressure response to exercise in childhood gives no further information about the risk of developing hypertension than a blood pressure measurement at rest.

A new approach to assessing maximal aerobic power in children: the Odense School Child Study.

In two experiments maximal aerobic power (VO2max) calculated from maximal mechanical power (Wmax) was evaluated in 39 children aged 9-11 years. A maximal multi-stage cycle ergometer exercise test was used with an increase in work load every 3 min. In the first experiment oxygen consumption was measured in 18 children during each of the prescribed work loads and a correction factor was calculated to estimate VO2max using the equation VO2max = 12.Wmax + 5.weight. An appropriate increase in work rate based on height was determined for boys (0.16 W.cm-1) and girls (0.15 W.cm-1) respectively. In the second experiment 21 children performed a maximal cycle ergometer exercise test twice. In addition to the procedure in the first experiment a similar exercise test was performed, but without measurement of oxygen uptake. Calculated VO2max correlated significantly (p less than 0.01) with those values measured in both boys (r = 0.90) and girls (r = 0.95) respectively, and the standard error of estimation for VO2max (calculated) on VO2max (measured) was less than 3.2%. Two expressions of relative work load (%VO2max and %Wmax) were established and found to be closely correlated. The relative work load in %VO2max could be predicted from the relative work load in %Wmax with an average standard error of 3.8%. The data demonstrate that calculated VO2max based on a maximal multi-stage exercise test provides an accurate and valid estimate of VO2max.

Physical fitness, physical activity and blood pressure in children.

In numerous studies the relationship between physical fitness, physical activity and blood pressure have been evaluated. However, only a minority of the reported studies are controlled. This report gives a review of cross-sectional studies in children and longitudinal dynamic training studies in young adults below the age of thirty dealing with physical fitness/physical activity and blood pressure.

A multicenter trial of immunotherapy with alginate--conjugated grass pollen extract.

Conjuvac, a new generation of allergen extracts, has been developed to meet the need for improved characterization, purification, and standardization. Conjuvac consists of a dialyzed, standardized aqueous allergen extract chemically conjugated to a sodium alginate carrier and lyophilized in single-dose vials, thus ensuring stability until reconstituted with sterile water just before each injection. A preliminary study of Conjuvac 2 Grass by Pegelow (1984) involving a small number of patients showed this extract to have potential advantages. Accordingly, a study involving more patients was undertaken: two different maintenance dose levels of Conjuvac 2 Grass were investigated and compared to a pyridine-extracted, alum-precipitated two-grass extract called Allpyral, which in previous double-blind trials has been shown to be effective. The trial, which included 125 patients with hay fever and which extended over 2 years, involved ten allergists from seven European countries. Overall, the Conjuvac high-dose regimen proved slightly superior to Allpyral without any increased incidence of side effects, and all treatments stimulated marked increases in specific IgG levels without raising IgE levels.