Prolonged recovery from exercise-induced asthma with increasing age in childhood.

It has been suggested that children with asthma recover more quickly from exercise-induced bronchoconstriction than adults. On the basis of clinical observation we hypothesized that recovery rate from exercise-induced asthma (EIA) in childhood also decreases with age. In 14 children (aged 7-12 years) with a history of EIA, we measured spontaneous recovery from bronchoconstriction induced by two different stimuli: exercise and histamine. The children visited the laboratory three times. After a screening exercise test on the first visit, standardized bronchoprovocation tests with either exercise or histamine were performed on the following two visits in random order. The degree of bronchoconstriction induced by histamine was matched for that observed after exercise. During recovery, forced expiratory volume in 1 second (FEV1) was measured repeatedly up to 2 hours postchallenge. The recovery rate (% increase in FEV1/min) was calculated from the linear slope of the time-response curve. Differences in recovery rate between the two stimuli were analyzed by paired t-test, and age-related differences were analyzed using multiple regression analysis. For the group as a whole, recovery rate was not different between the two stimuli (mean +/- SD: 1.22 +/- 0.91 for exercise, and 1.46 +/- 0.65, for histamine, P = 0.31). However, the recovery rate for exercise-induced bronchoconstriction decreased significantly with age (r = -0.74, P = 0.003), in contrast to the recovery rate for histamine (r = -0.15, P = 0.60). Consequently, in the oldest age group (11-12 years, n = 5) recovery rate from exercise challenge was significantly slower than in the younger age group (7-10 years, n = 9), i.e., 0.54 +/- 0.17 and 1.60 +/- 0.93, respectively, P = 0.009, and slower than the recovery rate from histamine challenge: 0.54 +/- 0.17 and 1.33 +/- 0.54, respectively, P = 0.03. In the younger age group the recovery rates from exercise and histamine were not different (1.60 +/- 0.93 and 1.54 +/- 0.73, respectively, P = 0.83). We conclude that recovery from EIA in childhood decreases with increasing age. These data suggest that the mechanism of exercise-induced asthma in childhood changes with age. This might be due to changes in mediator production or response to mediator release.

Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma.

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.

[Turkish children with recurrent abdominal pain and fever: familial Mediterranean fever]. / Turkse kinderen met recidiverende buikpijn en koorts: familiale mediterrane koorts.

Four children of Turkish origin, three boys aged 12, 8 and 7 years, and a girl aged 5 years, presented with clinical symptoms of familial Mediterranean fever. They had the characteristic episodes of fever combined with abdominal pain, thoracic pain, general malaise or arthralgia. Familial Mediterranean fever is an autosomal recessive genetic disorder restricted to people originating from the Middle East. The causative gene (MEFV) and many missense mutations have been identified. The clinical syndrome is characterised by self-limiting febrile episodes accompanied by inflammation of the serous membranes, resulting in peritonitis, pleuritis or synovitis. In untreated patients systemic amyloidosis may develop, which manifests as renal insufficiency. The diagnosis is based on the characteristic medical history and is confirmed by DNA analysis. Meanwhile, treatment with colchicine can be started. This is effective in 90% of affected patients. Being aware of the prevalence of familial Mediterranean fever in immigrant populations can improve the quality of life and prevent long-term complications.

Occurrence of a late response to exercise in asthmatic children: multiple regression approach using time-matched baseline and histamine control days.

At the present time, there is still controversy concerning the presence of a late asthmatic response (LAR) to exercise challenge in asthma. We have, therefore, investigated the occurrence of a LAR after exercise in asthmatic children visiting an out-patient clinic, using time-matched baseline and histamine control days, and a statistical analysis according to recently published recommendations. After a screening exercise day, 17 children (aged 7-14 yrs) randomly performed, on three subsequent study days, either: a second standardized exercise challenge; or a histamine challenge whilst matching the bronchoconstriction after exercise; or measurement of baseline lung function without any challenge. Measurements of forced expiratory volume in one second (FEV1) were made repeatedly during 8 h. Analysis was performed using multiple regression analysis for each patient, with FEV1 as the dependent, and test day (exercise or control) and clock time as independent variables during the period 2-8 h after exercise. A significant interaction (p < 0.05) between test day and clock time was considered to be indicative of a LAR. Fifteen children completed the study. All children showed an early asthmatic reaction to exercise (range 14-62% fall in FEV1). In two children, a significant interaction (p < 0.05) was found between test day and clock time. However, the difference in FEV1 between exercise and control days for each clock time did not exceed the 99.6% confidence limits of normal diurnal variation in any of the children. We conclude that, in children with mild-to-moderate asthma, a LAR to exercise does not occur. This suggests that exercise is only a symptomatic trigger of asthma. Whether exercise is capable of inducing inflammation needs to be further investigated.

Sample size estimation in studies monitoring exercise-induced bronchoconstriction in asthmatic children.

BACKGROUND: The repeatability of the response to standardised treadmill exercise testing using dry air and monitoring of heart rate in asthmatic children suffering from exercise-induced bronchoconstriction (EIB) has not been well established. METHODS: Twenty seven asthmatic children with known EIB performed standardised exercise testing twice within a period of three weeks. The tests were performed on a treadmill while breathing dry air. During both tests heart rate had to reach 90% of the predicted maximum. Response to exercise was expressed as % fall in forced expiratory volume in one second (FEV1) from baseline and as area under the curve (AUC) of the time-response curve. RESULTS: The intra-class correlation coefficients for % fall and AUC (log-transformed) were 0.57 and 0.67, respectively. From these data, power curves were constructed that allowed estimations to be made of sample sizes required for studies of EIB in children. These indicated that, if a drug is expected to reduce EIB by 50%, as few as 12 patients would be sufficient to demonstrate this effect (90% power) using a parallel design study. CONCLUSIONS: Standardised exercise testing for EIB using dry air and monitoring of heart rate is adequately repeatable for use in research and clinical practice in children with asthma.