K Knol

Follow−up of asthma from childhood to adulthood: Influence of potential childhood risk factors on the outcome of pulmonary function and bronchial responsiveness in adulthood

The outcome of asthma in 406 children, aged 8 to 12 years, was studied. Follow-up in adulthood was 86%, with a mean age of 24.7 years and a mean interval of follow-up of 14.8 years. The predictive value of gender and various childhood variables on the adult level of pulmonary function (forced expiratory volume in 1 second [FEV1]) and bronchial responsiveness in adulthood was assessed. An increase in mean percent predicted FEV1 from childhood to adulthood was found, both in subjects with (76%) and without (24%) current respiratory symptoms. The only childhood variable predictive of adult level of FEV1 was the level of percent predicted FEV1 (p < 0.01). The proportion of subjects with a histamine provocative concentration causing a 10% decrease in FEV1 less than or equal to 16 mg/ml decreased significantly in adulthood. The degree of bronchial responsiveness had increased slightly in adults with symptoms (p = 0.87), whereas it had decreased significantly in subjects without symptoms (p < 0.01). Female subjects were significantly more responsive in adulthood than male subjects (p = 0.047). The childhood degree of bronchial responsiveness significantly predicted the presence of bronchial responsiveness in adulthood (p = 0.02). We conclude that childhood percent predicted FEV1 is relevant to predict the outcome of the adult pulmonary function level, whereas female gender and the childhood degree of bronchial responsiveness are important for the prediction of adult degree of bronchial responsiveness among children with asthma.

BUDESONIDE AND TERBUTALINE OR TERBUTALINE ALONE IN CHILDREN WITH MILD ASTHMA - EFFECTS ON BRONCHIAL HYPERRESPONSIVENESS AND DIURNAL-VARIATION IN PEAK FLOW

The effects of treatment with budesonide (200 micrograms twice daily) and terbutaline (500 micrograms four times daily) has been compared with the effects of placebo and terbutaline in 27 children with mild asthma, aged 7-14 years, in a double blind, randomised placebo controlled study over eight weeks. Bronchial responsiveness (PC20 histamine), lung function, the amplitude of diurnal variation in peak expiratory flow (PEF), and symptom scores were measured. Baseline FEV1 was over 70% predicted and PC20 histamine less than 8 mg/ml. Twelve children were treated with budesonide and terbutaline and 15 with placebo and terbutaline. After four and eight weeks of treatment the change in PC20 was significantly greater after budesonide and terbutaline than after terbutaline alone by 2.1 (95% CI 0.5-3.8) and 1.3 (95% CI 0.1-2.5) doubling doses respectively. Mean FEV1 did not change in either group. The change in afternoon and nocturnal PEF was significantly greater after budesonide and terbutaline than after terbutaline alone. The amplitude of diurnal variation in PEF did not change significantly in either group. Peak flow reversibility decreased in the budesonide group. There were no differences between treatments for cough and dyspnoea, but wheeze improved in the budesonide group. The children with mild asthma treated with budesonide and terbutaline showed improvement in bronchial responsiveness, afternoon and nocturnal PEF, and symptoms of wheeze and a fall in peak flow reversibility by comparison with those who received terbutaline alone.

ALLERGY IN SUBJECTS WITH ASTHMA FROM CHILDHOOD TO ADULTHOOD

We studied the change from childhood to adulthood in skin test reactivity to house dust, animal dander, grass pollen, and molds, and, in addition, the change in number of blood eosinophils. The study was carried out in a group of 119 children with asthma, aged 6 to 14 years first observed between 1966 and 1969. In the present study, 101 subjects (85%) were reinvestigated after a mean period of 16 years; 43% had current symptoms. Skin test reactivity to all allergens and the number of subjects with positive skin tests to more than one allergen increased from childhood to adulthood. Subjects with allergic rhinitis (38%) had a higher number of positive skin tests to grass pollen in both childhood and adulthood than subjects without allergic rhinitis. Fifty-three children and 10 adults had atopic dermatitis. Atopic dermatitis occurred with equal frequency in children who did and in children who did not have current symptoms later in life. No differences in skin test reactivity to allergens were found between smoking and nonsmoking subjects. Although the smoking period was relatively short, smoking was correlated with eosinophilia in adulthood. The mean number of eosinophils decreased significantly between the first and second survey. The outcome of childhood asthma as defined by current symptoms was not predicted by skin reactivity to allergens, eosinophilia, atopic dermatitis, or allergic rhinitis in childhood.

Peak flow variation in childhood asthma: relationship to symptoms, atopy, airways obstruction and hyperresponsiveness

Although home recording of peak expiratory flow (PEF) is considered useful in managing asthma, little is known about the relationship of PEF variation to other indicators of disease activity. We examined the relationship of PEF variation, expressed in various ways, to symptoms, atopy, level of lung function, and airways hyperresponsiveness in schoolchildren with asthma. One hundred and two asthmatic children (aged 7-14 yrs) recorded symptoms and PEF (twice daily) in a diary for 2 weeks after withdrawal of all anti-inflammatory maintenance medication. PEF variation was expressed as amplitude % mean, as standard deviation and coefficient of variation of all recordings, and as low % best (lowest PEF as percentage of the highest of all values). Atopy and level of forced expiratory volume in one second (FEV1) % predicted were not significantly related to PEF variation. The provocative dose of histamine causing a 20% fall in FEV1 (PD20) and symptom scores were significantly, but weakly, related to PEF variation. The index, low % best, proved easy to calculate and effective in identifying a short-term episode of reduced PEF. We conclude that peak expiratory flow variation in children with stable, moderately severe asthma is significantly, but weakly, related to symptoms and airways hyperresponsiveness. These three phenomena, therefore, all provide different information on the actual disease state. Expressing peak expiratory flow variation as low % best is easy to perform and appears to be clinically relevant.

Influence of a positive family history and associated allergic diseases on the natural course of asthma

The outcome of childhood asthma was studied in a cohort of 406 asthmatic children, with emphasis on the influence of family history for allergic disease, as well as the influence of associated allergic diseases on prognosis. Sixty‐two per cent had a positive family history for atopy. In young adulthood no differences, either in symptoms or lung function were demonstrated in comparison to subjects with a negative family history. Fifty‐two per cent of the children had no other allergic disease, 48% had either eczema or hay fever or both. When subjects were stratified based on associated allergic disease, no differences in outcome in adulthood were revealed either. It is concluded that neither a positive family history, nor concurrent associated allergic diseases in the child contribute to the prognosis of asthma from childhood to young adulthood. Therefore, environmental factors as well as patient characteristics (including lung function level, level of bronchial responsiveness) are likely to be more important for the prognosis.

CHANGE IN AIRWAY RESPONSIVENESS TO INHALED HOUSE DUST FROM CHILDHOOD TO ADULTHOOD

Between 1966 and 1969, housedust (HD) inhalation provocation tests were performed in 119 children with asthma. Between 1984 and 1987, 101 of the 119 subjects (85%) were reinvestigated. Thirty-one of these 101 adults who participated in a study on the outcome of childhood asthma were rechallenged with HD after a mean interval of 16 years to establish the change in airway responsiveness to HD from childhood to adult life. In the childhood study in these 31 subjects, six had no response (NAR); six, an early response (EAR); eight, a late (LAR); and eleven subjects, an EAR followed by an LAR (dual asthmatic response [DAR]) to the inhalation of HD. In the second survey, two of the subjects with NAR in the first study had a bronchoconstrictor response to HD. Five subjects with an EAR or an LAR response in childhood had NAR as an adult. The eleven subjects with a DAR during childhood also had a response to HD as an adult; five had an EAR, and six adults again had a DAR. Eleven of the 13 adults (85%) with current respiratory symptoms had a response to HD during the second survey. Although they were symptom free, 11 of the other 18 adults (61%) responded on inhalation of HD. One of the 18 subjects without (6%), and six of the 13 subjects (46%) with current respiratory symptoms, had a provocative concentration of histamine in FEV1 10% of baseline less than or equal to 16 mg/ml. We conclude that, although respiratory symptoms disappear in one half the children with asthma and although adults may believe that they have outgrown their disease, adults still have the potency to respond to inhaled allergens. Most children do outgrow their respiratory symptoms but not the susceptibility of their airways to allergens.

Recovery of FEV1 after histamine challenge in asthmatic children

Factors that influence the time necessary for complete recovery of FEV1 after inhaling histamine were analysed in forty‐five children with asthma. These included the initial bronchial obstruction (baseline FEV1), the provocation dose of histamine producing a 20% fall in FEV1 (PD20) and the fall in FEV1 after the histamine challenge. In addition it was also investigated whether a second challenge carried out after complete recovery of FEV1 would produce a reproducible PD20‐histamine value. The time for complete recovery varied widely from 15 to more than 75 min. The time needed for complete recovery of FEV1 after the histamine challenge seems to be mainly determined by the PD20 value. The other factors such as initial bronchial obstruction and the fall in FEV1 after the challenge showed no significant relationship with the recovery time. A second challenge with histamine resulted in a highly reproducible PD20 value. The clinical implication of this study is that other tests can only be performed when FEV1 has returned to 95% of baseline.

Hypercalcaemia in a child with miliary tuberculosis

Hypercalcaemia and hypercalciuria were diagnosed in a 21-week-old boy with miliary tuberculosis. The tuberculosis was treated with isoniazid, rifampin and streptomycin. After 2 months, streptomycin was replaced by ethambutol. The hypercalcaemia was treated initially with prednisone, which decreased the serum 1,25 (OH)2 cholecalciferol level but the serum calcium level remained unaltered. After calcium and vitamin D restriction, the serum calcium level normalized within 1 day. The patients tuberculosis was treated and he remains well.

RESPIRATORY-INFECTIONS AND VASCULAR RINGS

ABSTRACT. Recurrent respiratory infections after the first years of life are not easily related to vascular rings as the cause of these infections. Therefore six cases of older children are presented in whom a vascular ring was the cause of their respiratory problems. None of them ever had stridor or swallowing problems in early infancy, and recurrent respiratory infections occurred later in life as a symptom of a vascular ring. Unfamil iarity with this association caused a delay in diagnosis and treatment in two patients and persistent lung damage in one child. Five of the 6 children recovered well after operation. The diagnosis can be made at an early stage if close inspection of the outline of the trachea on the chest radiograph shows an impression from the right side.

THE EFFECT OF REDUCTION OF MAINTENANCE TREATMENT ON CIRCADIAN VARIATION IN PEAK EXPIRATORY FLOW-RATE VALUES IN ASTHMATIC-CHILDREN

ABSTRACT. We investigated in well controlled asthmatic children whether it is possible to predict by measuring daytime forced expiratory volume in one second, the decline in nocturnal peak expiratory flow rate values after withdrawal of maintenance medication. Forced expiratory volume in one second and peak expiratory flow rate were measured in the outpatient clinic, on the last day with medication. Peak expiratory flow rates were then measured every four hours on days 4, 5 and 6 without medication. Seventeen children showed an amplitude in circadian peak expiratory flow rate values of more than 20% (group I) and nine children showed an amplitude of 20% or less on the three study days (group II). Mean values ± SEM were 34.7±2.1% and 10.5±1.5%, respectively. Forced expiratory volume in one second values were comparable in both groups. Daytime peak expiratory flow rate values before and after withdrawal, remained on the same level in both groups. In group I peak expiratory flow rate values of 24.00 and 08.00 hours on day 6 were significantly lower (p<0.05) than on day 4. The results indicate that history and daytime pulmonary function measurements alone, are insufficient to assess the clinical situation and suggest that a decrease in early morning peak expiratory flow rate value (08.00 hours) is an early sign of deterioration of the disease state, after reduction of medication.