New insights into the second generation antihistamines.

Second generation antihistamines are recognised as being highly effective treatments for allergy-based disease and are among the most frequently prescribed and safest drugs in the world. However, consideration of the therapeutic index or the benefit/risk ratio of the H1 receptor antagonists is of paramount importance when prescribing this class of compounds as they are used to treat non-life threatening conditions. There are many second generation antihistamines available and at first examination these appear to be comparable in terms of safety and efficacy. However, the newer antihistamines in fact represent a heterogeneous group of compounds, having markedly differing chemical structures, adverse effects, half-life, tissue distribution and metabolism, spectrum of antihistaminic properties, and varying degrees of anti-inflammatory effects. With regard to the latter, there is growing awareness that some of these compounds might represent useful adjunct medications in asthma therapy. In terms of safety issues, the current second generation grouping includes compounds with proven cardiotoxic effects and others with the potential for adverse drug interactions. Moreover, some of the second generation H1 antagonists have given cause for concern regarding their potential to cause a degree of somnolence in some individuals. It can be argued, therefore, that the present second generation grouping is too large and indistinct since this was based primarily on the concept of separating the first generation sedating compounds from nonsedating H1 antagonists. Although it is too early to talk about a third generation grouping of antihistamines, future membership of such a classification could be based on a low volume of distribution coupled with a lack of sedating effects, drug interactions and cardiotoxicity.

Cigarette smoking habits among schoolchildren.

STUDY OBJECTIVE: Cigarette smoking is a major preventable cause of morbidity and mortality worldwide. Most adult smokers start smoking regularly some time before 18 years of age. The aim of this study was to determine the age at which children begin cigarette smoking, to study the environmental factors that influence children to smoke, and to understand the reasons why children smoke. The results of this study may help lead to the development of more effective smoking prevention programs. METHODS: We carried out a cross-sectional survey of all students in grades 6 to 11 (ages: 11 to 17 years) in two high schools in the Jerusalem area, using an anonymous self-completion questionnaire. The students were asked questions regarding the age at which they began smoking, initiation, their smoking habits, their reasons for smoking, and their views on children who smoke. In addition, they were asked about the smoking status of their parents, siblings, and friends. Finally they were asked about the health hazards of smoking. RESULTS: Of the 847 students who answered the questionnaire, 35% stated that they had smoked at least once and 14% stated that they were currently smoking. The percentage of students who were currently smoking increased gradually with age to 36%. There was a sharp increase in experimental smoking after seventh grade (ages 12 to 13 years). Having a friend who smoked substantially increased the likelihood of smoking, whereas parental smoking or having a sibling who smoked did not increase the likelihood of smoking. The most common reason for starting to smoke was "to try something new" (55%). There was a significant difference between the views of students with different smoking statuses regarding children who smoke: nonsmoking children associated more negative characteristics to smoking. All of the children studied were well aware of the health hazards of cigarette smoking. CONCLUSIONS: Smoking is highly prevalent among schoolchildren in Jerusalem. The increase in the rate of smoking at the age of 12 years indicates that smoking prevention programs need to be started at an earlier age. Peer pressure is a very strong stimulus for smoking in children. Since children are aware of the health hazards of smoking, prevention policy should be aimed more at associating smoking with negative images and addressing peer pressure.

Frequency of nocturnal symptoms in asthmatic children attending a hospital out-patient clinic.

Since nocturnal symptoms indicate more severe asthma, we investigated their frequency in a hospital-based population of asthmatic children. Recognition of these symptoms offers the possibility to introduce appropriate treatment. We studied 796 consecutive children with asthma (mean (SD) age 9 (4) yrs) attending a hospital clinic, to determine whether these nocturnal symptoms predicted that daytime activities would be affected, and also the patients' perception of disease severity. At the end of a regular out-patient clinic visit, the answers to seven different questions concerning nocturnal symptoms in the previous 3 weeks were recorded. The forced expiratory volume in one second (FEV1) was > or = 90% predicted in 98% of the population that was able to perform lung function measurements (72% of the total population). In 38% of the patients with nocturnal symptoms, these symptoms were reported spontaneously. When asked for, nocturnal symptoms were reported by 47% of the children; 6% every night and 34% at least once a week. Cough was the most frequently reported symptom (31%). Children with nocturnal symptoms had a lower FEV1, scored their perception of asthma as more severe, and had their daytime activities affected more than those without nocturnal symptoms. Doctors should specifically ask about nocturnal symptoms, as not all patients with nocturnal symptoms report them spontaneously and they predict more severe disease.

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.

Risk factors for the persistence of respiratory symptoms in childhood asthma.

We studied the prognosis of childhood asthma in a cohort of 406 children 8 to 12 yr of age when enrolled. Subjects were followed for a mean of 14.8 yr after their initial evaluation, with a follow-up rate of 86%. The mean age at follow-up was 24.7 yr. We assessed the predictive value of sex and various childhood variables on the outcome of symptoms and medication use in adulthood. Although only 19% of subjects were still under a physician's supervision at the time of follow-up, 76% had respiratory symptoms, 32% used maintenance medication, and 22% used medication intermittently. The incidence of cigarette smoking was disturbingly high (33%). In adulthood, women were more likely than men to have symptoms (85 versus 72%, respectively). The childhood symptom severity and the childhood degree of bronchial responsiveness in combination with a low %FEV1 were also related to the outcome of asthma in adulthood. The high prevalence of symptoms in adults at follow-up coupled with the low rate of physician supervision and medication usage suggest that more aggressive treatment may be indicated in asthmatic children.

Cessation of long-term treatment with inhaled corticosteroid (budesonide) in children with asthma results in deterioration. The Dutch CNSLD Study Group.

Inhaled corticosteroid has been shown to be effective in the management of asthma. However, there is a lack of studies that assess the effect of cessation after long-term treatment with inhaled corticosteroid. This question was addressed in 28 children with stable asthma, aged 11 to 18 yr of age, who had completed 28 to 36 months of treatment with inhaled corticosteroid (budesonide 200 micrograms 3 times/day) and inhaled beta-2-agonist (salbutamol 200 micrograms 3 times/day). The children were randomized in a 1:2 ratio in a double-blind study either to continue budesonide (n = 8) during a period of 6 months or to decrease the dose of budesonide (n = 20) within 2 months, followed by placebo for 4 months. Treatment with salbutamol 600 micrograms daily was continued in both groups. Eight children from the tapering-off group withdrew, mainly due to symptoms of asthma, compared with none in the continuous treatment group. Five patients in the tapering-off group experienced exacerbations for which prednisolone was given, compared with none in the continuous treatment group. After tapering-off, symptoms of asthma and additional bronchodilator use increased, and both FEV1% predicted and PD20 histamine (provocation dose of histamine causing a 20% fall in FEV1) decreased, whereas these all remained unchanged in the group that continued treatment with inhaled corticosteroid. We conclude that in this study long-term treatment with 600 micrograms budesonide daily suppressed underlying mechanisms of asthma, but did not cure the disease.

[Mild sequelae 12 years following massive aspiration of barium sulfate in the lungs]. / Geringe restverschijnselen 12 jaar na massale bariumsulfaat-aspiratie in de longen.

A twelve-year-old girl, who as a baby underwent an investigation of the oesophagus and stomach with barium roentgen contrast fluid, during which there was massive aspiration of barium contrast into the right lung, at follow-up showed no abnormalities, apart from slight signs of peribronchial granulomatosis or fibrosis. If there is an enhanced risk of aspiration or an oesophago-tracheal fistula is suspected it is better to use an isotonic water-soluble contrast fluid.

Changes in respiratory symptoms and airway hyperresponsiveness after 27 years in a population-based sample of school children.

We wanted to test the hypothesis that childhood airway hyperresponsiveness, even in the absence of respiratory symptoms, is a risk factor for respiratory disease in adulthood. In a childhood survey of 1963, three groups of 20 children aged 8-11 yrs, were selected from a population sample: 1) a group with recurrent respiratory symptoms (symptomatic group); 2) a group with no symptoms but a positive family history of atopy; and 3) a control group. All children completed assessment of symptoms, atopy, lung function, and airway hyperresponsiveness. At the adulthood survey 27 yrs later, 85% of the original sample were reinvestigated. Only 10 out of 19 subjects (53%) of the original symptomatic group still had symptoms. The significant difference of forced expiratory volume in one second (FEV1) % predicted in childhood between the symptomatic and the control group had disappeared. The prevalence of airway hyperresponsiveness had decreased in all groups. In asymptomatic hyperresponders it had normalized at adult age. The asymptomatic hyperresponders in childhood had lower levels of lung function, both in childhood and in adulthood. In univariate and multivariate analyses, respiratory symptoms at adult age were related to childhood atopy. Results suggest that childhood atopy is a risk factor for respiratory symptoms in young adulthood, but that mild childhood airway hyperresponsiveness is not.

Assessment of bronchodilator response in children with asthma. Dutch CNSLD Study Group.

The bronchodilator response (BDR) in forced expiratory volume in one second (FEV1) is routinely assessed to estimate the reversibility of airways obstruction. However, there is no consensus on how the BDR should be expressed, and recommendations applying to children are lacking. Similarly, the relationship between BDR and nonspecific bronchial hyperresponsiveness to histamine (BHR) has not been elucidated. These questions were addressed in 116 children, 7-16 yrs of age, with stable asthma after withdrawal of all pulmonary maintenance medication. Inclusion criteria were an initial FEV1 between 55-90% predicted, and/or FEV1/forced vital capacity (FVC) between 50-75%, as well as a fall in FEV1 of 20% or more when challenged with up to 150 micrograms histamine. The change in FEV1 (delta FEV1) 20 min after inhalation of 800 micrograms salbutamol was expressed in four ways: as an absolute difference (delta FEV1(l)), as a percentage of predicted FEV1 (delta FEV1%pred) or initial FEV1 (delta FEV1%init), and as a percentage of the deficit in FEV1 (delta FEV1%(pred-init)). delta FEV1%init and delta FEV1%pred were not related to age and stature of the children; delta FEV1%(pred-init) was related to stature, whilst delta FEV1(l) was related to both age and stature. All indices correlated with initial FEV1. However, this is an artefact introduced by relating change to initial value, rather than to the mean of initial and final value. In fact, BDR, expressed as delta FEV1%pred, was only slightly greater in children with the lowest initial airway calibre (p = 0.08), unlike delta FEV1%init. BDR was weakly related to BHR.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Dutch CNSLD Study Group.

The effect of long-term treatment with inhaled corticosteroid on exercise-induced asthma (EIA) was studied in 55 children, aged 7-18 yrs (mean 12 yrs). We also compared the time course of stabilization of EIA to that of other indicators of airway responsiveness, such as peak expiratory flow (PEF) variation and the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1). All children participated in an ongoing multicentre study to compare the effects of long-term treatment either with the beta 2-agonist salbutamol (600 micrograms.day-1) plus the inhaled corticosteroid budesonide (600 micrograms.day-1) (BA+CS), or salbutamol plus placebo (BA+PL), on airway calibre, airway responsiveness and symptoms. After a median follow-up of 22 months, the study design had to be changed, because of the high number of drop-outs on BA+PL. At that time, the treatment regimen of all children who had not withdrawn was changed into BA+CS. At the moment of change, and after 2 and 8 months of treatment, a treadmill exercise test was performed in two centres. Eighteen of the 22 children (82%) who were treated with BA+PL from the beginning had EIA, compared to 18 of the 33 children (55%) who were treated with BA-CS (p < 0.05). After 2 and 8 months of treatment with BA+CS in the patients previously on BA+PL this percentage decreased to 59 and 55%, respectively, and was not significantly different between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Skin reactivity and eosinophil count in relation to the outcome of childhood asthma.

The aim of this study was to determine whether an association can be found between childhood skin reactivity and the outcome of asthma in young adulthood in a group of 406 asthmatic children, of whom 348 (86%) could be followed up in adulthood. A complete data set on skin tests and eosinophil count was available in 259 allergic subjects. They were stratified into three classes, according to initial skin test score in childhood. An increase in skin reactivity was noted from childhood to adulthood, while the differences in skin reactivity between the three classes remained significant. In childhood, a marked difference in total eosinophil count was found between the classes. Towards adulthood, a decrease in eosinophil count was noted, and the differences between the classes were no longer significant. The children with lowest skin reactivity also had the lowest symptom score in childhood. In adulthood, the prevalence of respiratory symptoms in this class was lower than in the other two classes. The prevalence of bronchial responsiveness to histamine was lowest in subjects with the lowest skin test score in childhood. Ventilatory parameters revealed no differences between the three classes. We conclude that although a low skin reactivity in childhood might be associated with a relatively favourable prognosis for asthma symptoms in adulthood, there is only limited evidence to support this hypothesis in our study.

Adrenergic response in children with asthma on exogenous stimuli.

In asthmatic children it was investigated whether the degree of impairment of the adrenergic response on exogenous stimuli is related to the magnitude of the 24-hour amplitude in airflow obstructions. Urinary-adrenaline and noradrenaline excretion after house dust mite (HDM) inhalation and after exercise was measured. Nine children with (group I), and nine without increased airflow obstruction overnight (group II) and nine age matched healthy children (group C) were included in the study. All patients showed an early obstructive reaction (EOR) after HDM challenge. Six children in group I and five in group II developed an EOR on exercise. A significant increase in urinary adrenaline excretion was observed after exercise in the control group (P < 0.05, values on the control and challenge day being 5.4 +/- 0.9 and 10.0 +/- 1.6 mumol/mol creat.). The same occurred for noradrenaline (P < 0.01, values being 28.2 +/- 2.5 and 49.0 +/- 5.7 mumol/mol creat.). Adrenergic response after both stimuli was impaired in the asthmatic groups, in group I more pronounced than in group II. Values from group I for adrenaline on the control day, HDM and exercise challenge were 6.0 +/- 0.8, 4.7 +/- 0.6, 6.0 +/- 1.0 and for noradrenaline 36.1 +/- 2.7, 27.2 +/- 2.3, 38.4 +/- 4.9 mumol/mol creat., respectively. Values from group II for adrenaline on these days were 5.6 42- 1.0, 3.7 42- 0.6 and 9.0 +/- 1.3 and for noradrenaline 28.3 +/- 3.2, 22.4 +/- 2.5, 41.3 +/- 5.9 mumol/mol creat., respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Smoking habits in medical students and physicians in Groningen, The Netherlands.

Smoking habits and attitudes towards smoking of medical students (n = 725), house officers (n = 126) and consultants (n = 236) of the University Hospital of Groningen were studied, in 1989 by means of a World Health Organization (WHO) questionnaire. Overall response rate was 84%. Twenty seven percent of the medical students are current smokers, 28% of the house officers and 34% of the consultants. There is a remarkable difference among medical specialists i.e: smoking prevalence is highest among psychiatrists and lowest among paediatricians. The prevalence of smoking in medical students and house officers is lower than in the Dutch population. Smoking habits of the consultants are similar to those of the general population. About 75% of the doctors reported having no experience with smoking cessation programmes. Doctors report a need for more skills and knowledge on smoking cessation programmes.