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Biomedical subjects

P L Brand

Publications and source records attributed to P L Brand.

8 recordsLinked to original sources

A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group.

BACKGROUND: The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. METHODS: In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. RESULTS: Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group. CONCLUSIONS: The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

Administration, Inhalation

Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group.

BACKGROUND: There is no agreement on how a bronchodilator response should be expressed. Ideally, the index used should be able to distinguish asthma from chronic obstructive lung disease and be independent of initial FEV1. METHODS: Two hundred and seventy four adults (aged 18-60 years) outpatients with obstructive airways disease were studied. Patients were divided into syndrome groups on the basis of a standardised history: asthma (n = 99), asthmatic bronchitis (n = 88), and chronic obstructive lung disease (n = 51); 36 subjects could not be attributed to any subgroup. FEV1 was measured before and 20 minutes after inhalation of 1000 micrograms terbutaline. Different expressions of bronchodilator response (delta FEV1) were compared with respect to their dependence on initial FEV1 and their efficacy in separating subjects with asthma from those with chronic obstructive lung disease. delta FEV1 was expressed as a percentage of initial FEV1 (delta FEV1%init), absolute value (delta FEV1[1]), percentage of predicted FEV1 (delta FEV1%pred), standardised residual (delta SR-FEV1), and percentage of maximal possible increase (delta FEV1%[pred-init]). RESULTS: delta FEV1%init was more dependent on initial FEV1 (p = -0.405) than delta FEV1[1] (r = -0.145), delta FEV1%pred (r = -0.166), and delta SR-FEV1 (r = -0.127). delta FEV1%[pred-init] reached infinity when initial FEV1 approached predicted levels. delta FEV1%pred had a higher likelihood ratio (1.71) for separating patients with asthma from those with chronic obstructive lung disease than other expressions of bronchodilator response. Asthmatic patients had larger mean bronchodilator responses than patients in other subgroups; this difference was largest for delta SR-FEV1 (F = 9.19) and delta FEV1%pred (F = 9.03); it was much smaller for delta FEV1%init (F = 5.89). Despite significant differences in mean response, there was a large overlap of individual responses between diagnostic subgroups. The bronchodilator response was continuously and unimodally distributed for all expressions. CONCLUSIONS: delta FEV1%pred appears to be the most useful method of expressing bronchodilator response, both for clinical and for research purposes. Reversibility of airways obstruction in response to a bronchodilator is a continuous variable and not a dichotomous triat. Any cut off level of a "positive" bronchodilator response is therefore arbitrary.

Adolescent

Perception of airway obstruction in a random population sample. Relationship to airway hyperresponsiveness in the absence of respiratory symptoms.

Subjects with asymptomatic airway hyperresponsiveness in epidemiologic studies may have variable airway obstruction that is not perceived as dyspnea. We tested the hypothesis that such subjects are less likely to report an increase in dyspnea during histamine-induced bronchoconstriction than symptomatic hyperresponders. A random population sample of 412 middle-aged subjects was studied. Before and after a standardized histamine challenge test, subjects recorded Borg scores for dyspnea: any increase in Borg score was considered significant. More than 80% of hyperresponsive subjects (PC10 histamine < or = 16 mg/ml) had no symptoms. The presence of prechallenge dyspnea was related to increased airways responsiveness and current smoking. An increase in Borg score was associated with younger age, more severe airway responsiveness, atopy, and female sex. The level of and increase in the Borg score were not significantly related to level and change in airway caliber (FEV1). In hyperresponsive subjects (PC10 < or = 16 mg/ml), subjects who reported dyspnea, wheeze, or asthma were more likely to show an increase in Borg score during histamine provocation than asymptomatic subjects (adjusted odds ratio 4.01, 95% confidence interval 1.01 to 16.00, p = 0.049), after adjustment for age, sex, smoking habits, FEV1, and atopy. This suggests that asymptomatic hyperresponders may have variable airway obstruction that is not recognized as breathlessness.

Adult

Long-term multicentre trial in chronic nonspecific lung disease: methodology and baseline assessment in adult patients. Dutch CNSLD Study Group.

Airways obstruction and airways hyperresponsiveness are two dominant features in patients with chronic nonspecific lung disease (asthma and chronic obstructive pulmonary disease (COPD)). We set up a study to determine whether long-term (3 yrs) therapeutic intervention directed at airways obstruction and hyperresponsiveness is superior to one directed at airways obstruction alone. Patients were selected on functional criteria (age, baseline forced expiratory volume in one second (FEV1), and airways hyperresponsiveness) and, furthermore, extensively characterized by history, smoking habits, allergy, reversibility of airways obstruction and quality of life. The methodology and practical problems of setting up this large multicentre study are outlined, together with an analysis of baseline data. Standardization of methods and techniques and recruitment of patients required much effort, recruitment taking about twice as long as expected. A 3 month feasibility study allowed us to eliminate minor problems in the protocol. Over a 16 month period, 274 adult patients (18-60 yrs) from the out-patient clinics of six university centres entered the study; 99 met the diagnostic criteria for asthma, 51 for COPD, 88 for asthmatic bronchitis, and 36 could not be classified. Their mean (SD) FEV1% pred was 65.1 (15.2)%. Their geometric mean provoking concentration of histamine producing a 20% fall in FEV1 (PC20 histamine) was 0.28 mg.ml-1. In a multiple regression analysis, more severe airways hyperresponsiveness was associated with lower prechallenge FEV1% pred (p less than 0.0001), higher pack-years of smoking (p = 0.0099), blood eosinophil count (p = 0.0004), skin test reactivity (p = 0.0047) and with female sex (p = 0.0302). We conclude that setting up long-term multicentre trials in chronic nonspecific lung disease (CNSLD) is feasible and that these may offer valuable information on treatment and outcome of the disease.

Adult

[Malrotation?].

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Digestive System Abnormalities

Relationship of airway hyperresponsiveness to respiratory symptoms and diurnal peak flow variation in patients with obstructive lung disease. The Dutch CNSLD Study Group.

This study reports on the relationship of airway hyperresponsiveness (AH) with respiratory symptoms and diurnal peak flow expiratory (PEF) variation in 221 hyperresponsive patients with moderately severe airways obstruction. The disease was in a stable phase in all patients. Closely adhering to the American Thoracic Society criteria, patients were divided into three syndrome diagnoses based on a standardized history: asthma (n = 81), asthmatic bronchitis (AB, n = 69), and chronic obstructive pulmonary disease [( COPD] n = 44); 27 subjects could not be placed in any group. Mean (+/- SEM) log2 PC20 histamine values were significantly lower in the asthmatic group (-2.77 +/- 0.20 mg/ml) than in the COPD (-0.89 +/- 0.29 mg/ml) and AB groups (-1.37 +/- 0.25 mg/ml; one-way ANOVA, p less than 0.001). However, considerable overlap of individual responses existed. Differences between the groups could not be attributed to differences in prechallenge FEV1 levels. For every level of FEV1, asthmatic subjects were more hyperresponsive than patients with COPD. The dependence of PC20 on prechallenge FEV1 was comparable in all groups. There was a significant correlation between the degree of AH and diurnal PEF variation (rho = -0.401, p less than 0.001), which was stronger in asthma (rho = -0.409) than in COPD (rho = -0.325). Despite this obvious association, a wide range of diurnal PEF variation values existed for every level of PC20, indicating that PEF variability and AH are not interchangeable. The relationships between symptoms and both AH levels and PEF variation were weak. No significant differences were found between syndrome diagnosis groups with respect to diurnal PEF variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Psychosocial aspects of the so-called short-bowel syndrome in children].

In a retrospective study of 16 patients with (congenital) bowel pathology, aged 2 to 12, attention was paid to the psychosocial aspects of the short bowel syndrome. Parents were interviewed and parents' and teachers' reports of children's behavioural and emotional problems were obtained. Parents as well as children appeared to have reached a reasonable level of adjustment. Parents' emotions concerning the period of hospitalisation still appeared to be strikingly strong. Although most children did not show obvious psychopathology, problems were observed in the areas of behaviour and attention, interfering with optimal school functioning in the case of some children.

Adaptation, Psychological