[When are bronchodilator agents sufficient in asthma/chronic obstructive pulmonary disease?].
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Publications and source records attributed to C van Weel.
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OBJECTIVE: To determine whether inhaled corticosteroids can be discontinued in the stable phase of asthma or chronic obstructive pulmonary disease (COPD) or if this therapy should be continued. DESIGN: Nonrandomized open uncontrolled 5-year trial. SETTING: Prospective study in general practice. PATIENTS: Forty-eight patients with steroid-dependent asthma or COPD who had shown a decline in forced expiratory volume in 1 second (FEV1) of at least 80 mL per year and at least one exacerbation per year during the first 2 years of bronchodilator treatment. Subjects were treated additionally with inhaled steroids for another 2 years and were finally given the option to stop using steroids. Sixteen patients were willing to stop using beclomethasone and were studied for another year. No recruitment bias took place in this consecutive sample in the fifth year of follow-up. Two of 16 patients developed carcinomas and dropped out. INTERVENTIONS: Two years of bronchodilator treatment alone (400 micrograms of salbutamol or 40 micrograms of ipratropium bromide four times daily), followed by 2 years of additional inhaled corticosteroid treatment (400 micrograms of beclomethasone two times daily), and finally 1 year of bronchodilator treatment alone. MAIN OUTCOME MEASURES: Decline in lung function (FEV1), change in bronchial hyperresponsiveness, indicated by a provocative concentration of histamine causing a 20% fall in FEV1 (PC20), morning peak expiratory flow rate (PEFR), diurnal PEFR, week-to-week variation of PEFR, bronchial symptoms, and exacerbations. RESULTS: The course of FEV1 during the year in which beclomethasone was discontinued was not significantly different when compared with the 2-year period of beclomethasone treatment. Neither did the course of PC20, morning PEFR, diurnal PEFR, symptom score, and exacerbation rate change. Only the week-to-week variation of the PEFR increased after discontinuing steroids. CONCLUSIONS: Discontinuing inhaled steroids is possible in some patients with asthma or COPD after 2 years of regular treatment. This might indicate that for certain groups of patients with mild asthma or COPD, periodic treatment schedules with inhaled steroids is the treatment policy for the future.
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OBJECTIVES: to study the relationship between chronic respiratory symptoms and bronchial hyperresponsiveness (BHR) in adolescence and young adulthood and to assess the possible predictive value of these symptoms for BHR. METHODS: a cross-sectional analysis: in a population sample of 551 subjects aged 10-23 years, data collected with a standardized questionnaire on respiratory symptoms were compared with the results of a histamine challenge test. RESULTS: 43% of the subjects reported one or more chronic respiratory symptoms; of these subjects 54% did not show BHR. Forty-two per cent of the subjects had a PC20 < or = 8.0 mg ml-1 histamine, of which 53% reported no chronic respiratory symptoms. Wheezing and breathlessness were related to the level of BHR, but only 'breathless when walking on the flat' was independently related to BHR; however, its predicted value for BHR was negligible. CONCLUSIONS: in adolescents and young adults the relationship between chronic respiratory symptoms and BHR is incomplete. A standardized questionnaire on respiratory symptoms does not provide adequate information to discriminate between those with and without BHR.
A historical cohort study was performed to assess cardiovascular morbidity and mortality in Type 2 (non-insulin-dependent) diabetic patients. The data were collected from 1967 to 1989 in four Dutch general practices performing the Continuous Morbidity Registration Nijmegen. Each newly diagnosed Type 2 diabetic patient fulfilling the WHO criteria (n = 265) was matched to a control patient for practice, sex, age, and social class. Inclusion started in 1967, the first year of the still ongoing, Continuous Morbidity Registration Nijmegen. On average, a follow-up of 6.8 years (range 1 month-22 years) was realized. Compared to the non-diabetic control patients, the Type 2 diabetic patients showed higher cardiovascular morbidity (risk ratio 1.76, 95% CI 1.34-2.30) and a higher mortality rate (risk ratio 1.54, 95% CI 1.07-2.23). Mortality after 10 years was 36% vs 20% (p < 0.01), the median survival time 16 years vs 19 years. The cumulative survival rates were significantly different (p < 0.01) between patients and controls in the age group 65-74 years. The higher mortality in Type 2 diabetic patients was completely due to an excess of cardiovascular death (risk ratio 2.05, 95% CI 1.24-3.37).
To evaluate the Micral test, a semiquantitative dipstick test, in a general practice setting, 317 Type 2 diabetic patients completed a screening for microalbuminuria by means of the Micral test as well as immuno-nephelometry with the Disc 120 immuno-nephelometer (Hyland, Nivelles, Belgium). Data were collected in 10 general practices performing the Nijmegen Monitoring Project. At a regular check-up each Type 2 diabetic patient was asked to collect first morning urine samples on three consecutive days. The sensitivity of the Micral test was 67%, the specificity 93%. Between the practices the sensitivity ranged from 58% to 81%, the specificity from 87% to 95%. Microalbuminuria, defined as a mean urine albumin concentration > or = 20 mg I-1 by nephelometry on three consecutive days, was found in 66 patients (21%). The first Micral test correctly picked out these patients with microalbuminuria in 70% of the cases and in 90% those patients without microalbuminuria. The diagnostic performance of the Micral test was further proved by a Receiver Operating Characteristic (ROC) curve. The Area Under the Curve (AUC) of the Micral test was 0.84 (95% CI 0.78-0.90). Micral test results of 0 and 10 should be regarded as negative.
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Relatively little is known about the influence of inhaled corticosteroids on general well-being (quality of life) in patients with asthma or COPD. In a 4-year prospective controlled study, we examined the influence of beclomethasone dipropionate (BDP), 400 micrograms, two times daily, on quality of life in 56 patients with asthma or COPD in comparison with the effects of BDP on symptoms and lung function. During the first 2 years, patients received only bronchodilator therapy with salbutamol or ipratropium bromide. During the third and fourth years, additional treatment with BDP was given. Fifty-six patients (28 with asthma, 28 with COPD) with an annual decline in the forced expiratory volume in 1 s (FEV1) of at least 80 mL/yr in combination with at least two exacerbations per year during bronchodilator therapy alone participated. Quality of life was assessed at the start and after 2 and 4 years by means of the Inventory of Subjective Health (ISH) and the Nottingham Health Profile (NHP). Although BDP significantly improved the course of lung function (FEV1)(p < 0.0001), it did not improve the ISH score or the six dimensions of the NHP neither in asthma nor in COPD. Beclomethasone dipropionate temporarily decreased respiratory symptoms during months 4 to 6 of BDP treatment in patients with asthma (p < 0.01) and during months 7 to 12 in patients with COPD (p < 0.05). A weak correlation was found both cross-sectionally and longitudinally between (change in) symptoms and quality of life on the one hand, and the (change in) FEV1 on the other. It was concluded that BDP did not improve the general well-being of patients with asthma or COPD as measured by these generic health instruments. However, BDP significantly improved the course of lung function and temporarily decreased the severity of symptoms. It seems probable that changes in quality of life would have been better detected by use of a disease-specific health instrument. Such an instrument was not available at the start of the study. Another possible explanation for these observations is that patients soon get used to different levels of lung function and learn to live with their disease. It is advised that disease-specific health instruments are used in future intervention studies and that quality of life is measured frequently during the early phase of the intervention, eg, once every month.
BACKGROUND: A previous two-year study of continuous and on demand bronchodilator therapy in patients with moderate asthma and chronic bronchitis showed a deterioration in lung function in those on continuous therapy. AIM: A two-year follow-up study was undertaken of patients who had been shown in the previous study to have non-steroid dependent (mild) asthma and chronic bronchitis, in order to investigate the effect of continuous and on-demand treatment with bronchodilator therapy. METHOD: Patients for the study were drawn from 29 general practices in the catchment area of the University of Nijmegen, the Netherlands. A total of 83 patients (27 with asthma and 56 with chronic bronchitis) were selected from a group of 160 patients who had completed the previous two-year bronchodilator trial. During these first two years the selected subjects had been shown to be non-steroid dependent (no rapid decline in lung function and a low number of exacerbations of their condition per year), and they were followed up for another two years of treatment with bronchodilator therapy. At the start of the four-year study, patients were randomly assigned to one of two parallel treatment groups: continuous treatment (dry powder inhalations of either salbutamol 1600 micrograms or ipratropium bromide 160 micrograms daily) or treatment on demand (only during exacerbations or periods of dyspnoea). Outcome parameters were the annual decline in lung function, changes in peak flow rate, bronchial hyper-responsiveness, exacerbation rate, respiratory symptoms and reported health. RESULTS: After correction for possibly confounding variables and for regression to the mean, the decline in lung function was 49 ml year in patients taking bronchodilators continuously and 51 ml year in patients using bronchodilators on demand, irrespective of the drug use. Continuously treated patients, whether suffering from asthma or chronic bronchitis, did not differ from patients treated on demand with respect to mean morning peak flow rate, diurnal (and week to week) variation of the peak flow rate, bronchial hyper-responsiveness, exacerbation rate and reported health. There was no difference between the long-term effects of salbutamol and ipratropium. CONCLUSION: Continuous use of bronchodilators over four years in patients with non-steroid dependent asthma or chronic bronchitis does not increase the decline in lung function which had been observed previously in patients with moderate asthma or chronic bronchitis during two years of continuous treatment with bronchodilators.
A retrospective analysis of the medical charts of 117 patients (50 men and 67 women) with multi-infarct dementia took place. All patients admitted to the psychogeriatric nursing home 'Joachim en Anna' in Nijmegen between 1980 and 1989 were studied. The aim of the study was to obtain epidemiological information and to investigate the prevalence of comorbid conditions, prognosis and mortality. The results were compared with patients with Alzheimer's disease. The patients remained in the institute for 1.4 years and the mean total duration of the disease was 5.3 years. About twenty-five percent died in the first three months of admission. Life expectation, counted from time of admission, was 6 years shorter in comparison with Dutch mortality tables. Morbidity frequently seen at admission included circulatory system diseases and cerebrovascular accidents. The risk factor hypertension was seen in a smaller percentage of patients than expected. During the stay the diseases most frequently diagnosed were respiratory and urinary tract infections, adverse effects of drugs, constipation and chronic ulcers of the skin. About twenty percent of the patients were struck by a (recurrent) cerebrovascular accident or a transient ischaemic attack. Most patients died of dehydration or bronchopneumonia. There was, apart from the diagnosis of multi-infarct dementia, no single patient aspect that could predict a poor prognosis. Nursing home patients with multi-infarct dementia are clearly different from patients with Alzheimer's disease. Time spent in the nursing home and duration of disease are shorter. They have more comorbid conditions, especially of a cardiovascular nature, and they have a poor life expectation.
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A total of 110 women who had reported urinary incontinence to their general practitioners were randomly assigned to a treatment or control group. Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence. The results were measured after 3 and 12 months by a research assistant on the basis of a constructed severity scale, an incontinence diary, and a comparison by the patients themselves of their previous and current conditions. After 3 months the control group were given the same treatment. After a further 3 and 12 months, they were assessed in exactly the same way as the treatment group. After 3 months about 60% of the patients were either dry or only mildly incontinent; the mean number of wet episodes had gone down from 20 to 7, and 74% of the women felt improved or cured. These results were later corroborated by the control group. After 12 months this successful outcome was improved slightly further. It may be concluded that the majority of women with incontinence can be successfully treated by the general practitioner. The effect of this treatment continues after one year.
The aim of the study was to investigate the relationship between presented morbidity in consecutive periods of time in the first 35 years of life. Data were collected in a large rural general practice from 1946 to 1990 and covered 103 persons born between 1946 and 1959 in a general practice in the east of The Netherlands. Morbidity scores were calculated for all registered diagnoses in 5-year periods. Morbidity was allocated to three degrees of seriousness, to all atopic disorders, and to eight important diagnosis groups. There were strong correlations between consecutive time periods for all but serious morbidity. The same pattern was found between 0-4 years of age and consecutive periods till the age of 20-25. After this age no significant correlations could be established. Atopic disorders were inter-related in the first 20 years of life. Strong correlations were also found for eczema and lower respiratory tract infections in the first 20 years, while strong correlations were found for accidents and nervous complaints between the ages of 20 and 35. We conclude that causes of morbidity presented in general practice in childhood and adulthood are strongly inter-related over consecutive 5-year periods.
Recently, we published data of a 2 year randomized controlled study in which the effects of continuous versus symptomatic bronchodilator treatment in patients with moderate asthma or chronic bronchitis were investigated. The results showed that FEV1 decline in the continuously treated group was significantly larger than in the symptomatically treated group (72 versus 20 ml/year, P < 0.05). We reanalysed these data in order to investigate the hypothesis that the continuous use of bronchodilators may mask a rapid decline in lung function. Lung function decline was assessed by regression analysis of seven FEV1 measurements. Respiratory symptoms were assessed by means of the MRC questionnaire every 12 months, and they were also recorded by the patients in a weekly report. Of the participating patients 144 completed the study. Increased lung function decline in the continuously treated group was not reflected in a significant deterioration of the symptoms. Moreover, the decline in FEV1 showed no correlation at all with changes in respiratory symptoms in continuously treated patients (r = -0.03, P = 0.80), whereas in the symptomatically treated group, there was a better relation (r = -0.32, P = 0.003) to changes in respiratory symptoms. These results show that continuous bronchodilation may indeed mask the worsening of the disease. This lack of awareness of deterioration of the disease is probably caused by the continuous symptom relief of bronchodilators. It may be misleading to both patients and physicians.
In a two-year randomized controlled study, we studied the effects of bronchodilator treatment on the lung function and the quality of life in patients with mild airflow obstruction. The patients were randomly divided to receive either continuous or symptomatic bronchodilator treatment. Within these treatment groups, they received salbutamol in the first year and ipratropium bromide in the second or vice versa. In addition, the quality of life of the patients was compared to that of the general population. One hundred and forty-four patients completed the study. When compared to the general population, these patients showed a serious impairment in quality of life. No differences between the two drugs were found, but the results indicated that FEV1 decline in the continuously treated group was significantly larger than in the symptomatically treated group. However, this was not reflected in a significant deterioration of the quality of life in the continuous group as measured by means of the Nottingham Health Profile and the Inventory of Subjective Health. Decline in FEV1 showed no correlation with changes in quality of life scores. This may be due to a relatively rapid adjustment of the patients to a decline in FEV1, as a result of which it has no direct effect on the experienced quality of life. Another reason may be that continuous bronchodilation masks the worsening of the disease. This lack of awareness might in turn be caused by the continuous symptom relief of bronchodilators.
STUDY OBJECTIVE: The aim of the study was to investigate the relationship between morbidity in early childhood and gender, birth order, and social class. DESIGN: The study used data collected in the Nijmegen Continuous Morbidity Registration. All presented morbidity and a number of personal data were available. SETTING: The survey population was regional; four general practices in the east of The Netherlands. PARTICIPANTS: The study population included all children born in the four practices from 1971 to 1984. They were followed up till the age of five (1537 children). MEASUREMENTS AND MAIN RESULTS: Morbidity of children in the first five years was allocated to three degrees of seriousness and to 14 diagnosis groups. The morbidity of all children was analysed for boys and girls, first-born, second-born, and later-born children, and low, middle, and high social class. Boys presented more morbidity than girls; in particular, nervous disorders, lower respiratory tract infections, and accidents. First-born children presented more morbidity than later-born children; in particular, non-serious diseases, nervous disorders, and colds. Lower social class children presented more moderately serious and non-serious morbidity, colds, lower respiratory tract infections, and skin diseases. Logistic regression analysis showed that high social class, being the first-born child, and male gender were the most important factors related to presented morbidity in general practice. CONCLUSIONS: High social class, low social class, gender, and being the first-born child were, in this sequence, related to morbidity in early childhood presented to the general practitioner in this study population.
The morbidity and mortality due to asthma and chronic bronchitis are still rising in several countries. The aim of this study was to investigate whether early detection of patients with fast progressive asthma or chronic bronchitis in general practice was possible from a cross-sectional assessment of symptoms, smoking behaviour, quality of life, physical signs of the chest, allergy, and lung function. Data of 162 patients who had participated in a long-term randomized controlled intervention study in general practice were analysed. Fifty-six out of the 162 patients showed fast progressive disease (FPD, a rapid annual decline in FEV1 in combination with a high exacerbation rate). Measurements at the start of the study were used in a logistic regression analysis in order to detect the patients at risk (with FPD). A lower maximal expiratory flow at 50% of expired volume (MEF50) was related to an increased risk of FPD in both asthma and chronic bronchitis (relative risks of 16.8 and 8.0 respectively, p less than 0.05). Most lung function indices, but also quality of life and pack years, were significant predictors of FPD in chronic bronchitis (p less than 0.05). However, it was not possible to detect FPD reliably with these predictors separately or even with the combination of several relevant clinical variables; 18% of the patients with chronic bronchitis and 22% of the patients with asthma were still misclassified. It was concluded from this study that more than one measurement over time (monitoring) is necessary to detect the patients at risk. Monitoring should include assessments of objective ventilatory function indices (PEFR, FEV1 or MEF50).