C.P. van Schayck

Detecting patients at a high risk of developing chronic obstructive pulmonary disease in general practice: cross sectional case finding study

Abstract Objectives: To investigate the effectiveness of case finding of patients at risk of developing chronic obstructive pulmonary disease, whether the method is suitable for use in general practice, how patients should be selected, and the time required. Design: Cross sectional study. Setting: Two semirural general practices in the Netherlands. Participants: 651 smokers aged 35 to 70 years. Main outcome measures: Short standardised questionnaire on bronchial symptoms for current smokers, lung function with a spirometer, and the quality of the spirometric curve. Results: Of the 201 smokers not taking drugs for a pulmonary condition, 169 produced an acceptable curve (fulfilling American Thoracic Society criteria). Of these, 30 (18%, 95% confidence interval 12% to 24%) had a forced expiratory volume in one second (FEV1) <80% of predicted. When smokers were preselected on the basis of chronic cough, the proportion with an FEV1 <80% of predicted increased to 27% (17 of 64; 12% to 38%). Chronic cough was a better predictor of airflow obstruction than other symptoms, such as wheeze and dyspnoea. The presence of two symptoms was a slightly better predictor than cough only (odds ratio 3.02 (1.37 to 6.64) v 2.50 (1.14 to 5.52)). Age was also a good predictor of obstruction; smokers over 60 with cough had a 48% chance of having an obstruction. The mean time needed for spirometry was four minutes. Detecting one smoker with an FEV1 <80% of predicted cost €5 to €10. Conclusions: Trained practice assistants could check all patients who smoke for chronic obstructive pulmonary disease at little cost to the practice. Cough and age are the most important predictors of the disease. By testing one smoker a day, an average practice could identify one patient at risk a week.

Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol

Recently, it was suggested that long-term administration of an inhaled beta 2-agonist might increase bronchial hyperresponsiveness (BHR) to histamine, possibly as a consequence of subsensitization to the inhaled beta 2-agonist. To test this hypothesis, we studied two groups of patients with asthma or with chronic obstructive pulmonary disease. An experimental group of 15 patients, inhaling 400 micrograms of salbutamol four times daily during 1 year and subsequently 40 micrograms of ipratropium bromide four times daily for 6 months, and a control group, consisting of 22 patients with the opposite treatment regimen. The BHR, the response in FEV1 to cumulative doses of salbutamol, and the number of beta 2-adrenoceptors and antagonist affinity of these receptors on circulating lymphocytes were assessed at the start of the study and at 6-month intervals for 1 1/2 years. The BHR increased significantly (p = 0.001) during the year salbutamol was inhaled and returned to about the value at the start of the study after inhaling ipratropium bromide for 6 months. No change occurred in the bronchodilating responses to cumulative doses of salbutamol, nor was any change observed in the number and the affinity of beta 2-adrenoceptors on lymphocytes. It was concluded that long-term use of salbutamol caused a small but significant increase in BHR. The increase in BHR was not caused by subsensitization of beta 2-adrenoceptors to salbutamol.

Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: “Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?” METHODS A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with “asthmatic features” were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 μg beclomethasone daily, six with 1600 μg budesonide daily, and eight with 800 μg beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated. RESULTS No baseline differences were observed (mean age 61 years, mean FEV145% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI –0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group. CONCLUSIONS This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.

Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 1990–2010: A Systematic Review of Epidemiological Studies

The prevalence of atopic eczema has been found to have increased greatly in some parts of the world. Building on a systematic review of global disease trends in asthma, our objective was to study trends in incidence and prevalence of atopic eczema. Disease trends are important for health service planning and for generating hypotheses regarding the aetiology of chronic disorders. We conducted a systematic search for high quality reports of cohort, repeated cross-sectional and routine healthcare database-based studies in seven electronic databases. Studies were required to report on at least two measures of the incidence and/or prevalence of atopic eczema between 1990 and 2010 and needed to use comparable methods at all assessment points. We retrieved 2,464 citations, from which we included 69 reports. Assessing global trends was complicated by the use of a range of outcome measures across studies and possible changes in diagnostic criteria over time. Notwithstanding these difficulties, there was evidence suggesting that the prevalence of atopic eczema was increasing in Africa, eastern Asia, western Europe and parts of northern Europe (i.e. the UK). No clear trends were identified in other regions. There was inadequate study coverage worldwide, particularly for repeated measures of atopic eczema incidence. Further epidemiological work is needed to investigate trends in what is now one of the most common long-term disorders globally. A range of relevant measures of incidence and prevalence, careful use of definitions and description of diagnostic criteria, improved study design, more comprehensive reporting and appropriate interpretation of these data are all essential to ensure that this important field of epidemiological enquiry progresses in a scientifically robust manner.

Underdiagnosis of asthma: is the doctor or the patient to blame? The DIMCA project

BACKGROUND It is important to diagnose asthma at an early stage as early treatment may improve the prognosis in the long term. However, many patients do not present at an early stage of the condition so the physician may have difficulty with the diagnosis. A study was therefore undertaken to compare the proportion of patients who underpresented their respiratory symptoms with the proportion of underdiagnosed cases of asthma by the general practitioner (GP). A secondary aim was to investigate whether bad perception of dyspnoea by the patient was a determining factor in the underpresentation of asthma symptoms to the GP. METHODS A random sample of 1155 adult subjects from the general population in the eastern part of the Netherlands was screened for respiratory symptoms and lung function and the results were compared with the numbers of asthma related consultations registered in the medical files of the GP. In subjects with reduced lung function the ability to perceive dyspnoea was investigated during a histamine provocation test in subjects who did and did not report their symptoms to their GP. RESULTS Of the random sample of 1155 subjects 86 (7%) had objective airflow obstruction (forced expiratory volume in one second (FEV1) below the reference value corrected for age, length, and sex minus 1.64SD on two occasions) and had symptoms suggestive of asthma. Of these 86 subjects only 29 (34%) consulted the GP, which indicates underpresentation by 66% of patients. Of all subjects with objective airflow obstruction who presented to their GP with respiratory symptoms, 23 (79%) were recorded in the medical files as having asthma, indicating underdiagnosis by the GP in 21% of cases. Of the subjects with objective airflow obstruction who visited the GP with respiratory symptoms 6% had bad perception of dyspnoea compared with 26% of those who did not present to the GP in spite of airflow obstruction (χ2 = 3.02, p = 0.08). CONCLUSIONS Underpresentation to GPs of respiratory symptoms by asthmatic patients contributes significantly to the problem of underdiagnosis of asthma. Underdiagnosis by the GP seems to play a smaller role. Furthermore, there are indications that underpresentation of symptoms by the patient is at least partly explained by a worse perception of dyspnoea.

Are patients with COPD psychologically distressed

This study was designed to assess the level of psychological distress in a heterogeneous group of patients with chronic obstructive pulmonary disease (COPD), and compare them with the general population and psychiatric outpatients. A total of 118 patients with COPD, a random sample of 500 subjects from the general population and 500 psychiatric outpatients participated in this study. The Dutch version of the Symptom Checklist-90-Revised was used to assess general psychological distress. The sample of patients with COPD experienced significantly more psychological distress than the general population and significantly less than psychiatric outpatients. Furthermore, no significant association was found between the severity of the pulmonary disease and the level of psychological distress, although patients with severe or very severe COPD appeared to be at increased risk of depression. Lastly, the pattern of psychological complaints seems comparable in depressed patients with COPD and psychiatric outpatients. Once patients with COPD report suffering from depressive symptoms, the level of distress seems to increase to that found in psychiatric outpatients. In conclusion, in clinical settings in which psychological complaints are not routinely assessed, the Beck Depression Inventory and Symptom Checklist-90-Revised are very useful for drawing attention to depression and psychological distress.

Self-management of asthma in general practice, asthma control and quality of life: a randomised controlled trial

Background: A study was undertaken to determine the effectiveness of asthma self-management in general practice. Methods: Nineteen general practices were randomly allocated to usual care (UC) or self-management (SM). Asthma patients were included after confirmation of the GP diagnosis. Follow up was 2 years. Patients kept diary cards and visited the lung function laboratory every 6 months. Outcomes were number of successfully treated weeks, limited activity days, asthma specific quality of life, forced expiratory volume in 1 second (FEV1), FEV1 reversibility, concentration of histamine provoking a fall in FEV1 of 20% or more (PC20 histamine), and amount of inhaled steroids. Results: A total of 214 patients were included in the study (104 UC/110 SM; one third of the total asthma population in general practice); 62% were female. The mean percentage of successfully treated weeks per patient in the UC group was 72% (74/103 weeks) compared with 78% (81/105 weeks) in the SM group (p=0.003). The mean number of limited activity days was 1.2 (95% CI 0.5 to 1.9) in the SM group and 3.9 (95% CI 2.5 to 5.4) in the UC group. The estimated increase in asthma quality of life score was 0.10 points per visit in the UC group and 0.21 points per visit in the SM group (p=0.055). FEV1, FEV1 reversibility, and PC20 histamine did not change. There was a saving of 217 puffs of inhaled steroid per patient in favour of the SM group (p<0.05). Conclusion: Self-management lowers the burden of illness as perceived by patients with asthma and is at least as effective as the treatment usually provided in Dutch primary care. Self-management is a safe basis for intermittent treatment with inhaled corticosteroids.

Association between health-related quality of life and consultation for respiratory symptoms: results from the DIMCA programme

In general practice, diagnosis of chronic obstructive pulmonary disease (COPD) is hampered by underpresentation. A substantial proportion of subjects experiencing respiratory complaints do not consult their general practitioner (GP). In this study, the relationship between disease-specific quality of life and presentation of respiratory symptoms to a GP is investigated. A random sample from the general population (undiagnosed subjects) was screened for symptoms and objective signs of COPD (n=1,155). The lung function of subjects with symptoms of COPD was monitored for 6 months. During this period, 48 new COPD patients with a persistently reduced lung function (forced expiratory volume in one second (FEV1) less than or equal to the predicted value minus 2 SD) were detected. A disease-specific quality-of-life questionnaire (chronic respiratory questionnaire (CRQ)) was administered and clinical and GP consultation data were collected. Multivariate analysis showed that quality-of-life impairments due to dyspnoea and fatigue and variability in lung function (bronchial hyperresponsiveness, reversibility and peak expiratory flow rate variability) were related to medical consultation. Only 31% of the newly detected patients reported that they had ever visited their GP for respiratory complaints. A similarly low percentage was found in the rest of the sample (26%). It is concluded that the mere presence of respiratory symptoms or a (gradually) reduced lung function is insufficient reason for patients to seek medical help. Subjects are more likely to consult their general practitioner once their quality of everyday life is affected or they experience variability in lung function.

Relation of the perception of airway obstruction to the severity of asthma.

BACKGROUND Patients with a poor perception of their symptoms of asthma seem to have an increased risk of an asthma attack. The influence of factors such as airway calibre, bronchial hyperresponsiveness, age and sex on the “perceptiveness” of a patient are poorly understood. It is of clinical importance to identify patients who are likely to have a poor perception of their symptoms. We have studied the perception of bronchoconstriction by asthmatic patients during a histamine provocation test and analysed the influence of bronchial obstruction, hyperresponsiveness, sex, and age. We were particularly interested to establish whether there was any difference in perception between subjects with a greater or lesser severity of asthma (expressed as bronchial obstruction, hyperresponsiveness). METHODS One hundred and thirty four patients with allergic asthma underwent a histamine provocation test. The FEV1 was measured after each inhalation of histamine. Subjects were asked to rate subjective quantification of the sensation of breathlessness on a visual analogue scale (VAS). The relationship between changes in VAS values and the reduction in FEV1 as a percentage of the baseline value was analysed by determining the linear regression slope (α) between the two parameters and indicates the perception of airway obstruction. Multiple regression analysis was performed to investigate the effect of baseline FEV1, bronchial hyperresponsiveness, sex and age on the “perceptiveness” for bronchoconstriction. RESULTS The median value of the slope α (indicating the perception of airway obstruction) was 0.91 (25–75th percentile: 0.48–1.45). Age and sex had no influence on the perception of bronchoconstriction. Both initial bronchial tone (baseline FEV1) and bronchial hyperresponsiveness (PC20) showed a significant correlation with the perception of bronchoconstriction. The regression coefficients for FEV1 and 2log PC20 in the multiple regression model were 0.20 and 0.10. Patients who had a low baseline FEV1 and/or a high bronchial responsiveness to histamine were more likely to show a low perceptiveness for bronchoconstriction during the challenge test. CONCLUSIONS Low baseline FEV1 and high bronchial responsiveness are associated with a low degree of “perceptiveness” for bronchoconstriction. This suggests that patients with a more severe degree of asthma either show adaptation of “perceptiveness” for airway obstruction or that low perceptiveness leads to more severe asthma.

Health problems and psychosocial work environment as predictors of long term sickness absence in employees who visited the occupational physician and/or general practitioner in relation to work: a prospective study

Aims: To determine whether psychosocial work environment and indicators of health problems are prospectively related to incident long term sickness absence in employees who visited the occupational physician (OP) and/or general practitioner (GP) in relation to work. Methods: The baseline measurement (May 1998) of the Maastricht Cohort Study, a prospective cohort study among 45 companies and organisations, was used to select employees at work who indicated having visited the OP and/or GP in relation to work. Self report questionnaires were used to measure indicators of health problems (presence of at least one long term disease, likeliness of having a mental illness, fatigue) and psychosocial work environment (job demands, decision latitude, social support, job satisfaction) as predictors of subsequent sickness absence. Sickness absence data regarding total numbers of sickness absence days were obtained from the companies and occupational health services during an 18 month period (between 1 July 1998 and 31 December 1999). Complete data were available from 1271 employees. Results: After adjustment for demographics and the other predictors, presence of at least one long term disease (OR 2.36; 95% CI 1.29 to 4.29) and lower level of decision latitude (OR 1.69; 95% CI 1.22 to 2.38) were the strongest predictors for sickness absence of at least one month. A higher likelihood of having a mental illness, a higher level of fatigue, a lower level of social support at work, and low job satisfaction were also significant predictors for long term sickness absence, but their effect was less strong. Conclusion: In detecting employees at work but at risk for long term sickness absence, OPs and GPs should take into account not only influence of the psychosocial work environment in general and level of decision latitude in particular, but also influence of indicators of health problems, especially in the form of long term diseases.