Quality of spirometry and related diagnosis in primary care with a focus on clinical use.

American and European societies' (ATS/ERS) criteria for spirometry are often not met in primary care. Yet, it is unknown if quality is sufficient for daily clinical use. We evaluated quality of spirometry in primary care based on clinical usefulness, meeting ATS/ERS criteria and agreement on diagnosis between general practitioners (GPs) and pulmonologists. GPs included ten consecutive spirometry tests and detailed history questionnaires of patients who underwent spirometry as part of usual care. GPs and two pulmonologists assessed the spirometry tests and questionnaires on clinical usefulness and formulated a diagnosis. In total, 149 participants covering 15 GPs were included. Low agreements were found on diagnosis between GPs and pulmonologists 1 (κ = 0.39) and 2 (κ = 0.44). GPs and pulmonologists rated >88% of the tests as clinically useful, although 13% met ATS/ERS criteria. This real-life study demonstrated that clinical usefulness of routine primary care spirometry tests was high, although agreement on diagnosis was low.

'Exacerbation-free time' to assess the impact of exacerbations in patients with chronic obstructive pulmonary disease (COPD): a prospective observational study.

COPD exacerbations are commonly quantified as rate per year. However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes. In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life. A total of 166 COPD patients reported symptom changes during 12 months. Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year. Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman's rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ). The correlation between exacerbation frequency and exacerbation-free weeks was -0.71 (p < 0.001). However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak (r = -0.25; p < 0.01). Smokers had less exacerbation-free weeks than non-smokers (ß = -5.709, p < 0.05). More exacerbation-free weeks were related to better CRQ Total (r = 0.22, p < 0.05), Mastery (r = 0.22, p < 0.05), and Fatigue (r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores. In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time. Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does.

A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention. METHOD: The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee. DISCUSSION: Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R2 of 0.82 and 0.74 (p < 0.01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981851.

Interaction in COPD experiment (ICE): a hazardous combination of cigarette smoking and bronchodilation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, characterised by poorly reversible, obstructive airflow limitation. Alongside other comorbidities, COPD is associated with increased morbidity and mortality resulting from cardiovascular disease - mainly heart failure and ischemic heart disease. Both diseases share an important risk factor, namely, smoking. About 50% of COPD patients are active cigarette smokers. Bronchodilation is the cornerstone of pharmaceutical treatment for COPD symptoms, and half of all COPD patients use long-acting bronchodilating agents. Discussion about these agents is currently focusing on the association with overall mortality and morbidity in COPD patients, of cardiovascular origin in particular. Bronchodilation diminishes the hyperinflated state of the lung and facilitates the pulmonary deposition of cigarette smoke by deeper inhalation into the smaller airways. Smaller particles, as in smoke, tend to penetrate and depose more in these small airways. In addition, bronchodilation indeed increases carbon monoxide uptake in the lungs, an important gaseous compound of cigarette smoke. Since the number of cigarettes smoked is positively correlated to mortality from cardiac events, we therefore hypothesise that chronic bronchodilation increases cardiovascular disease and mortality in COPD patients who continue smoking by increasing pulmonary retention of pathogenic smoke constituents. Indeed, a recent meta-analysis is suggestive that long-acting anticholinergics might increase cardiovascular disease if patients exceed a certain number of cigarettes smoked. To demonstrate the fundamental mechanism of this pathogenic interaction we will perform a randomised placebo-controlled cross-over trial to investigate the effect of maximum bronchodilation on the retention of cigarette smoke constituents. In 40 moderate to severe COPD patients we measure the inhaled and exhaled amount of tar and nicotine, as well during maximum bronchodilation as during administration of placebo. The fraction of retention of tar and nicotine is subsequently calculated for both circumstances and analysed for association with bronchodilation. Further observational cohort studies or randomised clinical trials designed to monitor cardiovascular events may well evaluate the interaction. Since many patients are at risk for this possibly hazardous interaction, its relevance to our society and healthcare is potentially great. The implication will be that the urgency to quit smoking is intensified. Besides, chronic bronchodilation - specifically long-acting bronchodilators - needs to be discouraged in smoking COPD patients that refuse to quit.

[Prevalence of and health care consumption for asthma and COPD in relation to ethnicity]. / Prevalentie en zorgconsumptie bij astma en COPD in relatie tot etniciteit.

OBJECTIVE: To determine whether there are differences in prevalence of and health care consumption for asthma and COPD between Dutch people of Turkish, Moroccan and Surinamese origin and indigenous Dutch people. DESIGN: Retrospective. METHOD: Based on data from the 'Second Dutch national study into morbidity and interventions in general practice', we compared the prevalence of asthma and COPD in the different ethnic groups. In addition, we compared the use of various airway medications and the number of general practice contacts between these ethnic groups. RESULTS: We analysed data of 240,067 indigenous Dutch, 2,942 Turkish, 2,416 Moroccan and 3,320 Surinamese subjects. Asthma is more prevalent among Surinamese and seems less prevalent among Moroccans. COPD seems less prevalent among immigrants than among the indigenous Dutch population. Immigrants tend to have less prescriptions of prophylactic maintenance airway medication and they also tend to have less airway-related general practice contacts than indigenous Dutch patients. CONCLUSION: Differences exist in the prevalence of and health care consumption for asthma and COPD between the different ethnic groups in the Netherlands. There seems to be underdiagnosis of COPD in immigrants. Moreover, immigrant asthma and COPD patients are probably undertreated.

Current clinical guideline definitions of airflow obstruction and COPD overdiagnosis in primary care.

The aim of the present study was to establish the agreement between two recommended definitions of airflow obstruction in symptomatic adults referred for spirometry by their general practitioner, and investigate how rates of airflow obstruction change when pre-bronchodilator instead of post-bronchodilator spirometry is performed. The diagnostic spirometric results of 14,056 adults with respiratory obstruction were analysed. Differences in interpretation between a fixed 0.70 forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) cut-off point and a sex- and age-specific lower limit of normal cut-off point for this ratio were investigated. Of the subjects, 53% were female and 69% were current or ex-smokers. The mean post-bronchodilator FEV(1)/FVC was 0.73 in males and 0.78 in females. The sensitivity of the fixed relative to the lower limit of normal cut-off point definition was 97.9%, with a specificity of 91.2%, positive predictive value of 72.0% and negative predictive value of 99.5%. For the subgroup of current or ex-smokers aged > or =50 yrs, these values were 100, 82.0, 69.2 and 100%, respectively. The proportion of false positive diagnoses using the fixed cut-off point increased with age. The positive predictive value of pre-bronchodilator airflow obstruction was 74.7% among current or ex-smokers aged > or =50 yrs. The current clinical guideline-recommended fixed 0.70 forced expiratory volume in one second/forced vital capacity cut-off point leads to substantial overdiagnosis of obstruction in middle-aged and elderly patients in primary care. Using pre-bronchodilator spirometry leads to a high rate of false positive interpretations of obstruction in primary care.

Impact of a spirometry expert system on general practitioners' decision making.

The present study assessed the impact of computerised spirometry interpretation expert support on the diagnostic achievements of general practitioners (GPs), and on GPs' decision making in diagnosing chronic respiratory disease. A cluster-randomised controlled trial was performed in 78 GPs who each completed 10 standardised paper case descriptions. Intervention consisted of support for GPs' spirometry interpretation either by an expert system (expert support group) or by sham information (control group). Agreement of GPs' diagnoses was compared with an expert panel judgement, which served as the primary outcome. Secondary outcomes were: additional diagnostic test rates; width of differential diagnosis; certainty of diagnosis; estimated severity of disease; referral rate; and medication or nonmedication changes. Effects were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). There were no differences between the expert support and control groups in the agreement between GPs and expert panel diagnosis of chronic obstructive pulmonary disease (OR (95% CI) 1.08 (0.70-1.66)), asthma (1.13 (0.70-1.80)), and absence of respiratory disease (1.32 (0.61-2.86)). A higher rate of additional diagnostic tests was observed in the expert support group (2.5 (1.17-5.35)). Computerised spirometry expert support had no detectable benefit on general practitioners' diagnostic achievements and the decision-making process when diagnosing chronic respiratory disease.

Lower inhaled steroid requirement with a fluticasone/salmeterol combination in family practice patients with asthma or COPD.

BACKGROUND: Previous studies on inhaled steroid and long-acting beta2-agonist combination products may not be representative for the asthma and chronic obstructive pulmonary disease (COPD) patients in family practice. OBJECTIVES: To compare in a group of doctor-diagnosed patients with asthma or COPD, the effects of a lower dose of fluticasone in a combination product with salmeterol with conventional treatment (i.e. a higher dose of fluticasone), both supplemented with as-needed use of a short-acting bronchodilator. METHODS: The study was a 12-week multicentre, randomized controlled, double-blind trial. In all, 41 family practices recruited 137 patients diagnosed with asthma and 40 patients diagnosed with COPD. Primary outcome was the forced expiratory volume in 1 second (FEV1) as percentage of predicted. Morning peak expiratory flow (PEF), symptom-free days, health status [Asthma Quality of Life Questionnaire (AQLQ) and St. George's Respiratory Questionnaire (SGRQ)], exacerbations, use of short-acting bronchodilators and adverse events were secondary outcomes. RESULTS: FEV1% predicted increased 2.6% (SD 8.3) in fluticasone/salmeterol- and 0.01% (SD 6.6) in fluticasone-treated patients (overall: P=0.036, asthma: P=0.025 and COPD: P=0.700). PEF increased in favour of fluticasone/salmeterol in asthma patients only (P=0.016). Fluticasone/salmeterol-treated asthma patients had 1.1 more symptom-free days per week (P=0.044); no such effect was observed for COPD (P=0.769). There were no differences in total AQLQ and SGRQ scores, exacerbations, use of reliever puffs or adverse effects. CONCLUSIONS: In family practice patients diagnosed with asthma, several treatment goals were better achieved with a lower dose of fluticasone and salmeterol in a combination product than with a higher dose of fluticasone. We found no differences between the two approaches for patients with COPD.

[Tiotropium, a long-acting bronchodilating agent for the treatment of COPD]. / Tiotropium, een lang werkende bronchusverwijder voor de behandeling van COPD.

The goals of COPD management according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline are: prevention of disease progression, relief of symptoms, improvement of exercise tolerance and the quality of life, prevention and treatment of exacerbations and complications, and reduction of mortality and adverse effects. These correspond to the goals formulated in the Dutch 'National transmural agreements on COPD'. Bronchodilators play a key role in the pharmacological treatment and with the availability of tiotropium, a long-acting anticholinergic bronchodilator, it has become important to decide at what moment this is indicated in COPD management. In comparative studies, tiotropium was an effective long-acting bronchodilator that had a favourable effect not only on lung function but also on the other parameters indicated in the GOLD guideline. When maintenance treatment with bronchodilators is needed, one should consider a long-acting bronchodilator. In view of the additive positive effects, tiotropium is the bronchodilator of choice. In case of severe symptoms, a combination of tiotropium with a long-acting beta2-sympathicomimetic agent is recommended.

Exacerbations and associated healthcare cost in patients with COPD in general practice.

BACKGROUND: Acute exacerbations are a characteristic clinical expression of chronic obstructive pulmonary disease (COPD). The objective of this study was to investigate the occurrence rate, management, and healthcare costs of exacerbations in patients with COPD in Dutch general practice. METHODS: Baseline data set from the COPD on Primary Care Treatment (COOPT) trial was used. Details on the occurrence and management of exacerbations were collected by systematic medical record review for the 2-year period preceding trial inclusion. RESULTS: The mean age of the 286 study subjects involved was 59.2 (SD 9.6) years, postbronchodilator FEV1 67.1% (SD 16.2) of predicted. Following ERS criteria, subjects suffered from: no (26%); mild (19%); moderate (40%); or severe (15%) airflow obstruction. The overall mean and median annual exacerbation rates were 0.88 (SD 0.79) and 0.5 (IQR 1.0), respectively. Exacerbation rate was not related to severity of airflow obstruction (p=0.628). Mean annual exacerbation costs per subject were 40 Euro, 53 Euro, 61 Euro and 92 Euro for the respective severity subgroups (p=0.012). The increase of costs in the more severe subgroups was mainly attributable to more physician consultations, diagnostic procedures, and prescription of reliever medication (e.g., bronchodilators, cough preparations). CONCLUSIONS: Occurrence of exacerbations did not depend on the severity of airflow obstruction, whereas the healthcare cost associated with exacerbations increased along with the severity of the disease.

Associations of depressive symptoms with gender, body mass index and dyspnea in primary care COPD patients.

BACKGROUND: It has been suggested that severe COPD is associated with depressive symptoms, possibly linked to exacerbations, dyspnea and hospitalisation. However, scarce data are available in primary care where most patients suffer from mild or moderate disease. OBJECTIVE: We aimed to reveal associations of depressive symptoms with demographic and clinical characteristics in mild to moderate COPD. METHODS: Cross-sectional data on lung function measurements, exacerbation frequency, dyspnea, comorbidity, smoking behaviour, body mass index (BMI), age, gender and depressive symptoms (Beck Depression Inventory) of 147 primary care patients were assessed in multiple logistic regression analyses. RESULTS: Patients suffered from mild to moderate obstruction (FEV1 63.6% pred, range 45.1% to 82.1%). Female gender (OR 4.8, 95% CI 2.1 to 10.8), BMI > 25 (OR 0.4, 95% CI 0.2 to 0.8) and current smoking (OR 2.3, 95% CI 1.01 to 5.3) were univariately associated with depressive symptoms, while in a multivariate logistic model only female gender (OR 4.0, 95% CI 1.6 to 9.9), BMI > 25 (OR 0.3, 95% CI 0.1 to 0.7) and dyspnea (OR 1.8, 95% CI 1.1 to 2.9) were independently associated with depressive symptoms. Conclusion. These data suggest that in primary care depressive symptoms in COPD seem to be related with female gender, BMI and dyspnea. In this study, lung function, exacerbation rate, smoking behaviour, age and comorbidity are not independently associated with depressive symptoms in COPD of mild to moderate severity.

Profiles of measured and perceived bronchodilation. A placebo-controlled cross-over trial comparing formoterol and salmeterol in moderate persistent asthma.

BACKGROUND AND OBJECTIVE: Long-acting beta(2)-agonists have acquired an indispensable position in the management of bronchial symptoms in patients with asthma. The objective of this study was to compare onset-of-action and clinical effectiveness of formoterol and salmeterol during 2 weeks of treatment. We also investigated the association between bronchodilator effects and perceived relieve of dyspnoea. METHODS: A multi-centre randomized double-blind placebo-controlled cross-over trial was performed in 35 subjects with moderate persistent asthma. Treatment periods existed of 2 weeks formoterol (12 microg bid), salmeterol (50 microg bid) and placebo, all administered by pressurized metered dose inhaler. FEV(1) and Visual Analogue Scale (VAS) scores were repeatedly measured until 180 min post-bronchodilation (post-BD), before as well as after each treatment period. Onset-of-action was defined as a >/=15% increase in FEV(1). Subjects kept diaries of morning and evening PEFR values and use of rescue bronchodilator. RESULTS: Formoterol and salmeterol both caused a significant increase in FEV(1) (0.45L [95% CI 0.01, 0.80] and 0.27L [95% CI 0.08, 0.62] respectively). At 3' post-BD, three times as many subjects demonstrated onset-of-action on formoterol compared to salmeterol (36% versus 13%, P = 0.063), at 6' post-BD 42% versus 27% (P = 0.063). VAS scores were similar for formoterol and salmeterol at pre-treatment assessment, but tended to be higher for formoterol after 2weeks treatment. No differences between formoterol and salmeterol were observed for PEFR values or use of rescue medication. 50% of the subjects preferred formoterol, 29% salmeterol (P < 0.001). Significant associations between FEV(1) and VAS ratings existed only at 10', 15' and 30' post-BD, not before or after these time points. CONCLUSION: The earlier described faster onset-of-action of formoterol as compared to a equipotent dosage of salmeterol was confirmed in this study. Perception of decreasing airflow obstruction may be delayed after acute bronchodilation.

Probability and determinants of relapse after discontinuation of inhaled corticosteroids in patients with COPD treated in general practice.

OBJECTIVE: The objective of the study was to assess the probability, and explore determinants of adverse respiratory outcome after discontinuation of inhaled corticosteroid (ICS) treatment in subjects with chronic obstructive pulmonary disease (COPD) diagnosed and treated in general practice. DESIGN: Prospective unblinded ICS withdrawal study. SUBJECTS: 201 ICS treated COPD patients with various degrees of airflow limitation from 45 Dutch general practices. MAIN OUTCOME MEASURES: Probability of and time to exacerbation or unremitting worsening of respiratory symptoms after ICS discontinuation. RESULTS: Mean age was 60.6 (S.D. 9.5) years, post-bronchodilator forced expiratory volume in 1s (FEV1) 65.6 (S.D. 15.7) % predicted. Overall probability of adverse respiratory outcome after ICS discontinuation was 0.37 (95% confidence interval (CI) 0.31, 0.44). Survival analysis showed that age, gender, smoking status and reversibility of airflow limitation were independent predictors of adverse respiratory outcome. For females, the adjusted hazard ratio was 2.14 (95% CI 1.31, 3.50) compared to males. For age, the hazard ratio was 1.05 (95% CI 1.02, 1.08) per year lived. CONCLUSION: Discontinuation of inhaled corticosteroids may harm patients with COPD. The probability of an adverse respiratory outcome may be higher in women, elderly patients, smokers and patients with higher bronchodilator reversibility while on inhaled steroid treatment.

Validity of spirometric testing in a general practice population of patients with chronic obstructive pulmonary disease (COPD).

OBJECTIVE: To investigate the validity of spirometric tests performed in general practice. METHOD: A repeated within subject comparison of spirometric tests with a "gold standard" (spirometric tests performed in a pulmonary function laboratory) was performed in 388 subjects with chronic obstructive pulmonary disease (COPD) from 61 general practices and four laboratories. General practitioners and practice assistants undertook a spirometry training programme. Within subject differences in forced expiratory volume in 1 second and forced vital capacity (DeltaFEV1 and DeltaFVC) between laboratory and general practice tests were measured (practice minus laboratory value). The proportion of tests with FEV1 reproducibility <5% or <200 ml served as a quality marker. RESULTS: Mean DeltaFEV1 was 0.069 l (95% CI 0.054 to 0.084) and DeltaFVC 0.081 l (95% CI 0.053 to 0.109) in the first year evaluation, indicating consistently higher values for general practice measurements. Second year results were similar. Laboratory and general practice FEV1 values differed by up to 0.5 l, FVC values by up to 1.0 l. The proportion of non-reproducible tests was 16% for laboratory tests and 18% for general practice tests (p=0.302) in the first year, and 18% for both in the second year evaluation (p=1.000). CONCLUSIONS: Relevant spirometric indices measured by trained general practice staff were marginally but statistically significantly higher than those measured in pulmonary function laboratories. Because of the limited agreement between laboratory and general practice values, use of these measurements interchangeably should probably be avoided. With sufficient training of practice staff the current practice of performing spirometric tests in the primary care setting seems justifiable.