Long-Term Cost-Effectiveness of Digital Inhaler Adherence Technologies in Difficult-to-Treat Asthma.

BACKGROUND: Digital inhalers can monitor inhaler usage, support difficult-to-treat asthma management, and inform step-up treatment decisions yet their economic value is unknown, hampering wide-scale implementation. OBJECTIVE: We aimed to assess the long-term cost-effectiveness of digital inhaler-based medication adherence management in difficult-to-treat asthma. METHODS: A model-based cost-utility analysis was performed. The Markov model structure was determined by biological and clinical understanding of asthma and was further informed by guideline-based assessment of model development. Internal and external validation was performed using the Assessment of the Validation Status of Health-Economic (AdViSHE) tool. The INCA (Inhaler Compliance Assessment) Sun randomized clinical trial data were incorporated into the model to evaluate the cost-effectiveness of digital inhalers. Several long-term clinical case scenarios were assessed (reduced number of exacerbations, increased asthma control, introduction of biosimilars [25% price-cut on biologics]). RESULTS: The long-term modelled cost-effectiveness based on a societal perspective indicated 1-year per-patient costs for digital inhalers and usual care (ie, regular inhalers) of €7,546 ($7,946) and €10,752 ($11,322), respectively, reflecting cost savings of €3,207 ($3,377) for digital inhalers. Using a 10-year intervention duration and time horizon resulted in cost savings of €26,309 ($27,703) for digital inhalers. In the first year, add-on biologic therapies accounted for 69% of the total costs in the usual care group and for 49% in the digital inhaler group. Scenario analyses indicated consistent cost savings ranging from €2,287 ($2,408) (introduction biosimilars) to €4,581 ($4,824) (increased control, decreased exacerbations). CONCLUSIONS: In patients with difficult-to-treat asthma, digital inhaler-based interventions can be cost-saving in the long-term by optimizing medication adherence and inhaler technique and reducing add-on biologic prescriptions.

Personalised exhaled nitric oxygen fraction (F ENO)-driven asthma management in primary care: a F ENO subgroup analysis of the ACCURATE trial.

BACKGROUND: The aim of this study was to identify patients who benefit most from exhaled nitric oxide fraction (F ENO)-driven asthma management in primary care, based on prespecified subgroups with different levels of F ENO. METHODS: We used data from 179 adults with asthma from a 12-month primary care randomised controlled trial with 3-monthly assessments of F ENO, asthma control, medication usage, costs of medication, severe asthma exacerbations and quality of life. In the original study, patients were randomised to either a symptom-driven treatment strategy (controlled asthma (Ca) strategy) or a F ENO+symptom-driven strategy (FCa). In both groups, patients were categorised by their baseline level of F ENO as low (<25 ppb), intermediate (25-50 ppb) and high (>50 ppb). At 12 months, we compared, for each prespecified F ENO subgroup, asthma control, asthma-related quality of life, medication usage, and costs of medication between the Ca and FCa strategy. RESULTS: We found a difference between the Ca and FCa strategy for the mean dosage of beclomethasone strategy of 223 µg (95% CI 6-439), p=0.04) and for the total costs of asthma medication a mean reduction of US$159 (95% CI US$33-285), p=0.03) in patients with a low baseline F ENO level. No differences were found for asthma control, severe asthma exacerbations and asthma-related quality of life in patients with a low baseline F ENO level. Furthermore, in patients with intermediate or high level of F ENO, no differences were found. CONCLUSIONS: In primary care, F ENO-driven asthma management is effective in patients with a low F ENO level, for whom it is possible to down-titrate medication, while preserving asthma control and quality of life.

Use of Opioids Increases With Age in Older Adults: An Observational Study (2005-2017).

AIM: Pain is increasingly treated with opioids. Potential harms of opioid therapy disproportionally affect older patients. This study aims to provide information on trends, nature and duration of opioid prescribing to older adults, in primary care and to explore differences between older patients from different ages. METHODS: Primary care data (2005-2017) were derived from routine electronic medical records of patients in Nivel Primary Care Database. All opioid prescriptions with Anatomical Therapeutic Chemical Classification (ATC) code N02A were selected (except for codeine). Diagnoses were recorded using the International Classification of Primary Care (ICPC). Patients were categorized in three age groups (65-74, 75-84, and ≥85 years). Descriptive analyses were used to describe the trend of opioid prescriptions for specific opioids, the duration of use and underlying diagnoses. RESULTS: 283,600 patients were included of which 32,287 had at least one opioid prescription in 2017. An increase in the number of older adults who received at least one opioid was seen between 2005 and 2017. The oldest patients were more likely to be prescribed an opioid, especially when it comes to strong opioids, the increase in the volume of prescribing was highest in this group. Moreover, over 40% of the oldest patients used strong opioids chronically. Strong opioids were mostly prescribed for musculoskeletal diagnoses. Cancer was the second most common diagnosis for strong opioids in the younger subgroups, whereas less specified diagnoses were as second in the oldest subgroup. CONCLUSION: Opioid prescription changes with increasing age in frequency, nature, and duration, despite higher harm risks among older patients. Because of the high prevalence of chronic use, it is important to monitor the patient throughout the treatment and to critically evaluate the initiation and continuation of opioid prescriptions.

Development and Validation of Personalized Prediction to Estimate Future Risk of Severe Exacerbations and Uncontrolled Asthma in Patients with Asthma, Using Clinical Parameters and Early Treatment Response.

BACKGROUND: Current level of asthma control can be easily assessed by validated instruments, but it is currently difficult to assess individuals' level of future risk. OBJECTIVE: Develop, and validate, a risk prediction score for level of future risk, including patient characteristics and information on early treatment response. METHODS: We used data of 304 adult patients with asthma from a 12-month primary care randomized controlled trial with 3-monthly assessments. With logistic regression we modeled the association between the level of future risk and patient characteristics including early treatment response. Future risk was defined as Asthma Control Questionnaire (ACQ) score of 1.5 or more at 12 months or the experience of at least 1 exacerbation during the final 6 months. We developed a risk prediction score on the basis of regression coefficients. RESULTS: Performance of the risk prediction score improved, taking into account data on early treatment response (area under receiver-operating curve [AUROC] = 0.84) compared with a model containing only baseline characteristics (AUROC = 0.78). The score includes 6 easy-to-obtain predictors: sex, ACQ score and exacerbations in the previous year at baseline and at first follow-up, and smoking status and exacerbations in the previous 3 months (indicating early treatment response). External validation yielded an AUROC of 0.77. The risk prediction score classified patients into 3 risk groups: low (absolute risk, 11.7%), intermediate (47.0%), and high (72.7%). CONCLUSIONS: We developed and externally validated a risk prediction score, quantifying both level of current asthma control and the guideline-defined future risk. Patients' individual risk can now be estimated in an easy way, as proposed but not specified, by asthma management guidelines.

Exacerbations in Adults with Asthma: A Systematic Review and External Validation of Prediction Models.

BACKGROUND: Several prediction models assessing future risk of exacerbations in adult patients with asthma have been published. Applicability of these models is uncertain because their predictive performance has often not been assessed beyond the population in which they were derived. OBJECTIVE: This study aimed to identify and critically appraise prediction models for asthma exacerbations and validate them in 2 clinically distinct populations. METHODS: PubMed and EMBASE were searched to April 2017 for reports describing adult asthma populations in which multivariable models were constructed to predict exacerbations during any time frame. After critical appraisal, the models' predictive performances were assessed in a primary and a secondary care population for author-defined exacerbations and for American Thoracic Society/European Respiratory Society-defined severe exacerbations. RESULTS: We found 12 reports from which 24 prediction models were evaluated. Three predictors (previous health care utilization, symptoms, and spirometry values) were retained in most models. Assessment was hampered by suboptimal methodology and reporting, and by differences in exacerbation outcomes. Discrimination (area under the receiver-operating characteristic curve [c-statistic]) of models for author-defined exacerbations was better in the primary care population (mean, 0.71) than in the secondary care population (mean, 0.60) and similar (0.65 and 0.62, respectively) for American Thoracic Society/European Respiratory Society-defined severe exacerbations. Model calibration was generally poor, but consistent between the 2 populations. CONCLUSIONS: The preservation of 3 predictors in models derived from variable populations and the fairly consistent predictive properties of most models in 2 distinct validation populations suggest the feasibility of a generalizable model predicting severe exacerbations. Nevertheless, improvement of the models is warranted because predictive performances are below the desired level.

Longitudinal outcomes of different asthma phenotypes in primary care, an observational study.

While asthma presentation is heterogeneous, current asthma management guidelines in primary care are quite homogeneous. In this study we aim to cluster patients together into different phenotypes, that may aid the general practitioner in individualised asthma management. We analysed data from the ACCURATE trial, containing 611 adult asthmatics, 18-50 year-old, treated in primary care, with one year follow-up. Variables obtained at baseline (n = 14), were assessed by cluster analysis. Subsequently, established phenotypes were assessed separately on important asthma outcomes after one year follow-up: asthma control (Asthma Control Questionnaire (ACQ)), quality of life (Asthma Quality of Life Questionnaire (AQLQ)), exacerbation-rate and medication-usage. Five distinct phenotypes were identified. The first phenotype was predominantly defined by their early onset atopic form of asthma. The second phenotype mainly consisted of female patients with a late onset asthma. The third phenotype were patients with high reversibility rates after bronchodilator usage. The fourth phenotype were smokers and the final phenotype were frequent exacerbators. The exacerbators phenotype had the worst outcomes for asthma control and quality of life and experienced the highest exacerbation-rate, despite using the most medication. The early onset phenotype patients were relatively well controlled and their medication dosage was low. ASTHMA: INDIVIDUALIZING TREATMENT BY PHENOTYPE: Asthma patients should be characterised according to their individual asthma type to ensure more targeted treatment. Even though asthma manifests itself in a wide variety of forms with differing degrees of severity, treatment of the disease often takes a broad, one-size-fits-all approach. To determine if asthma can indeed be split into distinct phenotypes, Rishi Khusial at the Leiden University Medical Center and co-workers across the Netherlands analysed data from 611 adult asthmatics treated in primary care, and followed them up after one year. The team identified five phenotypes in the primary care cohort, including one group with early onset asthma, another whose asthma responded well to bronchodilators, and a group classed as frequent exacerbators. Further analysis of long-term asthma outcomes showed clear differences between phenotypes, particularly in terms of asthma control and quality of life.

Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model.

BACKGROUND: Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management. METHODS: We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+FeNO. Final models were corrected for overoptimism by shrinking the regression coefficients; predictive performance was assessed by the area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test. Models were externally validated in a data set including patients with severe asthma (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes). RESULTS: 80/611 (13.1%) participants experienced ≥1 severe exacerbation. Five predictors (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous hospital admission for asthma and ≥1 severe exacerbation in the previous year) were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer-Lemeshow p value 0.35). Adding spirometry and FeNO subsequently improved discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78 to 0.81), respectively). External validation yielded AUROCs of 0.69 (95% CI 0.63 to 0.75; 0.63 to 0.75 and 0.63 to 0.75) for the three models, respectively; calibration was best for the spirometry ­model. CONCLUSIONS: A simple history-based model extended with spirometry identifies patients who are prone to asthma exacerbations. The additional value of FeNO is modest. These models merit an implementation study in clinical practice to assess their utility. TRIAL REGISTRATION NUMBER: NTR 1756.

Symptom- and fraction of exhaled nitric oxide-driven strategies for asthma control: A cluster-randomized trial in primary care.

BACKGROUND: Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (Feno), allow further tailoring of treatment. OBJECTIVE: We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or Feno-driven controlled asthma (FCa). METHODS: In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score <1.50); (2) aiming at Ca (ACQ score <0.75); and (3) aiming at FCa (ACQ score <0.75 and Feno value <25 ppb). During 12 months' follow-up, treatment was adjusted every 3 months by using an online decision support tool. Outcomes were incremental cost per quality-adjusted life year gained, asthma control (ACQ score), quality of life (Asthma Quality of Life Questionnaire score), asthma medication use, and severe exacerbation rate. RESULTS: Six hundred eleven participants were allocated to the PCa (n = 219), Ca (n = 203), or FCa (n = 189) strategies. The FCa strategy improved asthma control compared with the PCa strategy (P < .02). There were no differences in quality of life (P ≥ .36). Asthma medication use was significantly lower for the PCa and FCa strategies compared with the Ca strategy (medication costs: PCa, $452; Ca, $551; and FCa, $456; P ≤ .04). The FCa strategy had the highest probability of cost-effectiveness at a willingness to pay of $50,000/quality-adjusted life year (86%; PCa, 2%; Ca, 12%). There were no differences in severe exacerbation rate. CONCLUSION: A symptom- plus Feno-driven strategy reduces asthma medication use while sustaining asthma control and quality of life and is the preferred strategy for adult asthmatic patients in primary care.

Comparison between an online self-administered and an interviewer-administered version of the Asthma Control Questionnaire: a cross-sectional validation study.

BACKGROUND: Online self-management programmes for asthma have recently become available. International guidelines suggest that the Asthma Control Questionnaire (ACQ) can be used in these programmes. In order to assess the current level of control and guide therapy, the same cut-off values are being used as in conventional asthma management. However, results might differ between different types of administration of the ACQ. AIMS: To assess the agreement between an online self-administered version of the ACQ and an interviewer-administered version at a routine visit. METHODS: Cross-sectional data from primary care asthma patients in the Asthma Control Cost Utility Randomized Trial Evaluation (ACCURATE) trial aged 18-50 years and prescribed inhaled steroids were analysed. We selected patients who self-administered an ACQ online and subsequently had an ACQ completed by a nurse practitioner within 7 days at a trial-related control visit. ACQ scores were calculated and agreement assessed by paired t-tests, Pearson's correlation coefficient and a Bland-Altman plot. RESULTS: A total of 351 patients were eligible (68% female, mean age 40 years). The time interval between the two versions was 3.2 days. There was a significant difference of 0.14 (95% CI 0.09 to 0.20; p<0.001) between the results of the online self-administered ACQ (mean 1.04±0.04) and the interviewer-administered ACQ results (0.90±0.04). The Pearson correlation coefficient was 0.79. The limits of agreement (-0.86, 1.14) exceeded the predefined minimal clinically important difference between results (±0.5). The Bland-Altman plot therefore showed insufficient agreement. CONCLUSIONS: Assessment of asthma control by the ACQ is influenced by the type of administration. Our results suggest that better control of asthma is perceived when interacting with a caregiver than by online self-assessment.

The acute effect of cigarette smoking on the high-sensitivity CRP and fibrinogen biomarkers in chronic obstructive pulmonary disease patients.

AIM: The evidence on the acute effects of smoking on biomarkers is limited. Our aim was to study the acute effect of smoking on disease-related biomarkers. METHODS: The acute effect of smoking on serum high sensitivity CRP (hs-CRP) and plasma fibrinogen and its association with disease severity was studied by challenging 31 chronic obstructive pulmonary disease patients with cigarette smoking and repeatedly measuring these biomarkers before and after smoking. RESULTS: Fibrinogen and hs-CRP increased directly after smoking by 9.4 mg/dl (95% CI: 4.2-14.5) and 0.13 mg/l (95% CI: 0.03-0.23), respectively. Fibrinogen levels remained elevated after 35 min, whereas hs-CRP normalized. Pearson's correlation coefficient between the hs-CRP change and chronic obstructive pulmonary disease severity was 0.25 (p = 0.06). CONCLUSION: Fibrinogen and hs-CRP increased directly after smoking in the chronic obstructive pulmonary disease patients. Their association with disease risk and/or progression remains to be demonstrated.

An autonomous mobile system for the management of COPD.

INTRODUCTION: Managing chronic disease through automated systems has the potential to both benefit the patient and reduce health-care costs. We have developed and evaluated a disease management system for patients with chronic obstructive pulmonary disease (COPD). Its aim is to predict and detect exacerbations and, through this, help patients self-manage their disease to prevent hospitalisation. MATERIALS: The carefully crafted intelligent system consists of a mobile device that is able to collect case-specific, subjective and objective, physiological data, and to alert the patient by a patient-specific interpretation of the data by means of probabilistic reasoning. Collected data are also sent to a central server for inspection by health-care professionals. METHODS: We evaluated the probabilistic model using cross-validation and ROC analyses on data from an earlier study and by an independent data set. Furthermore a pilot with actual COPD patients has been conducted to test technical feasibility and to obtain user feedback. RESULTS: Model evaluation results show that we can reliably detect exacerbations. Pilot study results suggest that an intervention based on this system could be successful.

Short-acting anticholinergic bronchodilation does not increase cardiovascular events in smokers with mild to moderate pulmonary obstruction.

BACKGROUND AND OBJECTIVE: We hypothesized that bronchodilation in patients with chronic obstructive pulmonary disease (COPD) increases the smoke-related risk to develop cardiovascular disease, and aimed to study the effect of short-acting anticholinergic bronchodilation and smoking on cardiovascular events. METHODS: We performed a secondary analysis on data from the Lung Health Study, a large randomized clinical trial of smokers with mild to moderate pulmonary obstruction, 35-60 years old, without cardiovascular comorbidity. We used Cox proportional survival analysis, controlling for several confounders, to study the effect on 5-year risk of fatal and/or non-fatal cardiovascular events. Secondary outcome encompassed fatal and non-fatal coronary events. RESULTS: Of 2745 participants, 23 (0.8%) died of cardiovascular disease. One hundred and sixty-two participants were hospitalized for a cardiovascular event, and 94 participants due to a coronary event. Survival analysis revealed no effect between smoking and short-acting anticholinergic bronchodilation on fatal and/or non-fatal cardiovascular events, hazard ratio = 1.12 (0.58-2.19), nor on coronary events, hazard ratio = 1.46 (0.60-3.56). CONCLUSIONS: Our study results show that short-acting anticholinergic bronchodilation had no detrimental effect on cardiovascular disease in smokers with mild to moderate pulmonary obstruction.

Cigarette smoke retention and bronchodilation in patients with COPD. A controlled randomized trial.

INTRODUCTION: Bronchodilators are the cornerstone for symptomatic treatment of chronic obstructive pulmonary disease (COPD). Many patients use these agents while persisting in their habit of cigarette smoking. We hypothesized that bronchodilators increase pulmonary retention of cigarette smoke and hence the risk of smoking-related (cardiovascular) disease. Our aim was to investigate if bronchodilation causes increased pulmonary retention of cigarette smoke in patients with COPD. METHODS: A double-blinded, placebo-controlled, randomized crossover trial, in which COPD patients smoked cigarettes during undilated conditions at one session and maximal bronchodilated conditions at the other session. Co-primary outcomes were pulmonary tar and nicotine retention. We performed a secondary analysis that excludes errors due to possible contamination. Secondary outcomes included the biomarkers C-reactive protein and fibrinogen, and smoke inhalation patterns. RESULTS: Of 39 randomized patients, 35 patients completed the experiment and were included in the final analysis. Bronchodilation did not significantly increase tar retention (-4.5%, p = 0.20) or nicotine retention (-2.6%, p = 0.11). Secondary analysis revealed a potential reduction of retention due to bronchodilation: tar retention (-3.8%, p = 0.13), and nicotine retention (-3.4%, p = 0.01). Bronchodilation did not modify our secondary outcomes. CONCLUSIONS: Our results do not support the hypothesis that cigarette tar and nicotine retention in COPD patients is increased by bronchodilation, whereas we observed a possibility towards less retention. TRIAL REGISTRATION: www.clinicaltrials.gov: NCT00981851.

Comprehensive self management and routine monitoring in chronic obstructive pulmonary disease patients in general practice: randomised controlled trial.

OBJECTIVE: To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients' management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice. DESIGN: 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial. SETTING: 15 general practices in the eastern part of the Netherlands. PARTICIPANTS: Patients with COPD confirmed by spirometry and treated in general practice. Patients with very severe COPD or treated by a respiratory physician were excluded. INTERVENTIONS: A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients' own initiative). OUTCOME MEASURES: The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score. Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients' management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale. RESULTS: 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55). At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant. Secondary outcomes did not differ, except for exacerbation management. Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58). CONCLUSIONS: Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice. Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group. TRIAL REGISTRATION: Clinical trials NCT00128765.

How do dyspnoea scales compare with measurement of functional capacity in patients with COPD and at risk of COPD?

BACKGROUND: In primary care, formal functional capacity testing is not always feasible. Guidelines for family practitioners suggest the use of dyspnoea scales to assess exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). AIMS: To examine whether the use of activity-based dyspnoea scales can substitute for actual functional capacity testing. METHODS: 128 subjects (49% at risk of COPD, 24% GOLD stage I, 17% GOLD stage II, 9% GOLD stage III) performed an Incremental Shuttle Walk Test (ISWT) and completed the Medical Research Council dyspnoea scale (MRC), Baseline Dyspnoea Index (BDI), Oxygen Cost Diagram (OCD), Clinical COPD Questionnaire (CCQ), and St George's Respiratory Questionnaire (SGRQ). RESULTS: Analysis of variance showed that the relationship between the ISWT and the MRC dyspnoea scale was statistically significant but moderate (p < 0.001, R2 = 0.166). Correlations between the ISWT and the other dyspnoea scales were also moderate (correlation coefficients 0.34-0.42). Combining the dyspnoea scales in one analysis resulted in a proportion of explained variance of the ISWT of 21.4% (R2 = 0.214). CONCLUSIONS: Dyspnoea scales cannot substitute for formal functional capacity testing. Authors of COPD guidelines should consider stating more specifically that the MRC and similar scales measure (self-reported) activity-related dyspnoea but cannot replace objectively measured functional capacity.

Accuracy and precision of desktop spirometers in general practices.

BACKGROUND: Spirometry has become an essential tool for general practices to diagnose and monitor chronic airways diseases, but very little is known about the performance of the spirometry equipment that is being used in general practice settings. The use of invalid spirometry equipment may have consequences on disease diagnosis and management of patients. OBJECTIVES: To establish the accuracy and precision of desktop spirometers that are routinely used in general practices. METHODS: We evaluated a random sample of 50 spirometers from Dutch general practices by testing them on a certified waveform generator using 8 standard American Thoracic Society waveforms to determine accuracy and precision. Details about the brand and type of spirometers, year of purchase, frequency of use, cleaning and calibration were inquired with a study-specific questionnaire. RESULTS: 39 devices (80%) were turbine spirometers, 8 (16%) were pneumotachographs, and 1 (2%) was a volume displacement spirometer. Mean age of the spirometers was 4.3 (SD 3.7) years. Average deviation from the waveform generator reference values (accuracy) was 25 ml (95% confidence interval 12-39 ml) for FEV(1) and 27 ml (10-45 ml) for FVC, but some devices showed substantial deviations. FEV(1) deviations were larger for pneumotachographs than for turbine spirometers (p < 0.0031), but FVC deviations did not differ between the two types of spirometers. In the subset of turbine spirometers, no association between age and device performance was observed. CONCLUSIONS: On average, desktop spirometers in general practices slightly overestimated FEV(1) and FVC values, but some devices showed substantial deviations. General practices should pay more attention to the calibration of their spirometer.

Bronchodilation and smoking interaction in COPD: a cohort pilot study to assess cardiovascular risk.

BACKGROUND: Smoking and bronchodilator treatment are both extensively studied as key elements in patients with chronic obstructive pulmonary disease. However, little is known about whether or not these elements interact in terms of developing cardiovascular diseases in patients with COPD. OBJECTIVES: To explore to what extent the risk of developing ischemic cardiovascular disease in COPD patients is mediated by smoking status, use of bronchodilators and--specifically--their interaction. METHODS: We performed an observational pilot study on a relatively healthy Dutch COPD cohort from a primary care diagnostic center database with full information on spirometry tests, smoking status, bronchodilator use and other prescribed medication. We defined first ischemic cardiovascular events as primary outcome, measured by first prescription of antiplatelet drugs and/or nitrates. Unadjusted analyses by Kaplan-Meier were followed by adjusted Cox' proportional hazards. RESULTS: 845 COPD patients, totaling 2,169 observation years, were included in the analyses. We observed an increased risk for nonfatal ischemic cardiovascular events by smoking (adjusted HR=3.58, p=0.001) and a protective effect of bronchodilators (adjusted HR=0.43, p=0.01). Although the protective effect of bronchodilators appears to be substantially minimized in patients that persist in smoking, we could not statistically confirm a hazardous interaction between bronchodilators and smoking (HR 2.50, p=0.21). CONCLUSION: Our study reveals bronchodilators may protect from ischemic cardiovascular events in a relatively 'healthy' COPD population. We did not confirm a hazardous interaction between bronchodilators and smoking, although we observed current smokers benefit substantially less from the protective effect of bronchodilators.

Validity of an automated telephonic system to assess COPD exacerbation rates.

Current tools for recording chronic obstructive pulmonary disease (COPD) exacerbations are limited and often lack validity testing. We assessed the validity of an automated telephonic exacerbation assessment system (TEXAS) and compared its outcomes with existing tools. Over 12 months, 86 COPD patients (22.1% females; mean age 66.5 yrs; mean post-bronchodilator forced expiratory volume in 1 s 53.4% predicted) were called once every 2 weeks by TEXAS to record changes in respiratory symptoms, unscheduled healthcare utilisation and use of respiratory medication. The responses to TEXAS were validated against exacerbation-related information collected by observations made by trained research assistants during home visits. No care assistance was provided in any way. Diagnostic test characteristics were estimated using commonly used definitions of exacerbation. Detection rates, compliance and patient preference were assessed, and compared with paper diary cards and medical record review. A total of 1,824 successful calls were recorded, of which 292 were verified by home visits (median four calls per patient, interquartile range three to five calls per patient). Independent of the exacerbation definition used, validity was high, with sensitivities and specificities between 66% and 98%. Detection rates and compliance differed extensively between the different tools, but were highest with TEXAS. Patient preference did not differ. TEXAS is a valid tool to assess COPD exacerbation rates in prospective clinical studies. Using different tools to record exacerbations strongly affects exacerbation occurrence rates.

Structuring and validating a cost-effectiveness model of primary asthma prevention amongst children.

BACKGROUND: Given the rising number of asthma cases and the increasing costs of health care, prevention may be the best cure. Decisions regarding the implementation of prevention programmes in general and choosing between unifaceted and multifaceted strategies in particular are urgently needed. Existing trials on the primary prevention of asthma are, however, insufficient on their own to inform the decision of stakeholders regarding the cost-effectiveness of such prevention strategies. Decision analytic modelling synthesises available data for the cost-effectiveness evaluation of strategies in an explicit manner. Published reports on model development should provide the detail and transparency required to increase the acceptability of cost-effectiveness modelling. But, detail on the explicit steps and the involvement of experts in structuring a model is often unevenly reported. In this paper, we describe a procedure to structure and validate a model for the primary prevention of asthma in children. METHODS: An expert panel was convened for round-table discussions to frame the cost-effectiveness research question and to select and structure a model. The model's structural validity, which indicates how well a model reflects the reality, was determined through descriptive and parallel validation. Descriptive validation was performed with the experts. Parallel validation qualitatively compared similarity between other published models with different decision problems. RESULTS: The multidisciplinary input of experts helped to develop a decision-tree structure which compares the current situation with screening and prevention. The prevention was further divided between multifaceted and unifaceted approaches to analyse the differences. The clinical outcome was diagnosis of asthma. No similar model was found in the literature discussing the same decision problem. Structural validity in terms of descriptive validity was achieved with the experts and was supported by parallel validation. CONCLUSIONS: A decision-tree model developed with experts in round-table discussions benefits from a systematic and transparent approach and the multidisciplinary contributions of the experts. Parallel validation provides a feasible alternative to validating novel models. The process of structuring and validating a model presented in this paper could be a useful guide to increase transparency, credibility, and acceptability of (future, novel) models when experts are involved.