Prevalence of Asthma Characteristics in COPD Patients in a Dutch Well-Established Asthma/COPD Service for Primary Care.

Purpose: Primary care COPD guidelines indicate that COPD patients with asthma characteristics should be treated as having asthma. This study aims to describe the prevalence of asthma characteristics in patients with a pulmonologist-confirmed working diagnosis of COPD or ACO. Patients and Methods: This retrospective cross-sectional study used real-life data (collected between 2007 and 2017) from a Dutch asthma/COPD-service, a structured web-based system in which pulmonologists support general practitioners in their diagnosis of patients with suspicion of obstructive lung disease. The prevalence of asthma characteristics (history of asthma, atopy, symptoms, and reversibility) and blood eosinophil (Eos) counts were assessed in patients with a working diagnosis of COPD or ACO. Results: Of the 14,141 patients, ≥40 years in the dataset, 4475 (31.6%) were diagnosed with asthma, 3532 (25.0%) with COPD, and 1276 (9.0%) with ACO. Asthma characteristics were present in 65.6% (n=1956) of the COPD and 90.9% (n=1059) of the ACO patients. Eos counts of ≥ 300 cells per µL were found in 35.7% (n=924) of the COPD patients and 35.3% (n=341) of the ACO patients. Conclusion: In this group of COPD and ACO patients remotely diagnosed by pulmonologists, a substantial proportion would be considered to have asthma characteristics according to the guidelines. This may explain the high number of inhaled corticosteroid (ICS) prescriptions found in primary care COPD patients. Prospective studies are necessary to identify patients who may or may not benefit from ICS containing treatment. Hence, personalized care in primary care can be optimized.

Feasibility and effectiveness of an asthma/COPD service for primary care: a cross-sectional baseline description and longitudinal results.

BACKGROUND: In 2007, an Asthma/chronic obstructive pulmonary disease (COPD) (AC) service was implemented in the North of the Netherlands to support General Practitioners (GPs) by providing advice from pulmonologists on a systematic basis. AIMS: To evaluate the feasibility and effectiveness of this service on patient-related outcomes. METHODS: We report baseline data on 11,401 patients and follow-up data from 2,556 patients. GPs can refer all patients with possible obstructive airway disease (OAD) to the service, which is conducted by the local laboratory. Patients are assessed in the laboratory using questionnaires and spirometry. Pulmonologists inspect the data through the internet and send the GP diagnosis and management advice. RESULTS: A total of 11,401 patients were assessed by the service, covering almost 60% of all adult patients with projected asthma or COPD in the area. In all, 46% (n = 5,268) of the patients were diagnosed with asthma, 18% (n = 2,019) with COPD and 7% (n = 788) with the overlap syndrome. A total of 740 (7%) patients were followed up after 3 months because the GP advised them to change medication. In this group, the proportion of unstable COPD patients (Clinical COPD Questionnaire (CCQ) ⩾ 1) decreased from 63% (n = 92) at baseline to 49% (n = 72). The proportion of patients with uncontrolled asthma (Asthma Control Questionnaire (ACQ) ⩾ 1.5) decreased from 41% (n = 204) to 23% (n = 115). In all, 938 (8%) patients were followed up after 12 months. From these patients, the proportion of unstable COPD patients (CCQ ⩾ 1) decreased from 47% (n = 115) to 44% (n = 107). The proportion of patients with uncontrolled asthma (ACQ⩾1.5) decreased from 16% (n = 95) to 14% (n = 85). CONCLUSION: The AC service assessed a considerable proportion of patients with OAD in the area, improved patients' outcomes, and is considered to be feasible and effective.

The minimal clinically important difference of the Control of Allergic Rhinitis and Asthma Test (CARAT): cross-cultural validation and relation with pollen counts.

BACKGROUND: The Control of Allergic Rhinitis and Asthma Test (CARAT) monitors control of asthma and allergic rhinitis. AIMS: To determine the CARAT's minimal clinically important difference (MCID) and to evaluate the psychometric properties of the Dutch CARAT. METHODS: CARAT was applied in three measurements at 1-month intervals. Patients diagnosed with asthma and/or rhinitis were approached. MCID was evaluated using Global Rating of Change (GRC) and standard error of measurement (s.e.m.). Cronbach's alpha was used to evaluate internal consistency. Spearman's correlation coefficients were calculated between CARAT, the Asthma Control Questionnaire (ACQ5) and the Visual Analog Scale (VAS) on airway symptoms to determine construct and longitudinal validity. Test-retest reliability was evaluated with intra-class correlation coefficient (ICC). Changes in pollen counts were compared with delta CARAT and ACQ5 scores. RESULTS: A total of 92 patients were included. The MCID of the CARAT was 3.50 based on GRC scores; the s.e.m. was 2.83. Cronbach's alpha was 0.82. Correlation coefficients between CARAT and ACQ5 and VAS questions ranged from 0.64 to 0.76 (P < 0.01). Longitudinally, correlation coefficients between delta CARAT scores and delta ACQ5 and VAS scores ranged from 0.41 to 0.67 (P < 0.01). Test-retest reliability showed an ICC of 0.81 (P < 0.01) and 0.80 (P < 0.01). Correlations with pollen counts were higher for CARAT than for ACQ5. CONCLUSIONS: This is the first investigation of the MCID of the CARAT. The CARAT uses a whole-point scale, which suggests that the MCID is 4 points. The CARAT is a valid and reliable tool that is also applicable in the Dutch population.

Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis.

Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background ("Dutch hypothesis"). We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses. Three loci showed potential involvement in both diseases: chr2p24.3, chr5q23.1 and chr13q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) κß pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p=9.96×10(-9)). The second replication phase, in seven independent cohorts, provided no significant replication. Expression quantitative trait loci (eQTL) analysis in blood cells and lung tissue on the top 20 associated SNPs identified two SNPs in COMMD10 that influenced gene expression. Inflammatory processes differ in asthma and COPD and are mediated by NF-κß, which could be driven by the same underlying genes, COMMD10 and DDX1. None of the SNPs reached genome-wide significance. Our eQTL studies support a functional role for two COMMD10 SNPs, since they influence gene expression in both blood cells and lung tissue. Our findings suggest that there is either no common genetic component in asthma and COPD or, alternatively, different environmental factors, e.g. lifestyle and occupation in different countries and continents, which may have obscured the genetic common contribution.

Budesonide/formoterol maintenance and reliever therapy in primary care asthma management: effects on bronchial hyperresponsiveness and asthma control.

BACKGROUND: The management of asthma has changed since the introduction of budesonide/formoterol (Symbicort®) as both maintenance and reliever therapy (SMART). SMART and its effects on bronchial hyperresponsiveness (BHR) have not been studied in primary care. AIMS: To compare the effects of SMART and guideline-driven usual care (UC) on BHR and clinical asthma severity in primary care practice. METHODS: Patients with mild-to-moderate stable asthma were randomised to receive SMART treatment (n=54) (budesonide/formoterol 80/4.5 µg Turbuhaler®, two puffs once daily and extra inhalations as needed) or UC treatment (n=48) for 12 months. Diary data, Asthma Control Questionnaire scores, forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) measurements were collected during run-in and after 1, 3, 6, and 12 months of treatment. BHR, measured as the dose of histamine provoking a fall in FEV1 of 20% (PD20-histamine), was determined at randomisation and after 12 months. RESULTS: One hundred and two patients with asthma participated in the study. The change in PD20-histamine during the study was not significantly different between the SMART and UC groups (p=0.26). The mean inhaled corticosteroid (ICS) dose was 326 µg beclomethasone dipropionate (BDP) equivalents/day (95% CI 254 to 399) with SMART, which was significantly lower (p<0.0001) than the mean ICS dose with UC treatment (798 µg BDP equivalents/day (95% CI 721 to 875). Morning and evening PEF values increased significantly with SMART treatment compared with UC; FEV1, symptoms and asthma control did not differ. CONCLUSIONS: Despite a 59% lower dose of ICS, BHR and other clinical outcomes remained stable during SMART treatment while PEF values improved.

An economic evaluation of budesonide/formoterol for maintenance and reliever treatment in asthma in general practice.

INTRODUCTION: In budesonide/formoterol (Symbicort(R) Turbuhaler(R), AstraZeneca, Lund, Sweden) maintenance and reliever therapy (SMART), patients with asthma take a daily maintenance dose of budesonide/formoterol, with the option of taking additional doses for symptom relief instead of a short-acting beta(2)-agonist (SABA). This study assesses the cost-effectiveness of SMART compared with usual care in patients with mild-to-moderate persistent asthma treated by general practitioners in the Netherlands from a societal perspective. METHODS: The study was linked to a randomized, active-controlled, open-label, multicenter, 12-month clinical trial, with a prospective collection of resource use. One hundred and two patients > or =18 years with mild-to-moderate persistent asthma and daily inhaled corticosteroids (ICS) prior to the trial were included. SMART was given as two inhalations of budesonide/formoterol (100/6 microg) once daily, plus additional doses as needed. The control group was treated according to guidelines, which prescribe medium daily doses of ICS plus an SABA if needed. A long-acting beta(2)-agonist (LABA) is added if necessary. Effectiveness was measured as the proportion of asthma-control days, Asthma Control Questionnaire (ACQ) scores, the net proportion of patients with relevant ACQ improvement, and the proportion of well-controlled patients. Costs included asthma medication, physician contacts, and absence from work. RESULTS: Mean total costs for SMART were 134.81 lower (95% CI: -439.48; 44.85). Production losses were 94.10 (95% CI: -300.60; 0.29) lower for SMART (10.77 vs. 104.87). No significant differences in health outcomes were seen, with 3.81 fewer asthma-control days per patient-year for SMART (95% CI: -36.8; 30.8), a 0.049 better ACQ score (95% CI: -0.21; 0.29), a 5.8% larger net proportion of improved patients (95% CI: t15.6%; 27.3%), and a 2.1% (95% CI: -25.5; 20.8%) smaller increase in the proportion of well-controlled patients. CONCLUSIONS: Treating primary care patients with mild-to-moderate persistent asthma with SMART instead of ICS plus bronchodilators does not affect health outcomes and does not increase costs; therefore, is likely to be an alternative for guideline-directed treatment, from a health and economic perspective.

Cognitive performance in patients with COPD.

BACKGROUND: Hypoxemic patients with Chronic Obstructive Pulmonary Disease (COPD) have impaired cognitive performance. These neuropsychological impairments are related to the degree of hypoxemia. So far, cognitive performance has not been tested in non-hypoxemic patients with COPD. METHODS: We recruited patients with stable COPD and PaO2 > 8.0 kPa (60 mmHg), as well as healthy subjects, who were matched for age, intelligence quotient (IQ), and level of education. Cognitive performance was studied by Stroop Colour Word Test, Trailmaking, digit-symbol of the Wechsler Adult Intelligence Scale, addition subtest of the Groningen Intelligence Test, and Story Recall. RESULTS: Thirty patients with COPD (FEV1 49.8% pred, mean age 64.8 yr) and 20 healthy volunteers (65.6 yr) were enrolled. COPD patients performed significantly worse on trailmaking B, the digit-symbol test, and on the addition subtest. There was no significant correlation between the tests of cognitive performance and disease specific health status (Chronic Respiratory Questionnaire). CONCLUSIONS: We conclude that even non-hypoxemic patients with COPD show significant impairments in cognitive performance. These impairments are not associated with deteriorations in health related quality of life. Prospective evaluation of the impact of treatment on cognitive performance in non-hypoxemic patients with COPD would be a logical subsequent study.