Improved prediction of COPD in at-risk patients using lung function pre-screening in primary care: a real-life study and cost-effectiveness analysis.

BACKGROUND: The importance of identifying chronic obstructive pulmonary disease (COPD) at an early stage is recognised. Improved and easily accessible identification of individuals at risk of COPD in primary care is needed to select patients for spirometry more accurately. AIMS: To explore whether use of a mini-spirometer can predict a diagnosis of COPD in patients at risk of COPD in primary care, and to assess its cost-effectiveness in detecting patients with COPD. METHODS: Primary care patients aged 45-85 years with a smoking history of >15 pack-years were selected. Data were collected on the Clinical COPD Questionnaire (CCQ), Medical Research Council (MRC) dyspnoea scale and smoking habits. Lung function (forced expiratory volume in 1 and 6 s; FEV1 and FEV6, respectively) was measured by mini-spirometer (copd-6), followed by diagnostic standard spirometry (COPD diagnosis post-bronchodilation ratio of FEV1 to forced vital capacity (FVC) <0.7). Time consumed was recorded. Univariate logistic regression and receiver operating characteristic (ROC) curves were used. RESULTS: A total of 305 patients (57% females) of mean (SD) age 61.2 (8.4) years, mean (SD) total CCQ 1.0 (0.8) and mean (SD) MRC 0.8 (0.8) were recruited from 21 centres. COPD was diagnosed in 77 patients (25.2%) by standard diagnostic spirometry. Using the copd-6 device, mean (SD) FEV1/FEV6 was 68 (8)% in patients with COPD and 78 (10)% in patients without COPD. Sensitivity and specificity at a FEV1/FEV6 cut-off of 73% were 79.2% and 80.3%, respectively. The area under the ROC curve was 0.84. Screening with the copd-6 device significantly predicted COPD. Gender, CCQ, and MRC were not found to predict COPD. CONCLUSIONS: Using the copd-6 as a pre-screening device, the rate of COPD diagnoses by standard diagnostic spirometry increased from 25.2% to 79.2%. Although the sensitivity and specificity of the copd-6 could be improved, it might be an important device for prescreening of COPD in primary care and may reduce the number of unnecessary spirometric tests performed.

Maintenance plus reliever budesonide/formoterol compared with a higher maintenance dose of budesonide/formoterol plus formoterol as reliever in asthma: an efficacy and cost-effectiveness study.

OBJECTIVE: To evaluate efficacy and cost-effectiveness of budesonide/formoterol (Symbicort) maintenance (one dose once or twice daily) plus additional doses as needed (Symbicort Maintenance And Reliever Therapy, SMART) compared with a higher fixed dose of budesonide/formoterol with formoterol as needed in patients with persistent asthma. STUDY DESIGN AND METHODS: 6-month, open, randomised study of 465 patients either not well controlled on an inhaled corticosteroid (ICS), or well controlled on a combination of ICS and a long-acting beta(2)-agonist (LABA). TREATMENTS: budesonide/formoterol 160/4.5 microg, one inhalation, once or twice daily maintenance plus additional doses as-needed (1 x SMART or 2 x SMART), or budesonide/formoterol 160/4.5 microg two inhalations twice daily plus formoterol 4.5 microg as needed (2 x 2 FIX + F). Children 6-11 years old used an 80/4.5 microg dose strength. Primary variables of efficacy were the changes in the Asthma Control Questionnaire (ACQ(5)) and morning peak expiratory flow (PEF). RESULTS: Mean age of patients 40 years (range 6-82 years); 53% female. No differences between the groups were found in ACQ(5) scores or asthma exacerbation rates. Morning PEF was higher in the 2 x 2 FIX + F group vs. the 1 x SMART and 2 x SMART groups (differences 13 L/min and 9 L/min, respectively; p < 0.002). The 1 x SMART group showed a significant decrease in asthma controlled days compared with the two other groups. No difference was seen between the 2 x SMART group and the 2 x 2 FIX + F group. Treatment costs were significantly lower in the SMART groups compared with the 2 x 2 FIX + F group. CONCLUSION: Compared with the 2 x 2 FIX + F treatment the use of budesonide/formoterol was 30-40% lower in the SMART groups while maintaining equal ACQ(5) scores. Daily asthma control improved equally with 2 x SMART compared to 2 x 2 FIX + F with a reduction in asthma medication cost. The one dose once daily maintenance treatment (1 x SMART) resulted in a low level of treatment failure (exacerbations) but led to more days with symptoms. Therefore, a daily dose of two inhalations seems to be the lowest appropriate dose in patients with moderate persistent asthma.

Short-term safety and tolerability of double-dose salmeterol/fluticasone propionate in adult asthmatic patients.

INTRODUCTION: The incidence of asthma exacerbations in patients receiving salmeterol/fluticasone propionate (Seretidetrade mark or Advair((R))) is low. However, when asthma control deteriorates, clinicians may instruct patients to double the dose of their inhaled corticosteroid medication for a short period. The purpose of this study was to demonstrate that doubling the dose of Seretidetrade mark for a period of 2 weeks in subjects with persistent asthma is safe and well tolerated. METHODS: This randomised, double-blind, parallel-group study was conducted in primary-care centres. Adults with a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of >/=70% predicted were stratified to receive a single dose of Seretidetrade mark 50mug/100mug, 50mug/250mug or 50mug/500mug twice daily from a Diskustrade mark inhaler for a 4-week run-in period, dependent on the dose of inhaled corticosteroid on entry. Subjects were then randomised to receive either an extra inhalation of the same dose of Seretidetrade mark received during the run-in (double dose) or an inhalation of matching placebo (single dose) for 14 days in a 2 : 1 ratio. Subjects were asked to record any adverse events, morning and evening heart rate (HR), peak flow and relief medication use in daily record cards. The primary endpoint was tremor as perceived by the subject. Clinic evaluations included HR, 12-lead ECG, and potassium and glucose levels. RESULTS: 110 and 208 subjects received single- and double-dose Seretidetrade mark, respectively. Only one subject experienced tremor. This was classified as mild and occurred in a subject receiving double-dose Seretidetrade mark (50mug/100mug). There was no difference between the treatment groups in the incidence of tremor (difference <1%; 95% CI -6, 8). Other salmeterol-related adverse events (palpitations, muscle cramps and headache) and fluticasone propionate-related events (oral candidiasis and hoarseness) occurred in a similar percentage of subjects in each treatment group. The treatment differences for morning and evening HR measurements showed small differences between the two groups (<2 beats/min). The adjusted mean treatment difference (double dose - single dose) in morning HR was 1.1 beats/min (95% CI 0.2, 2.0) and evening HR was 0.9 beats/min (95% CI 0.1, 1.7). Seven percent of subjects receiving single-dose Seretidetrade mark and 8% receiving double-dose Seretidetrade mark had a QTc change from baseline in the interval 30-59 msec. No increases above 59 msec were seen in either group. There were no clinically significant changes from baseline for potassium levels. Two percent of subjects in the single dose and <1% in the double-dose group had a change from a non-clinically significant baseline blood glucose assessment to a clinically significant abnormality at the end of treatment. CONCLUSION: In circumstances in which a physician may be considering doubling the dose of Seretidetrade mark for a short period of time in adult asthmatics, this study demonstrates that doubling the dose for a period of 2 weeks is safe and well tolerated.

COPD health care in Sweden - A study in primary and secondary care.

OBJECTIVES: To map out-patients with Chronic Obstructive Pulmonary Disease (COPD) with special reference to patients suffering from acute exacerbations, and to describe COPD health care structure and process in Swedish clinical practice in a real life setting. DESIGN: Retrospective, non-interventional, epidemiological survey. SETTING: 141 hospital based out patient clinics (OPC, n=30) and primary health care clinics (PC, n=111) were included in the structure evaluation. SUBJECTS: 1004 COPD diagnosed patients from 100 of the centres (OPC, n=26) participated in the process evaluation. METHODS: All Swedish OPC (n=40) and a random sample of 180 PC were asked to answer a questionnaire regarding COPD care. In addition, data from 10 randomly selected patients with a documented COPD disease were analysed from the centres. RESULTS: Spirometers were available at all OPCs and at 99% of the PCs. Spirometry had been performed in 52% of PC-patients and in 89% of OPC-patients during the last 2 years prior to the study. More severe patients, as judged by investigator and lung function data, were treated at OPCs than at PCs. Physiotherapists, occupational therapists and dieticians were available at >80% of centres. Exacerbation rate was higher at PCs without a specialized nurse, 2.2/year versus 0.9/year at centres with a specialized nurse. CONCLUSIONS: Special attention to COPD, marked by a specialised nurse in primary care improves the quality, as assessed by a lower number of exacerbations. The structure of COPD care in Sweden for diagnosed individuals seems satisfactory, but could be improved mainly through higher availability and educational activities.