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Background: Symptomatic relief is an important treatment goal for patients with COPD. To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines. The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms., Methods: This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international). Subjects completed the E-RS as part of a daily eDiary. Tests of reliability, validity, and responsiveness were conducted in each dataset., Results: In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74). RS-Total scores correlated significantly with the following criterion variables (Spearman's rho; p < 0.01, all comparisons listed here): FEV1% predicted (-0.19, -0.14, -0.15); St. George's Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (-0.30, -0.14) and incremental shuttle walk (ISWT) (-0.18) tests. Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity. RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001). RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001). Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed., Conclusions: Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials., Trial Registration: MPEX: NCT00739648 ; AZ1: NCT00949975 ; AZ 2: NCT01023516.

Background: To correctly estimate the cost-effectiveness of treatments that reduce COPD exacerbations, the utility gains from preventing exacerbations need to be measured. This requires utility measurement during exacerbations., Aim: To assess the ability of the EQ-5D to detect the recovery from moderate COPD exacerbations., Methods: In the US, 65 COPD and/or chronic bronchitis patients (≥40 years old smokers or ex-smokers with a history of 10 pack-years) were enrolled within 48 h of symptom onset of the exacerbation. Patients completed the EQ-5D at enrollment and after 7, 14 and 42 days. Symptoms and medication use were recorded in diaries. Change over time and loss of quality-adjusted life years (QALYs) due to the exacerbation was estimated. Using standardized response mean (SRM) as the metric of responsiveness, we compared the responsiveness of the EQ-5D to the responsiveness of morning peak expiratory flow rate, rescue medication use and symptom scores. SRMs were also used to assess whether patients with greater improvements in peak expiratory flow rate, rescue medication use, symptom scores, clinician global impression of change, and patient global impression of change had a greater improvement in EQ-5D than patients with smaller improvement., Results: Mean utility index scores (standard deviation) using the US value set were 0.683 (0.209), 0.726 (0.216), 0.768 (0.169) and 0.760 (0.181) at days 1, 7, 14 and 42, respectively. The mean of each patient's lowest index score, either at visit 1 or visit 2, was 0.651 (0.213). Over the course of 6 weeks there was a highly significant improvement in mean utility. The greatest improvement was seen between day 7 and day 14. Patients lost on average 0.00896 QALY (0.0086) or 3.27 (3.13) quality-adjusted life days during the exacerbation. The EQ-5D (SRM: 0.653) was more responsive to change than peak expiratory flow (0.269), rescue medication use (0.343) and sputum symptom scores (0.322) and equally responsive as cough (0.587) and dyspnea (0.638) symptom scores., Conclusion: The EQ-5D is responsive to the recovery from a moderate COPD exacerbation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: To assess the responsiveness of the Cough and Sputum Assessment Questionnaire (CASA-Q) in COPD and chronic bronchitis patients recovering from an acute exacerbation. The 20-item questionnaire with a 7-day recall assesses the frequency and severity of cough and sputum and their impact on everyday life in clinical (trial) settings. The four domains (cough/sputum symptom and impact) use scales from 0 to 100, with lower scores indicating higher symptom/impact levels., Methods: Outpatients were enrolled within 48h of symptom onset of their exacerbation. Treatment was initiated at the discretion of the investigator, and patients observed for 6 weeks. During study visits, 59 eligible patients completed the CASA-Q at enrolment, week 1, 2 and 6. Responsiveness was assessed by calculating standardized effect sizes., Results: Of the 19 male and 40 female patients with a mean (standard deviation, SD) age of 61.1 (10.5) years, all were classified by their physician to have improved or recovered after six weeks. The mean (SD) CASA-Q sores for the cough symptom, cough impact, sputum symptom and sputum impact domains increased from 32.6 (21.0), 40.7 (22.4), 37.4 (20.1), 47.1 (24.2) at enrolment to 54.0 (19.8), 63.7 (21.3), 55.1 (19.0), 65.5 (20.5) at week 6, respectively. Standardized effect sizes for patients improved or recovered from their exacerbation at week 6 were above 1.0 for the cough domains and at least 0.77 for the sputum domains., Conclusions: The CASA-Q was responsive to symptom changes in patients recovering from an exacerbation., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: To assess the discriminative properties of the EuroQol five-dimension questionnaire (EQ-5D) with respect to COPD severity according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria in a large multinational study., Methods: Baseline EQ-5D visual analog scale (VAS) scores, EQ-5D utility scores, and St. George Respiratory Questionnaire scores were obtained from a subset of patients in the Understanding the Potential Long-term Impact on Function with Tiotropium trial, which was a 4-year placebo-controlled trial designed to assess the effect of tiotropium on the rate of decline in FEV(1) in COPD patients aged > or = 40 years, an FEV(1) of < 70% predicted, an FEV(1)/FVC ratio of < or = 70%, and a smoking history of >/= 10 pack-years., Results: A total of 1,235 patients (mean post bronchodilator FEV(1), 48.8% predicted) from 13 countries completed the EQ-5D. The EQ-5D VAS and utility scores differed significantly among patients in GOLD stages 2, 3, and 4, also after correction for age, sex, smoking, body mass index (BMI), and comorbidity (p < 0.001). The mean EQ-5D VAS scores for patients in GOLD stages 2, 3, and 4 were 68 (SD, 16), 62 (SD, 17), and 58 (SD, 16), respectively. The mean utility scores were 0.79 (SD, 0.20) for patients in GOLD stage 2, 0.75 (SD, 0.21) for patients in GOLD stage 3, and 0.65 (SD, 0.23) for patients in GOLD stage 4. Effect sizes for the difference in utility scores between patients in GOLD stages 3 and 4 were more than twice as high as those for the difference between patients in GOLD stages 2 and 3. Gender, postbronchodilator FEV(1) percent predicted, the number of hospital admissions and emergency department visits in the year prior to baseline measurements, measures of comorbidity, and BMI were independently associated with EQ-5D utility. EQ-5D utility scores also differed between patients from different countries. French patients especially had lower utility scores than US patients. Utility scores calculated with the US value set were on average 5% higher than those calculated with the UK value set., Conclusions: Increasing severity of COPD was associated with a significant decline in EQ-5D VAS scores and utility scores. These results demonstrate that a generic instrument can assess COPD impact on quality of life and that the scores discriminate between patient groups of known severity. These utility scores will be useful in cost-effectiveness assessments.

Introduction: The Patient Satisfaction and Preference Questionnaire (PASAPQ) is a multi-item measure of respiratory inhalation device satisfaction and preference designed to be easily understood and administered to patients with asthma and COPD. This study assessed its validity, reliability and responsiveness and explored the between-group difference in PASAPQ scores that is meaningful., Methods: The field test version was developed using literature, focus groups and expert opinion. Item reduction followed. The assessment of the validity, reliability and responsiveness of the PASAPQ utilized data from two clinical studies comparing devices delivering the same medication, and was performed with pre-specified criteria. A minimally important difference (MID) was estimated using both anchor- and distribution-based approaches., Results: Two factors of the PASAPQ, 'performance' and 'convenience', were consistent across studies. Missing and out-of-range data were minimal (<1%) and respondents used a full range of response options. All items correlated most highly with their hypothesized scale and all exceeded the minimum correlation criteria of 0.40. Cronbach's alfa was high (0.87-0.94), providing support for internal reliability for the PASAPQ. Correlations of the overall satisfaction item with the performance domain ranged from 0.78 to 0.91, the convenience domain ranged from 0.54 to 0.71, and the total score ranged from 0.78 to 0.90. These moderate-to-strong correlations provide substantial support for the validity of the PASAPQ domains and total score. Discriminate validity was assessed by calculating PASAPQ scores for patients' ratings of the device that they preferred compared with the other, non-preferred device. The preferred device was rated higher on all satisfaction measures, supporting the ability of the PASAPQ to discriminate between preferred and non-preferred devices. Although a difference of 3 or 4 points may be sufficient to observe a small effect difference between groups, most of the MID estimates were in the 8-10 point range., Discussion and Conclusion: Our analyses across asthma, COPD and patients with mixed respiratory disease (with features of both COPD and asthma), study designs and data sets lead us to conclude that the PASAPQ is a practical, valid, reliable and responsive instrument for measuring respiratory device satisfaction. Furthermore, a difference in satisfaction scores between treatment groups of 10 points is, conservatively, a difference that is meaningful to patients.