Impact of exacerbations on adherence and outcomes of pulmonary rehabilitation in patients with COPD.

BACKGROUND AND OBJECTIVE: Dropout or lack of response is an important issue in pulmonary rehabilitation (PR), which underlines the need to identify predictors of dropout and response. Acute exacerbations (AEs) of COPD may influence dropout rates and PR response. We aimed to assess differences in dropout and outcomes of PR between COPD with and without AEs. METHODS: Clinically stable patients with moderate-to-very severe COPD (age: 64.1 ± 9.1 years, 55.6% males, forced expiratory volume in 1 s (FEV1 ): 48.6 ± 20.0% predicted) were assessed during PR (inpatient and outpatient). Mild-to-moderate AEs were defined as 'the prescription of systemic glucocorticosteroids and/or antibiotics, following an acute increase in respiratory symptoms'. Severe AEs were defined as 'a hospital admission due to an AE'. Health status was measured by COPD Assessment Test (CAT), COPD-specific version of the St George's Respiratory Questionnaire (SGRQ-C) and Clinical COPD Questionnaire (CCQ). Symptoms of anxiety and depression were measured by Hospital Anxiety and Depression Scale (HADS). Exercise capacity was measured with the 6-min walking test (6MWT) and constant work rate test (CWRT). RESULTS: A total of 518 patients were assessed during a pre-rehabilitation assessment. Four hundred and seventy-six patients started PR, of whom 419 (88.0%) completed it. A larger proportion of patients who dropped out had a severe AE during PR (20.0% vs 3.5%, P < 0.001). Completers with severe AE showed a deterioration in 6MWT, while completers without AE and with mild-to-moderate AE improved (-24.8 (95% CI: -94.0 to 44.5) vs 24.2 (95% CI: 16.0 to 32.5) vs 25.1 (95% CI: 14.0 to 36.3) metres, P = 0.042). No other significant differences were observed in outcomes comparing completers with and without AE during PR. CONCLUSION: Mild-to-moderate AEs do not affect dropout or response of PR, although severe AEs are associated with dropout. AEs should not lead to discontinuation of PR, as response is in general not affected.

Measurement properties of the Timed Up & Go test in patients with COPD.

We aimed to investigate the construct validity of the Timed Up & Go (TUG) test in chronic obstructive pulmonary disease (COPD), to identify characteristics related to an abnormal TUG time and to examine the responsiveness of the TUG to pulmonary rehabilitation (PR). TUG time was assessed before and after comprehensive PR in 500 COPD patients, and compared cross-sectionally in 100 non-COPD subjects. Physical health outcomes, mental health outcomes, symptom-related outcomes and multidimensional indices were assessed in COPD patients only. Good convergent and discriminant validity was demonstrated by fair-to-moderate correlation with physical health outcomes, symptom-related outcomes and multidimensional indices ( rs = 0.18-0.70) and by little correlation with mental health outcomes ( rs = 0.21-0.26). COPD patients had a worse TUG time than non-COPD subjects, demonstrating known-groups validity. A TUG time of 11.2 seconds had good sensitivity (0.75) and specificity (0.83) for identifying patients with a baseline 6-minute walk distance <350 m. TUG time improved after PR ( p < 0.0001) and a change of 0.9-1.4 seconds was identified as clinically important. The TUG is valid and responsive in COPD. An abnormal result is indicative of poor health outcomes. This simple test provides valuable information and can be adopted in clinical and research settings.

The physical, mental, and social impact of COPD in a population-based sample: results from the Longitudinal Aging Study Amsterdam.

Chronic obstructive pulmonary disease (COPD) is associated with substantial health impact that may already become apparent in early disease. This study aims to examine the features of subjects with COPD in a Dutch population-based sample and compare their physical status, mental status, and social status to non-COPD subjects. This study made use of Longitudinal Aging Study Amsterdam (LASA) data. Demographics, clinical characteristics, self-reported diseases, post-bronchodilator spirometry, physical, mental, and social status were assessed. A number of 810 subjects (50.5% male, mean age 60.5 ± 2.9 years) were included. Subjects with COPD (n = 68, mean FEV1 67.6 [IQR 60.4-80.4] %.) had a slower walking speed than non-COPD subjects, p = 0.033. When compared to non-COPD subjects, COPD subjects gave a lower rating on their health (physical subscale of SF-12: 15 [IQR 16.0-19.0] vs. 18 [IQR 11.0-17.0] points) and life (EQ5D VAS: 75 [IQR 70.0-90.0] vs. 80 points [IQR 65.0-85.5]) surveys. COPD subjects also had a more impaired disease-specific health status (CAT: 9.5 ± 5.9 vs. 6.7 ± 5.2, respectively), were less likely to have a partner (69% vs. 84%, respectively) and received emotional support less often (24% vs. 36%, respectively) compared to non-COPD subjects (All comparisons p < 0.001). In a population-based sample, subjects with COPD had a reduced physical performance, a more impaired disease-specific health status and were more socially deprived compared to non-COPD subjects. These impairments need to be taken into consideration when setting up a management program for patients with mild COPD.

Determinants of functional, peak and endurance exercise capacity in people with chronic obstructive pulmonary disease.

BACKGROUND: Exercise limitation in COPD is multi-factorial. The contribution of cardiac function to exercise capacity is not clear. METHODS: Potential determinants of the different constructs of exercise capacity (functional, peak and endurance exercise capacity using the 6-minute walk distance (6MWD), peak oxygen uptake (VO2peak) and peak work load, and sub-maximal constant work rate test (CWRT) cycle time, respectively) were analysed. RESULTS: Data were collected in 516 people with COPD (56% male, age (mean ±â€¯SD) 64 ±â€¯9 years, FEV1% predicted 49 ±â€¯20%). Participants had reduced exercise capacity (6MWD 424 ±â€¯124 m, 67 ±â€¯18% predicted; VO2peak 1090 ±â€¯414 ml/min, 66 ±â€¯30% predicted; peak work load 70 ±â€¯34 watts, 56 ±â€¯27% predicted; CWRT cycle time (median (IQR)) 225 (169-328) seconds). Cardiac function measures, including echocardiography and N-terminal pro-brain natriuretic peptide level, were independently significantly correlated with exercise capacity. In multiple regression analyses adjusted for age and gender, 72% (p < 0.001) of the 6MWD variance could be explained, with the timed up-and-go test accounting for 32% of the variance. For VO2peak, 60% (p < 0.001) of the variance could be explained, with FEV1 accounting for 30% of the variance. Quadriceps total work was a significant determinant of all exercise tests. CONCLUSIONS: Cardiac function is related to exercise capacity, however is not a primary determinant. Determinants of the different constructs of exercise capacity vary, but there is a strong relationship between quadriceps force and functional and endurance exercise performance, and between lung function and peak exercise capacity.

Responsiveness and MCID Estimates for CAT, CCQ, and HADS in Patients With COPD Undergoing Pulmonary Rehabilitation: A Prospective Analysis.

OBJECTIVES: Pulmonary rehabilitation enhances health status and mood status in patients with chronic obstructive pulmonary disease (COPD). The aim was to determine the responsiveness of St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), COPD Clinical Questionnaire (CCQ), and Hospital Anxiety and Depression Scale (HADS) to pulmonary rehabilitation in patients with COPD, and estimate minimum clinically important differences (MCIDs) for CAT, CCQ, and HADS. DESIGN: A prospective analysis. MCIDs were estimated with anchor-based (anchor: SGRQ) and distribution-based methods. Newly estimated MCIDs were compared to known MCID estimates from a systematic literature search. SETTING: Newly estimated MCIDs were calculated in patients treated in pulmonary rehabilitation. PARTICIPANTS: A subsample of 419 individuals with COPD (55.4% male, mean age 64.3 ± 8.8 years) were included from the Chance study. MEASUREMENTS: Health status was measured with SGRQ, CAT, and CCQ, before and after pulmonary rehabilitation. Mood status was assessed using HADS. RESULTS: 419 patients with COPD (forced expiratory volume in the first second 37.3% ± 12.1% predicted) completed pulmonary rehabilitation. SGRQ (-9.1 ± 14.0 points), CAT (-3.0 ± 6.8 points), CCQ (-0.6 ± 0.9 points), HADS-Anxiety (-1.7 ± 3.7 points), and HADS-Depression (-2.1 ± 3.7 points) improved significantly. New MCIDs were estimated for CAT (range: -3.8 to -1.0 points), CCQ (range: -0.8 to -0.2 points), HADS-Anxiety (range: -2.0 to -1.1 points), and HADS-Depression (range: -1.8 to -1.4 points). CONCLUSIONS: The SGRQ, CAT, CCQ, and HADS are responsive to pulmonary rehabilitation in patients with COPD. We propose MCID estimates ranging between -3.0 and -2.0 points for CAT; -0.5 and -0.3 points for CCQ, -1.8 and -1.3 points for HADS-Anxiety, and -1.7 and -1.5 points for HADS-Depression.

Redefining Cut-Points for High Symptom Burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. METHODS: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.

Sputum microbiology predicts health status in COPD.

BACKGROUND: Spontaneous sputum production occurs in a subset of COPD patients; however, its clinical relevance has not been established. Differences in health status and clinical outcomes between patients with and without positive sputum cultures are unknown. OBJECTIVE: To compare clinical characteristics and health status of spontaneous sputum producers with a positive culture (SC+) and negative culture (SC-) with nonsputum producers (NP) in a cohort of COPD patients referred for pulmonary rehabilitation. METHODS: In total, 518 clinically stable patients with mild-to-very severe COPD were recruited (mean age: 64.1±9.1 years, 55.6% males, forced expiratory volume in 1 second 48.6%±20.0% predicted). Health status was measured using COPD Assessment Test, St George's Respiratory Questionnaire, and the Clinical COPD Questionnaire. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Exercise capacity was measured using the 6-minute walking distance. Spontaneously expectorated sputum was cultured for microbiology. RESULTS: Almost one-third of patients spontaneously produced sputum (n=164, 31.7%). Despite comparable lung function, SC+ reported more frequent exacerbations than NP (≥2 exacerbations <1 year: 43 [81.1%] vs 179 [50.6%], P<0.001). COPD Assessment Test total score and the Clinical COPD Questionnaire total score were significantly worse in SC+ than NP (23.9±6.1 vs 21.1±6.7, P=0.012; 3.1±1.0 vs 2.5±1.0, P=0.002; respectively). Hospital Anxiety and Depression Scale-D score was significantly higher in SC+ than NP (8.7±4.1 vs 7.2±4.3, P=0.046). CONCLUSION: Spontaneous sputum production is common in COPD. Particularly, patients with positive cultures have worse health status and more symptoms of depression. Impact on disease progression and long-term outcomes remain to be established. CLINICAL TRIAL REGISTRATION: NTR3416, registered at www.trialregister.nl.

Burden of COPD in patients treated in different care settings in the Netherlands.

INTRODUCTION: Care for patients with chronic obstructive pulmonary disease (COPD) can be provided in primary, secondary or tertiary care. Whether and to what extent patients with COPD treated in various healthcare settings differ in disease burden and healthcare utilization remains unknown. Therefore, daily symptoms, functional mobility, mood status, health status and healthcare utilization were compared between COPD patients in various care settings, to explore possibilities for healthcare-optimization. METHODS: Current data are part of the Chance study. Demographics, functional mobility (Care Dependency Scale (CDS); Timed-Up-and-Go (TUG) test), mood status (Hospital Anxiety and Depression scale (HADS)), health status (COPD Assessment test (CAT); Clinical COPD questionnaire (CCQ); COPD specific St. George Respiratory questionnaire (SGRQ-C)), received treatments and severity of physical and psychological symptoms were assessed in subjects with and without COPD. RESULTS: 836 subjects (100 primary care patients, 100 secondary care patients, 518 tertiary care patients and 118 non-COPD subjects) were included. The burden of disease significantly increased from primary care to tertiary care. However, in all three healthcare settings a high percentage of patients with an impaired health status was observed (i.e. CAT ≥10 points, 68.0% vs. 91.0% vs. 94.5%, respectively). Furthermore, many patients treated in secondary care remain highly symptomatic despite treatment, while others with low burden of disease would allow for de-intensification of care. CONCLUSION: This study revealed important shortcomings and challenges for the care of COPD patients in the Netherlands. It emphasizes the need for detailed patient characterization and more individualized treatment, independent of the healthcare setting.

Impact of cardiovascular comorbidities on COPD Assessment Test (CAT) and its responsiveness to pulmonary rehabilitation in patients with moderate to very severe COPD: protocol of the Chance study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Patients with COPD are characterised by a reduced health status, which can be easily assessed by the COPD Assessment Test (CAT). Previous studies show that health status can be worsened by the presence of comorbidities. However, the impact of cardiovascular comorbidities on health status as assessed with CAT is not sufficiently investigated. Therefore, the current study has the following objectives: (1) to study the clinical, (patho)physiological and psychosocial determinants of the CAT, and impact of previously established and/or newly diagnosed cardiovascular comorbidities on health status in tertiary care patients with COPD; (2) to assess the effects of pulmonary rehabilitation on CAT scores in patients with COPD; (3) to develop reference values for the CAT in Dutch elderly patients without COPD; and (4) to validate the CAT in a broad sample of Dutch patients with COPD. METHODS AND ANALYSIS: The COPD, Health status and Comorbidities (Chance) study is a monocentre study consisting of an observational cross-sectional part and a longitudinal part. Demographic and clinical characteristics will be assessed in primary care, secondary care and tertiary care patients with COPD, and in patients without COPD. To assess health status, the CAT, Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) will be used. The longitudinal part consists of a comprehensive pulmonary rehabilitation programme in 500 tertiary care patients. For the cross-sectional part of the study, 150 patients without COPD, 100 primary care patients and 100 secondary care patients will be assessed during a single home visit. ETHICS AND DISSEMINATION: The Medical Ethical Committee of the Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands (METC 11-3-070), has approved this study. The study has been registered at the Dutch Trial Register (NTR 3416).

The 2014 Updated GOLD Strategy: A Comparison of the Various Scenarios.

Background: The 2014 updated Global initiative for chronic Obstructive Lung Disease (GOLD) strategy added the St. George's Respiratory Questionnaire (SGRQ) as the fourth possible symptoms measure. The impact of the suggested tools for symptoms of COPD and the different definitions of future risk on the frequency distribution and clinical characteristics of the GOLD groups remain unknown. Methods: Demographic and clinical characteristics were assessed in 542 patients with COPD (57.7% male, age 64.6 [9.0] years, FEV1 54.7 [22.3]% predicted). Health status was assessed by the COPD-specific SGRQ and symptoms of anxiety and depression by the Hospital Anxiety and Depression Scale, anxiety (HADS-A) and depression (HADS-D) subscale. Cohen's Kappa was used to assess agreement between groups. Results: Level of agreement in frequency distribution using the modified Medical Research Council dyspnea (mMRC) scale ≥2, COPD Assessment Test (CAT) ≥10, Clinical COPD Questionnaire (CCQ) ≥1 and SGRQ ≥25 was moderate to very good. Best agreement was reached between CCQ and SGRQ (К = 0.838 or 0.851, p<0.001). Patients classified in mMRC GOLD A reported higher SGRQ scores, higher HADS-A and HADS-D scores compared to patients classified in CAT GOLD A or SGRQ GOLD A. Outcomes were comparable between the risk assessment groups. Conclusions: Choice of the symptom measure impacts GOLD groups more than choice of the exacerbation risk assessment. Health care professionals should be aware that patients are heterogeneous in terms of health status and symptoms of anxiety and depression based on the symptom measure used.