Inspiratory muscle training does not improve clinical outcomes in 3-week COPD rehabilitation: results from a randomised controlled trial.

The value of inspiratory muscle training (IMT) in pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) is unclear. The RIMTCORE (Routine Inspiratory Muscle Training within COPD Rehabilitation) randomised controlled trial examined the effectiveness of IMT added to pulmonary rehabilitation.In total, 611 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received a 3-week inpatient pulmonary rehabilitation, of which 602 patients were included in the intention-to-treat analyses. The intervention group (n=300) received highly intensive IMT and the control group (n=302) received sham IMT. The primary outcome was maximal inspiratory pressure (PImax). The secondary outcomes were 6-min walk distance, dyspnoea, quality of life and lung function. Outcomes were assessed pre- and post-pulmonary rehabilitation. ANCOVA was used.The intervention group showed higher effects in PImax (p<0.001) and forced inspiratory volume in 1 s (p=0.013). All other outcomes in both study groups improved significantly, but without further between-group differences. Sex and pulmonary rehabilitation admission shortly after hospitalisation modified quality of life effects.IMT as an add-on to a 3-week pulmonary rehabilitation improves inspiratory muscle strength, but does not provide additional benefits in terms of exercise capacity, quality of life or dyspnoea. A general recommendation for COPD patients to add IMT to a 3-week pulmonary rehabilitation cannot be made.

The Impact of Loneliness on Outcomes of Pulmonary Rehabilitation in Patients with COPD.

Psychological factors such as negative affect have been demonstrated to impact course and treatment of chronic obstructive pulmonary disease (COPD). However, little is known about the respective impact of social factors. In several other chronic diseases, loneliness has been shown to predict morbidity, but little is known about its impact on COPD. Therefore, this study examined the associations between loneliness and outcome measures of a pulmonary rehabilitation program (PR). Before and after a 3-week inpatient PR program, patients with COPD (N = 104) underwent a 6-min walking test to measure functional exercise capacity. Loneliness was assessed with the Loneliness Scale. The Medical Outcomes Study 36-item short form, 9-item Patient Health Questionnaire, and 7-item General Anxiety Disorder questionnaire were administered as measures of health-related quality of life (HQoL), depression, and anxiety, respectively. Multiple regression analyses showed that at the start of PR, more loneliness was associated with worse levels of functional exercise capacity, HQoL, depression, and anxiety, but with greater improvements in functional exercise capacity and HQoL over the course of PR, even after controlling for age, sex, lung function, and smoking status. Patients with stronger decreases in loneliness from start to end of PR showed stronger improvements in functional exercise capacity and HQoL over the course of PR. The present study shows that subjective loneliness is associated with relevant treatment outcomes in patients with COPD undergoing pulmonary rehabilitation. Therefore, loneliness should be addressed in patients with COPD as it could play a significant role in their disease progression.

A multicentre validation of the 1-min sit-to-stand test in patients with COPD.

Our aim was to comprehensively validate the 1-min sit-to-stand (STS) test in chronic obstructive pulmonary disease (COPD) patients and explore the physiological response to the test.We used data from two longitudinal studies of COPD patients who completed inpatient pulmonary rehabilitation programmes. We collected 1-min STS test, 6-min walk test (6MWT), health-related quality of life, dyspnoea and exercise cardiorespiratory data at admission and discharge. We assessed the learning effect, test-retest reliability, construct validity, responsiveness and minimal important difference of the 1-min STS test.In both studies (n=52 and n=203) the 1-min STS test was strongly correlated with the 6MWT at admission (r=0.59 and 0.64, respectively) and discharge (r=0.67 and 0.68, respectively). Intraclass correlation coefficients (95% CI) between 1-min STS tests were 0.93 (0.83-0.97) for learning effect and 0.99 (0.97-1.00) for reliability. Standardised response means (95% CI) were 0.87 (0.58-1.16) and 0.91 (0.78-1.07). The estimated minimal important difference was three repetitions. End-exercise oxygen consumption, carbon dioxide output, ventilation, breathing frequency and heart rate were similar in the 1-min STS test and 6MWT.The 1-min STS test is a reliable, valid and responsive test for measuring functional exercise capacity in COPD patients and elicited a physiological response comparable to that of the 6MWT.

Effectiveness of pulmonary rehabilitation for patients with asthma: study protocol of a randomized controlled trial (EPRA).

BACKGROUND: Asthma patients are enrolled in multimodal pulmonary rehabilitation (PR) programs. However, available data for the effectiveness of PR in asthma are sparse. Therefore, the primary aim of this randomized control trial (RCT) is to evaluate short-term (end of rehabilitation) and intermediate-term effectiveness (3 months after rehabilitation) of PR for patients with asthma regarding asthma control (primary outcome) and other outcomes. Secondly, moderator effects of gender, age, baseline asthma control, quality of life, and anxiety will be examined. Thirdly, a longitudinal follow-up study will explore the course of the outcomes over one year and the annual costs. METHODS: The EPRA study is a single-center randomized controlled waiting-list trial in the Bad Reichenhall Clinic. Inclusion criteria include a referral diagnosis for uncontrolled asthma, no cognitive impairment and no very severe co-morbidities that indicate significantly greater illness morbidity than asthma alone. In the intervention group (IG), participants will start PR within 4 weeks after randomization; participants of the control group (CG) will start PR 20 weeks after randomization. Data will be assessed at randomization (T0), after 4 weeks (T1; IG: begin of PR), 7 weeks (T2; IG: end of PR), and 20 weeks (T3, CG: begin of PR). The primary outcome is asthma control at T2/T3. Secondary outcomes are health-related quality of life, functional exercise capacity, dyspnea, anxiety, depression, subjective self-management skills, illness perceptions, sick leave and subjective work ability. Outcomes will be analyzed with analysis of covariance, including baseline values of the respective outcomes as covariates. Healthcare costs will be analyzed with a gamma model with a log-link. A longitudinal follow-up study will generate additional data at 3/6/9/12 months after PR for both IG and CG. Latent change models will be used to analyze the course of the primary and secondary outcomes. Annual cost differences before and after rehabilitation will be compared by paired t-test. DISCUSSION: This RCT will determine the effectiveness of a complex inpatient PR for asthma patients concerning asthma control. Furthermore, important medical and economic information regarding the effectiveness of PR as part of the long-term management of patients with uncontrolled asthma will be generated. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00007740 , May 15, 2015). Protocol version: 1.0 (December, 23, 2016).

Validity of a Self-administered Questionnaire Version of the Transition Dyspnea Index in Patients with COPD.

The transition dyspnea index (TDI) is among the most widely used instruments in chronic obstructive pulmonary disease (COPD) patients to measure changes in dyspnea over time. In its original version it is used as guideline for a structured interview to assess the impact of daily activities on dyspnea in the three subdomains: functional impairment, magnitude of task, and magnitude of effort. However, the TDI is sometimes used as a self-administered paper-and-pencil questionnaire. The validity of this questionnaire format has not been tested, which was the aim of the present study. We tested 190 patients with COPD at start and end of a 3-week inpatient pulmonary rehabilitation program (PR). Dyspnea was assessed with the modified Medical Research Council Scale (mMRC), a questionnaire version of the TDI, and an interview version of the TDI. Group means for the TDI questionnaire and interview version were widely comparable for the TDI summary score and the three TDI subdomains. The scores of both TDI versions were strongly correlated and showed comparable, but only weak, correlations with changes during PR in spirometric lung function and mMRC. Improvement in dyspnea after PR was observed in 89% of patients when using the summary score of the questionnaire TDI, but only in 34% of patients when using the mMRC. The results suggest that a self-administered questionnaire format of the TDI is an adequate instrument for assessing changes in activity-related dyspnea during PR in patients with COPD. The responsiveness of this instrument to effects of PR appears greater than the responsiveness of the mMRC.

The impact of disease-specific fears on outcome measures of pulmonary rehabilitation in patients with COPD.

Anxiety is a highly prevalent psychological comorbidity in patients with chronic obstructive pulmonary disease (COPD) and has detrimental effects on pulmonary rehabilitation (PR) outcomes. It has been suggested that disease-specific fears could play an even more important role in COPD patients' disease progression. However, little is known about how different disease-specific fears impact COPD. This study examined how different disease-specific fears relate to different PR outcome measures in COPD patients and how these relationships evolve over the course of PR. Before and after a 3-week inpatient PR program, COPD patients (N = 104) underwent a 6-min walking test to measure functional exercise capacity. Disease-specific fears (fear of physical activity, fear of dyspnea, fear of disease progression, fear of social exclusion) were assessed with the COPD-Anxiety-Questionnaire-Revised. Health-related quality of life (HQoL), COPD health status, dyspnea in daily life, depression, and anxiety were measured using validated questionnaires. Multiple regression showed that greater disease-specific fears at the start of PR were associated with worse functional exercise capacity, HQoL, health status, and depression at the start and end of PR (controlling for age, sex, lung function, smoking status, and general anxiety). Patients who showed a stronger decrease in disease-specific fears improved more in PR outcome measures over the course of PR. Furthermore, different disease-specific fears were related to different PR outcome measures. The results show that disease-specific fears are associated with treatment outcome measures, both cross-sectionally and prospectively. Therefore, disease-specific fears should be addressed in COPD patients as they might play a significant role in disease progression.

Baseline health status and setting impacted minimal clinically important differences in COPD: an exploratory study.

OBJECTIVES: Minimal clinically important differences (MCIDs) are used as fixed numbers in the interpretation of clinical trials. Little is known about its dynamics. This study aims to explore the impact of baseline score, study setting, and patient characteristics on health status MCIDs in chronic obstructive pulmonary disease (COPD). STUDY DESIGN AND SETTING: Baseline and follow-up data on the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and St. George's Respiratory Questionnaire (SGRQ) were retrospectively analyzed from pulmonary rehabilitation (PR) and routine clinical practice (RCP). Anchor- and distribution-based MCID estimates were calculated and tested between settings, gender, age, Global initiative for Obstructive Lung Disease (GOLD) classification, comorbidities, and baseline health status. RESULTS: In total, 658 patients were included with 2,299 change score measurements. MCID estimates for improvement and deterioration ranged for all subgroups 0.50-6.30 (CAT), 0.10-0.84 (CCQ), and 0.33-12.86 (SGRQ). Larger MCID estimates for improvement and smaller ones for deterioration were noted in patients with worse baseline health status, females, elderly, GOLD I/II patients, and patients with less comorbidities. Estimates from PR were larger. CONCLUSION: Baseline health status and setting affected MCID estimates of COPD health status questionnaires. Patterns were observed for gender, age, spirometry classification, and comorbidity levels. These outcomes would advocate the need for tailored MCIDs.

Thresholds for clinically important deterioration versus improvement in COPD health status: results from a randomised controlled trial in pulmonary rehabilitation and an observational study during routine clinical practice.

OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease. Preventing deterioration of health status is therefore an important therapy goal. (Minimal) Clinically Important Differences ((M)CIDs) are used to interpret changes observed. It remains unclear whether (M)CIDs are similar for both deterioration and improvement in health status. This study investigates and compares these clinical thresholds for three widely-used questionnaires. DESIGN AND SETTING: Data were retrospectively analysed from an inhouse 3-week pulmonary rehabilitation (PR) randomised controlled trial in the German Klinik Bad Reichenhall (study 1), and observational research in Dutch primary and secondary routine clinical practice (RCP) (study 2). PARTICIPANTS: Patients with COPD aged ≥18 years (study 1) and aged ≥40 years (study 2) without respiratory comorbidities were included for analysis. PRIMARY OUTCOMES: The COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) were completed at baseline and at 3, 6 and 12 months. A Global Rating of Change scale was added at follow-up. Anchor-based and distribution-based methods were used to determine clinically relevant thresholds. RESULTS: In total, 451 patients were included from PR and 207 from RCP. MCIDs for deterioration ranged from 1.30 to 4.21 (CAT), from 0.19 to 0.66 (CCQ), and from 2.75 to 7.53 (SGRQ). MCIDs for improvement ranged from -3.78 to -1.53 (CAT), from -0.50 to -0.19 (CCQ), and from -9.20 to -2.76 (SGRQ). Thresholds for moderate improvement versus deterioration ranged from -5.02 to -3.29 vs 3.89 to 8.14 (CAT), from -0.90 to -0.72 vs 0.42 to 1.23 (CCQ), and from -15.85 to -13.63 vs 7.46 to 9.30 (SGRQ). CONCLUSIONS: MCID ranges for improvement and deterioration on the CAT, CCQ and SGRQ were somewhat similar. However, estimates for moderate and large change varied and were inconsistent. Thresholds differed between study settings. TRIAL REGISTRATION NUMBER: Routine Inspiratory Muscle Training within COPD Rehabilitation trial: #DRKS00004609; MCID study: #UMCG201500447.

Investigating sensitivity, specificity, and area under the curve of the Clinical COPD Questionnaire, COPD Assessment Test, and Modified Medical Research Council scale according to GOLD using St George's Respiratory Questionnaire cutoff 25 (and 20) as reference.

BACKGROUND: In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ ≥1, CAT ≥10, and mMRC scale ≥2 to indicate symptomatic patients. The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George's Respiratory Questionnaire (SGRQ) ≥25, as suggested by GOLD, following sensitivity and specificity analysis. In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (≥25 and ≥20). MATERIALS AND METHODS: Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care. Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires. RESULTS: Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥25 were: study A, 0.99, 0.43, and 0.96 for CCQ ≥1, 0.92, 0.48, and 0.89 for CAT ≥10, and 0.68, 0.91, and 0.91 for mMRC ≥2; study B, 0.87, 0.77, and 0.9 for CCQ ≥1, 0.76, 0.73, and 0.82 for CAT ≥10, and 0.21, 1, and 0.81 for mMRC ≥2. Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥20 were: study A, 0.99, 0.73, and 0.99 for CCQ ≥1, 0.91, 0.73, and 0.94 for CAT ≥10, and 0.66, 0.95, and 0.94 for mMRC ≥2; study B, 0.8, 0.89, and 0.89 for CCQ ≥1, 0.69, 0.78, and 0.8 for CAT ≥10, and 0.18, 1, and 0.81 for mMRC ≥2. CONCLUSION: Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (≥25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels. The correspondence with the mMRC scale seemed satisfactory, though not optimal. The SGRQ threshold of ≥20 corresponded slightly better than SGRQ ≥25, recently suggested by GOLD 2015, with the established cutoff points for the CCQ, CAT, and mMRC scale.

Health status instruments for patients with COPD in pulmonary rehabilitation: defining a minimal clinically important difference.

The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George's Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.