12-months follow-up of pulmonary tele-rehabilitation versus standard pulmonary rehabilitation: A multicentre randomised clinical trial in patients with severe COPD.

Between March 2016 and October 2017, we randomised 134 patients with severe COPD from 8 hospitals in the Capital Region of Denmark to participate in either standardised, outpatient pulmonary rehabilitation (control group) or on-line, supervised and home-based tele-rehabilitation (intervention group). We found no difference between the groups in the primary outcome: six minutes walking distance (6MWD) after completion of the programme. The current study presents results from the 12-month follow-up with assessment of the 6MWD and analyses of hospitalisation and mortality. There were no significant differences between or within the groups in the 6MWD one year after completion of the programme.

Supervised pulmonary tele-rehabilitation versus pulmonary rehabilitation in severe COPD: a randomised multicentre trial.

RATIONALE: Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD. Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported. Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR). OBJECTIVE: To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR. METHODS: In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly). Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks' follow-up from baseline. The primary analysis was based on the intention-to-treat principle. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised. The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: -6.6 to 24.9)) or at 22 weeks' follow-up (-5.3 metres (95% CI: -28.9 to 18.3)). More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01). CONCLUSION: PTR was not superior to conventional PR on the 6MWD and we found no differences between groups. As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design. Trial registration number ClinicalTrials.gov (NCT02667171), 28 January 2016.

Inspiratory muscle strength and walking capacity in patients with COPD.

Purpose: It has been suggested that patients with inspiratory muscle weakness could benefit from specific inspiratory muscle training (IMT). We aimed to examine the frequency of patients with inspiratory muscle weakness in a Danish hospital-based outpatient pulmonary rehabilitation program, and to evaluate the association between inspiratory muscle strength and peripheral muscle strength and walking capacity. Methods: Maximal Inspiratory Pressure (MIP) was assessed in 97 patients with COPD (39 men, 58 women, mean age years 70 ± 9, forced expiratory volume in 1 s ((FEV1) = 35 ± 10% pred.). The impact of MIP on knee-extension strength, walking distance, and symptom burden was evaluated using multiple linear regression analyses. Results: The MIP of the patients with COPD was 63 (95% CI 59; 67) cmH2O and it was significantly reduced compared to gender and age-matched reference values 76 (95% CI 73; 79) cmH2O (p < 0.001). Seven patients (7.2%) were under the lower limit of normal. MIP was negatively correlated with increasing age, female gender, decreasing knee-extension strength and lower FEV1% pred. Walking distance was associated with knee-extension strength and it was not associated with MIP. Conclusion: Maximal inspiratory pressure was reduced in patients with COPD but only a few patients had a weak MIP. Whilst MIP was associated with leg muscle strength, it was not associated with walking distance or symptoms.

Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been associated with exacerbations of COPD. However, characterization of these in individuals with clinically stable COPD is lacking. The aim of this study was to characterize the collagen remodeling in stable COPD by the serological assessment of neo-epitopes. DESIGN AND METHODS: Sixty-eight subjects with clinically stable COPD were included into the study at baseline, and 27 came back for a four weeks follow-up visit. Serum and plasma levels of neo-epitopes were assessed for the evaluation of collagen type III (C3M), IV (C4M, C4Ma3, P4NP 7S), and VI (C6M, Pro-C6) remodeling. RESULTS: C3M, C4M, C4Ma3, P4NP 7S, and C6M levels were significantly elevated in COPD subjects compared with healthy controls (p<0.0001 to p=0.044). Each neo-epitope biomarker was significantly correlated between serum and plasma (p<0.0001) and most biomarkers were stable in the majority of patients from baseline to week four. Serum C6M levels were weakly correlated with FEV1% predicted (r=-0.274, p=0.025) and serum Pro-C6 levels were elevated in subjects with previous exacerbations (p=0.014). C3M, C4Ma3, C6M, and P4NP 7S were weakly correlated with MRC dyspnea scores (p<0.01). No associations were seen with BMI, smoking, duration of COPD, blood oxygen saturation, shuttle walk test distance, GOLD grades, or CAT scores. CONCLUSIONS: Serological biomarkers of collagen remodeling were elevated in subjects with COPD as compared with healthy individuals. Biomarker levels were significantly correlated with measures of dyspnea, indicating a relationship with degree of symptoms, while only C6M showed a weak but significant association with lung function. Biomarker levels were not related to GOLD grades, which was in line with previous studies indicating that ECM remodeling may be related to disease activity rather than severity.

Prognostic value of C-reactive protein, leukocytes, and vitamin d in severe chronic obstructive pulmonary disease.

Inflammatory biomarkers predict mortality and hospitalisation in chronic obstructive pulmonary disease (COPD). Yet, it remains uncertain if biomarkers in addition to reflecting disease severity add new prognostic information on severe COPD. We investigated if leukocytes, C-reactive protein (CRP), and vitamin D were independent predictors of mortality and hospitalisation after adjusting for disease severity with an integrative index, the i-BODE index. In total, 423 patients participating in a pulmonary rehabilitation programme, with a mean value of FEV1 of 38% of predicted, were included. Mean followup was 45 months. During the follow-up period, 149 deaths (35%) were observed and 330 patients (78.0%) had at least one acute hospitalisation; 244 patients (57.7%) had at least one hospitalisation due to an exacerbation of COPD. In the analysis (Cox proportional hazards model) fully adjusted for age, sex, and i-BODE index, the hazard ratio for 1 mg/L increase in CRP was 1.02 (P=0.003) and for 1×10(9)/L increase in leukocytes was 1.43 (P=0.03). Only leukocyte count was significantly associated with hospitalisation. Vitamin D was neither associated with mortality nor hospitalisation. Leukocytes and CRP add little information on prognosis and vitamin D does not seem to be a useful biomarker in severe COPD in a clinical setting.

Validation of the i-BODE index as a predictor of hospitalization and mortality in patients with COPD participating in pulmonary rehabilitation.

Abstract The aim of this study was to examine the value of the i-BODE index to predict hospital admission and to confirm its usefulness to predict mortality in a Danish population. The incremental shuttle walking test (ISWT) is widely used in the UK and Europe and previous work has examined the replacement of the 6MWT with the ISWT within the BODE index for predicting the prognosis of COPD (i-BODE). The 674 patients included in the analysis participated in a 7-week pulmonary rehabilitation program from 2002 to 2011. The National Health Services Central Register ascertained vital status and provided information on all hospital admissions. The mean follow-up period was 66 months (range 11-118 months). Cox proportional hazards model was used to identify factors that significantly predicted mortality and time to first hospital admission. The i-BODE index as well as body mass index, MRC dyspnea grade, and exercise capacity (ISWT) were significantly associated with all-cause mortality. The adjusted hazard ratio for death per one point increase in the i-BODE score was 1.28 (95% confidence interval 1.20 to 1.37). The i-BODE index was also a significant predictor of hospitalization, both for all causes and COPD exacerbation. Patients in the highest i-BODE quartile had a median time to first hospitalization of 17 months compared to 51 months for patients in the lowest quartile. The i-BODE index is a significant predictor of hospital admission and thus health care utilization, and also mortality.

The long-term effect of ambulatory oxygen in normoxaemic COPD patients: a randomised study.

AIM: To study the long-term benefits of ambulatory oxygen (AO) in combination with pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) patients experiencing exertional desaturation. PATIENTS AND METHODS: Normoxaemic COPD who participated in outpatient PR and desaturated >4% and <90% during endurance shuttle walk test (ESWT) were randomised to control (n=23) or AO 2 L/min from a portable oxygen concentrator (n=22) to be used during exercise. PR consisted of supervised training for 20 weeks combined with unsupervised daily training at home followed by 13 weeks without supervised training. RESULTS: Only 45 of 165 eligible patients wanted to participate. Mean forced expiratory volume in 1 s=32% (SD 13.8) and Medical Research Council (MRC)=4.5 (3-5). Supplemental oxygen improved oxygen saturation during ESWT by 2.3% (95% CI: 1.2%-3.5%; p<0.001). In the study period of 33 weeks, 10 and 6 patients withdrew from the AO group and control group, respectively. Patients spent an average of 7.9 h/week on oxygen. PR improved ESWT by 18,076 s (95% CI: 101-258 s; p<0.001) and St. George's Respiratory Questionnaire (SGRQ) score by 2.6 units (95% CI: 0.1-5.1 s; p=0.04) after 7 weeks, and these gains remained at 33 weeks of evaluation. There were no differences between the AO group and control group at 33 weeks of evaluation with regard to change in ESWT (223 vs. 241 s; p=0.32), change in SGRQ (-3.6 vs. -4.5 units, 0.91), and number of patients with acute exacerbation in COPD (AECOPD), hospital admission or dropout (17 of 22 vs. 20 of 23, p=0.59). CONCLUSIONS: AO seems not to provide additional beneficial effects in patients with COPD participating in pulmonary rehabilitation and experiencing exertional desaturation without severe resting hypoxaemia.

A comparison of the assessment of quality of life with CAT, CCQ, and SGRQ in COPD patients participating in pulmonary rehabilitation.

BACKGROUND: The aim of this study was to compare the COPD specific health-related quality of life (HR-QoL) instruments, the St George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and COPD Clinical Questionnaire (CCQ), in terms of feasibility and correlations in COPD patients participating in pulmonary rehabilitation (PR). METHODS/MATERIALS: Ninety consecutive patients with mainly severe COPD who participated in a 7-week PR programme were assessed with CAT, CCQ, SGRQ. In addition to evaluating the scores obtained by the questionnaires we also assessed the need of help and the time needed to complete the questionnaires. RESULTS: Patients had mean FEV(1) = 38.7% of predicted value and poor quality of life (mean SGRQ total score 51.1, CAT 1.81, and CCQ 26.5 units). There were good correlations between the overall scores for the three HR-QoL instruments: CAT versus CCQ, r = 0.77; CAT versus SGRQ, r = 0.73; and CCQ versus SGRQ, r = 0.75 (p < 0.001 for all correlations). The average time to complete the questionnaires was 578 seconds for SGRQ, 107 seconds for CAT, and 134 seconds for CCQ. The need for assistance while answering the questionnaire was 86.5% for SGRQ, 53.9% for CAT, and 36.0% for CCQ. CONCLUSIONS: we observed a good correlation between the SGRQ, CCQ and CAT in this group of patients with severe COPD undergoing pulmonary rehabilitation. We found that CAT and CCQ have the advantage of being easier and faster to complete than the SGRQ. The need for help with the completion of the questionnaires was especially seen in patients with low education level.

Vitamin d status in patients with chronic obstructive pulmonary disease who participate in pulmonary rehabilitation.

PURPOSE: Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease; however, no study has evaluated the influence of vitamin D status on effects of pulmonary rehabilitation (PR). METHODS: We studied 311 patients, who participated in a 7-week outpatient PR. Vitamin D status was assessed at entry and examined for association with patient characteristics, dropout from PR, and effect on endurance shuttle walk time. RESULTS: Vitamin D level 25 nM was seen in 61 (19.6%) of the patients. They were significantly younger, were more frequently on long-term oxygen therapy, had higher body mass index and fat-free mass index, had worse quality of life score, tended to have lower percent predicted value for forced expiratory volume in the first second of expiration, and more frequently were current smokers. They had a 3-time higher risk of dropout from the PR program (P = .003) compared with patients with normal vitamin D status and a poorer improvement in endurance shuttle walk time (P = .03). DISCUSSION: In conclusion, vitamin D deficiency was significantly associated with higher dropout rates from PR, and there was a tendency toward a poorer improvement in endurance shuttle walk time.

Shuttle walking test as predictor of survival in chronic obstructive pulmonary disease patients enrolled in a rehabilitation program.

BACKGROUND: The Incremental Shuttle Walking Test (ISWT) is used to assess exercise capacity in chronic obstructive pulmonary disease (COPD) and is employed as an outcome measure for pulmonary rehabilitation. We studied the value of this test in predicting survival in COPD patients enrolled in a rehabilitation program. METHODS: A total of 416 patients performed an ISWT before entering a 7-week outpatient pulmonary rehabilitation program. Their survival was observed over a mean period of 4.5 years (range = 1.2-7.2 years). RESULTS: During the observation period, 169 (40.6%) patients died. Univariate analyses showed that the ISWT as well as age, gender, present and previous tobacco smoking, forced expiratory volume in 1 second, body mass index, oxygen saturation at rest, long-term oxygen therapy, Medical Research Council dyspnea score, and treatment with oral corticosteroids were significantly associated with survival. Multivariate analysis, including relevant confounders, revealed that low ISWT was independently associated with poor survival (P = .001). The association was not linear and the risk of dying increased markedly when ISWT was lower than 170 m (RR = 2.84, 95% CI: 2.05-3.93). CONCLUSION: This study shows that the ISWT is a strong and independent predictor of survival in patients with COPD enrolled in a rehabilitation program.

Long-term effects of 1-year maintenance training on physical functioning and health status in patients with COPD: A randomized controlled study.

PURPOSE: To examine whether maintenance training (MT) for 1 year improved the long-term effects of a 7-week chronic obstructive pulmonary disease (COPD) rehabilitation program. METHODS: After a 7-week outpatient rehabilitation program, 96 patients with COPD were randomized to either an MT group (n = 55) or a control group (n = 41). Both groups were requested to continue unsupervised training at home. The MT group received weekly supervised training the first 6 months, supervised training every second week the next 6 months, and finally no supervised training the last 6 months of the 18-month study period. Primary effect parameters were Endurance Shuttle Walk Test (ESWT) time and health status (St. George's Respiratory Questionnaire, SGRQ). Secondary effect parameters were adherence to supervised training, dropout rates, and hospitalization. RESULTS: Compared with the control group, the MT group had significantly better ESWT times at 3 and 6 months (+43.9 seconds; P= .03, and +75.1 seconds; P= .02) and insignificantly higher ESWT time at 12 months (+66.6 seconds; P= .40). SGRQ total score declined gradually after the 7-week program with no difference between the 2 groups, and after 18 months, the score was 1.7 units (95% confidence interval: -0.7 to 4.1) worse than at randomization. There was no difference between the 2 groups regarding dropout rates or hospitalization. DISCUSSION: Weekly MT for 12 months improved walking time but had no influence on health-related quality of life or hospital admissions, compared with unsupervised daily training at home. The effect of the MT was closely related to adherence to the program.

EuroQoL in assessment of the effect of pulmonary rehabilitation COPD patients.

BACKGROUND: The effect of pulmonary rehabilitation on EuroQol in COPD patients has not been investigated previously. METHODS/MATERIALS: Two hundred and twenty nine consecutive COPD patients who had completed a 7-week pulmonary rehabilitation programme were assessed with EuroQol five-dimension questionnaire (EQ-5D), endurance shuttle walk test (ESWT), and the St George's Respiratory Questionnaire (SGRQ) before and after the programme, and at the 3-month follow-up visit. RESULTS: Two hundred and two (88.4%) patients had FEV(1)<50% predicted and all but four (1.7%) had dyspnoea score at least 3 on MRC scale. At completion of the programme, statistical significant improvements were seen for ESWT 157.3s; p<0.001, EQ-5D utility score -0.019; p=0.03, EQ-5D VAS -2.1; p=0.056, SGRQ total score -2.8 units; p<0.001. The effects of rehabilitation on ESWT and SGRQ were maintained at 3-month follow-up (158.9s and -2.9 units), while the effect on EQ-5 utility decreased (0.013; p=0.18). At baseline, there was a maximum score ("ceiling effect") for EQ-5D utility and EQ VAS in 29 (12.7%) and five (2.2%) of the patients, respectively. After rehabilitation these number increased to 41 (17.9%) and seven (3.1%). CONCLUSIONS: In COPD patients receiving rehabilitation, responsiveness of EQ-5D utility was poor. One explanation might be a "ceiling effect" of this instrument.

[Rehabilitation of patients with chronic obstructive pulmonary disease. Effect of a 7-week programme after 12 months]. / Rehabilitering af patienter med kronisk obstruktiv lungesygdom. Tolvmånederseffekten af et syvugersprogram.

INTRODUCTION: Pulmonary rehabilitation in COPD improves exercise tolerance and health status, but these effects have been shown to decline after stopping the training programme. This study has examined the long-term effect on exercise tolerance and health status of a 7-week rehabilitation programme combined with extensive training at home. MATERIALS AND METHODS: 209 consecutive COPD patients who had completed a 7-week pulmonary rehabilitation programme were assessed with the endurance shuttle walk test (ESWT) and the St George's Respiratory Questionnaire (SGRQ) at baseline and at 7, 20, 33 and 59 weeks. RESULTS: 77 (36.8%) of the patients dropped out during the study period. Among the 132 patients who competed the 59-week evaluation, the initial improvement in the ESWT time was 100% (p < 0.001) and 3.8 units (p < 0.001) in the SGRQ. These effects were maintained at the 59-week evaluation (ESWT 63% above baseline; p = 0.02 and improved SGRQ 3.3 units compared with baseline; p < 0.001). CONCLUSION: A relatively simple and inexpensive 7-week rehabilitation programme with extensive training at home was sufficient to maintain the long-term effect on exercise tolerance and health status.