Functional capacity and dyspnea during follow-up after acute pulmonary embolism.

BACKGROUND: Dissecting the determinants of functional capacity during long-term follow-up after acute pulmonary embolism (PE) can help to better characterize a patient population with persisting limitation. METHODS: In a prospective cohort study, consecutive unselected survivors of acute PE underwent 3- and 12-month follow-up, including six-minute walking distance (6MWD) and dyspnea assessment with the modified Medical Research Council (mMRC) scale. We used reference equations adjusting for age, sex, and anthropometric measurements to define abnormal 6MWD. RESULTS: Overall, 323 of 363 (89.0%) patients had at least one recorded 6MWD value at one year. At 3 months, the prevalence of abnormal 6MWD was 21.9% and at 12 months it was 18.3%. At 3 and 12 months, 58.8% and 52.1% with abnormal 6MWD did not report dyspnea, respectively. On average and during follow-up, 6MWD significantly improved with time, while the mMRC dyspnea scale did not. Abnormal 6MWD was associated with younger age (odds ratio per decade, 0.91; 95% CI, 0.88-0.94), higher body mass index (1.10; 1.03-1.17), smoking (3.53; 1.34-9.31), intermediate- or high-risk PE (3.21; 1.21-8.56), and higher mMRC grading (2.28; 1.59-3.27). Abnormal 6MWD at 3 months was associated with the prospectively defined endpoint of post-PE impairment (3.72; 1.50-9.28) and with poor disease-specific and generic health-related quality of life. CONCLUSION: Three months after PE, 37% of patients reported dyspnea and 22% had abnormal 6MWD. After a year, 20% still had abnormal 6MWD. Dyspnea correlated with abnormal 6MWD, but over 50% of patients with abnormal 6MWD did not report dyspnea. Abnormal 6MWD predicted subsequent post-pulmonary embolism impairment and worse long-term quality of life. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register Identifier DRKS00005939.

Sacubitril/Valsartan in the Treatment of Heart Failure With Reduced Ejection Fraction Focusing on the Impact on the Quality of Life: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

There exists a paucity of research data reported by analyses performed on randomized clinical trials (RCTs) that encompass quality of life (QOL) and the aftermath for patients suffering from heart failure with reduced ejection fraction (HFrEF). This systematic review and meta-analysis of randomized clinical trials (RCTs) have been done to evaluate the drug sacubitril/valsartan in the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) with a clear focus on the effect it bestows on measures of physical exercise tolerance and quality of life. A thorough systematic search was done in databases including Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Embase, and PubMed from 1 January 2010 to 1 January 2023. The search only included published RCTs on adult patients aged 18 and above, with heart failure with reduced ejection fraction (HFrEF). Data analysis was performed by using the software RevMan 5.4 (Cochrane Collaboration, London, United Kingdom). The included studies' bias risk was assessed using the Cochrane Collaboration's Risk of Bias tool. The quality of evidence for the primary outcome was done using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. This systematic review and meta-analysis of RCTs yielded 458 studies, of which eight randomized clinical trials were included and analyzed. The meta-analysis of the included trials shows that the I2 value is 61% (i.e., I2 > 50%), demonstrating a substantial heterogeneity within the studies. The left ventricular ejection fraction (LVEF) expressed in percentage was reported in the five studies, and thereby, a subgroup analysis that yielded a confidence interval (CI) of 95% had the standard mean difference of 0.02 (-0.02, 0.07). The trials had disparity between the reporting of effect on peak oxygen consumption (VO2), measured through cardiopulmonary exercise testing (CPET) methods, six-minute walking test (6MWT), overall physical activity, and exercise capacity. Sacubitril/valsartan did not exponentially improve peak VO2 or 6MWT in these trials; however, the patient-reported data suggested that the quality of life was modestly influenced by the drug. A subgroup analysis was performed using the pooled effect value by the random effects model. The findings showed that the sacubitril/valsartan group significantly was better than the control group in improving HFrEF-associated health-related quality of life (HRQoL). This study is a systematic review and meta-analysis of randomized clinical trials that evaluated the drug sacubitril/valsartan in treating heart failure with reduced ejection fraction (HFrEF) and focused on its tangible effect on the measures of physical exercise tolerance and quality of life. It depicts that the statistical scrutiny due to the lack of significant data and parity across studies did not impart significant improvement of either LVEF, peak VO2, or 6MWT with the use of sacubitril/valsartan; however, the reported exercise tolerance, including daytime physical activity, had a modest impact with the said drug. The pooled values demonstrated that the sacubitril/valsartan group significantly outperformed the control group in improving HFrEF HRQoL.

The correlation between six-minute walking distance and maximum phonation time in healthy adults.

Objectives: This study aimed to determine the association between six-minute walking distance (6MWD) and maximum phonation time (MPT) in healthy adults. Patients and methods: The cross-sectional study was conducted with 50 sedentary nonsingers (32 females, 18 males; mean age: 33.5±8.3 years; range, 18 to 50 years) between February 2021 and April 2021. Subjects with a history of smoking, respiratory symptoms in the last two weeks, and heart, lung, musculoskeletal, and balance problems were excluded. The measurements of MPT and 6MWD were carried out by two different assessors blinded to each other. Results: The mean MPT was higher in male subjects (27.4±7.4 sec vs. 20.6±5.1 sec, p<0.001). In the bivariate analysis, there was a significant correlation between MPT and 6MWD (r=0.621, p<0.001), as well as body height (r=0.421, p=0.002) and the mean fundamental frequency (r=-0.429, p=0.002); however, no association was found with age, body weight, and the mean sound pressure level. After multiple regression, 6MWD was the only factor associated with MPT (p=0.002). Conclusion: There is a significant association between 6MWD and MPT in healthy adults, and the results suggest that aerobic capacity might have a role in improving the ability to sustain phonation.

Thirty-second sit-to-stand test as an alternative for estimating peak oxygen uptake and 6-min walking distance in women with breast cancer: a cross-sectional study.

PURPOSE: To determine whether the 30-s sit-to-stand (30STS) test can be a valid tool for estimating and stratifying peak oxygen uptake (VO2peak) and 6-min walking distance (6MWD) in women with breast cancer. METHODS: This cross-sectional study uses data from the ONCORE randomized controlled trial, including 120 women aged 18-70 years with early-stage breast cancer under treatment with anthracycline and/or anti-HER2 antibodies. Participant characteristics were collected at baseline and pooled data from functional assessment (30STS test, relative and absolute VO2peak, and 6MWD) were collected at baseline and post-intervention (comprehensive cardio-oncology rehabilitation program vs. usual care). Bivariate correlations and multivariate linear regression analyses were performed to study the relationship between functional test variables. RESULTS: The number of repetitions in the 30STS test showed (i) a moderate correlation with relative VO2peak (ml/kg/min) (r = 0.419; p < 0.001; n = 126), (ii) a weak correlation with absolute VO2peak (ml/min) (r = 0.241; p = 0.008; n = 120), and (iii) a moderate correlation with the 6MWD (r = 0.440; p < 0.001; n = 85). The ONCORE equations obtained from the multivariate regression models allowed the estimation of VO2peak and 6MWD (r2 = 0.390; r2 = 0.261, respectively) based on the 30STS test, and its stratification into tertiles (low, moderate, and high). CONCLUSION: The 30STS test was found to be a useful tool to estimate VO2peak and/or 6MWD in women with early-stage breast cancer. Its use may facilitate the assessment and stratification of functional capacity in this population for the implementation of therapeutic exercise programs if cardiopulmonary exercise testing (CPET) or 6MWT are not available. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03964142. Registered on 28 May 2019. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03964142.

Cardiorespiratory coupling is associated with exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. METHODS: This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). RESULTS: The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64-0.97), n = 43) and a desynchronized group (median 0.23 (0.02-0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. CONCLUSION: This is the first result studying the heart-lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Effect of high-flow nasal therapy during early pulmonary rehabilitation in patients with severe AECOPD: a randomized controlled study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is airway inflammation characterized and low daily physical activity. Most pulmonary rehabilitation (PR) programs are often provided to stable patients, but fewer training programs are specific for hospitalized patients with acute exacerbation (AE). Patients with AECOPD experience increased dyspnea sensations and systemic inflammation during exercise training. High-flow nasal therapy (HFNT) reduces the minute volume, lowers the respiratory rate, and decreases the work of breathing. However, it is not clear whether HFNT is efficient during exercise training. In this study, we investigated the effects of HFNT during exercise training in an early PR program among hospitalized patients with severe AECOPD. METHODS: We enrolled COPD patients hospitalized due to AE. They were randomized into two groups according to their status into HFNT PR and non-HFNT PR groups. This study collected basic data, and also assessed a pulmonary function test, 6-min walking test, blood inflammatory biomarkers, and arterial gas analysis at the baseline, and at 4 and 12 weeks of the intervention. Data were analyzed using SPSS statistical software. RESULT: We recruited 44 AECOPD patients who completed the 12-week PR program. The HFNT PR program produced significant improvements in exercise tolerance as assessed by the 6-min walking distance (6MWD), reduced dyspnea sensations in the modified Medical Research Council (mMRC), and decreased systemic inflammation as evidenced by the a lower C-reactive protein (CRP) level. A reduction in the length of hospitalization was achieved with PR in the 1-year follow-up in the two groups. The HFNT PR group showed better trends of reduced air trapping in the delta inspiration capacity (IC) and an increased quality of life according to the COPD assessment test (CAT) than did the non-HFNT PR group. CONCLUSIONS: HFNT during exercise training in early PR increases exercise tolerance and reduces systemic inflammation in hospitalized patients with severe AECOPD.

Impact of age on the recovery of six-minute walking distance after lung cancer surgery: a retrospective cohort study.

PURPOSE: The aim was to investigate the relationship of age for recovery of six-minute walking distance (6MWD), pulmonary function, and health-related quality of life (HRQOL) after lung cancer surgery. METHODS: Primary outcome was the 6MWD recovery until 6 months after surgery. Secondary outcome was the recoveries of forced expiratory volume in 1 s (FEV1) and HRQOL until 6 months after surgery. Linear mixed-effects model was used to estimate the association of age to the outcomes. RESULTS: A total of 311 lung cancer patients were included. All the 6MWD, FEV1, and HRQOL decreased after surgery (- 32 m, - 0.39L, and - 2 scores, respectively, p = 0.027-p < 0.001). While 6MWD increased every month after surgery (5 m/month, 95% confidence interval (CI); 4-7, p < 0.001), the recovery decreased, as the age increased 1 standard deviation (SD) (i.e., 9 years) (- 2 m/month; 95% CI - 3 to - 1, p < 0.001). While FEV1 increased every month after surgery (0.03 L/month; 95% CI 0.02-0.03, p < 0.001), the recovery increased, as the age increased by 1 SD (0.01 L/month; 95% CI 0.00-0.01, p = 0.003), which was opposite to the 6MWD recovery. While the postoperative HRQOL recovered every month (2 score/month; 95% CI 1-2, p < 0.001), there was no significant association between the recovery and age (0 score/month; 95% CI - 1 to 0, p = 0.5). CONCLUSIONS: The 6MWD recovery delayed in elderly patients, which was not related to their FEV1-and HRQOL recoveries. Postoperative walking training would be important for the elderly lung cancer patients.

Preoperative exercise capacity is associated with the prevalence of postoperative delirium in elective cardiac surgery.

BACKGROUND: Postoperative delirium (POD) is a critical complication that is closely associated with mortality and major morbidity in elective cardiac surgery. The identification of patients at risk for POD is crucial but has not been fully explored. AIMS: The aim of this study was to determine the predictive value of the assessment of preoperative exercise capacity for POD. METHODS: We enrolled 313 consecutive patients (mean age, 68.6 ± 14.8 years) undergoing elective cardiac surgery. We measured physical functions such as the 6-minute walking distance (6MWD) and Timed Up-and-Go test (TUG) before surgery. The assessment of delirium was conducted every 8 h from the day of surgery to 5 days after surgery using the Intensive Care Delirium Screening Checklist. RESULTS: POD occurred in 46 patients (14.6%). Age, 6MWD, TUG, serum hemoglobin, estimated glomerular filtration rate, and length of intensive care unit stay were significantly different based on the presence or absence of POD (p < 0.05 for each). After multivariate analysis, 6MWD remained a statistically significant indicator for developing POD (OR 0.98; p = 0.02). The cut-off value of 6MWD for predicting POD was 345 m (AUC = 0.75; p = 0.001). CONCLUSIONS: Poor exercise capacity was found to be an independent predictor of POD following elective cardiac surgery. This finding suggests the importance of preoperative functional evaluation in the prevention and management of POD in cardiac surgery patients.

A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy.

This 48-week, randomized, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. A nonsignificant treatment difference (P = 0.415) in the change from baseline in six-minute walk distance (6MWD; primary efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week 48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair climb ascent velocity, and 10-meter walk/run velocity) gave consistent findings. Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity. The increased standard deviation alone, due to less stringent inclusion/exclusion criteria, reduced the statistical power from pre-specified 90% to actual 53%. Therefore, a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300-400 meters and ability to rise from floor. A statistically significant improvement in 6MWD of 35.4 meters (P = 0.039) in favor of drisapersen was observed in this subpopulation. Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects.

Pulmonary rehabilitation for patients with moderate or severe obstructive pulmonary disease / 中华物理医学与康复杂志

Objective To observe any curative effect of applying comprehensive pulmonary rehabilitation in moderate and severe cases of chronic obstructive pulmonary disease (COPD).Methods A total of 135 persons hospitalized with moderate or severe COPD were randomly divided into a rehabilitation group of 75 and acontrol group of 60.Both groups were given routine treatment,while the rehabilitation group was additionally provided with a comprehensive pulmonary rehabilitation regimen,including health education,exercise training,respiratory function training,respiratory muscle training,psychological support and nutritional intervention for six months.Before and after the treatment,both groups were evaluated using their walking distance within 6 minutes (6MWD),an anhelation index,a COPD assessment test (CAT),the Beck anxiety and depression scale,a nutritional assessment and indexes of pulmonary function and blood gases.Results After the intervention the average 6 MWD,anhelation index,CAT score,Beck anxiety and depression scores,forced expiratory volume,forced vital capacity and PaO2 of the rehabilitation group were all significantly better than before the treatment and better than those of the control group.Conclusion For moderate and severe COPD patients,comprehensive pulmonary rehabilitation effectively strengthens their moving ability,pulmonary function and arterial partial pressure of oxygen,while relieving anhelation,anxiety and depression.

Effects of Tai Chi on exercise capacity and health-related quality of life in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Tai Chi is a traditional Chinese mind-body exercise that has been widely practiced in the People's Republic of China for many centuries. This exercise has also been applied as a training modality in pulmonary rehabilitation programs for stable chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis aimed to assess the effects of Tai Chi on exercise capacity and health-related quality of life (HRQoL) in COPD patients. METHODS: Electronic databases (PubMed, Embase, Web of Science, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, China National Knowledge Infrastructure, and China Biology Medicine disc) were searched. Entries published from January 1980 to March 2014 were included in the search. Eligible studies included those that involved randomized controlled trials and those that lasted for at least 12 weeks. The primary outcome measures were six-minute walking distance (6 MWD), St George's Respiratory Questionnaire (SGRQ), and Chronic Respiratory Disease Questionnaire (CRQ). Effect estimates were pooled with random-effects meta-analysis. RESULTS: Eleven articles involving 824 patients met the inclusion criteria. All included articles compared COPD patients in a Tai Chi group versus COPD patients in nonexercise and/or physical exercise groups. The meta-analysis showed that compared with the nonexercise group, the COPD patients practicing Tai Chi demonstrated significantly enhanced 6 MWD (mean difference 35.99, 95% confidence interval [CI] 15.63-56.35, P=0.0005), decreased SGRQ total score (mean difference -10.02, 95% CI -17.59, -2.45, P=0.009), and increased CRQ total score (mean difference 0.95, 95% CI 0.22-1.67, P=0.01). Compared with the physical exercise group, the Tai Chi group showed significantly reduced SGRQ total score (mean difference -3.52, 95% CI -6.07, -0.97, P=0.007), but no statistical significance was found for 6 MWD between the two groups (mean difference 13.65, 95% CI -1.06, 28.37, P=0.07) in COPD patients. CONCLUSION: Preliminary evidence suggests that Tai Chi has beneficial effects on exercise capacity and HRQoL in COPD patients. This exercise can be recommended as an effective alternative training modality in pulmonary rehabilitation programs. Further studies are required to support the preliminary evidence and to observe the long-term effects of Tai Chi.

Functional and psychological variables both affect daily physical activity in COPD: a structural equations model.

BACKGROUND: Daily physical activity (DPA) level is reduced in patients with COPD. The aim of this study was to investigate the association of DPA with functional and psychological variables in these patients. METHODS: 155 COPD patients (102 males, median (IQR) age 62 years (54-69 years), predicted FEV1 60% (40-75%) were included. We assessed DPA (DigiWalker SW-200), functional capacity and psychological factors. RESULTS: DPA level was significantly associated with all functional capacity variables and two psychological variables (Perceived Physical Ability Subscale, depression subscale of the Hospital Anxiety and Depression Scale). The six-minute walking distance and St. George Respiratory Questionnaire activity score explained 37% of the variance of DPA in a regression analysis. A structural equations model revealed that psychological variables indirectly explained DPA through functional capacity variables. DPA was stronger associated with functional capacity variables and weaker with psychological variables in patients with lower functional status than in patients with higher functional status. CONCLUSIONS: Higher levels of DPA are associated with better functional capacity, but interestingly, DPA is also affected by psychological factors, though only indirectly, via functional capacity. The effect of specific treatment addressing psychological factors on DPA level and exercise tolerance needs further investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00614796.

Changes in six-minute walking distance during pulmonary rehabilitation in patients with COPD and in healthy subjects.

BACKGROUND: The six-minute walking distance (6MWD) test has demonstrated validity and reliability to assess changes in functional capacity following pulmonary rehabilitation in patients with chronic obstructive lung disease. However, no attempt has been made to establish an iterative measurement of 6MWD during the overall period of pulmonary rehabilitation. Therefore, the aim of this study was to evaluate the impact of a twelve-week rehabilitation program on the iterative weekly measurement of 6MWD in chronic obstructive pulmonary disease (COPD) patients and healthy subjects. METHODS: Twenty-six patients with COPD and nine age-matched healthy subjects were studied. Measurements were taken at baseline and after twelve weeks except for the 6MWD. The exercise measurements included a six-minute walking test (6MWT) and an incremental exercise test. Oxygen saturation, heart rate, and dyspnea will be monitored during all these tests. RESULTS: At baseline there were significant differences between groups, except in age, body mass index, and oxygen saturation. After 12 weeks, there was no significant change in lung function in patients with COPD and healthy subjects. The 6MWD, peak oxygen uptake (.)VO(2peak) and anaerobic threshold increased significantly after training in both groups (P < 0.01). The averaged trace of the 6MWD of patients with COPD and healthy subjects was followed-up respectively by a logarithmic and linear fitting. 6MWD showed a plateau after eight weeks in patients with COPD, however, it increased continually overall in healthy subjects. CONCLUSION: Both patients with COPD and healthy subjects demonstrated functional responses to training but with somewhat different patterns in quality of the improvement of the 6MWD.