Lifestyle Walking Intervention for Patients With Heart Failure With Reduced Ejection Fraction: The WATCHFUL Trial.

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

Preworkout dietary nitrate magnifies training-induced benefits to physical function in late postmenopausal women: a randomized pilot study.

To inform end points for future work, we explored the utility of preworkout (i.e., an acute dose before training) beetroot juice (BRJ) combined with exercise (BRJ + EX) to augment indices of physical function in postmenopausal women compared with exercise only (EX). A two-arm pilot study was used to compare 24 postmenopausal women following an 8-wk, circuit-based exercise intervention. Participants were randomized to BRJ + EX (n = 12) or EX (n = 12). BRJ + EX participants consumed 140 mL of BRJ 120-180 min (only) before training for 7 wk, then discontinued during the final week to mitigate carryover effects. Physical function indices were 6-min walk test (6MWT), estimated V̇o2peak, heart rate recovery (HRR), and maximal knee extensor power (Pmax). A treadmill task was used to measure V̇o2 on-kinetics wherein mean response time (MRT) coincided with the duration to reach 63% of steady-state V̇o2. Results showed greater changes (Δ) among BRJ + EX participants for 6MWT distance (40 ± 23 m vs. 8 ± 25 m; P = 0.003, d = 1.35), ΔV̇o2peak (1.5 ± 0.9 mL·kg-1·min-1 vs. 0.3 ± 1.0 mL·kg-1·min-1; P = 0.008, d = 1.20), and ΔHRR (-10 ± 6 beats/min vs. -1 ± 9 beats/min; P = 0.017, d = 1.05). Large and medium effect sizes favoring BRJ + EX were detected for ΔPmax (P = 0.07, d = 0.83) and ΔMRT (P = 0.257, d = 0.50), respectively. In postmenopausal women, BRJ + EX appears to magnify some adaptive benefits to physical function including aerobic capacity and recovery beyond that of training without BRJ. Investigation into contributing mechanisms is needed.NEW & NOTEWORTHY Though exercise training represents the principal strategy to combat age-related decline, the attendant effects of menopause weaken aspects of exercise adaptation compared with premenopausal women and age-matched men. Here we provide important initial evidence that preworkout (i.e., an acute dose before training) beetroot juice coupled with an 8-wk, circuit-based exercise training intervention may uniquely benefit late postmenopausal women by enhancing indices of physical function including aerobic capacity and recovery.

Associations between 6-minute walk distance and physiologic measures and clinical outcomes in myositis-associated interstitial lung disease.

OBJECTIVE: The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD). METHOD: We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high resolution CT, and various physician/patient reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally. RESULTS: Twenty participants with a median age of 57, 55% male and 85% white were analyzed. Baseline 6MWD did not associate with baseline PFTs. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with UCSD dyspnea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by short form 36 also correlated with 6MWD over time. CONCLUSIONS: : Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient reported outcomes of dyspnea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03215927.

Performance fatigability in adults with spinal muscular atrophy treated long-term with nusinersen.

INTRODUCTION/AIMS: Persons with spinal muscular atrophy (pwSMA) report progressive muscle weakness but also reduced endurance when performing repetitive tasks in daily life, referred to as "performance fatigability" (PF). Data regarding the effects of the new disease-modifying drugs on PF are scarce. Thus, our main objective was to examine PF in adult ambulatory pwSMA treated long-term with nusinersen. METHODS: Six-minute walk test (6MWT) data from 14 adult pwSMA treated with nusinersen for up to 70 months were retrospectively analyzed to determine PF. Performance fatigability was defined as the percentage change in the distance covered between the last and first minute of the 6MWT. In addition, relationships between PF and other clinical features were assessed. RESULTS: Performance fatigability was found in 12/14 pwSMA (85.7%) prior to treatment. The mean distance walked in the sixth minute (71.1 m) was shorter than the distance covered in the first minute (81.8 m), corresponding to a mean PF of 13.1% (95% confidence interval (CI): 6.5-19.6, p = .0007). During treatment with nusinersen, there was a mean reduction in PF of 5.6% (95% CI: -10.0 to -1.3, p = .0148). We found no relationship between PF and fatigue as measured by the Fatigue Severity Scale. DISCUSSION: This study demonstrates the presence of PF as an independent component of motor impairment and as a potential therapeutic target in our cohort of adult ambulatory pwSMA. Furthermore, the observations in our cohort suggest that nusinersen may have a beneficial effect on PF.

Establishing how much improvement in lung function and distance walked is clinically important for adult patients with Pompe disease.

BACKGROUND AND PURPOSE: Pompe disease is a rare, inheritable, progressive metabolic myopathy. This study aimed to estimate the minimal clinically important difference (MCID) for an improvement in forced vital capacity in the upright seated position (FVCup) and the 6-min walk test (6MWT) after a year of treatment with enzyme replacement therapy. METHODS: Data were obtained from two prospective follow-up studies. Between-group and within-group MCIDs were estimated using anchor-based methods. Additionally, a distribution-based method was used to generate supportive evidence. As anchors, self-reported change in health and in physical functioning, shortness of breath and a categorization of the Short-Form 36 Physical Component Summary score were used. Anchor appropriateness was assessed using Spearman correlations (absolute values ≥0.29) and a sufficient number of observations in each category. RESULTS: In all, 102 patients had at least one FVCup or 6MWT measurement during enzyme replacement therapy. Based on the anchors assessed as appropriate, the between-group MCID for an improvement in FVCup ranged from 2.47% to 4.83% points. For the 6MWT, it ranged from 0.35% to 7.47% points which is equivalent to a distance of 2.18-46.61 m and 1.97-42.13 m for, respectively, a man and a woman of age 50, height 1.75 m and weight 80 kg. The results of the distribution-based method were within these ranges when applied to change in the outcome values. CONCLUSION: The MCIDs for FVCup and 6MWT derived in this study can be used to interpret differences between and within groups of patients with Pompe disease in clinical trials and cohort studies.

What Happens to Frailty in the First Year After Lung Transplantation?

BACKGROUND: Frailty is prevalent in lung transplant (LTx) candidates, but the impact and subsequent frailty trajectory is unclear. This study aimed to investigate frailty over the first year after LTx. METHOD: Post-LTx recipients completed a thrice weekly 12-week directly supervised exercise rehabilitation program. Edmonton Frail Scale (EFS) was used to assess frailty. Primary outcome was 6-Minute Walk Distance (6MWD) measured at pre-LTx, prerehabilitation, postrehabilitation, and 1 year post-LTx. RESULTS: 106 of 139 recruited participants underwent LTx: mean age 58 years, 48% male, 52% with chronic obstructive pulmonary disease. Mean (± SD) frailty scores pre-LTx and 1 year post-LTx were 5.54 ± 2.4 and 3.28 ±1.5. Mean 6MWD improved significantly for all: prerehabilitation 326 m (SD 116), versus postrehabilitation 523 m (SD 101) (p < 0.001) versus 1 year 512 m (SD 120) (p < 0.001). There were significant differences between an EFS > 7 (frail) and EFS ≤ 7 (not frail) for 6MWD, grip strength (GS), anxiety, and depression. Postrehabilitation, there were no significant differences in 6MWD, GS, anxiety, or depression while comparing EFS > 7 versus ≤ 7. At 1 year, there was a significant difference in depression but not 6MWD, GS, or anxiety between those EFS ≤ 7 and > 7 (p = 0.017). CONCLUSION: Participants in a structured post-LTx rehabilitation program improved in functional exercise capacity (6MWD), GS, depression, and anxiety. For frail participants exercise capacity, depression, anxiety, and GS were well managed in rehabilitation with no significant differences between those who were not frail. Pre-LTx frailty may be reversible post-LTx and should not be an absolute contraindication to LTx.

Hippocampal functional connectivity mediates the association between cardiorespiratory fitness and cognitive function in healthy young adults.

OBJECTIVE: Higher cardiorespiratory fitness (CRF) induces neuroprotective effects in the hippocampus, a key brain region for memory and learning. We investigated the association between CRF and functional connectivity (FC) of the hippocampus in healthy young adults. We also examined the association between hippocampal FC and neurocognitive function. Lastly, we tested whether hippocampal FC mediates the association between 2-Min Walk Test (2MWT) and neurocognitive function. METHODS: 913 young adults (28.7 ± 3.7 years) from the Human Connectome Project were included in the analyses. The 2MWT performance result was used as a proxy for cardiovascular endurance. Fluid and crystalized composite neurocognitive scores were used to assess cognition. Resting-state functional MRI data were processed to measure hippocampal FC. Linear regression was used to examine the association between 2MWT, hippocampal FC, and neurocognitive outcomes after controlling for age, sex, years of education, body mass index, systolic blood pressure, and gait speed. RESULTS: Better 2MWT performance was associated with greater FC between the anterior hippocampus and right posterior cingulate and left middle temporal gyrus. No associations between 2MWT and posterior hippocampal FC, whole hippocampal FC, and caudate FC (control region) were observed. Greater anterior hippocampal FC was associated with better crystalized cognition scores. Lastly, greater FC between the anterior hippocampus and right posterior cingulate mediated the association between better 2MWT scores and higher crystalized cognition scores. CONCLUSIONS: Anterior hippocampal FC may be one underlying neurophysiological mechanism that promotes the association between 2MWT performance and crystalized composite cognitive function in healthy young adults.

Impact of Body Mass Index and VO2 Max on Symptoms, Physical Activity, and Physical Function in a Multinational Sample of People with HIV.

People with HIV (PWH) are at increased risk for metabolic disorders affecting body mass index (BMI), chronic symptoms, and impaired physical function and capacity. Although physical activity improves health and well-being, PWH often do not meet activity recommendations necessary to achieve these benefits. Despite the known impact of symptoms, physical activity, and physical function on health, little is known about the relationships and interactions between these variables and BMI and maximum oxygen consumption during exercise (VO2 max) in a multinational population of PWH. We examined the relationship of BMI with PROMIS-29 measures, physical activity, strength, flexibility, and VO2 max in a diverse sample of PWH. Additionally, we examined the relationship of VO2 max with PROMIS-29 measures. Data from 810 PWH who participated in a cross-sectional study conducted by the International Nursing Network for HIV Research (Study VII) were analyzed. Participants were recruited from 8 sites across the United States, Thailand, and South Africa. BMI was calculated from collected height and weight data. Physical function and symptoms were assessed using the PROMIS-29 measure. Physical activity was assessed using the 7-day Physical Activity Recall. VO2 max was calculated using sex at birth, age, BMI and the 6-minute Walk Test. Data were analyzed using descriptive, correlational, and regression statistical analyses. Participants had an average age of 49.1 (± 11.1) years, 44% were female, and the average BMI of the sample group was 27 kg/m2 (± 6.7). Increased BMI was associated with decreased 6-minute Walk Test (ß=-2.18, p < 0.001), flexibility (ß=-0.279, p < 0.001), and VO2 max (ß=-0.598, p < 0.001), even after controlling for covariates (age, sex at birth, country, years living with HIV, and antiretroviral therapy status). BMI was not associated with self-reported physical activity. Increased VO2 max was associated with increased physical function (ß = 0.069, p < 0.001), and decreased pain (ß=-0.047, p < 0.006), even after controlling for covariates (country, years living with HIV, and antiretroviral therapy status). Future research should explore development of effective and sustainable symptom self-management interventions in PWH accounting for the potential impact of BMI and VO2 max.

Quality of life and somatic physical function of patients with colorectal cancer who underwent oxaliplatin-based systemic chemotherapy: a prospective study.

INTRODUCTION: This study aimed to study the potential effects of oxaliplatin-based chemotherapy on cardiorespiratory fitness, handgrip strength (HGS), body composition, and quality of life (QoL) of stages III-IV colorectal cancer (CRC) patients before the first cycle (T0) and after the last cycle of systemic adjuvant/neoadjuvant chemotherapy (T1). METHODS: Cardiorespiratory fitness, HGS, body composition, and QoL were evaluated with the six-minute walk test (6MWT), hydraulic hand dynamometer, body composition analyzer, and Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire in both T0 and T1, respectively. RESULTS: Twenty-eight CRC patients were included in this study. The total walked distance (TWD) was found to be decreased from T0 to T1 (499.72 m vs. 488.56 m); however, this change was not significant (z = -.706, p = 0.48). Type of chemotherapy whether adjuvant or neoadjuvant also showed no significant effect on TWD (z = -.1.372, p = .17 vs z = -1.180, p = .238, respectively). The QoL was significantly decreased (T0 = 118.35 vs T1 = 110.77, t = 2.176,p = 0.05). The TWD was significantly correlated with the physical well-being (PWB) subscale of FACT-C (r = .64, p = 0.001) as well as with HGS (r = .46, p = .018) in T0. After controlling for age, type of chemotherapy, and type of regimen, the HGS did not show a significant difference from T0 to T1 (F(1,23) = 1.557, p = .22, ηp2 = .06). However, the effect of time x gender showed significant difference from T0 to T1 (F(1,23) = 4.906, p = .037, ηp2 = .17). CONCLUSION: This study showed the decreased QoL and physical well-being of CRC patients who underwent oxaliplatin-based treatment. In addition, the gender effect of decreased HGS should be considered further when planning an oncological rehabilitation program.

Recovery of surgery in the elderly (ROSE) program: The efficacy of a multi-modal prehabilitation program implemented in frail and pre-frail elderly undergoing major abdominal surgery.

BACKGROUND: Major abdominal surgery is associated with a high rate of post-operative complications with increased risk of adverse surgical outcomes due to the presence of frailty. This study aims to evaluate the effectiveness of the multimodal Recovery of Surgery in the Elderly (ROSE) prehabilitation program with supervised exercise in mitigating postoperative functional decline when compared to standard care. METHOD: The ROSE program enrolled ambulant patients who were 65 years and above, had a Clinical Frailty Scale score of 4 or more and were planned for major abdominal surgery. Participation in supervised exercise sessions before surgery were compared with standard physiotherapy advice. The primary outcome was 6-min walk test (6MWT) distance assessed at baseline, after prehabilitation and 30 days follow-up after surgery. Secondary outcomes included physical performance, length of hospital stay and postoperative morbidity. RESULTS: Data from 74 eligible patients, 37 in each group, were included. Median age was 78 years old. Forty-two patients (22 in Prehab group and 20 in control group) with complete 6MWT follow-up data at 30 days follow-up were analysed for outcomes. Most patients underwent laparoscopic surgery (63.5%) and almost all of the surgeries were for abdominal malignancies (97.3%). The Prehab group had an increase in 6MWT distance at the 30-day follow up, from a baseline mean (SD) of 277.4 (125) m to 287.6 (143.5) m (p = 0.415). The 6MWT distance in the control group decreased from a baseline mean (SD) of 281.7 (100.5) m to 260.1 (78.6) m at the 30-day follow up (p = 0.086). After adjusting for baseline 6MWT distance and frailty score, the Prehab group had significantly higher 6MWT distance at 30-day follow-up than control (difference in adjusted means 41.7 m, 95% confidence interval 8.7-74.8 m, p = 0.015). There were no significant between-group differences in the secondary outcomes. CONCLUSION: A multimodal prehabilitation program with supervised exercise within a short time frame can improve preoperative functional capacity and maintain baseline functional capacity in frail older adults undergoing major abdominal surgery.

The heart rate response to the 6-min walk test in atrial fibrillation patients with or without beta-blockers: Referring to patients with sinus rhythm.

BACKGROUND: The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF patients treated with BB have a similar HR response to 6MWT as the AF and sinus rhythm (SR) patients without BB treatment at the same resting HR level. METHODS: The before-after study involving 74 AF patients was to evaluate the effect of BB treatment (pre-BB and with BB). The comparison study included 74 BB-treated AF patients (with BB), 74 matched AF patients without BB (no BB), and 74 SR patients. The percentage increase amplitude of HR (HR-PIA) in 6MWT was calculated: [(the exercise HR - the resting HR)/(the resting HR)] × 100%. RESULTS: The before-after study showed that BB treatment decreased the resting and mean exercise HR (98.6 ± 15.2 vs. 85.5 ± 11.2 bpm and 121.3 ± 17.3 vs. 109.0 ± 16.7 bpm) during 6MWT. The comparison study demonstrated that against the SR, the AF with BB and no BB groups have higher mean exercise HR-PIA (28.2 ± 17.1% and 22.0 ± 9.6%, vs. 6.9 ± 3.7%) when their resting HR is similar. Moreover, the mean exercise HR-PIA was also significantly higher in the with BB group than in the no BB group. CONCLUSION: In AF patients with relatively higher resting HR, BB treatment could decrease the resting and exercise HR during 6MWT. However, BB treatment could not effectively attenuate the exercise HR rise as compared with AF without BB treatment, even with similar resting HR levels.

Percent Predicted vs. Absolute Six-Minute Walk Distance as Predictors of Lung Transplant-Free Survival in Fibrosing Interstitial Lung Diseases.

INTRODUCTION: Fibrosing interstitial lung diseases (ILDs) often progress despite treatment and become life-threatening, with lung transplant (LTx) remaining the only curative option. Six-minute walk distance (6MWD) is increasingly recognized as reliable predictor of clinical course, especially when longitudinally considered. The use of reference equations to express 6MWD as percent predicted (6MWD%) has not been previously studied in fibrosing ILDs. We sought to investigate whether the prognostic power of 6MWD% is superior to that of 6MWD expressed in meters (6MWD-m). METHODS: A retrospective, multicenter cohort analysis was conducted on both idiopathic pulmonary (IPF) and non-IPF fibrosing ILD patients. Patients were divided into a discovery (n = 211) and a validation (n = 260) cohort. Longitudinal changes of 6MWD% and lung function parameters were simultaneously considered. LTx-free survival at 3 years from baseline was the endpoint. Competing risks of death and LTx were considered. RESULTS: Baseline 6MWD% and its longitudinal changes were significant predictors of LTx-free survival and independent from lung function variables. In both cohorts, on multivariate cox proportional hazard regression analysis, receiver operating characteristics analysis and Kaplan-Meier estimates, 6MWD% was consistently, but only slightly superior to 6MWD-m as a predictor of LTx-free survival. CONCLUSION: 6MWD% has only a slight, yet detectable advantage over 6MWD-m as a predictor of survival in fibrosing ILDs. Utilizing 6MWD% may aid in risk stratification, treatment monitoring, and LTx timing optimization. However, available reference equations do have predicting limitations. Refined predictive equations and standardizing reporting practices are therefore needed to further enhance the clinical utility of 6MWD% in fibrosing ILDs.

Minimal Clinically Important Difference in the 6-minute-walk Distance for Patients with Pulmonary Arterial Hypertension.

Rationale: The 6-minute-walk distance (6MWD) is an important clinical and research metric in pulmonary arterial hypertension (PAH); however, there is no consensus about what minimal change in 6MWD is clinically significant. Objectives: We aimed to determine the minimal clinically important difference in the 6MWD. Methods: We performed a meta-analysis using individual participant data from eight randomized clinical trials of therapy for PAH submitted to the U.S. Food and Drug Administration to derive minimal clinically important differences in the 6MWD. The estimates were externally validated using the Pulmonary Hypertension Association Registry. We anchored the change in 6MWD to the change in the Medical Outcomes Survey Short Form physical component score. Measurements and Main Results: The derivation (clinical trial) and validation (Pulmonary Hypertension Association Registry) samples were comprised of 2,404 and 537 adult patients with PAH, respectively. The mean ± standard deviation age of the derivation sample was 50.5 ± 15.2 years, and 1,849 (77%) were female, similar to the validation sample. The minimal clinically important difference in the derivation sample was 33 meters (95% confidence interval, 27-38), which was almost identical to that in the validation sample (36 m [95% confidence interval, 29-43]). The minimal clinically important difference did not differ by age, sex, race, pulmonary hypertension etiology, body mass index, use of background therapy, or World Health Organization functional class. Conclusions: We estimated a 6MWD minimal clinically important difference of approximately 33 meters for adults with PAH. Our findings can be applied to the design of clinical trials of therapies for PAH.

Validity and reliability of measurement of peripheral oxygen saturation during the 6-Minute Walk Test in patients with systemic sclerosis.

Peripheral oxygen saturation (SpO2) using the fingers may have important limitations due to Raynaud's phenomenon and sclerodactyly in patients with systemic sclerosis (SSc). Sensors located at more central body positions may be more accurate as these as less prone to Raynaud attacks. To determine the validity and reliability of the SpO2 measured at the finger, forehead, and earlobe during the 6-Minute Walk Test (6MWT). Eighty two patients with SSc had an arterial line placed while performing the 6MWT. Peripheral oxygen saturation was simultaneously measured by finger, forehead, and earlobe sensors and compared to the arterial oxygen saturation (SaO2) measured before and after the 6MWT. 40 patients repeated the 6MWT one week later to determine re-test reliability. We used Bland-Altman plots to display the agreement between SpO2 and SaO2. The intraclass correlation coefficient for repeated measurement of minimum SpO2 was calculated. The mean difference between SpO2 and SaO2 after the 6MWT was - 3% (SD: ± 5), 0% (SD: ± 2), and 1% (SD: ± 2) for the finger, forehead, and earlobe, respectively. The minimum SpO2 measured at the finger demonstrated the poorest re-test reliability: The ICC (95% CI) showed good agreement using the ear and forehead probe (ICCear = 0.89 [95% CI 0.80; 0.94]; ICCforehead = 0.77 [95% CI 0.60; 0.87]), while a modest reliability was found using the finger probe (ICCfinger = 0.65 95% CI [0.43; 0.80]). SpO2 should be measured using either the earlobe or forehead during the 6MWT in patients with SSc. Clinical Trials.Gov (NCT04650659).

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial.

BACKGROUND: Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease. METHODS: In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension. RESULTS: Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33). CONCLUSION: In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. TRIAL REGISTRATION: (NCT03873298, MOH_2018-04-24_002331).

Understanding changes in pulmonary function and functional status in breast cancer patients after systemic chemotherapy and radiotherapy: a prospective study.

BACKGROUND: Respiratory complications in breast cancer (BC) patients after chemotherapy (CT) and radiotherapy (RT) have been well acquainted and these complications should be investigated to prevent secondary problems and/or improve BC patients' clinical outcomes. Therefore, this study aimed to assess the potential acute effect of systemic chemotherapy and radiotherapy on respiratory function and functional status of patients with breast cancer. METHODS: A total of 25 BC patients who were candidates for systemic chemotherapy and radiotherapy were recruited after oncological examination and included in this study. Respiratory function and functional status were assessed with the Pulmonary Function Test (PFT) and the Six-Minute Walk Test (6MWT), respectively. Patients were assessed before CT (c0), after CT (c1), and after RT (r1). RESULTS: 25 BC patients were assessed in c0 and c1 while only 15 out of 25 patients (60%) were assessed in r1. The actual values of Forced vital capacity (FVC) (t = 2.338, p =.028), Forced expiratory volume in 1s (FEV1 (t = 2.708, p =.012), and the forced expiratory flow of between 25% and 75% of vital capacity (FEF25-75%) (t = 2.200, p =.038) were found significantly different after systemic CT. Inspiratory (MIP) and expiratory (MEP) muscle strength also did not show a significant change from c0 to c1. A significant effect of the type of surgery was found (Wilks' lambda, F [1, 19] = 6.561, p =.019, ηp2 = 0.25) between c0 and c1 in actual FVC value. The main effect of time was found significant in FVC (F [2, 28] = 4.840, p =.016, ηp2 = 0.25) from c0 to r1. Pairwise comparisons with Bonferroni correction showed that there was a significant difference between c0 and r1 (p =.037). DISCUSSION: The present study showed decreased FVC and FEV1 actual values and percent predicted rates from baseline to the completion of treatment. Since the interactional effect of the type of surgery was significant, we suggest that clinical and demographic factors such as age should be considered when interpreting the early changes in PFT. In addition, the significant linear trend of decreasing in some specific outcomes in respiratory function also highlighted the need for continuous monitoring of potential respiratory problems in patients with BC from baseline to the completion of chemotherapy and radiotherapy.

Oxygen saturation recovery after 6-minute walk test in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The six-minute walk test (6MWT) is widely used to assess functional capacity and prognosis in patients with idiopathic pulmonary fibrosis (IPF). However, studies on oxygen saturation recovery after the 6MWT in patients with IPF are rare. In our study, we investigated the relationship between oxygen saturation recovery time and dyspnea, fatigue, quality of life, prognostic markers and pulmonary hypertension (PH). METHODS: In this cross-sectional study, IPF patients diagnosed according to current guidelines and followed up in our Interstitial Lung Disease Outpatient Clinic between 2021 and 2022 were included. Demographics, data from spirometry, diffusion capacity measurement, arterial blood gas analysis, transthoracic echocardiography and the 6MWT were recorded. The oxygen saturation recovery time, distance saturation product (DSP), gender-age-physiology (GAP) index and composite physiological index (CPI) scores were calculated. Dyspnea severity was assessed by the modified Medical Research Council (mMRC) and Dyspnoea-12 (D-12) scales, fatigue severity by the Multidimensional Fatigue Inventory (MFI-20) and quality of life by the St George's Respiratory Questionnaire (SGRQ). RESULTS: Fifty IPF patients (34 men, 16 women, age: 66.8 ± 7.3 years) were included in the study. The mean FVC was 77.8 ± 19.3%, the DLCO was 52.9 ± 17.1%, the 6-minute walk distance (6MWD) was 385.7 ± 90.6 m, the GAP index was 3.5 ± 1.5, and the CPI was 43.7 ± 14.1. Oxygen saturation after the 6MWT reached pretest values at an average of 135.6 ± 73.5 s. The oxygen saturation recovery time was longer in patients with higher GAP index scores (Rs = 0.870, p < 0.001), CPI scores (Rs = 0.906, p < 0.001), desaturation (Rs = 0.801, p < 0.001), FVC%/DLCO% (Rs = 0.432, p = 0.002), sPAP (Rs = 0.492, p = 0.001), TRV (Rs = 0.504, p = 0.001), mMRC (Rs = 0.913, p < 0.001), MFI-20 (Rs = 0.944, p < 0.001), D-12 scale (Rs = 0.915, p < 0.001) and SGRQ scores (Rs = 0.927, p < 0.001); lower FVC (%) (Rs=-0.627, p < 0.001), DLCO (%) (Rs=-0.892, p < 0.001), PaO2 (Rs=-0.779, p < 0.001), DSP (Rs=-0.835, p < 0.001), and 6MWD (Rs=-0.763, p < 0.001). A total of twenty patients (40%) exhibited an increased risk of PH. According to our multiple regression analysis, oxygen saturation recovery time was independently associated with the GAP index (p = 0.036), the lowest oxygen saturation occurring during the 6MWT (p = 0.011) and the SGRQ score (p < 0.001). CONCLUSIONS: Our results showed that oxygen saturation recovery time is associated with dyspnea, fatigue, quality of life, increased risk of PH and prognostic markers in IPF. Therefore, we recommend continuous measurement of oxygen saturation after 6MWT until pretest values are reached.

Defining the role of exertional hypoxemia and pulmonary vasoconstriction on lung function decline, morbidity, and mortality in patients with chronic obstructive lung disease - the PROSA study: rationale and study design.

BACKGROUND: Chronic obstructive lung disease (COPD) has diverse molecular pathomechanisms and clinical courses which, however, are not fully mirrored by current therapy. Intermittent hypoxemia is a driver of lung function decline and poor outcome, e.g., in patients with concomitant obstructive sleep apnea. Transient hypoxemia during physical exercise has been suggested to act in a similar manner. The PROSA study is designed to prospectively assess whether the clinical course of COPD patients with or without exertional desaturation differs, and to address potential pathophysiological mechanisms and biomarkers. METHODS: 148 COPD patients (GOLD stage 2-3, groups B or C) will undergo exercise testing with continuous pulse oximetry. They will be followed for 36 months by spirometry, echocardiography, endothelial function testing, and biomarker analyses. Exercise testing will be performed by comparing the 6-min walk test (6MWT), bicycle ergometry, and a 15-sec breath-hold test. Exertional desaturation will be defined as SpO2 < 90% or delta-SpO2 ≥ 4% during the 6MWT. The primary endpoint will be the rate of decline of FEV1(LLN) between COPD patients with and without exertional desaturation. DISCUSSION: The PROSA Study is an investigator-initiated prospective study that was designed to prove or dismiss the hypothesis that COPD patients with exertional desaturation have a significantly more rapid rate of decline of lung function as compared to non-desaturators. A 20% difference in the primary endpoint was considered clinically significant; it can be detected with a power of 90%. If the primary endpoint will be met, exercise testing with continuous pulse oximetry can be used as a ubiquitously available, easy screening tool to prospectively assess the risk of rapid lung function decline in COPD patients at an early disease stage. This will allow to introduce personalized, risk-adapted therapy to improve COPD outcome in the long run. PROSA is exclusively funded by public funds provided by the European Research Council through an ERC Advanced Grant. Patient recruitment is ongoing; the PROSA results are expected to be available in 2028. TRIAL REGISTRATION: The PROSA Study has been prospectively registered at clinicaltrials.gov (register no. NCT06265623, dated 09.02.2024).

Reference values for the 6-min walking test in children and adolescents living in a moderate altitude region of Peru.

BACKGROUND: The assessment of cardiorespiratory fitness is important because it allows the identification of subgroups with poor health status and the targeting of effective intervention strategies to improve health. OBJECTIVE: To compare the cardiorespiratory capacity of children and adolescents living in a moderate altitude region of Peru with international studies and to develop reference values for the 6-min walk test (6MWT) according to age and sex. METHODOLOGY: A descriptive cross-sectional study of schoolchildren from a region of moderate altitude in Peru was carried out. A total of 704 schoolchildren (400 males and 304 females) with an age range of 6 to 17 years were studied. Weight, standing height, waist circumference (WC), body mass index (BMI) and tri-ponderal mass index (TMI) were evaluated. The 6MWT was assessed in a straight line over a distance of 30 m. Percentiles were created through the LMS method [L (skewness: lambda), M (median: mu) and S (coefficient of variation: Mu)]. RESULTS: There were discrepancies in cardiorespiratory fitness performance with international studies by age and sex. The schoolchildren in the study reached stability and the highest number of meters in the last two age ranges (14 to 15 years: 698.1 m and 16 to 17 years 686.3 m in males). While females (14 to 15 years: 698.1 m and 16 to 17 years: 686.3 m). The proposed percentile values show ascending values as age advances. The cut-off points adopted are: low cardiorespiratory fitness < p25, moderate p25 to p75 and high cardiorespiratory fitness p > 75. CONCLUSION: We verified that the cardiorespiratory fitness evaluated by means of the 6MWT is ascending with the course of age. Even the performance with other countries is heterogeneous at early and middle ages, stabilizing during adolescence. The proposed reference values can be used to evaluate and monitor cardiorespiratory fitness during physical education classes.

Physical activity based on daily steps in patients with chronic musculoskeletal pain: evolution and associated factors.

BACKGROUND: People with chronic musculoskeletal pain (CMSP) often have low physical activity. Various factors can influence the activity level. The aim of this study was to monitor physical activity, assessed by the number of steps per day, over time in people with CMSP and identify factors that could be associated with this activity feature. METHODS: This prospective study involved people undergoing rehabilitation following an orthopedic trauma that had led to CMSP. At entry, participants completed self-reported questionnaires assessing pain, anxiety, depression, catastrophyzing, kinesiophobia, and behavioural activity patterns (avoidance, pacing and overdoing). They also underwent functional tests, assessing walking endurance and physical fitness. To determine daily step counts, participants wore an accelerometer for 1 week during rehabilitation and 3 months post-rehabilitation. The number of steps per day was compared among three time points: weekend of rehabilitation (an estimate of pre-rehabilitation activity; T1), weekdays of rehabilitation (T2), and post-rehabilitation (T3). Linear regression models were used to analyze the association between daily steps at T2 and at T3 and self-reported and performance-based parameters. RESULTS: Data from 145 participants were analyzed. The mean number of steps was significantly higher during T2 than T1 and T3 (7323 [3047] vs. 4782 [2689], p < 0.001, Cohen's d = 0.769, and 4757 [2680], p < 0.001, Cohen's d = 0.693), whereas T1 and T3 results were similar (p = 0.92, Cohen's d = 0.008). Correlations of number of steps per day among time points were low (r ≤ 0.4). Multivariable regression models revealed an association between daily steps at T2 and pain interfering with walking, anxiety and overdoing behaviour. Daily steps at T3 were associated with overdoing behaviour and physical fitness. CONCLUSIONS: Despite chronic pain, people in rehabilitation after an orthopedic trauma increased their physical activity if they were given incentives to do so. When these incentives disappeared, most people returned to their previous activity levels. A multimodal follow-up approach could include both therapeutic and environmental incentives to help maintain physical activity in this population.