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.

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.

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).

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).

Functioning of post-COVID-19 patients: a cross-sectional study at the outpatient clinic for long-term effects.

BACKGROUND: After COVID-19 infection, long-term impacts on functioning may occur. We studied the functioning of patients with post-COVID-19 condition (PCC) and compared them to controls without PCC. METHODS: This cross-sectional study consisted of 442 patients with PCC referred to rehabilitation at the Helsinki University Hospital (HUS) Outpatient Clinic for the Long-Term Effects of COVID-19, and 198 controls without PCC. Functioning was assessed with a questionnaire including WHODAS 2.0. Patients underwent physical testing including a hand grip strength test (HGST) and a 6-minute walking test (6MWT). Lifestyle was assessed by questionnaire and comorbidities were collected as ICD-10 codes from the HUS Data Lake on the HUS Acamedic platform. RESULTS: The WHODAS 2.0 average total score was 34 (SD 18) (moderate functional limitation) for patients with PCC and 6 (SD 8) (normal or mild limitation) for the controls. The disability was higher in all aspects of WHODAS 2.0 in patients with PCC. Bivariate binomial and multivariable regression analyses showed that the presence of comorbidities, anxiety, depression, and smoking predicted a WHODAS 2.0 score of 24 (moderate functional limitation) or above in the PCC group. The average 6MWT distance was 435 m (SD 98 m) in patients with PCC and 627 m (SD 70 m) in controls. HGST measurements showed no significant differences from controls. CONCLUSIONS: In conclusion, patients with PCC had significantly reduced functioning based on WHODAS 2.0 scores and the 6MWT results. Comorbidities, anxiety, depression, and smoking were associated with moderate or severe limitations in functioning. Findings support that PCC is multifactorial and requires a holistic approach to rehabilitation.

The post-COVID-19 condition (PCC) has been shown to negatively impact functioning, quality of life, and mental health, with cognitive and physical impairments being prevalent.This study found that patients with PCC had significantly reduced functioning compared to controls.Key factors predicting severe disability included comorbidities, smoking, and mental health issues like anxiety and depression.The reduced functioning in patients with PCC appears to be multifactorial and not only related to COVID-19 infection.

Evaluation of handgrip strength in children with pulmonary hypertension.

BACKGROUND: Handgrip strength is a crucial indicator of upper extremity muscular strength and is vital for monitoring disorders like cardiac diseases that restrict a patient's physical activity and result in muscle atrophy. The aim of our study was to evaluate whether muscle strength loss is present in patients with pulmonary hypertension and whether this test can be an alternative to 6-minute walk test. MATERIALS AND METHODS: The study included 39 healthy children who were admitted to the outpatient clinic and 16 children with a diagnosis of pulmonary hypertension who were being followed in our centre. We assessed the differences in upper extremity handgrip strength using the Jamar Hydraulic Hand Dynamometer device among both healthy children and those diagnosed with pulmonary hypertension. Moreover, we compared the handgrip strength of pulmonary hypertension patients with significant prognostic indicators such as NYHA class, 6-minute walk test, and pro-brain natriuretic peptide. RESULTS: The mean dominant handgrip strength was 20.8 ± 12 kg in the patient group and 21.6 ± 12.4 kg in the control group (p = 0.970). Handgrip strength was shown to be negatively connected with pro-brain natriuretic peptide (r = -0.565, p = 0.023) and positively correlated with 6-minute walk test (r = 0.586, p = 0.022) during the patient group evaluation. CONCLUSION: Six-minute walk test needs a customised physical area (30 m of a straight hallway) and trained personnel for applying the test. The handgrip strength test, a different muscle strength indicator, can be used to more clearly and simply indicate the decline in patients' ability for effort. Additionally, it was found in our study that handgrip strength decreased as pro-brain natriuretic peptide levels rose, a crucial measure in the monitoring of pulmonary hypertension.

Measurement of Physical Activity by Actigraphy in Infants and Young Children with Pulmonary Arterial Hypertension.

OBJECTIVE: To evaluate the feasibility, tolerability, and adherence with wearable actigraphy devices among infants and children with pulmonary arterial hypertension (PAH). STUDY DESIGN: This multicenter, prospective, observational study included children ages 0-6 years with and without PAH. Participants wore the ActiGraph wGT3X-BT on the hip and FitBit Inspire on the wrist during waking hours for 14 days. Steps, vector magnitude counts per minute, activity intensity, heart rate, and heart rate variability were compared between groups. RESULTS: Forty-seven participants (18 PAH, 29 control) were enrolled from 10 North American sites. PAH patients were mostly functional class II (n = 16, 89%) and treated with oral medications at the time of enrollment. The number of wear days was not significantly different between the groups (ActiGraph: 10 [95% CI: 5.5, 12.2] in PAH vs 8 [4, 12] in control, P = .20; FitBit 13 [10, 13.8] in PAH vs 12 [8, 14] in control, P = .87). Complete data were obtained in 81% of eligible ActiGraph participants and 72% of FitBit participants. PAH participants demonstrated fewer steps, lower vector magnitude counts per minute, more sedentary activity, and less intense physical activity at all levels compared with control participants. No statistically significant differences in heart rate variability were demonstrated between the 2 groups. CONCLUSIONS: Measurement of physical activity and other end points using wearable actigraphy devices was feasible in young children with PAH. Larger studies should determine associations between physical activity and disease severity in young patients with PAH to identify relevant end points for pediatric clinical trials.

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

BACKGROUND: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management. METHODS: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System. CONCLUSION: The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency.

BACKGROUND: The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF. METHODS: In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration. RESULTS: Of 760 patients included in the 2 trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281 ± 103 meters. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r = 0.31; P < 0.0001) and week 24 (r = 0.43; P < 0.0001). Respective estimates (95% confidence intervals) of MCID in 6MWT at weeks 12 and 24 were 14 meters (5;23) and 15 meters (3;27) for a "little improvement" (vs no change), 20 meters (10;30) and 24 meters (12;36) for moderate improvement vs a "little improvement,", -11 meters (-32;9.2) and -31 meters (-53;-8) for a "little deterioration" (vs no change), and -84 meters (-144;-24) and -69 meters (-118;-20) for "moderate deterioration" vs a "little deterioration". CONCLUSIONS: The MCID for improvement in exercise capacity in the 6MWT was 14 meters-15 meters in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data.

Associations between lower extremity muscle fat fraction and motor performance in myotonic dystrophy type 2: A pilot study.

INTRODUCTION/AIMS: Although muscle structure measures from magnetic resonance imaging (MRI) have been used to assess disease severity in muscular dystrophies, little is known about how these measures are affected in myotonic dystrophy type 2 (DM2). We aim to characterize lower extremity muscle fat fraction (MFF) as a potential biomarker of disease severity, and evaluate its relationship with motor performance in DM2. METHODS: 3-Tesla MRIs were obtained from nine patients with DM2 and six controls using a T1W-Dixon protocol. To calculate MFF, muscle volumes were segmented from proximal, middle, and distal regions of the thigh and calf. Associations between MFF and motor performance were calculated using Spearman's correlations (ρ). RESULTS: Mean age of DM2 participants was 62 ± 11 y (89% female), and mean symptom duration was 20 ± 12 y. Compared to controls, the DM2 group had significantly higher MFF in the thigh and the calf segments (p-value = .002). The highest MFF at the thigh in DM2 was located in the posterior compartment (39.7 ± 12.9%) and at the calf was the lateral compartment (31.5 ± 8.7%). In the DM2 group, we found a strong correlation between the posterior thigh MFF and the 6-min walk test (ρ = -.90, p-value = .001). The lateral calf MFF was also strongly correlated with the step test (ρ = -0.82, p-value = .006). DISCUSSION: Our pilot data suggest a potential correlation between lower extremity MFF and some motor performance tests in DM2. Longitudinal studies with larger sample sizes are required to validate MFF as a marker of disease severity in DM2.

Home-based prehabilitation improves physical conditions measured by ergospirometry and 6MWT in colorectal cancer patients: a randomized controlled pilot study.

PURPOSE/BACKGROUND: Prehabilitation aims to improve physical condition in the preoperative period and, therefore, decrease the loss of cardiopulmonary capacity postoperatively, with the aim of reducing complications and promoting an early recovery. This study aims to evaluate the impact of home-based prehabilitation on the physical condition of patients treated surgically for colorectal cancer. METHODS: A prospective and randomized clinical study was conducted on 60 patients during two periods from October 2018 to February 2019 and from September 2019 to September 2020, in a single university hospital. Patients were randomized into two study groups (30 per group): prehabilitation vs. standard care. Changes in physical condition, measured at diagnosis, the day before surgery, and at 6-8 weeks after surgery using the cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) were evaluated. RESULTS: Prehabilitation reduced postoperative complications (17.4% vs. 33.3%, p = 0.22) and hospital stay (5.74 vs. 6.67 days, p = 0.30). 6MWT showed a significant improvement in the prehabilitation group (+78.9 m). Six weeks after surgery, prehabilitation showed a significant improvement in the 6MWT (+68.9 m vs. -27.2 m, p = 0.01). Significant differences were also observed in the ergospirometry between the diagnosis and postoperative study (+0.79 METs vs. -0.84 METs, p = 0.001). A strong correlation was observed between CPET and 6MWT (0.767 (p < 0.001)). CONCLUSION: Home prehabilitation achieved lower overall postoperative complications than standard care and reached significant improvements in 6MWT and CET. A strong correlation was observed between CET and 6MWT, which allows validation of 6MWT as a valid and reliable measure of functional exercise capacity in colorectal patients when other, more specific and expensive tests are not available. TRIAL REGISTRATION: Registered in ClinicalTrials.gov in August 2018 with registration number https://clinicaltrials.gov/study/NCT03618329?cond=Prehabilitation%20cancer&term=arroyo&distance=50&rank=1  (NCT03618329). Initial results published in Supportive Care in Cancer: Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic. DOI: https://doi.org/10.1007/s00520-021-06343-1 .

Three-Month FVC Change: A Trial Endpoint for Idiopathic Pulmonary Fibrosis Based on Individual Participant Data Meta-analysis.

Rationale: Novel therapies for idiopathic pulmonary fibrosis (IPF) are in development, but there remains uncertainty about the optimal trial endpoint. An earlier endpoint would enable assessment of a greater number of therapies in adaptive trial designs. Objectives: To determine whether short-term changes in FVC, DlCO, and six-minute-walk distance could act as surrogate endpoints to accelerate early-phase trials in IPF. Methods: Individual participant data (IPD) from IPF clinical trials were included in a two-step random-effects meta-analysis to determine whether baseline or 3-month changes in FVC, DlCO, and 6-minute-walk distance were associated with mortality or disease progression in placebo arms. Three-month and 12-month FVC decline endpoints were compared with treatment arm data from antifibrotic studies by meta-regression. Measurements and Main Results: IPD were available from 12 placebo cohorts totaling 1,819 participants, with baseline and 3-month changes in all physiological variables independently associated with poorer outcomes. Treatment data were available from six cohorts with 1,684 participants. For each 2.5% relative decline in FVC over 3 months, there was an associated 15% (adjusted hazard ratio, 1.15; 95% confidence interval [CI], 1.06-1.24; I2 = 59.4%) and 20% (adjusted hazard ratio, 1.20; 95% CI, 1.12-1.28; I2 = 18.0%) increased risk for mortality in untreated and treated individuals, respectively. An FVC change treatment effect was observed between treatment and placebo arms at 3 months (difference in FVC change of 42.9 ml; 95% CI, 24.0-61.8 ml; P < 0.001). Conclusions: IPD meta-analysis demonstrated that 3-month changes in physiological variables, particularly FVC, were associated with mortality among individuals with IPF. FVC change over 3 months may hold potential as a surrogate endpoint in IPF adaptive trials.

Clinical values of diaphragmatic movement in patients with chronic obstructive pulmonary disease.

BACKGROUND: The limitation of activity due to dyspnea in chronic obstructive pulmonary disease (COPD) patients is affected by diaphragmatic dysfunction and reduced lung function. This study aimed to analyze the association between diaphragm function variables and forced expiratory volume in the first second (FEV1) and to estimate the clinical significance of diaphragm function in the correlation between COPD severity and lung function. METHODS: This prospective, single-center, cross-sectional observational study enrolled 60 COPD patients in a respiratory outpatient clinic. Data for baseline characteristics and the dyspnea scale were collected. Participants underwent a pulmonary function test (PFT), a 6-minute walk test (6MWT), and diaphragm function by ultrasonography. RESULTS: The right excursion at forced breathing showed the most significant correlation with FEV1 (r = 0.370, p = 0.004). The cutoff value was 6.7 cm of the right diaphragmatic excursion at forced breathing to identify the FEV1 above 50% group. In the group with a right diaphragmatic excursion at forced breathing < 6.7 cm, modified Medical Research Council (mMRC), St. George's Respiratory Questionnaire and the total distance of 6MWT showed no difference between groups with FEV1 under and above 50% (p > 0.05). In the group with ≥ 6.7 cm, mMRC and the total distance of 6MWT showed a significant difference between FEV1 under and above 50% (p = 0.014, 456.7 ± 69.7 m vs. 513.9 ± 60.3 m, p = 0.018, respectively). CONCLUSION: The right diaphragmatic forced excursion was closely related to FEV1, and analysis according to the right diaphragmatic forced excursion-based cut-off value showed a significant difference between both groups. When the diaphragm function was maintained, there was a lot of difference in the 6MWT's factors according to the FEV1 value. Our data suggest that diaphragmatic function should be performed when interpreting PFT.

The Added Value of Remote Technology in Cardiac Rehabilitation on Physical Function, Anthropometrics, and Quality of Life: Cluster Randomized Controlled Trial.

BACKGROUND: Cardiovascular diseases (CVDs) cause most deaths globally and can reduce quality of life (QoL) of rehabilitees with cardiac disease. The risk factors of CVDs are physical inactivity and increased BMI. With physical activity, it is possible to prevent CVDs, improve QoL, and help maintain a healthy body mass. Current literature shows the possibilities of digitalization and advanced technology in supporting independent self-rehabilitation. However, the interpretation of the results is complicated owing to the studies' high heterogeneity. In addition, the added value of this technology has not been studied well, especially in cardiac rehabilitation. OBJECTIVE: We aimed to examine the effectiveness of added remote technology in cardiac rehabilitation on physical function, anthropometrics, and QoL in rehabilitees with CVD compared with conventional rehabilitation. METHODS: Rehabilitees were cluster randomized into 3 remote technology intervention groups (n=29) and 3 reference groups (n=30). The reference group received conventional cardiac rehabilitation, and the remote technology intervention group received conventional cardiac rehabilitation with added remote technology, namely, the Movendos mCoach app and Fitbit charge accelerometer. The 12 months of rehabilitation consisted of three 5-day in-rehabilitation periods in the rehabilitation center. Between these periods were two 6-month self-rehabilitation periods. Outcome measurements included the 6-minute walk test, body mass, BMI, waist circumference, and World Health Organization QoL-BREF questionnaire at baseline and at 6 and 12 months. Between-group differences were assessed using 2-tailed t tests and Mann-Whitney U test. Within-group differences were analyzed using a paired samples t test or Wilcoxon signed-rank test. RESULTS: Overall, 59 rehabilitees aged 41 to 66 years (mean age 60, SD 6 years; n=48, 81% men) were included in the study. Decrement in waist circumference (6 months: 1.6 cm; P=.04; 12 months: 3 cm; P<.001) and increment in self-assessed QoL were greater (environmental factors: 0.5; P=.02) in the remote technology intervention group than the reference group. Both groups achieved statistically significant improvements in the 6-minute walk test in both time frames (P=.01-.03). Additionally, the remote technology intervention group achieved statistically significant changes in the environmental domain at 0-6 months (P=.03) and waist circumference at both time frames (P=.01), and reference group achieve statistically significant changes in waist circumference at 0-6 months (P=.02). CONCLUSIONS: Remote cardiac rehabilitation added value to conventional cardiac rehabilitation in terms of waist circumference and QoL. The results were clinically small, but the findings suggest that adding remote technology to cardiac rehabilitation may increase beneficial health outcomes. There was some level of systematic error during rehabilitation intervention, and the sample size was relatively small. Therefore, care must be taken when generalizing the study results beyond the target population. To confirm assumptions of the added value of remote technology in rehabilitation interventions, more studies involving different rehabilitees with cardiac disease are required. TRIAL REGISTRATION: ISRCTN Registry ISRCTN61225589; https://www.isrctn.com/ISRCTN61225589.

Exercise Capacity and Biomarkers Among Children and Adolescents With Sickle Cell Disease.

BACKGROUND: Sickle cell disease is the most common genetic hemoglobinopathy globally and systemically affects body functioning, decreasing exercise capacity. OBJECTIVE: To assess exercise capacity through the 6-minute walk test (6MWT) and biomarkers in children and adolescents with sickle cell disease. MATERIALS AND METHODS: Cross-sectional study involving 20 children and adolescents from Brazil. Demographic and socioeconomic data were obtained. Baseline measurements included biomarkers (red blood cells, hemoglobin, hematocrit, white blood cells, platelets, reticulocytes, lactate dehydrogenase, creatine phosphokinase, C-reactive protein, interleukin 6, and fetal hemoglobin). The following data were obtained before, during, and after the 6MWT: heart rate, blood pressure, and peripheral oxygen saturation. RESULTS: Eighteen children and adolescents ages 5-14 years old were analyzed, 61.1% boys, 100% black or brown, and 61.1% in primary education, with low household income. The average distance walked in 6MWT was 463.8 (137.7) m, significantly less than the predicted value (P < .001). The distance of 6MWT was associated positively with age (P = .042) and inversely with reticulocyte count (P = .42) and interleukin 6 (P = .00). Age modified the effect of interleukin 6 in younger children (P = .038). CONCLUSION: Our findings suggest increased baseline levels of biomarkers of hemolysis and inflammation impact on 6MWT performance.

[A wearable six-minute walk-based system to predict postoperative pulmonary complications after cardiac valve surgery: an exploratory study].

In recent years, wearable devices have seen a booming development, and the integration of wearable devices with clinical settings is an important direction in the development of wearable devices. The purpose of this study is to establish a prediction model for postoperative pulmonary complications (PPCs) by continuously monitoring respiratory physiological parameters of cardiac valve surgery patients during the preoperative 6-Minute Walk Test (6MWT) with a wearable device. By enrolling 53 patients with cardiac valve diseases in the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, the grouping was based on the presence or absence of PPCs in the postoperative period. The 6MWT continuous respiratory physiological parameters collected by the SensEcho wearable device were analyzed, and the group differences in respiratory parameters and oxygen saturation parameters were calculated, and a prediction model was constructed. The results showed that continuous monitoring of respiratory physiological parameters in 6MWT using a wearable device had a better predictive trend for PPCs in cardiac valve surgery patients, providing a novel reference model for integrating wearable devices with the clinic.

Effect of pulmonary rehabilitation programme including either O2 inhalation or noninvasive ventilation in patients with chronic obstructive pulmonary disease.

Background: Pulmonary rehabilitation (PR) is crucial in managing chronic obstructive pulmonary disease (COPD) and enhancing functional capacity and health status. Oxygen therapy and noninvasive ventilation (NIV) may be needed to be incorporated into rehabilitation to augment the effectiveness of physical training. Objectives: To compare and assess the impact of the PR programme alone and with augmentation with O2 or NIV on COPD patients. Methods: Seventy-five COPD patients were equally divided into three groups: group 1 patients performed 8 week-PR programme only. Group 2 performed the PR programme while receiving O2. Group 3 completed the PR programme plus NIV. Modified Borg scale, VO2 max, modified Medical Research Council Dyspnea Scale, 6-minute walk test, COPD assessment test score, spirometric measures and arterial blood gases were assessed before and after the programme. Results: The outcome measurements showed meaningful improvement compared with the baseline in the three studied groups. However, VO2 max in group 3 showed higher significant improvement than both groups 1 and 2. Regarding 6-minute walk test, groups 2 and 3 had a higher significant improvement than group 1. COPD assessment test score in group 3 showed higher significant improvement than groups 1 and 2. Arterial blood gases in groups 2 and 3 showed significant increase in partial pressure of arterial oxygen and arterial oxygen saturation, but group 3 only had a significant decrease in PaCO2. Conclusion: O2 supplementation and NIV help severe to very severe COPD patients to perform higher exercise intensity, so they augment the benefits of PR.

Utility of the breath-holding test in patients with systemic sclerosis.

OBJECTIVES: Cardiopulmonary involvement is a major cause of death in patients with SSc. This study evaluated the clinical utility and reliability of breath-holding test (BHT) in evaluating cardiopulmonary function in patients with SSc. METHODS: Seventy-two prospectively enrolled patients with SSc underwent BHT and the 6 min walk test (6MWT), along with measurements of the Borg dyspnoea scale and Scleroderma Health Assessment Questionnaire (SHAQ). Data on pulmonary function test and echocardiography were also collected. Validity was assessed based on the correlations between the best BHT and relevant clinical parameters. To assess the reliability of BHT, an additional 31 patients with SSc underwent BHTs twice within 2 week intervals. RESULTS: Mean (s.d.) best BHT time was 38.4 (15.7) s, and 6MWT distance was 473.5 (95.5) m. BHT showed significant correlations with the Borg dyspnoea scale before (r = -0.367, P < 0.001) and after (r = -0.285, P = 0.016) testing, whereas 6MWT were correlated with the Borg dyspnoea scale after (r = -0.351, P = 0.002) but not before (r = -0.113, P = 0.343) testing. BHT time was correlated with diffusing capacity for carbon monoxide (%, r = 0.426, P < 0.001), forced vital capacity (litres, r = 0.373, P = 0.001), pulmonary arterial systolic pressure (mmHg, r = -0.272, P = 0.031) and SHAQ score (r = -0.470, P < 0.001), but not with left ventricular ejection fraction (%, r = -0.135, P = 0.263). BHT showed excellent reliability, with an intraclass correlation coefficient (2, 1) of 0.943 (95% CI: 0.88, 0.97). CONCLUSION: BHT, a simple and less time-consuming test, shows excellent reliability and significant correlation with the Borg scale, SHAQ and pulmonary parameters. These results suggest that BHT might be a useful surrogate marker of pulmonary capacity in SSc patients. TRIAL REGISTRATION NUMBER: NCT04484948.

Evidence for impaired chronotropic responses to and recovery from 6-minute walk test in women with post-acute COVID-19 syndrome.

NEW FINDINGS: What is the central question of this study? Are chronotropic responses to a 6-minute walk test different in women with post-acute coronavirus disease 2019 (COVID-19) syndrome compared with control subjects? What is the main finding and its importance? Compared with control subjects, the increase in heart rate was attenuated and recovery delayed after a 6-minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Such alterations have potential to constrain not only exercise tolerance but also participation in free-living physical activity in women during post-acute recovery from COVID-19. ABSTRACT: The short-term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well defined. However, the implications of cardiopulmonary sequelae, persisting beyond acute illness, on physical function are largely unknown. Herein, we characterized heart rate responses to and recovery from a 6-minute walk test (6MWT) in women ∼3 months after mild-to-moderate SARS-CoV-2 infection compared with non-infected control subjects. Forty-five women (n = 29 SARS-CoV-2; n = 16 controls; age = 56 ± 11 years; body mass index = 25.8 ± 6.0 kg/m2 ) completed pulmonary function testing and a 6MWT. The SARS-CoV-2 participants demonstrated reduced total lung capacity (84 ± 8 vs. 93 ± 13%; P = 0.006), vital capacity (87 ± 10 vs. 93 ± 10%; P = 0.040), functional residual capacity (75 ± 16 vs. 88 ± 16%; P = 0.006) and residual volume (76 ± 18 vs. 93 ± 22%; P = 0.001) compared with control subjects. No between-group differences were observed in 6MWT distance (P = 0.194); however, the increase in heart rate with exertion was attenuated among SARS-CoV-2 participants compared with control subjects (+52 ± 20 vs. +65 ± 18 beats/min; P = 0.029). The decrease in heart rate was also delayed for minutes 1-5 of recovery among SARS-CoV-2 participants (all P < 0.05). Women reporting specific symptoms at the time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Our findings provide evidence for marked differences in chronotropic responses to and recovery from a 6MWT in women several months after acute SARS-CoV-2 infection.

The 6-minute walk test predicts mortality in a pulmonary nontuberculous mycobacteria-predominant bronchiectasis cohort.

BACKGROUND: Bronchiectasis is a chronic lung condition frequently associated with nontuberculous mycobacteria pulmonary (NTM) disease. Persons with these conditions are at increased risk of mortality. Patient reported outcome (PRO) instruments and the 6-minute walk test (6MWT) have been shown to predict mortality for several lung conditions, but these measures have not been fully evaluated for bronchiectasis and NTM. METHODS: We conducted a retrospective cohort study among adult patients enrolled in a natural history study of bronchiectasis at the National Heart, Lung, and Blood Institute. Electronic medical records were queried for demographic, clinical, microbiologic, radiographic, and PRO instrument data: St. George's Respiratory Questionnaire (SGRQ), Medical Research Council Dyspnea Scale, and the Pulmonary Symptom Severity Score (PSSS). The study baseline date was defined as the patient's first visit after January 1st, 2015 with a SGRQ or 6MWT completed. Follow-up was defined as the interval between the study baseline visit and date of death or December 31st, 2019. Sex-stratified Cox proportional-hazards regression was conducted to identify predictors of mortality. Separate models were run for each PRO and 6MWT measure, controlling for age, body mass index (BMI), fibrocavitary disease status, and M. abscessus infection. RESULTS: In multivariable Cox proportional-hazards regression models, the PSSS-severity (aHR 1.29, 95% CI 1.04-1.59), the 6MWT total distance walked (aHR 0.938, 95% CI 0.896-0.981) and distance saturation product (aHR 0.930, 95% CI 0.887-0.974) independently predicted mortality. In addition, BMI was significantly predictive of mortality in all models. CONCLUSIONS: The 6MWT and a PRO instrument capturing symptom severity are independently predictive of mortality in our cohort of bronchiectasis patients.