Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.

Evaluation of the relationship between intercostal muscle oxygenation measured by near-infrared spectroscopy and exercise capacity in group E COPD patients.

Near-infrared spectroscopy (NIRS) can be used to demonstrate muscle metabolism and oxygenation. NIRS-based oximeters enable the noninvasive measurement of static and dynamic muscle oxygenation. This study aimed to evaluate the relationship between NIRS readings and exercise capacity in group E COPD patients. The prospective study included 40 patients with group E COPD who presented to our outpatient clinic between May 2021 and June 2022. The patients were evaluated with pulmonary function testing, 6-Minute Walk Test (6MWT), echocardiography, and dyspnea and quality of life assessments. NIRS muscle oxygen saturation (SmO2) levels at the start and end of the 6MWT were obtained. 6MWT distance was positively correlated with intercostal SmO2 and fingertip SO2 at the start (R = 0.679, p ≤ 0.001 and R = 0.321, p = 0.04, respectively) and end of the 6MWT (R = 0.693, p ≤ 0.001 and R = 0.635, p ≤ 0.001, respectively) and negatively correlated with the number of hospitalizations due to exacerbations in the last year and mean pulmonary arterial pressure (R = - 0.648, p ≤ 0.001 and R = - 0.676, p ≤ 0.001, respectively). SF-36 score was positively correlated with intercostal SmO2 at the beginning of the 6MWT (R = 0.336, p = 0.03). Intercostal SmO2 levels at the start of the 6MWT positively correlated with diffusing capacity of the lung for carbon dioxide (DLCO) (R = 0.388, p = 0.01) and ratio of DLCO to alveolar volume (DLCO/VA) levels (R = 0.379, p = 0.02), and these correlations persisted more strongly after the 6MWT (R = 0.524, p = 0.01; R = 0.500, p = 0.01, respectively). NIRS is a practical and noninvasive method for measuring muscle oxygenation and can be used as an alternative to 6MWT in the evaluation of exercise capacity in patients with group E COPD.

A wearable device perspective on the standard definitions of disability progression in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a leading cause of disability among young adults, but standard clinical scales may not accurately detect subtle changes in disability occurring between visits. This study aims to explore whether wearable device data provides more granular and objective measures of disability progression in MS. METHODS: Remote Assessment of Disease and Relapse in Central Nervous System Disorders (RADAR-CNS) is a longitudinal multicenter observational study in which 400 MS patients have been recruited since June 2018 and prospectively followed up for 24 months. Monitoring of patients included standard clinical visits with assessment of disability through use of the Expanded Disability Status Scale (EDSS), 6-minute walking test (6MWT) and timed 25-foot walk (T25FW), as well as remote monitoring through the use of a Fitbit. RESULTS: Among the 306 patients who completed the study (mean age, 45.6 years; females 67%), confirmed disability progression defined by the EDSS was observed in 74 patients, who had approximately 1392 fewer daily steps than patients without disability progression. However, the decrease in the number of steps experienced over time by patients with EDSS progression and stable patients was not significantly different. Similar results were obtained with disability progression defined by the 6MWT and the T25FW. CONCLUSION: The use of continuous activity monitoring holds great promise as a sensitive and ecologically valid measure of disability progression in MS.

Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen.

INTRODUCTION/AIMS: Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3. METHODS: We conducted a multicenter retrospective cohort study, including adult ambulant patients with SMA3, data available on 6-minute walk test (6MWT) and Hammersmith Functional Motor Scale-Expanded (HFMSE) at baseline and at least at 6 months of treatment with nusinersen. We investigated fatigability, estimated as 10% or higher decrease in walked distance between the first and sixth minute of the 6MWT, at baseline and over the 14-month follow-up. RESULTS: Forty-eight patients (56% females) were included. The 6MWT improved after 6, 10, and 14 months of treatment (p < 0.05). Of the 27 patients who completed the entire follow-up, 37% improved (6MWT distance increase ≥30 m), 48.2% remained stable, and 14.8% worsened (6MWT distance decline ≥30 m). Fatigability was found at baseline in 26/38 (68%) patients and confirmed at subsequent time points (p < 0.05) without any significant change over the treatment period. There was no correlation between fatigability and SMN2 copy number, sex, age at disease onset, age at baseline, nor with 6MWT total distance and baseline HFMSE score. DISCUSSION: Fatigability was detected at baseline in approximately 2/3 of SMA3 walker patients, without any correlation with clinical features, included motor performance. No effect on fatigability was observed during the 14-month treatment period with nusinersen.

Effect of robot-assisted gait training on improving cardiopulmonary function in stroke patients: a meta-analysis.

OBJECTIVE: Understanding the characteristics related to cardiorespiratory fitness after stroke can provide reference values for patients in clinical rehabilitation exercise. This meta- analysis aimed to investigate the effect of robot-assisted gait training in improving cardiorespiratory fitness in post-stroke patients, compared to conventional rehabilitation training. METHODS: PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, CBM, CNKI and Wanfang databases were searched until March 18th, 2024. Randomized controlled trials (RCTs) comparing the effectiveness of robot-assisted gait training versus control group were included. The main outcome variable was peak oxygen uptake. 6-minute walking test, peak heart rate, peak inspiratory expiratory ratio as our secondary indicators. RevMan 5.3 software was used for statistical analysis. RESULTS: A total of 17 articles were included, involving 689 subjects. The results showed a significant effect for robot-assisted gait training to improve VO2peak (MD = 1.85; 95% CI: -0.13 to 3.57; p = 0.04) and 6WMT (MD = 19.26; 95% CI: 10.43 to 28.08; p < 0.0001). However, no significant difference favouring robot-assisted gait training were found in HRpeak (MD = 3.56; 95% CI: -1.90 to 9.02; p = 0.20) and RERpeak (MD = -0.01; 95% CI: -0.04 to 0.01; p = 0.34). CONCLUSION: These results showed that robot-assisted gait training may have a beneficial effect in improving VO2peak and 6WMT, with a moderate recommendation level according to the GRADE guidelines.

Assessing the Effect of Data Quality on Distance Estimation in Smartphone-Based Outdoor 6MWT.

As a result of technological advancements, functional capacity assessments, such as the 6-minute walk test, can be performed remotely, at home and in the community. Current studies, however, tend to overlook the crucial aspect of data quality, often limiting their focus to idealised scenarios. Challenging conditions may arise when performing a test given the risk of collecting poor-quality GNSS signal, which can undermine the reliability of the results. This work shows the impact of applying filtering rules to avoid noisy samples in common algorithms that compute the walked distance from positioning data. Then, based on signal features, we assess the reliability of the distance estimation using logistic regression from the following two perspectives: error-based analysis, which relates to the estimated distance error, and user-based analysis, which distinguishes conventional from unconventional tests based on users' previous annotations. We highlight the impact of features associated with walked path irregularity and direction changes to establish data quality. We evaluate features within a binary classification task and reach an F1-score of 0.93 and an area under the curve of 0.97 for the user-based classification. Identifying unreliable tests is helpful to clinicians, who receive the recorded test results accompanied by quality assessments, and to patients, who can be given the opportunity to repeat tests classified as not following the instructions.

Perceived exertion is not a substitute for fatiguability in spinal muscular atrophy.

INTRODUCTION/AIMS: Fatiguability and perceived fatigue are common unrelated symptoms in ambulatory individuals with spinal muscular atrophy (SMA). Ratings of perceived exertion (RPE) measures the sense of effort during an activity and has been used as a proxy for fatigue. Relationships between perceived fatigue, fatiguability, and RPE have been described in healthy populations, but the relationship in SMA has not been examined. METHODS: Eighteen ambulatory individuals with SMA and 16 age-matched controls (age, 13 to 57 years; 26 [76.5%] males) performed the 6-minute walk test (6MWT) and cardiopulmonary exercise tolerance test (CPET) and completed the International Physical Activity Questionnaire---short form (IPAQ). RPE was collected during the CPET and 6MWT. Fatiguability was measured during the 6MWT. Physical activity (PA) volume was calculated using the IPAQ. Wilcoxon rank-sum tests were used to compare groups. Spearman correlation coefficients evaluated associations between variables. SMA subgroups were predetermined using 6MWT distances of over or under 300 meters. RESULTS: There were no significant associations between fatiguability and RPE or PA in SMA (P > .05). PA was strongly associated with 6MWT RPE (r = 0.71) in SMA individuals who walked fewer than 300 meters (n = 7). There were no significant associations between any variables in controls (P > .05). DISCUSSION: RPE is not associated with fatiguability in SMA. The possible association of PA and RPE may reflect the increased intensity of the 6MWT in weaker patients. RPE represents a sense of effort during exercise and should not be used as a substitute for fatiguability but may be a measure of patient experience during exercise.

Differential associations of emotional and physical domains of the MacNew Heart with changes in 6-min walking test.

AIMS: Cardiac rehabilitation (CR), a key component of secondary prevention in cardiac patients, contributes fundamentally to improved cardiovascular health outcomes. Health-related quality of life (HRQOL) represents a widely employed outcome measure in CR, yet, its predictive properties on exercise capacity change during CR are poorly understood. Aim of this study was to examine the association between baseline HRQOL and its subdomains on improvement of exercise capacity during CR. METHODS: Study participants were 13,717 inpatients of six Swiss CR clinics from 2012 to 2018. We measured HRQOL at admission to CR with the MacNew Heart (MNH) questionnaire and exercise capacity at admission and discharge using the six minutes walking test (6MWT). Following factorial analyses, we performed univariate and multivariate analyses to test the predictive properties of baseline global HRQOL and its domains for improvement in exercise capacity, adjusting for demographic and clinical characteristics. RESULTS: Mean improvement in 6MWT was 114 m (SD = 90), achieved after 17.4 days (SD = 5.5). Lower emotional HRQOL (b = 7.85, p = < .001, 95% CI [- 5.67, 10.03]) and higher physical HRQOL (b = - 5.23, p < .001, 95% CI [- 6.56, - 3.90]) were associated with less improvement in the 6MWT. Global MNH and social HRQOL showed no association with exercise capacity improvement. CONCLUSION: Patients entering CR with low emotional and high physical HRQOL are at risk for a lower gain in exercise capacity during CR. Global MNH alone does not provide a reliable assessment of HRQOL; thus a focus on specific domains of HRQOL is needed.

Radiological findings based comparison of functional status in patients who have post-covid lung injury or idiopathic pulmonary fibrosis.

BACKGROUND: Following COVID-19 infection, some patients acquired lung injury and fibrosis. Idiopathic pulmonary fibrosis is characterized by lung fibrosis. Both post-COVID lung injury and idiopathic pulmonary fibrosis cause loss of respiratory function and involvement of the lung parenchyma. We aimed to compare respiratory related functional characteristics and radiological involvement between post-COVID lung injury and idiopathic pulmonary fibrosis. METHODS: A single center, cross-sectional study was applied. Patients with post-COVID lung injury and idiopathic pulmonary fibrosis included in the study. All patients underwent the 6-minute walk test, as well as the Borg and MRC scales. Radiological images were evaluated and scored for lung parenchymal involvement. The impact of post-COVID lung injury and idiopathic pulmonary fibrosis on respiratory functions of were compared. The relationship of functional status and radiological involvement, as well as the effect of potential confounding factors were investigated. RESULTS: A total of 71 patients were included in the study. Forty-eight (67.6%) of the patients were male and the mean age was 65.4 ± 10.3 years. Patients with post-COVID lung injury had greater 6-minute walk test distance and duration, as well as higher oxygen saturations. The MRC and Borg dyspnea scores were comparable. At radiologic evaluation, ground glass opacity scores were higher in patients with post-COVID lung injury, whereas pulmonary fibrosis scores were higher in patients with idiopathic pulmonary fibrosis. However, the total severity scores were similar. While pulmonary fibrosis score was found to have a negative correlation with 6-minute walk test distance, test duration, and pre- and post-test oxygen saturation levels, there was a positive correlation with oxygen saturation recovery time and MRC score. There was no relationship between ground glass opacity and the functional parameters. CONCLUSIONS: Despite having equal degrees of radiological involvement and dyspnea symptom severity, PCLI patients exhibited higher levels of functional status. This might be due to different pathophysiological mechanisms and radiological involvement patterns of both diseases.

SMART System in the Assessment of Exercise Tolerance in Adults.

Health-oriented physical activity should meet two key criteria: safety and an optimal level of exercise. The system of monitoring and rationalization of training (SMART) was designed to meet them. SMART integrates a custom-configured inertial measurement unit (IMU) and a sensor with real-time heart rate measurement (HR) using a proprietary computer application. SMART was used to evaluate the safety and exercise load with 115 study participants: 51 women (44.35%) and 64 men (55.65%) aged 19 to 65 years. The exercise test was the 6MWT test. In 35% of the participants, the mean HR exceeded the recognized safe limit of HR 75% max. Ongoing monitoring of HR allows for optimal exercise and its safety. Step count data were collected from the SMART system. The average step length was calculated by dividing the distance by the number of steps. The aim of the present study was to assess the risk of excessive cardiovascular stress during the 6MWT test using the SMART system.

Inertial Sensor Algorithm to Estimate Walk Distance.

The "total distance walked" obtained during a standardized walking test is an integral component of physical fitness and health status tracking in a range of consumer and clinical applications. Wearable inertial sensors offer the advantages of providing accurate, objective, and reliable measures of gait while streamlining walk test administration. The aim of this study was to develop an inertial sensor-based algorithm to estimate the total distance walked using older subjects with impaired fasting glucose (Study I), and to test the generalizability of the proposed algorithm in patients with Multiple Sclerosis (Study II). All subjects wore two inertial sensors (Opals by Clario-APDM Wearable Technologies) on their feet. The walking distance algorithm was developed based on 108 older adults in Study I performing a 400 m walk test along a 20 m straight walkway. The validity of the algorithm was tested using a 6-minute walk test (6MWT) in two sub-studies of Study II with different lengths of a walkway, 15 m (Study II-A, n = 24) and 20 m (Study II-B, n = 22), respectively. The start and turn around points were marked with lines on the floor while smaller horizontal lines placed every 1 m served to calculate the manual distance walked (ground truth). The proposed algorithm calculates the forward distance traveled during each step as the change in the horizontal position from each foot-flat period to the subsequent foot-flat period. The total distance walked is then computed as the sum of walk distances for each stride, including turns. The proposed algorithm achieved an average absolute error rate of 1.92% with respect to a fixed 400 m distance for Study I. The same algorithm achieved an absolute error rate of 4.17% and 3.21% with respect to an averaged manual distance for 6MWT in Study II-A and Study II-B, respectively. These results demonstrate the potential of an inertial sensor-based algorithm to estimate a total distance walked with good accuracy with respect to the manual, clinical standard. Further work is needed to test the generalizability of the proposed algorithm with different administrators and populations, as well as larger diverse cohorts.

Comparison of Different Physical Activity Measures in a Cardiac Rehabilitation Program: A Prospective Study.

Concordant assessments of physical activity (PA) and related measures in cardiac rehabilitation (CR) is essential for exercise prescription. This study compared exercise measurement from an in-person walk test; wearable activity tracker; and self-report at CR entry, completion (8-weeks) and follow-up (16-weeks). Forty patients beginning CR completed the Six-Minute Walk Test (6MWT), Physical Activity Scale for the Elderly (PASE), and wore Fitbit-Flex for four consecutive days including two weekend days. The sample mean age was 66 years; 67% were male. Increased exercise capacity at CR completion and follow-up was detected by a 6MWT change in mean distance (39 m and 42 m; p = 0.01, respectively). Increased PA participation at CR completion was detected by Fitbit-Flex mean change in step counts (1794; p = 0.01). Relative changes for Fitbit-Flex step counts and a 6MWT were consistent with previous research, demonstrating Fitbit-Flex's potential as an outcome measure. With four days of data, Fitbit-Flex had acceptable ICC values in measuring step counts and MVPA minutes. Fitbit-Flex steps and 6MWT meters are more responsive to changes in PA patterns following exposure to a cardiac rehabilitation program than Fitbit-Flex or PASE-estimated moderate-vigorous PA (MVPA) minutes. Fitbit-Flex step counts provide a useful additional measure for assessing PA outside of the CR setting and accounts for day-to-day variations. Two weekend days and two weekdays are needed for Fitbit-Flex to estimate PA levels more precisely.

Amputee Fall Risk Classification Using Machine Learning and Smartphone Sensor Data from 2-Minute and 6-Minute Walk Tests.

The 6-min walk test (6MWT) is commonly used to assess a person's physical mobility and aerobic capacity. However, richer knowledge can be extracted from movement assessments using artificial intelligence (AI) models, such as fall risk status. The 2-min walk test (2MWT) is an alternate assessment for people with reduced mobility who cannot complete the full 6MWT, including some people with lower limb amputations; therefore, this research investigated automated foot strike (FS) detection and fall risk classification using data from a 2MWT. A long short-term memory (LSTM) model was used for automated foot strike detection using retrospective data (n = 80) collected with the Ottawa Hospital Rehabilitation Centre (TOHRC) Walk Test app during a 6-min walk test (6MWT). To identify FS, an LSTM was trained on the entire six minutes of data, then re-trained on the first two minutes of data. The validation set for both models was ground truth FS labels from the first two minutes of data. FS identification with the 6-min model had 99.2% accuracy, 91.7% sensitivity, 99.4% specificity, and 82.7% precision. The 2-min model achieved 98.0% accuracy, 65.0% sensitivity, 99.1% specificity, and 68.6% precision. To classify fall risk, a random forest model was trained on step-based features calculated using manually labeled FS and automated FS identified from the first two minutes of data. Automated FS from the first two minutes of data correctly classified fall risk for 61 of 80 (76.3%) participants; however, <50% of participants who fell within the past six months were correctly classified. This research evaluated a novel method for automated foot strike identification in lower limb amputee populations that can be applied to both 6MWT and 2MWT data to calculate stride parameters. Features calculated using automated FS from two minutes of data could not sufficiently classify fall risk in lower limb amputees.

A Mobile Application to Perform the Six-Minute Walk Test (6MWT) at Home: A Random Walk in the Park Is as Accurate as a Standardized 6MWT.

The six-minute walk test (6MWT) provides an objective measurement of a person's functional exercise capacity. In this study, we developed a smartphone application that allows cardiac patients to do a self-administered 6MWT at home on a random trajectory. In a prospective study with 102 cardiovascular disease patients, we aimed to identify the optimal circumstances to perform a smartphone-measured 6MWT, i.e., the best algorithm and the best position to wear the smartphone during the test. Furthermore, we investigated if a random walk is as accurate as a standardized 6MWT. When considering both the reliability and accuracy of the distance walked, the best circumstances to perform a standardized smartphone-measured 6MWT are wearing the smartphone in a strap around the patient's arm and using an algorithm that relies on the processed step count data acquired from Google Fit. Furthermore, we demonstrated that a smartphone-measured walk along a random trajectory is as accurate to determine a cardiac patient's functional exercise capacity as a standardized (smartphone-measured) 6MWT. We conclude this paper by presenting how our 6MWT application can be used in a home setting to remotely follow up on cardiac patients' functional exercise capacity.

Does Opuntia ficus-indica Juice Supplementation Improve Biochemical and Cardiovascular Response to a 6-Minute Walk Test in Type 2 Diabetic Patients?

Background and objectives: The purpose of this study was to evaluate the effect of Opuntia ficus-indica juice (OFIJ) on performance and biochemical and physiological responses to a 6 min walking test (6MWT) in diabetic patients. Materials and Methods: Twenty diabetic patients performed a 6MWT at 07:00 h. During each test session, they were asked to drink 70 mL/day of natural OFIJ or placebo (PLA) for 4 days. Results: the results showed that cardiovascular parameters increased significantly after the 6MWT under both conditions. While, cortisol, HbA1c, cholesterol total (CT), triglycerides (TG), as well as low-density lipoprotein (LDL) were not modified between without and with supplementation. Likewise, no significant variation in performance was observed for PLA and OFIJ (p > 0.05). The cardiovascular parameters (heart rate max (HRmax), diastolic blood pressure (DBP), and systolic blood pressure (SBP)), lipid profile (CT, TG, LDL, and high-density lipoprotein HDL), hormonal parameters (insulin and glucagon), HbA1c and lactate ([La]) did not present any significant modification either between PLA or OFIJ (p > 0.05). Muscle-damage markers (creatine kinase (CK) and lactate dehydrogenase (LDH)], cortisol, and liver parameters (i.e., oxidative stress marker, γGT, and total bilirubin) as well as glucose (GLC) were affected by supplementation (p < 0.05) before and after the 6MWT, but this change was significant only for OFIJ (p < 0.05). Conclusion: OFIJ had an antioxidant capacity, improved performance of the 6MWT, and reduced muscle-damage markers and glucose level in type 2 diabetic patients.

Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis.

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

The 6-Minute Walk Test: Indications and Guidelines for Use in Outpatient Practices.

The 6-Minute Walk Test (6MWT) is a standardized tool used to measure lung impairment. It is used in outpatient primary and pulmonary practices to objectively assess functional exercise capacity and hypoxemia in patients with chronic lung disease. Screening for functional decrease in exercise tolerance and hypoxemia aids in initiating and maintaining the use of oxygen supplementation to improve functional improvement in chronic lung patients. It has new applications for recovering COVID-19 pneumonia patients to assess for clinical compromise. Discussion includes elements and guideline recommendations for 6MWT, indications for use, appropriate patient populations appropriate, safety, coding, and current reimbursement insurance guidelines.

Physical function after lung transplantation for late-onset noninfectious pulmonary complications after allogeneic hematopoietic stem cell transplantation.

PURPOSE: Late-onset noninfectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are fatal, and lung transplantation is the only curative treatment. Although lung transplantation for LONIPCs may confer good survival rates, it is unclear whether or how impaired physical functioning is restored. Thus, this study aimed to investigate the long-term course and associated changes in physical functions after lung transplantation in patients with LONIPCs after allo-HSCT. METHODS: This prospective cohort study enrolled 15 patients who received lung transplantation for LONIPCs after allo-HSCT between 2012 and 2018. Dyspnea scores, performance status, physical function, and exercise tolerance were assessed before lung transplantation and up to 2 years after transplantation. RESULTS: Two years after lung transplantation, the dyspnea scores and performance status improved, but did not recover completely. Physical function was assessed using the knee extensor strength (KES) and 6-min walk test (6MWT); the results were poor until 3 months after transplantation but improved over 2 years. The 6MWT distance showed improvement to a nearly healthy level (562.7 m). Recovery of exercise tolerance was associated with recovery in % vital capacity (%VC; r=0.5) and KES (r=0.4) from 3 months to 2 years after lung transplantation. Furthermore, a flat thorax, which is a characteristic of patients with LONIPCs, affected the %VC at 2 years after transplantation (r=0.8). CONCLUSION: Lung transplantation for LONIPCs may restore impaired physical function. A multifaceted rehabilitation program should be considered, especially to improve muscle weakness and pulmonary function.

Plasma HMGB1 levels and physical performance in ICU survivors.

PURPOSE: Physical impairment after critical illness is recognized as a part of the post-intensive care syndrome (PICS). About one third of intensive care unit (ICU) survivors suffer from long-term physical disability, yet the underlying pathophysiological mechanisms remain poorly understood. The pro-inflammatory alarmin, high mobility group box 1 (HMGB1), promotes muscle dysfunction in experimental models, and HMGB1 stays elevated in some patients after ICU discharge. Accordingly, we investigated the relationship between HMGB1 plasma levels and physical performance in ICU survivors. METHODS: Prospective cohort study of 100 ICU survivors from the general ICU at the Karolinska University Hospital, Sweden. Patients returned for follow up at 3 (58 patients) and 6 months (51 patients) after ICU discharge. Blood samples were collected, and a 6-minute walk test (6-MWT), a handgrip-strength test (HST), and a timed-stands test (TST) were performed. RESULTS: Compared to reference values of the different physical tests, 16% of patients underperformed at all tests at 3 months and 12% at 6 months. All test results, except hand-grip strength left, improved significantly over the follow-up period (P < .05). There was no significant association between plasma HMGB1 levels at 3 and 6 months and scores on the three tests (6-MWT, TST, and HST) (P = .50-0.69). CONCLUSION: In this follow-up study of ICU survivors, we found no significant association between plasma HMGB1 levels and physical performance. Additional follow-up studies of HMGB1 plasma levels and muscle function in ICU survivors are still warranted. EDITORIAL COMMENT: HMGB-1, a marker of cell damage and activation, is known to increase in ICU patients. In study participants at 3- to 6-month post-ICU stay, HMGB-1 levels were still elevated, although no association to the primary outcome, physical performance, was found. Mechanisms for failure to recover physical performance post-ICU remain unclear, and investigations into cause of post-intensive care syndrome need to continue. TRIAL REGISTRATIONS: ClinicalTrials.gov identifier NCT02914756.

Residual respiratory impairment after COVID-19 pneumonia.

INTRODUCTION: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. METHOD: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). RESULTS: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. CONCLUSION: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.