Exercise-Induced Oxygen Desaturation Increases Arterial Stiffness in Patients with COPD During the 6WMT.

Objective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD. Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO2) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO2 during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study. Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was -0.53 (-0.95 to -0.31) in non-EID group, -0.20 (-1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038). Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity.

BACKGROUND: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population. METHODS AND RESULTS: Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035). CONCLUSION: ID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.

Exercise pulmonary hypertension in patients with systemic sclerosis based on updated guidelines.

Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis (SSc) remains unknown. We aimed to investigate the characteristics of exercise pulmonary hypertension (ex-PH) in patients with systemic sclerosis (SSc), which are unknown. We retrospectively examined 77 patients with SSc who underwent symptom-limited exercise testing using a cycle ergometer with right heart catheterization at our hospital. Nineteen patients with postcapillary PH were excluded. Fifty-eight patients (median age, 63 years; 55 women) were divided into the overt-PH (n = 18, mean pulmonary arterial pressure [PAP] > 20 mmHg and pulmonary vascular resistance > 2 Wood units at rest), ex-PH (n = 19, mean PAP/cardiac output slope > 3), and non-PH (n = 21) groups. Exercise tolerance and echocardiography results were compared among the groups. Peak oxygen consumption was high in the non-PH group, intermediate in the ex-PH group, and low in the overt-PH group (14.5 vs. 13.0 vs. 12.5 mL/kg/min, p = 0.043), and the minute ventilation/peak carbon dioxide production slope was also intermediate in the ex-PH group (32.2 vs. 32.4 vs. 43.0, p = 0.003). The tricuspid annular plane systolic excursion/systolic PAP ratio decreased from non-PH to ex-PH to overt-PH (0.73 vs. 0.69 vs. 0.55 mm/mmHg, p = 0.018). In patients with SSc, exercise PH may represent an intermediate condition between not having PH and overt PH, according to the new guidelines.

Longitudinal strain correlates with 6-minute walk distance whereas ejection fraction and diastolic parameters do not.

BACKGROUND: Impaired functional capacity is a common symptom in patients with heart failure. Standard measures of left ventricular (LV) function, such as ejection fraction (EF) and LV diastolic parameters, do not correlate with measures of functional capacity. The aim of this study is to determine if measures of global and regional LV strain better correlate with 6-minute walk distance than does EF or measures of LV diastolic function. METHODS: 120 patients referred to a cardiology clinic for evaluation of known or suspected heart failure were approached for enrollment. Of those 120 patients, 58 had an echocardiogram within 3 months of enrollment with images adequate for regional and global strain assessment, had no contra-indication to exercise testing, and had no previously documented non-cardiac explanation for dyspnea on exertion. In those 58 patients, 6-minute walk distance was measured, LV EF was determined with Simpson's biplane method, and global and regional longitudinal strain were measured with TomTec Image Arena 4.5.1 software. RESULTS: LV EF had no correlation with 6-minute walk distance (r = 0.22, p = 0.09) even when controlling for age, gender, and BMI (p = 0.07). No measures of LV diastolic function (including E velocity, Deceleration Time, e' annular velocities, or E/e') had a correlation with 6-minute walk distance. Multiple measures of global and regional LV longitudinal systolic function had a correlation with 6-minute walk distance. Longitudinal strain of the basal LV segments had the strongest correlation with 6-minute walk distance (r= -0.36, p = 0.005), and correlation persisted after controlling for age, gender, BMI, and systolic blood pressure (p = 0.004). CONCLUSIONS: Longitudinal strain correlates with a measure of functional capacity, but LVEF and traditional measures of LV diastolic dysfunction do not. Measures of longitudinal strain, especially in basal LV segments, will likely be an important marker of clinically relevant LV function.

Effectiveness of pulmonary rehabilitation programmes and/or respiratory muscle training in patients with post-COVID conditions: a systematic review.

BACKGROUND: The term "post-COVID-19 condition" refers to the symptomatology that appears between four to twelve weeks after Covid-19 infection. These symptoms can persist for weeks or even months, significantly diminishing the quality of life for affected individuals. The primary objective of this study was to assess the effectiveness of pulmonary rehabilitation programs and/or respiratory muscle training on respiratory sequelae in patients with post-COVID condition. METHODS: The literature search was conducted in the following databases: PubMed, PEDro, Embase, Cochrane, Scopus, and Web of Science. Randomized clinical trials were included in which participants were aged 18 years or older. Articles were excluded if at least one of the therapies did not involve pulmonary rehabilitation or respiratory muscle training, if the participants were COVID positive, if studies lacked results, and finally, if interventions were conducted without supervision or at home. This review only encompasses supervised non-virtual interventions. This study adheres to the PRISMA statement and has been registered in the PROSPERO database (CRD42023433843). RESULTS: The outcomes obtained in the included studies are assessed across the following variables: Exercise capacity using the 6-minute walk test, Dyspnea, fatigue, Pulmonary function, Maximum inspiratory pressure, and Quality of life. CONCLUSION: Despite the absence of a specific treatment at present, it was evident from this review that a well-structured pulmonary rehabilitation program that incorporates both aerobic and muscular strength exercises along with techniques and inspiratory muscle exercises was the most effective form of treatment.

Effects of exercise training on cardiac output in subjects with heart failure with preserved ejection fraction (HFpEF) - a protocol for a systematic review and meta-analysis.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) commonly experience exercise intolerance, resulting in reduced cardiorespiratory fitness. This is characterised by a decreased maximal oxygen uptake (V̇O2peak), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO2). While exercise training has been shown to improve V̇O2peak in HFpEF patients, the effects on CO remain unclear. The aim of this study is to systematically review and analyse the current evidence on the effects of supervised exercise training on CO in patients with HFpEF. METHODS: We will systematically search for literature describing the effects of supervised exercise training on CO in patients with HFpEF. All eligible studies published before 30 June 2023 in the following electronic databases will be included: MEDLINE (Ovid), Embase (Ovid), SPORTDiscus (EBSCOhost), and CENTRAL (Cochrane Library). Effect sizes will be extracted for CO before and after a supervised exercise training intervention at rest and maximal exercise. Mass of heterogeneity (I2) will be calculated, and either fixed-effect models or random-effect models will be used for meta-analysis. To detect a potential publication bias, funnel plot analyses will be performed. DISCUSSION: While several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O2peak, CO, and a-vDO2 are much scarcer, especially in patients with HFpEF. From a physiological perspective, measuring CO before and after supervised exercise training seems to be a reasonable way to accurately operationalise a potential improvement in cardiac function. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022361485.

Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance.

ABSTRACT: Arroum, T, Hish, GA, Burghardt, KJ, Ghamloush, M, Bazzi, B, Mrech, A, Morse, PT, Britton, SL, Koch, LG, McCully, JD, Hüttemann, M, and Malek, MH. Mitochondria transplantation: Rescuing innate muscle bioenergetic impairment in a model of aging and exercise intolerance. J Strength Cond Res 38(7): 1189-1199, 2024-Mitochondria, through oxidative phosphorylation, are crucial for energy production. Disease, genetic impairment, or deconditioning can harm muscle mitochondria, affecting energy production. Endurance training enhances mitochondrial function but assumes mobility. Individuals with limited mobility lack effective treatments for mitochondrial dysfunction because of disease or aging. Mitochondrial transplantation replaces native mitochondria that have been damaged with viable, respiration-competent mitochondria. Here, we used a rodent model selectively bred for low-capacity running (LCR), which exhibits innate mitochondrial dysfunction in the hind limb muscles. Hence, the purpose of this study was to use a distinct breed of rats (i.e., LCR) that display hereditary skeletal muscle mitochondrial dysfunction to evaluate the consequences of mitochondrial transplantation. We hypothesized that the transplantation of mitochondria would effectively alleviate mitochondrial dysfunction in the hind limb muscles of rats when compared with placebo injections. In addition, we hypothesized that rats receiving the mitochondrial transplantation would experience an improvement in their functional capacity, as evaluated through incremental treadmill testing. Twelve aged LCR male rats (18 months old) were randomized into 2 groups (placebo or mitochondrial transplantation). One LCR rat of the same age and sex was used as the donor to isolate mitochondria from the hindlimb muscles. Isolated mitochondria were injected into both hindlimb muscles (quadriceps femoris, tibialis anterior (TA), and gastrocnemius complex) of a subset LCR (n = 6; LCR-M) rats. The remaining LCR (n = 5; LCR-P) subset received a placebo injection containing only the vehicle without the isolated mitochondria. Four weeks after mitochondrial transplantation, rodents were euthanized and hindlimb muscles harvested. The results indicated a significant (p < 0.05) increase in mitochondrial markers for glycolytic (plantaris and TA) and mixed (quadricep femoris) muscles, but not oxidative muscle (soleus). Moreover, we found significant (p < 0.05) epigenetic changes (i.e., hypomethylation) at the global and site-specific levels for a key mitochondrial regulator (transcription factor A mitochondrial) between the placebo and mitochondrial transplantation groups. To our knowledge, this is the first study to examine the efficacy of mitochondrial transplantation in a rodent model of aging with congenital skeletal muscle dysfunction.

Strength training improves functional capacity of individuals with chronic heart failure: Randomized clinical trial.

INTRODUCTION: Chronic heart failure (CHF) is characterized by dyspnea, exercise intolerance and impaired quality of life. Physical exercise is a key point in the treatment of these outcomes. OBJECTIVE: To evaluate the effect of 24 weeks of two different training strategies on functional capacity, muscle strength and quality of life in individuals with CHF. METHODS: The following tests and evaluations were performed before and after 24 weeks of training: exercise test, one-repetition maximum test (1- RM) and Minnesota Living with Heart Failure Questionnaire (MLHFQ). Subjects were randomized according to the modality they would perform first: aerobic training group (ATG - n=6) or strength training group (STG - n=7). RESULTS: The sample consisted of 13 individuals (10 men), aged 55 ± 12 years and a left ventricular ejection fraction (LVEF) of 38.8 ± 5.3%. There was a significant increase in V'O 2peak only in STG (STG: 26.92 ± 9.81 vs 30.52 ± 8.39 mL.kg -1 .min -1 - p=0.025; ATG: 19.60 ± 7,00 vs 22.42 ± 8.54 mL.kg -1 .min -1 - p=0.119). Both groups showed significant improvements in muscle strength (STG: 45 ± 17 vs 51 ± 20 kg - p=0.001; ATG: 38 ± 19 vs 42 ± 20 kg - p=0.012). There was no significant difference in quality of life (STG: 30 ± 18 vs 24 ± 20 - p=0.109; ATG: 36 ± 16 vs 26 ± 15 - p=0.143). CONCLUSION: The early implementation of strength training improves functional capacity and muscle strength of individuals with CHF.

Adoption of the cardiopulmonary exercise test in the exercise ability and cardiopulmonary function rehabilitation of coronary artery disease (CAD) patients.

BACKGROUND: This study aimed to explore the application of cardiopulmonary exercise testing in coronary artery disease (CAD) patients, evaluate its impact on exercise ability and cardiopulmonary function in patients with coronary heart disease (CHD), and promote the application of cardiopulmonary exercise testing in CAD management. METHODS: Fifty CHD patients after percutaneous coronary intervention (PCI) were recruited and randomly enrolled into the control (Ctrl) group and intervention (Int) group. Routine health education and health education combined with RT training were carried out for the two groups. Blood lipid levels and lung function were compared between the two groups after intervention. Cardiac function was evaluated by Doppler ultrasonography, and cardiopulmonary fitness and exercise ability were evaluated by a cardiopulmonary exercise test (CPET). The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were employed to evaluate negative emotions. The 36-item short-form (SF-36) was adopted to evaluate quality of life. RESULT: Compared with those in the Ctrl group, the levels of serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) decreased in the Int group, while the levels of high-density lipoprotein increased (P < 0.05). The quantitative load results showed that compared with the Ctrl group, the heart rate (HR) and self-perceived fatigue degree of the Int group decreased, and the ST segment increased (P < 0.05). Compared with the Ctrl group, the left ventricular ejection fraction (LVEF), forced expiratory volume at 1 s (FEV1), ratio of forced expiratory volume to forced vital volume (FEV1/FVC%), and maximum chase volume (MVV) increased in the Int group, while the left ventricular end diastolic diameter and left ventricular end contractile diameter decreased (P < 0.05). The results of the CPET showed that compared with the Ctrl group, minute ventilation/carbon dioxide production slope, VE/VCO2 - Peak, anaerobic threshold (AT), peak oxygen pulse (VO2/HR peak), oxygen uptake efficiency platform (OUEP), increasing power exercise time (IPEt), HR recovery 1 min after exercise, peak load power (Watt peak), and value metabolic equivalent (Watt peak) increased in the Int group (P < 0.05). Compared with the Ctrl group, the SAS and SDS scores in the Int group decreased (P < 0.05). The results of the quality of life evaluation showed that compared with the Ctrl group, the score of the SF-36 dimensions increased in the Int group (P < 0.05). CONCLUSION: RT training can reduce postoperative blood lipid and quantitative load levels in CAD patients and improve adverse mood. Furthermore, it can improve patients' cardiopulmonary function, cardiopulmonary fitness, exercise ability, and quality of life.

Impaired longitudinal systolic-diastolic coupling and cardiac response to exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), impaired augmentation of stroke volume and diastolic dysfunction contribute to exercise intolerance. Systolic-diastolic (S-D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during early diastole. Impaired S-D coupling may contribute to the impaired cardiac response to exercise in patients with HCM. METHODS: Patients with HCM (n = 25, age = 47 ± 9 years) and healthy adults (n = 115, age = 49 ± 10 years) underwent a cardiopulmonary exercise testing (CPET) and echocardiogram. S-D coupling was defined as the ratio of LV longitudinal excursion of the mitral annulus during early diastole (EDexc) and systole (Sexc) and compared between groups. Peak oxygen uptake (peak V̇O2) (Douglas bags), cardiac index (C2H2 rebreathe), and stroke volume index (SVi) were assessed during CPET. Linear regression was performed between S-D coupling and peak V̇O2, peak cardiac index, and peak SVi. RESULTS: S-D coupling was lower in HCM (Controls: 0.63 ± 0.08, HCM: 0.56 ± 0.10, p < 0.001). Peak V̇O2 and stroke volume reserve were lower in patients with HCM (Peak VO2 Controls: 28.5 ± 5.5, HCM: 23.7 ± 7.2 mL/kg/min, p < 0.001, SV reserve: Controls 39 ± 16, HCM 30 ± 18 mL, p = 0.008). In patients with HCM, S-D coupling was associated with peak V̇O2 (r = 0.47, p = 0.018), peak cardiac index (r = 0.60, p = 0.002), and peak SVi (r = 0.63, p < 0.001). CONCLUSION: Systolic-diastolic coupling was impaired in patients with HCM and was associated with fitness and the cardiac response to exercise. Inefficient S-D coupling may link insufficient stroke volume generation, diastolic dysfunction, and exercise intolerance in HCM.

Echocardiographic assessment for cardiopulmonary function in patients with congenital heart disease-related pulmonary arterial hypertension.

BACKGROUND: For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity. METHODS: A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO2) and the carbon dioxide ventilation equivalent slope (VE/VCO2 slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters. RESULTS: The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO2 and VE/VCO2 slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO2 slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO2 ≤ 15 mL/kg/min and a VE/VCO2 slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters. CONCLUSIONS: TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance.

Predicting the effects of surgically determined parameters on exercise tolerance in Fontan patients.

The Fontan physiology is a surgically created circulation for patients with a single functioning ventricle. Patients with this circulation tend to have lower exercise tolerance compared to those with a normal circulation. Important computational and experimental work has been done to investigate this reduction in exercise tolerance. However, there are few systematic modeling studies that focus on the effect of several surgically determined parameters within the same framework. We propose a mathematical model to describe the Fontan circulation under exercise. We then formulate a heuristic based on clinical data from Fontan patients to estimate exercise tolerance. The model is used to investigate the effect of three important surgically determined parameters on exercise tolerance: the systemic arterial compliance, the systemic-venous to pulmonary-venous fenestration, and the resistance of the total cavopulmonary connection.

Re-evaluating the Need for Routine Maximal Aerobic Capacity Testing within Fighter Pilots.

INTRODUCTION: There is a current belief in aviation suggesting that aerobic training may reduce G-tolerance due to potential negative impacts on arterial pressure response. Studies indicate that increasing maximal aerobic capacity (V˙o2 max) through aerobic training does not hinder G-tolerance. Moreover, sustained centrifuge training programs revealed no instances where excessive aerobic exercise compromised a trainee's ability to complete target profiles. The purpose of this review article is to examine the current research in the hope of establishing the need for routine V˙o2-max testing in air force pilot protocols.METHODS: A systematic search of electronic databases including Google Scholar, PubMed, the Aerospace Medical Association, and Military Medicine was conducted. Keywords related to "human performance," "Air Force fighter pilots," "aerobic function," and "maximal aerobic capacity" were used in various combinations. Articles addressing exercise physiology, G-tolerance, physical training, and fighter pilot maneuvers related to human performance were considered. No primary data collection involving human subjects was conducted; therefore, ethical approval was not required.RESULTS: The V˙o2-max test provides essential information regarding a pilot's ability to handle increased Gz-load. It assists in predicting G-induced loss of consciousness by assessing anti-G straining maneuver performance and heart rate variables during increased G-load.DISCUSSION: V˙o2-max testing guides tailored exercise plans, optimizes cardiovascular health, and disproves the notion that aerobic training hampers G-tolerance. Its inclusion in air force protocols could boost readiness, reduce health risks, and refine training for fighter pilots' safety and performance. This evidence-backed approach supports integrating V˙o2-max testing for insights into fitness, risks, and tailored exercise.Zeigler Z, Acevedo AM. Re-evaluating the need for routine maximal aerobic capacity testing within fighter pilots. Aerosp Med Hum Perform. 2024; 95(5):273-277.

Influencing factors of sedentary behaviour in people with chronic obstructive pulmonary disease: a systematic review.

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) are more likely to adopt a sedentary lifestyle. Increased sedentary behaviour is associated with adverse health consequences and reduced life expectancy. AIM: This mixed-methods systematic review aimed to report the factors contributing to sedentary behaviour in people with COPD. METHODS: A systematic search of electronic databases (Medline, CINAHL, PsycINFO and Cochrane Library) was conducted and supported by a clinician librarian in March 2023. Papers were identified and screened by two independent researchers against the inclusion and exclusion criteria, followed by data extraction and analysis of quality. Quantitative and qualitative data synthesis was performed. RESULTS: 1037 records were identified, 29 studies were included (26 quantitative and 3 qualitative studies) and most studies were conducted in high-income countries. The most common influencers of sedentary behaviour were associated with disease severity, dyspnoea, comorbidities, exercise capacity, use of supplemental oxygen and walking aids, and environmental factors. In-depth findings from qualitative studies included a lack of knowledge, self-perception and motivation. However, sedentarism in some was also a conscious approach, enabling enjoyment when participating in hobbies or activities. CONCLUSIONS: Influencers of sedentary behaviour in people living with COPD are multifactorial. Identifying and understanding these factors should inform the design of future interventions and guidelines. A tailored, multimodal approach could have the potential to address sedentary behaviour. PROSPERO REGISTRATION NUMBER: CRD42023387335.

Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.

The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study.

BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.

Maintenance Pulmonary Rehabilitation: An Update and Future Directions.

The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend pulmonary rehabilitation (PR) for individuals with COPD to improve exercise capacity and health-related quality of life (HRQOL) and reduce symptoms of dyspnea. For cost-effectiveness in COPD care, PR is second only to smoking cessation. However, PR programs typically last 9-12 weeks. The benefits of PR in terms of exercise capacity and HRQOL often decrease toward pre-PR levels as early as 3-6 months after completing PR if patients do not continue to engage in exercise. This review will (1) briefly summarize the efficacy data that informed the 2023 American Thoracic Society (ATS) clinical practice guidelines for maintenance PR, (2) discuss exercise components of maintenance PR studied since 2020 when the last papers were included in the ATS guidelines, (3) explore future directions for delivery of maintenance PR using technology-mediated models, and (4) examine the need for behavior change techniques informed by theoretical models that underpin long-term behavior change. This review will focus on persons with COPD who have completed an out-patient core initial PR program as most of the data on maintenance PR have been published in this patient population. Core PR typically implies a facility-based initial intensive structured program. All patients who complete a core initial PR program should be counseled by PR staff at the discharge visit to engage in ongoing exercise. This usual care is equally as important as referral to a formal PR maintenance program. It is critical to emphasize that usual care after core initial PR means all patients should be supported to participate in regular ongoing exercise, regardless of whether supervised maintenance PR is available. Currently, the optimal frequency, exercise and/or physical activity content, and delivery mode for maintenance PR in persons with COPD and other chronic respiratory diseases remain unknown. Patient safety and degree of in-person supervision required due to the severity of the underlying lung disease need to be considered. Future research of maintenance PR should be underpinned by behavior change techniques. Finally, in the setting of finite resources, balancing the competing priorities of core initial programs with those of maintenance PR programs needs to be achieved.

Respiratory Assist Devices in Pulmonary Rehabilitation.

Patients with advanced lung disease, especially patients with COPD, suffer from dyspnea at rest that worsens during the performance of even limited physical activities. The causes of dyspnea are multifactorial and are related to structural changes found in the parenchymal compartment of the lung as well as the airway and pulmonary vasculature. Alterations in any of the lung compartments may have negative consequences for the physiological performance of exercise. Respiratory assist devices that attenuate the pathophysiological derangements induced by the underlying lung disease, and/or unload the increased work of breathing, can enhance the performance of exercise, and help to produce more robust training effects in patients with lung disease. Herein we review the data that examines these approaches using respiratory assist devices to improve exercise outcomes in patients with COPD.

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).