6-min Walk Distance Research Articles

The prognostic value of right ventricular outflow tract velocity time integral in patients with pulmonary hypertension.

Right ventricular (RV) failure is one of the leading causes of death in patients with pulmonary hypertension (PH). Conventional echocardiographic parameters are not included in risk stratification and follow-up for prognostic assessment due to PH's diverse nature and the RV's complex geometry. RV outflow tract velocity time integral (RVOT VTI) is a simple, non-invasive estimate of pulmonary flow and an echocardiographic surrogate of RV stroke volume. In this study, we aimed to define the prognostic value of RVOT VTI in PH patients. Sixty-three subjects with idiopathic PAH (IPAH) (n=23), connective tissue disease-associated PAH (CTD-associated PAH) (n=19) and chronic thromboembolic pulmonary hypertension (CTEPH) (n=21) were retrospectively included. A comprehensive two-dimensional echocardiographic evaluation, including RVOT-VTI measurement, was performed during the follow-up and the New York Heart Association functional class (NYHA FC), 6min walk distance (6MWD) and brain natriuretic peptide (BNP) levels were recorded. The median age of the whole cohort was 63years (52-68), and 47 (74.6%) of the patients were women. The median follow-up period was 20months (11-33), and 20 (31.7%) patients died in this period. BNP values were higher [317 (210-641) vs 161 (47-466), P=0.02], and 6MWD values were lower [197.5±89.5 vs 339±146.3, P<0.0001] in the non-survivor group, and the non-survivor group had a worse NYHA-FC (P=0.02). Among echocardiographic data, tricuspid annular plane systolic excursion (TAPSE) (15.4±4.8 vs 18.6±4.2, P=0.01) and RVOT VTI (11.9±4.1 vs 17.2±4.3, P<0.0001) values were lower whereas right atrial area (RAA) (26.9±10.1 vs 22.2±7.1, P=0.04) values were higher in the non-survivor group. The area under curve of the RVOT VTI for predicting mortality was 0.82 [95% confidence interval (CI) 0.715-0.940, P<0.0001], and the best cut-off value was 14.7cm with a sensitivity of 80% and specificity of 77%. Survival was significantly lower in subjects with RVOT VTI≤14.7cm (log-rank P<0.0001). Survival rates for patients with RVOT VTI≤14.7cm were 70% at 1year, 50% at 2years, %29 at 3years and 21% at 5years. The univariate determinants of all-cause mortality were BNP [hazard ratio (HR) 1.001 (1.001-1.002), P=0.001], 6MWD [HR 0.994 (0.990-0.999), P=0.012] and NYHA-FC III-IV [HR 3.335 (1.103-10.083), P=0.03], TAPSE [HR 0.838 (0.775-0.929), P=0.001], RAA [HR 1.072 (1.013-1.135), P=0.016] and RVOT VTI [HR 0.819 (0.740-0.906), P<0.0001]. RVOT VTI was found to be the only independent determinant of mortality [HR 0.857 (0.766-0.960), P=0.008]. The decreased RVOT VTI predicts mortality in patients with PH and each 1mm decrease in RVOT VTI increases the risk of mortality by 14.3%. This parameter might serve as an additional parameter in the follow-up of these patients especially when 6MWD and NYHA-FC could not be determined.

The effect of a hybrid structured pulmonary rehabilitation education program for patients with lung cancer with a high risk of postoperative pulmonary complications: A quasi-experimental study

PurposeThe absence of standardized protocols and education are the main obstacles to perioperative pulmonary rehabilitation (PR), especially for patients with high-risk factors of postoperative pulmonary complications (PPCs). We aimed to explore the effect of a hybrid structured pulmonary rehabilitation education program (SPREP) on patients with lung cancer at high risk of PPCs. MethodsA quasi-experimental trial with a pre-post test design was conducted. The control group (n = 53) adopted routine perioperative pulmonary rehabilitation, while the intervention group (n = 53) received SPREP. Respiratory function, 6-min walk distance, Borg dyspnea scale, quality of life, anxiety–depression scores at admission, discharge, 2 weeks and 3 months post-discharge, and incidence of PPCs were compared between the two groups. ResultsThere were no significant differences on the 6-min walk distance and Borg Dyspnoea Scale at discharge between the two groups (P > 0.05), whereas the intervention group showed improved performance at the remaining time points (P < 0.05). In addition, the intervention group had improved exercise capacity, pulmonary function and quality of life, reduced levels of anxiety and depression at discharge, 2 weeks post-discharge and 3 months post-discharge (P < 0.05). In addition, incidence of PPCs was significantly reduced in the intervention group, especially postoperative pneumonia. ConclusionsThe SPREP could show significant benefits in enhancing exercise capacity, lung function, and quality of life, while diminishing the occurrence of PPCs and mitigating the levels of anxiety and depression, future large RCT need to further explore the efficacy. Trial registrationThis study was registered with the China Clinical Trial Registration Center (ChiCTR) under the Clinical Trial Registration Number [ChiCTR2200066698].

Tele-rehabilitation for Type II diabetics with heart failure with preserved ejection fraction.

This study aims to determine whether tele-rehabilitation has similar effects to conventional face-to-face physical rehabilitation for diabetic patients with heart failure with preserved ejection fraction (HFpEF). Demographic, laboratory, diagnostic and rehabilitation information for patients with type 2 diabetes with HFpEF were extracted from disease-specific databases. Outcome measures, including the Short Physical Performance Battery (SPPB), 6-minute walk distance, frailty status, European Quality of Life 5-Dimension 5-Level questionnaire (EQ-5D-5L) and reduction in HbA1c from admission, patients who received tele-rehabilitation therapy were compared to those received face-to-face rehabilitation. In this study, 90 patients with type 2 diabetes and HFpEF using tele-rehabilitation were matched with 90 patients with type 2 diabetes and HFpEF using face-to-face physical rehabilitation. Improvements in the results of the SPPB scores, 6-min walk distance and gait speed and EQ-5D-5L were noted from the follow-up time point 3 months to 6 months in both two groups. There were no significant differences in functional tests and quality of life between the two groups. Our study proved that mobile-based tele-rehabilitation programs are non-inferior to face-to-face physical rehabilitation for diabetes patients after HFpEF. In addition, adherence to the telerehabilitation program showed that the novel technology was accepted well and could be an alternative to the conventional face-to-face rehabilitation program.

Characteristics and risk profiles of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension living permanently at >2500 m of high altitude in Ecuador.

Over 80 Mio people worldwide live >2500 m, including at least as many patients with pulmonary vascular disease (PVD), defined as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), as elsewhere (estimated 0.1‰). Whether PVD patients living at high altitude have altered disease characteristics due to hypobaric hypoxia is unknown. In a cross-sectional study conducted at the Hospital Carlos Andrade Marin in Quito, Ecuador, located at 2840 m, we included 36 outpatients with PAH or CTEPH visiting the clinic from January 2022 to July 2023. We collected data on diagnostic right heart catheterization, treatment, and risk factors, including NYHA functional class (FC), 6-min walk distance (6MWD), and NT-brain natriuretic peptide (BNP) at baseline and at last follow-up. Thirty-six PVD patients (83% women, 32 PAH, 4 CTEPH, mean ± SD age 44 ± 13 years, living altitude 2831 ± 58 m) were included and had the following baseline values: PaO2 8.2 ± 1.6 kPa, PaCO2 3.9 ± 0.5 kPa, SaO2 91 ± 3%, mean pulmonary artery pressure 53 ± 16 mmHg, pulmonary vascular resistance 16 ± 4 WU, 50% FC II, 50% FC III, 6MWD 472 ± 118 m, BNP 490 ± 823 ng/L. Patients were treated for 1628 ± 1186 days with sildenafil (100%), bosentan (33%), calcium channel blockers (33%), diuretics (69%), and oxygen (nocturnal 53%, daytime 11%). Values at last visit were: FC (II 75%, III 25%), 6MWD of 496 ± 108 m, BNP of 576 ± 5774 ng/L. Compared to European PVD registries, ambulatory PVD patients living >2500 m revealed similar blood gases and relatively low and stable risk factor profiles despite severe hemodynamic compromise, suggesting that favorable outcomes are achievable for altitude residents with PVD. Future studies should focus on long-term outcomes in PVD patients dwelling >2500 m.

Better efficacy of sequential combination with balloon pulmonary angioplasty after long-term riociguat for patients with inoperable chronic thromboembolic pulmonary hypertension.

The present study aimed to evaluate the efficacy of long-term riociguat sequentially combined with balloon pulmonary angioplasty (BPA) for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Eight inoperable CTEPH patients were enrolled in this study, who have been administrated riociguat 2.5 mg three times daily for about 8 years, then underwent several sessions of BPA procedures. Data are prospectively collected to evaluate clinical outcomes, hemodynamics, exercise capacity, and right heart size and function by echocardiography at baseline, 8 years after riociguat, and 3 months after the final BPA. Eight patients (mean age 54.9 ± 11.4 years) were treated with riociguat 2.5 mg three times daily for 95.0 ± 10.7 months. Cardiac index (CI) (1.5 ± 0.5 L/min/m2 to 2.4 ± 0.6 L/min/m2, p = 0.005), 6 min walking distance (6MWD) (329.6 ± 87.5 m to 418.1 ± 75.8 m, p = 0.016), and pulmonary vascular resistance (PVR) (1336.9 ± 320.2 dyn·s·cm-5 to 815.4 ± 195.6 dyn·s·cm-5, p = 0.008) were significant improvement after riociguat treatment. Mean 4.1 ± 1.6 additional combinational BPA sessions and mean 18.8 ± 8.1 balloon dilations were performed. Mean pulmonary artery pressure (54.1 ± 11.1 mmHg to 33.6 ± 7.7 mmHg, p = 0.002) and PVR (815.4 ± 195.6 dyn·s·cm-5 to 428.3 ± 151.2 dyn·s·cm-5, p＜0.001) were further decreased. CI (2.4 ± 0.6 L/min/m2 to 2.7 ± 0.7 L/min/m2, p = 0.028) and 6MWD (418.1 ± 75.8 m to 455.7 ± 100.0 m, p = 0.038) were increased significantly. After long-term riociguat treatment, sequential combination with BPA delivered considerably incremental benefits on exercise capacity and pulmonary hemodynamics, as well as right heart size and function of technically inoperable CTEPH patients.

Efficacy and cerebral mechanisms of acupuncture for chronic obstructive pulmonary disease: study protocol for a multicenter, randomized controlled neuroimaging trial.

Although acupuncture is recommended by chronic obstructive pulmonary disease (COPD) treatment guidelines owing to its effects on dyspnea, the underlying neurobiological mechanisms of these effects remain unclear. This study aims to evaluate the efficacy of acupuncture in patients with stable COPD and explore the possible involvement of specific brain regions. This is a prospective, multicenter, single-blind, randomized controlled trial. A total of 90 participants will be recruited from three centers and will be randomly assigned in a 1:1 ratio to undergo acupuncture at acupoints on the disease-affected meridian (DAM) or non-acupoints on the non-affected meridian (NAM), in addition to routine pharmacological treatments. All participants will undergo 30 min of acupuncture three times a week for 8 weeks and will be followed up for 12 months. The primary outcome will be the severity of dyspnea, as measured using the Borg Dyspnea Scale and a visual analog scale at rest and after exercise. The secondary outcomes will include the multidimensional profile of dyspnea using Dyspnea-12, the modified Medical Research Council Dyspnea Scale, and the COPD assessment test; quality of life assessments using St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale; and additional measurements of exacerbation frequency, pulmonary function, and the 6-min walking distance. Magnetic resonance imaging (MRI) will be performed before and after exercise to explore the potential neurobiological mechanisms of exertional dyspnea. Anxiety and depression will be measured and analyzed for their correlation with the activation of specific brain areas involved in dyspnea. This randomized controlled trial aims to use a multidimensional evaluation of the efficacy of acupuncture in relieving dyspnea in patients with COPD in terms of emotion and quality of life and explore the neurobiological mechanisms underlying the effects of acupuncture on dyspnea from an imaging perspective. It is expected to provide strong evidence to support the use of acupuncture in relieving dyspnea in patients with COPD and those with aother diseases involving dyspnea. Additionally, it provides novel insights into the central mechanisms of acupuncture intervention and dyspnea. Chinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2300071725.

Effect of change in hepato-renal function and cardiac rehabilitation on mortality in patients with heart failure

BackgroundPatients with heart failure (HF) often suffer from hepato-renal dysfunction. The associations between hepato-renal function changes and mortality remain unclear. Further, the effect of cardiac rehabilitation (CR) on mortality and motor functions in patients with HF and hepato-renal dysfunction requires investigation. MethodsWe reviewed 2522 patients with HF (63.2 % male; median age: 74 years). The association between changes in hepato-renal function assessed by the Model for End-stage Liver Disease eXcluding INR (MELD-XI) score and mortality was examined. The association of CR participation with mortality and physical functions was investigated in patients with HF with decreased, unchanged, and increased MELD-XI scores. ResultsDuring the follow-up period, 519 (20.6 %) patients died. Worsened MELD-XI score was independently associated with all-cause death [adjusted hazard ratio (aHR): 1.099; 95 % confidence interval (CI): 1.061–1.138; p < 0.001]. CR participation was associated with low mortality, even in the increased MELD-XI score group (aHR: 0.498; 95 % CI: 0.333–0.745; p < 0.001). Trajectory of the MELD-XI score was not associated with physical function changes. There were no time by MELD-XI score interaction effects on handgrip strength (p = 0.084), leg strength (p = 0.082), walking speed (p = 0.583), and 6-min walking distance (p = 0.833) in patients participating in outpatient CR. ConclusionsHepato-renal dysfunction predicts high mortality. CR participation may be helpful for a better prognosis of patients with HF and hepato-renal dysfunction.

The impact of traditional mind-body exercises on pulmonary function, exercise capacity, and quality of life in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterized primarily by airflow obstruction, significantly impacting patients' quality of life. Traditional mind-body exercises, as a non-pharmacological intervention for COPD, have become a new research focus. To assess the impact of traditional mind-body exercises (Tai Chi, Qigong, Yoga) on pulmonary function, exercise capacity, and quality of life in COPD patients. Additionally, to identify the most suitable form of traditional mind-body exercise for different indicators. Searches were conducted in databases such as Web of Science, PubMed, EBSCOhost, CNKI, etc., to collect randomized controlled trials (RCTs) evaluating the intervention of traditional mind-body exercises (Tai Chi, Yoga, Qigong) in COPD. The Cochrane evaluation tool was applied for methodological quality assessment of the included literature. Statistical analysis and sensitivity analysis were performed using Revman 5.4 software, while publication bias was assessed using R software. This study included 23 studies with a total of 1862 participants. Traditional mind-body exercises improved patients' FEV1% index (WMD = 4.61, 95%CI [2.99, 6.23]), 6-min walk distance (SMD = 0.83, 95%CI [0.55, 1.11]), and reduced patients' SGRQ score (SMD = -0.79, 95%CI [-1.20, -0.38]) and CAT score (SMD = -0.79, 95%CI [-1.20, -0.38]). Qigong showed the most significant improvement in FEV1% and 6MWT, while Tai Chi primarily improved 6MWT, and the effect of Yoga was not significant. Sensitivity analysis indicated stable and reliable research conclusions. Traditional mind-body exercises are effective rehabilitation methods for COPD patients, significantly improving pulmonary function, exercise capacity, and quality of life. They are suitable as complementary interventions for standard COPD treatment. [https://www.crd.york.ac.uk/prospero/display-record.php?ID=CRD42023495104], identifier [CRD42023495104].

Association of computed tomography-derived muscle mass and quality with delayed acquisition independent walking after cardiovascular surgery.

In the context of cardiovascular surgery, the foremost concern lies in delayed functional recovery, as typified by the acquisition of independent walking after surgery, among older patients with decline in skeletal muscle mass and quality. Computed tomography (CT), which is typically employed for the preoperative assessment of pathological conditions in patients undergoing cardiovascular surgery, is also suitable for screening for potential decline in skeletal muscle mass and quality. The aim of this study was to examine the predictive capabilities of CT-derived parameters such as muscle mass and muscle quality for the delayed acquisition of independent walking in the postoperative period. This retrospective study enrolled consecutive Japanese patients who underwent elective cardiovascular surgery between May 2020 and January 2023. In total, 139 patients were included in the analyses. Based on the preoperative CT image, the psoas muscle volume index (PMVI) and psoas muscle attenuation (PMA) were calculated. Information on patient characteristics, including preoperative physical fitness such as handgrip strength/body mass index (GS/BMI), short physical performance battery (SPPB), and 6-min walking distance (6MWD), were obtained from the medical records. We defined delayed acquisition of independent walking after surgery as the inability to walk 100m within 4days after surgery. The median age of the patients was 72 (interquartile: 64-78) years, and 74.8% (104/139) were men; 47.5% corresponded to the delayed group. The areas under the curves of SPPB, GS/BMI, 6MWD, PMVI, and PMA against delayed acquisition of independent walking after surgery were 0.68 [95% confidence interval (CI): 0.59 to 0.77], 0.72 (95% CI: 0.63 to 0.80), 0.73 (95% CI: 0.65 to 0.82), 0.69 (95% CI: 0.60 to 0.78), and 0.78 (95% CI: 0.70 to 0.85), respectively. In the multivariate logistic regression analysis, low PMA was significantly associated with delayed acquisition of independent walking even after adjustment for patient characteristics including physical fitness [model 1: SPPB (OR, 1.14; 95% CI: 1.03-1.25), model 2: GS/BMI (OR, 1.13; 95% CI: 1.03-1.25), and model 3: 6MWD (OR, 1.14; 95% CI: 1.03-1.25)], but PMVI was not. Our study revealed a strong association between PMA, a marker of CT-derived muscle quality, and the postoperative delay in achieving independent walking in patients who underwent cardiovascular surgery. The technique to obtain information on muscle quality during the time period before surgery may be an option for timely therapeutic intervention in patients who may have delayed acquisition of independent walking after surgery.

The effect of a selenium-based anti-inflammatory strategy on postoperative functional recovery in high-risk cardiac surgery patients - A nested sub-study of the sustain CSX trial

AimThe cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. Materials and methodsThis prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. Key findings174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed – 269] vs. 160 m [IQR: not performed – 252], p = 0.80 and 400 m [IQR: 299–461] vs. 375 m [IQR: 65–441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SignificanceA perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease.

Background/Objectives: Pulmonary hypertension (PH) often accompanies chronic lung diseases. Several chronic lung diseases with PH portends unfavorable outcomes. We investigated which variables in this cohort of patients with chronic lung disease and PH predicts mortality. Methods: This is a retrospective analysis of patients with chronic lung disease and PH at a single tertiary, academic center. The underlying lung disease included were COPD, IPF, other fibrotic ILD, non-fibrotic ILD, fibrotic sarcoidosis, and CPFE. All patients had right heart catheterization diagnostic of PH as well as pulmonary function testing data including 6 min walk testing. Univariable and multivariate Cox regression was performed to identify variables associated with mortality. Results: We identified 793 patients with chronic lung disease and PH. In total, 144 patients died prior to potential lung transplant. In multivariable Cox regression IPF, other fibrotic ILD, non-fibrotic ILD, and CPFE were significantly associated with an increased risk of mortality. Severe PH (PVR > 5 WU), FEV1 < 30% predicted, FVC < 40% predicted, 6 min walk distance < 150 m were also significantly associated with an increased risk of mortality. Conclusions: Carrying a diagnosis of IPF, CPFE, fibrotic ILD, or non-fibrotic ILD with PH has an increased risk of mortality as compared to COPD with PH. Hemodynamic, PVR > 5 WU, 6 min walk test less than 150 m, as well as spirometric data including FEV1 < 30% and FVC < 40% predicted were independently associated with an increased risk of death.

Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed. Clinical Trials.gov registration: NCT03743636.

Comparative analysis of the addition of empagliflozin versus doubling the furosemide dose in decompensated heart failure.

This study aims to compare the addition of SGLT2 inhibitors or doubling the diuretic dose in patients receiving treatment with beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), or angiotensin receptor blockers (ARB), as well as mineralocorticoid receptor antagonists (MRA), for heart failure with reduced ejection fraction (HFrEF) who present to the emergency department with decompensated heart failure. This study is a single-center and prospective analysis. A total of 980 decompensated heart failure (HFrEF) patients receiving optimal medical therapy (OMT) according to the 2021 European heart failure guidelines were randomized in a 2:1 ratio into the furosemide and empagliflozin treatment arms. The analysis includes patient clinical characteristics, laboratory results, and echocardiographic data. Factors influencing rehospitalization were identified through multivariate Cox regression analysis. Log-rank analysis was employed to assess factors affecting rehospitalization. The mean age of the patients was 67.9years, with 52.1% being men. There was no significant impact of demographic, clinical, or echocardiographic factors on rehospitalization at 1 month; only the effect of treatment subgroups on rehospitalization was observed (p = 0.039). Significant echocardiographic and clinical improvements were seen in both treatment arms. The empagliflozin group exhibited significant improvements in 6-min walk distance, heart rate, body weight, NT-pro BNP levels, and eGFR level compared to the furosemide group. The rate of rehospitalization in the first month was significantly lower in those receiving empagliflozin (28.7%) compared to those receiving a double dose of furosemide (40.2%) (log-rank p = 0.013). This study provides valuable insights into the management of decompensated HFrEF and demonstrates that SGLT2 inhibitors offer benefits beyond glycemic control in this patient group. The significant reduction in rehospitalization rates and improvements in echocardiographic parameters underscore the potential of SGLT2 inhibitors in reducing acute heart failure episodes.

Clinical Utility of Pulmonary Rehabilitation in Diffuse Parenchymal Lung Diseases

Background: Pulmonary rehabilitation (PR) can help in improving the exercise capacity and quality of life (QoL) in diffuse parenchymal lung diseases (DPLDs), even in end-stage lung diseases listed for lung transplant. With the paucity of literature from the Indian population, the current study assessed PR’s benefits on the respiratory functions and exercise capacity in DPLD. Methods: This prospective interventional study was conducted over 18 months in patients with diagnosed stable DPLD who were previously not involved in any PR program. All the enrolled patients underwent 12-week in-hospital, supervised PR program, which included exercise training with increasing load, endurance training, resistance training, flexibility training, and stretching. The patients were evaluated for the measures at baseline and after 12 weeks of a rehabilitation program. Results: There was a significant improvement in respiratory capacity forced expiratory volume in 1 s (FEV1), 6-min walk distance (6MWD), Modified Medical Research Council (MMRC), and total St. George’s Respiratory Questionnaire scores (P &lt; 0.05) after the completion of the PR program. Among the outcome parameters, there were no significant differences in the PO2 and FEV1/forced vital capacity ratio (P &gt; 0.05) etiologically; the improvement was significant for all outcome parameters except MMRC and symptom score in the idiopathic pulmonary fibrosis (IPF) group (P = 0.165). In the non-IPF group, the improvement was significant for all outcome parameters except PO2 (P = 0.9). On multivariate linear regression, age was the only independent factor for 6MWD (P = 0.0002; 95% confidence interval [CI]: −5.019–−1.665) and MMRC (P = 0.005; 95% CI: 0.007–0.037). Conclusion: This study reveals that PR is effective for people with DPLD in decreasing the symptoms and improving the exercise capacity and QoL. Clinical improvement is greater in those with non-IPF compared to IPF, but both groups as a whole achieved clinically significant improvements. An adaptation of the PR regimen as per age may be necessary for optimizing the clinical benefits.

Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension

BackgroundAbnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH.MethodsBiospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction.ResultsResistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27–5.33; P < .0087). Comparisons of ML–derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62–0.79) for PAH.ConclusionsThis work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.

Impact of foot sole insensitivity and reduced nerve conduction velocity on postural control and functional gait

Peripheral neuropathy is characterized by decreased foot sole sensitivity and slowed nerve conduction velocity, leading to impaired postural control and functional gait performance. This study assessed the differential effects of reduced foot sole sensitivity and slowed nerve conduction velocity on postural control and functional gait. Thirty-five participants were evaluated for two main clinical symptoms: the H-index and foot sole sensitivity. Two times the square of the height (H) of the individual divided by the latency (T) between the onsets of the M- and H-waves of the H-reflex were used to calculate the H-index (2 &amp;times; [H/T]2). Foot sole sensitivity was evaluated using a monofilament on five sites at the bottom of the foot. Participants were categorized into three symptomological groups: (i) less affected (LA), (ii) moderately affected (MA), and (iii) severely affected (SA), based on their H-index ranges of 78.0 &amp;ndash; 109.4, 42.8 &amp;ndash; 76.6, and 45.6 &amp;ndash; 75.5 cm2/ms2, respectively, and foot sole sensitivity score ranges of 6 &amp;ndash; 10, 6 &amp;ndash; 10, and 0 &amp;ndash; 5, respectively. Outcome variables included center of pressure (COP) standard deviation in the anteroposterior direction and COP average velocity (Vavg) during 30 s of eyes-open quiet standing, as well as 6-min walk distance (6MWD) and timed-up-and-go duration (TUG). Multivariate analysis revealed significant group differences (P &lt; 0.05), with post hoc analysis showing significant differences between LA and SA in Vavg (F4,30 = 3.752; P = 0.014). Discriminant analysis revealed Vavg as the primary determinant, while 6MWD and TUG were secondary determinants of group separation. Notably, enhanced functional gait was associated solely with sensitive foot soles and heightened nerve conduction velocity within the LA group, not in the MA or SA groups. Disease severity mediated the specific effects on postural control and functional gait, underscoring the importance of tailoring rehabilitation protocols to address individual symptoms.

Pulmonary hypertension across the spectrum of left heart and lung disease.

Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2-3), but this group is not well-characterized. Patients with PH enrolled in the prospective, NHLBI-sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2-3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2-3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2-3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2-3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N-terminal pro-B-type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2-3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6-min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.86), and patients with G2-3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38-0.86). Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2-3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease. ClinicalTrials.gov NCT02980887.

Impact of Real-Time Assessment of Pulse Oximetry on the 6-Min Walk Distance in Patients With Chronic Respiratory Disease.

Continuous monitoring of pulse oximetry (SpO2 ) is recommended during the 6-min walk test (6MWT) to ensure that the lowest SpO2 is recorded. In this case, severe exercise-induced desaturation (EID; SpO2 < 80%) triggers walking interruption by the examiner. Our main objective was to assess the impact of this approach on 6MWT distance in patients with chronic respiratory diseases and, second, to evaluate the safety of the test without interruption due to severe EID. 6MWTs with continuous monitoring of SpO2 were prospectively performed in subjects with chronic respiratory disease. The participants were randomly allocated to walk with or without SpO2 real-time assessment. SpO2 visualization during the test execution was available only in the first group, and walking interruption was requested by the examiner if SpO2 < 80%. One hundred forty-five participants were included in each group (68.6% females, 62 [52-69] y old) without differences in demographic and resting lung function parameters between them. The main respiratory conditions were COPD (n = 101), asthma (n = 73), pulmonary hypertension (n = 47), and interstitial lung disease (n = 39). The walked distance was similar comparing groups (349.5 ± 117.5 m vs 351.2 ± 105.4 m). Twenty-five subjects presented with severe EID in the group with real-time SpO2 assessment, and 20 subjects had severe EID in the group without real-time assessment respectively (overall prevalence of 15.5%). The 23 participants who had their test interrupted by the examiner due to severe EID in the first group (2 subjects stopped by themselves due to excessive symptoms) walked a shorter distance compared to the 11 subjects with severe EID without test interruption in the second group (9 subjects stopped by themselves due to excessive symptoms): 240.6 ± 100.2 m versus 345.9 ± 73.4 m. No exercise-related serious adverse events were observed. Interruption driven by severe EID reduced the walked distance during the 6MWT. No serious adverse event, in turn, was observed in subjects with severe desaturation without real-time SpO2 assessment.

Recovery of the Japanese orthopedic association back pain evaluation questionnaire score and walking ability following lumbar spinal stenosis surgery.

We investigated the recovery of the Japanese orthopedic association back pain evaluation questionnaire (JOABPEQ) scores and 6min walk distance (6MWD) in patients after surgery for lumbar spinal stenosis and identified the items among 25 questions of JOABPEQ that showed recovery. A total of 227 patients (average age 71.5years; SD: 7.5; 121 men) were included from a single center. The outcome measures were JOABPEQ, visual analog scale (VAS), and 6MWD and obtained preoperatively and at 1, 3, 6, and 12months postoperatively. Mixed-model repeated measures were used to compare the variables at each time point between the surgery groups. The JOABPEQ, VAS, and 6MWD scores generally improved at 1month postoperatively compared with those obtained preoperatively, and some parameters further improved at 3months. However, improvement in the lumbar spine dysfunction item of JOABPEQ was delayed, showing improvement at 3months postoperatively for decompression surgery (average score: pre, 64.6; 3months, 78.5) and 6months postoperatively for fusion surgery (average score: Pre, 64.3; 6months, 77.1). Responses to the individual JOABPEQ questions generally improved after surgery. No significant changes in lumbar spine dysfunction occurred in the fusion group. Our results demonstrated the early postoperative recovery course of JOABPEQ and 6MWD. In the fusion group, significant changes in lumbar spine dysfunction started at 6months postoperatively. These findings could help medical staff explain postoperative recovery to patients after lumbar spinal stenosis surgery and in their decision making regarding surgery.

Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results.

Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. Patients with PH-COPD (mean pulmonary arterial pressure ≥30 mmHg and pulmonary vascular resistance ≥4 WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72 µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.