Predictors and changes of physical activity in idiopathic pulmonary fibrosis

Background Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival. Methods PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. Results Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI >= 25 kg/m(2) and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9-78.8); p = 0.009]. Conclusion Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis

Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response

Background: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment. Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31+CD42b-) and activated (CD31+CD42b-CD62E+), as well as circulating PCs (CD34+CD133+CD45low) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy. Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH

Real-world walking cadence in people with COPD

Introduction: The clinical validity of real-world walking cadence in people with COPD is unsettled. Our objective was to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence. Methods: We assessed walking cadence (steps per minute during walking bouts longer than 10 s) from 7 days' accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during a 12-month follow-up were recorded from patient reports and medical registries. Results: Participants were mostly male (80%) and had mean±sd age of 68±8 years, post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57±19% predicted and walked 6880±3926 steps·day-1. Mean walking cadence was 88±9 steps·min-1, followed a normal distribution and was highly stable within-person (intraclass correlation coefficient 0.92, 95% CI 0.90-0.93). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV1, 6-min walk distance, physical activity (steps·day-1, time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (incidence rate ratio 0.94 per step·min-1, 95% CI 0.91-0.99, p=0.009). Conclusions: Higher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as a future prognostic marker and clinical outcome.ISGlobal acknowledges support from the grant CEX2018–000806-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Programme

Iron replacement and redox balance in non-anemic and mildly anemic iron deficiency COPD patients: insights from a clinical trial

In COPD patients, non-anemic iron deficiency (NAID) is a common systemic manifestation. We hypothesized that in COPD patients with NAID, iron therapy may improve systemic oxidative stress. The FACE (Ferinject assessment in patients with COPD and iron deficiency to improve exercise tolerance) study was a single-blind, unicentric, parallel-group, placebo-controlled clinical trial (trial registry: 2016-001238-89). Sixty-six patients were enrolled (randomization 2:1): iron arm, n = 44 and placebo arm, n = 22, with similar clinical characteristics. Serum levels of 3-nitrotyrosine, MDA-protein adducts, and reactive carbonyls, catalase, superoxide dismutase (SOD), glutathione, Trolox equivalent antioxidant capacity (TEAC), and iron metabolism biomarkers were quantified in both groups. In the iron-treated patients compared to placebo, MDA-protein adducts and 3-nitrotyrosine serum levels significantly declined, while those of GSH increased and iron metabolism parameters significantly improved. Hepcidin was associated with iron status parameters. This randomized clinical trial evidenced that iron replacement elicited a decline in serum oxidative stress markers along with an improvement in GSH levels in patients with stable severe COPD. Hepcidin may be a surrogate biomarker of iron status and metabolism in patients with chronic respiratory diseases. These findings have potential clinical implications in the management of patients with severe COPD

Roles of the physical environment in health-related quality of life in patients with chronic obstructive pulmonary disease

Rationale: Many clinical and psychological factors are known to influence the health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD). However, research on whether environmental factors, such as air pollution, noise, temperature, and blue/green spaces also influence HRQL in COPD has not been systematically investigated. Objective: To assess the relationship between air pollution, road traffic noise, temperature, and distance to blue/green spaces and respiratory-specific HRQL in COPD. Methods: We used cross-sectional data from a multicenter study in 407 stable mild-to-very severe COPD patients from Barcelona (Catalonia). Patients answered the COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ). Individual residential exposure to air pollutants (nitrogen dioxide [NO2] and particulate matters of varying aerodynamic diameters [PM2.5, PM10, and PM2.5absorbance]), road traffic noise (Lden), and land surface temperature were estimated using long-term averages from land-use regression models, 24-h noise maps, and land surface temperature maps, respectively. We measured residential distances to blue/green spaces from the Urban Atlas. We used mixed-effect negative binomial (for CAT) and linear (for CCQ) regression models, adjusted for potential confounders, with a random effect by center. Results: Of those patients, 85 % were male and had a mean (SD) age of 69 (9) years, CAT score of 12 (7), CCQ-total score of 1.4 (1.0), and post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 (18) %predicted. We found that NO2 and PM2.5absorbance were associated with worsened CAT and CCQ-mental scores, e.g., 0.15-unit change in CAT score [regression coefficient (β) = 0.15; 95 % confidence interval (CI) = 0.03, 0.26] per interquartile range in NO2 [13.7 μg/m3]. Greater distances to blue/green spaces were associated with worsened CCQ-mental scores [0.08; 0.002, 0.15]. Conclusions: Our study showed that increased air pollution, particularly NO2 and PM2.5absorbance and greater distances to blue/green spaces negatively influence HRQL in COPD patients. These findings have important implications for the WHO promotion to develop healthy cities for our future

Determinants of study completion and response to a 12-month behavioral physical activity intervention in chronic obstructive pulmonary disease: A cohort study

Objectives: Physical activity is key to improve the prognosis of chronic obstructive pulmonary disease (COPD). To help to tailor future interventions we aimed to identify the baseline characteristics of COPD patients which predict 12-month completion and response to a behavioral physical activity intervention. Methods: This is a 12-month cohort study of the intervention arm of the Urban Training randomized controlled trial (NCT01897298), an intervention proven to be efficacious to increase physical activity. We considered baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics as potential determinants of completion and response. We defined completion as attending the 12-month study visit. Among completers, we defined response as increasing physical activity ≥1100 steps/day from baseline to 12 months, measured by accelerometer. We estimated the factors independently for completion and response using multivariable logistic regression models. Results: Of a total of 202 patients (m (SD) 69 (9) years, 84% male), 132 (65%) completed the study. Among those, 37 (28%) qualified as responders. Higher numbers of baseline steps/day (OR [95% CI] 1.11 [1.02-1.21] per increase of 1000 steps, p<0.05) and living with a partner (2.77 [1.41-5.48], p<0.01) were related to a higher probability of completion while more neighborhood vulnerability (0.70 [0.57-0.86] per increase of 0.1 units in urban vulnerability index, p<0.01) was related to a lower probability. Among the completers, working (3.14 [1.05-9.33], p<0.05) and having an endocrino-metabolic disease (4.36 [1.49-12.80], p<0.01) were related to a higher probability of response while unwillingness to follow the intervention (0.21 [0.05-0.98], p<0.05) was related to a lower probability. Conclusions: This study found that 12-month completion of a behavioral physical activity intervention was generally determined by previous physical activity habits as well as interpersonal and environmental physical activity facilitators while response was related to diverse factors thought to modify the individual motivation to change to an active lifestyle

Heart Rate Recovery After 6-min Walking Test Predicts Acute Exacerbation in COPD

INTRODUCTION: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR1) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR1 predicts acute exacerbations (AECOPD). METHODS: Hundred one COPD patients (FEV1 (SD) 53 (19) % predicted) were prospectively recruited in a multi-center study. HRR1 after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR1). Linear and logistic regression was used to identify predictors of HRR1 and AECOPD, respectively. The best HRR1 cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months. RESULTS: Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR1 (r 2 = 0.51, p = 0.001). Among several potential covariates, HRR1 emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85-0.97; p = 0.02). The ROC analysis indicated that subjects with HRR1 less than 14 beats (AUC, 0.71 [CI] 0.60-0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR1, p = 0.004 [log-rank test]). CONCLUSIONS: HRR1 after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients

Heart Rate Recovery After 6-min Walking Test Predicts Acute Exacerbation in COPD

INTRODUCTION: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR1) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR1 predicts acute exacerbations (AECOPD). METHODS: Hundred one COPD patients (FEV1 (SD) 53 (19) % predicted) were prospectively recruited in a multi-center study. HRR1 after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR1). Linear and logistic regression was used to identify predictors of HRR1 and AECOPD, respectively. The best HRR1 cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months. RESULTS: Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR1 (r 2 = 0.51, p = 0.001). Among several potential covariates, HRR1 emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85-0.97; p = 0.02). The ROC analysis indicated that subjects with HRR1 less than 14 beats (AUC, 0.71 [CI] 0.60-0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR1, p = 0.004 [log-rank test]). CONCLUSIONS: HRR1 after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients

Feasibility, tolerability, and effects of exercise-based prehabilitation after neoadjuvant therapy in esophagogastric cancer patients undergoing surgery: an interventional pilot study

Patients requiring surgery for locally advanced esophagogastric cancer often require neoadjuvant therapy (NAT), which may have a detrimental impact on cardiorespiratory reserve. The aims of this study were to investigate the feasibility and tolerability of a 5-week preoperative high-intensity interval training program after NAT, and to assess the potential effects of the training protocol on exercise capacity, muscle function, and health-related quality of life (HRQL). We prospectively studied consecutive patients with resectable locally advanced esophageal and gastric cancer in whom NAT was planned (chemo- or chemoradiotherapy). Feasibility was assessed with the TELOS (Technological, Economics, Legal, Operational, and Scheduling) components, and data on exercise tolerability (attendance and occurrence of adverse or unexpected events). Exercise capacity was assessed with peak oxygen uptake (VO2peak) in a cardiopulmonary exercise test at baseline, post-NAT, and following completion of a high-intensity interval exercise training (25 sessions). Changes in muscle strength and HRQL were also assessed. Of 33 recruited subjects (mean age 65 years), 17 received chemoradiotherapy and 16 chemotherapy. All the TELOS components were addressed before starting the intervention; from a total of 17 questions considered as relevant for a successful implementation, seven required specific actions to prevent potential concerns. Patients attended a mean of 19.4 (6.4) exercise sessions. The predefined level of attendance (≥15 sessions of scheduled sessions) was achieved in 27 out of 33 (81.8%) patients. Workload progression was adequate in 24 patients (72.7%). No major adverse events occurred. VO2peak decreased significantly between baseline and post-NAT (19.3 vs. 15.5 mL/Kg/min, P < 0.05). Exercise led to a significant improvement of VO2peak (15.5 vs. 19.6 mL/kg/min, P < 0.05). Exercise training was associated with clinically relevant improvements in some domains of HRQL, with the social and role function increasing by 10.5 and 11.6 points, respectively, and appetite loss and fatigue declining by 16 and 10.5, respectively. We conclude that a structured exercise training intervention is feasible and safe following NAT in patients with esophagogastric cancer, and it has positive effects to restore exercise capacity to baseline levels within 5 weeks with some improvements in HRQL

Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial

Background: Supplemental oxygen delivered with standard oxygen therapy (SOT) improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Although high-flow nasal cannula oxygen therapy (HFNC) improves oxygenation in other respiratory diseases, its impact on exercise performance has never been evaluated in IPF patients. We hypothesized that HFNC may improve exercise capacity in IPF subjects compared to SOT. Methods: This was a prospective, crossover, pilot randomized trial that compared both oxygenation methods during a constant submaximal cardiopulmonary exercise test (CPET) in IPF patients with exertional oxygen saturation (SpO2) ≤ 85% in the 6-min walking test. The primary outcome was endurance time (Tlim). Secondary outcomes were muscle oxygen saturation (StO2) and respiratory and leg symptoms. Results: Ten IPF patients [71.7 (6) years old, 90% males] were included. FVC and DLCO were 58 ± 11% and 31 ± 13% pred. respectively. Tlim during CPET was significantly greater using HFNC compared to SOT [494 ± 173 vs. 381 ± 137 s, p = 0.01]. HFNC also associated with a higher increase in inspiratory capacity (IC) [19.4 ± 14.2 vs. 7.1 ± 8.9%, respectively; p = 0.04], and a similar trend was observed in StO2 during exercise. No differences were found in respiratory or leg symptoms between the two oxygen devices. Conclusions: This is the first study demonstrating that HFNC oxygen therapy improves exercise tolerance better than SOT in IPF patients with exertional desaturation. This might be explained by changes in ventilatory mechanics and muscle oxygenation. Further and larger studies are needed to confirm the benefits of HFNC in IPF patients and its potential usefulness in rehabilitation programs