The Impact of Acute Exercise on Hemostasis and Angiogenesis Mediators in Patients With Continuous-Flow Left Ventricular Assist Devices: A Prospective Observational Pilot Study.

Impaired primary hemostasis and dysregulated angiogenesis, known as a two-hit hypothesis, are associated with gastrointestinal (GI) bleeding in patients with continuous-flow left ventricular assist devices (CF-LVADs). Exercise is known to influence hemostasis and angiogenesis in healthy individuals; however, little is known about the effect in patients with CF-LVADs. The objective of this prospective observational study was to determine whether acute exercise modulates two-hit hypothesis mediators associated with GI bleeding in patients with a CF-LVAD. Twenty-two patients with CF-LVADs performed acute exercise either on a cycle ergometer for approximately 10 minutes or on a treadmill for 30 minutes. Blood samples were taken pre- and post-exercise to analyze hemostatic and angiogenic biomarkers. Acute exercise resulted in an increased platelet count (p < 0.00001) and platelet function (induced by adenosine diphosphate, p = 0.0087; TRAP-6, p = 0.0005; ristocetin, p = 0.0009). Additionally, high-molecular-weight vWF multimers (p < 0.00001), vWF collagen-binding activity (p = 0.0012), factor VIII (p = 0.034), angiopoietin-1 (p = 0.0026), and vascular endothelial growth factor (p = 0.0041) all increased after acute exercise. This pilot work demonstrates that acute exercise modulated two-hit hypothesis mediators associated with GI bleeding in patients with CF-LVADs.

Thoracic Society of Australia and New Zealand position statement: The safe clinical use of sputum induction for bio-sampling of the lower airways in children and adults.

Sputum induction is widely used in clinical settings for collection of biological samples from the lower airways. However, in recent years sputum induction has been associated with serious adverse events and even death. This position statement was commissioned by the Thoracic Society of Australia and New Zealand to address major adverse events of two deaths associated with sputum induction that have occurred in Australia in 2021, and outlines best practice for the safe use of sputum induction. The statement resulted from systematic literature searches by a multi-disciplinary group including respiratory physicians, nurses and physiotherapists (paediatric and adults focused). Consumers had input to an advanced draft of the position statement. The position statement covers indications for sputum induction, informed consent, scope of practice of personnel administering the procedure, infection control considerations, details about the sputum induction procedure, safety considerations and risk assessment in clinical settings.

Use of supplemental oxygen during exercise testing and training for people with chronic obstructive pulmonary disease: a survey of Australian pulmonary rehabilitation programs.

OBJECTIVES: The aims of this study were to determine, in Australian pulmonary rehabilitation programs for people with COPD: (1) whether oxygen saturation (SpO2) was monitored during exercise testing; (2) whether supplemental oxygen was available during exercise testing and/or training; (3) whether oxygen was prescribed during exercise training; and the reason for providing oxygen; (4) whether a protocol was available for supplemental oxygen prescription during exercise training. METHODS: This was a cross-sectional multi-center study using a purposed-designed survey. De-identified survey data were analyzed and the absolute number and percentage of responses were recorded for each question. RESULTS: The survey was sent to 261 pulmonary rehabilitation programs and 142 surveys (54%) were available for analysis. Oxygen saturation was monitored during exercise testing in 92% of programs. Supplemental oxygen was available in the majority of programs during exercise testing (82%) and training (84%). The rationale cited by 87 programs (73%) for prescribing oxygen during exercise training was maintaining SpO2 above a threshold ranging from SpO2 80-88%. Forty-five (32%) programs had a protocol for oxygen prescription during exercise training. CONCLUSION: While monitoring of SpO2 during exercise testing and using supplemental oxygen during testing and training is common in Australian pulmonary rehabilitation programs, few programs had a protocol in place for the prescription of supplemental oxygen for people with COPD who were not on long-term oxygen therapy. This may be due to lack of strong evidence to support the use of supplemental oxygen during exercise training.

Oxygen compared to air during exercise training in COPD with exercise-induced desaturation.

Almost half the patients referred to pulmonary rehabilitation with chronic obstructive pulmonary disease (COPD) desaturate during exercise. Although oxygen supplementation may ameliorate oxygen desaturation, the effects on outcomes of exercise training have not been rigorously evaluated. This study aimed to determine whether supplemental oxygen during exercise training was more effective than medical air in improving exercise capacity and health-related quality of life (HRQoL) in people with COPD.People with COPD who demonstrated oxygen desaturation <90% during the 6-min walk test were recruited to this multicentre trial with randomisation (independent, concealed allocation) to either an Oxygen group or Air group, blinding (participants, exercise trainers and European Respiratory Journal assessors) and intention-to-treat analysis. Both groups received the respective gas from concentrators via nasal prongs at 5 L·min-1 during exercise training consisting of treadmill and cycle exercise, three times per week for 8 weeks. Primary outcomes were the endurance shuttle walk test (ESWT) time and Chronic Respiratory Disease Questionnaire (CRQ)-Total score.111 participants (60 males), mean±sd age 69±7 years, with moderate to severe COPD were recruited and 97 completed (Oxygen group n=52; Air group n=45). At the end of the 8-week training programme there were no between-group differences in change in ESWT (mean difference 15 s (95% CI -106-136 s) or change in CRQ-Total (0.0 points (95% CI -0.3-0.3 points)). Within-group changes at end-training were significant for ESWT and CRQ-Total (all p<0.01).Exercise capacity and HRQoL improved in both groups, with no greater benefit from training with supplemental oxygen than medical air.

Relating exercise-induced desaturation and gas-exchange in pulmonary artery hypertension.

We measured pulmonary gas exchange during six minute walk test (6MWT) in patients with idiopathic (IPAH) and congenital heart disease-related pulmonary hypertension (CHDPH), and determined the relationship between the degree of desaturation and changes in minute ventilation to carbon dioxide production V˙EV˙CO2 and end-tidal partial pressure for carbon dioxide (PetCO2) in both groups. Fifty-two patients (IPAH, n = 28; CHDPH, n = 24) completed 6MWT with simultaneous pulmonary gas exchange. Whilst no significant difference in six minute walk distance was observed between groups (IPAH: 529 ± 89; CHDPH: 476 ± 119 m, p = 0.10), oxygen uptake, carbon dioxide production, and minute ventilation were higher in IPAH than CHDPH (p < 0.01). In addition, CHDPH desaturated to a greater extent than IPAH with a lower post-6MWT SPO2 (IPAH: 92.3 ± 7.9; CHDPH: 73.3 ± 14.9%, p < 0.01). The change in SpO2 correlated to the change in V˙E/V˙CO2 (r=-0.44, p = 0.02) and PetCO2 (r = 0.49, p < 0.01) for CHDPH, but not IPAH. The exercise-induced hypoxic stimulus during 6MWT in CHDPH may be associated with an enhanced ventilatory response.

Quantification of biventricular strain and assessment of ventriculo-ventricular interaction in pulmonary arterial hypertension using exercise cardiac magnetic resonance imaging and myocardial feature tracking.

BACKGROUND: Right ventricular (RV) failure is the main cause of mortality in pulmonary arterial hypertension (PAH). Exercise testing helps identify early RV maladaptation and systolic dysfunction and facilitates therapy. Myocardial strain has been shown to be more sensitive than ejection fraction (EF) in detecting subclinical ventricular contractile dysfunction. Chronic pressure overload in PAH had been associated with changes in left ventricular (LV) filling. PURPOSE: To compare biventricular strains and ventriculo-ventricular interaction in PAH and controls using cardiac magnetic resonance feature tracking (cMRI-FT) and to determine the reproducibility of strain analysis. STUDY TYPE: Prospective. POPULATION: Nine PAH and nine control subjects. FIELD STRENGTH/SEQUENCE: 1.5T MRI balanced steady state free precession. ASSESSMENT: RV and LV longitudinal strain (EllRV and EllLV ) were derived using the mid-axial images. Radial (ErrLV ) and circumferential strain (EccLV ) were derived using the mid-ventricular short-axis images. Relationships between strain and volumetric parameters were assessed at rest and during submaximal in-magnet exercise. STATISTICAL TESTS: Comparison of rest-to-exercise data between PAH and controls was analyzed using two-way repeated measures analysis of variance. The relationship between volumetric parameters and cMRI-FT were assessed using Pearson's correlation. Reproducibility was assessed by using Bland-Altman plots. RESULTS: PAH had significantly lower EllRV at rest (-16.6 ± 2.7 vs. -20.1 ± 3.6, P = 0.03) despite normal RVEF. During exercise, RV systolic contractile reserve measured by EllRV was significantly reduced in PAH (PInteraction = 0.02). In PAH, indexed RV end-systolic volume (ESVi) significantly correlated with EccLV and ErrLV at rest (r = -0.65 and r = -0.70, P < 0.05) and with ErrLV during exercise (r = -0.43, P < 0.05). High observer agreement was demonstrated. DATA CONCLUSION: Despite normal resting RVEF, RV systolic function and contractile reserve as measured by EllRV was significantly reduced in PAH. The close relation between RVESVi with EccLV and ErrLV provides evidence of systolic ventriculo-ventricular interaction in PAH. Exercise cMRI-FT may provide a quantitative metric for detection of subclinical RV dysfunction in PAH. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1427-1436.

Study protocol for a randomised controlled trial of exercise training in pulmonary hypertension (ExTra_PH).

BACKGROUND: Exercise training is an integral component of evidence-based management programs for many chronic cardiac and respiratory conditions. Despite this, there are limited high-quality studies available on the significance of exercise training in pulmonary hypertension (PH). The aim of this study is to evaluate the short and long-term effectiveness of exercise training in PH patients in terms of exercise capacity, quality of life, cardiac function and disease progression. METHODS: This randomized control trial will aim to recruit 50 medically stable PH patients categorised as New York Heart Association functional classification II-III. Participants will be randomly allocated to either the supervised exercise training group or usual care group for the 8-week study period. Exercise training will be conducted in an outpatient setting. Measurements at baseline and following the 8-week study period include exercise capacity (6 min walk distance and cardiopulmonary exercise test), cardiac function (exercise cardiac magnetic resonance imaging [CMRI] and echocardiography), health-related quality of life (Cambridge Pulmonary Hypertension Outcome Review), adverse responses to exercise training and time to clinical worsening. In addition, participants will be followed up for a minimum of 2 year period from commencement of the study so as to monitor long-term clinical outcomes i.e. time to clinical worsening. DISCUSSION: This study will determine whether an 8-week outpatient based supervised exercise training program is safe and beneficial for medically stable PH patients in the short and long term. This will be the first study to examine the impact of exercise training on right heart function using exercise CMRI. Results from the study will contribute new knowledge in relation to the impact of exercise training on cardiac function, long-term prognosis and inform clinical practice guidelines for this patient population. Moreover, the study will add to our understanding regarding the efficacy of exercise training in individuals with PH in an outpatient setting. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry: ACTRN12616001467426 . Registered 21st October, 2016.

Shuttle walk tests in people with COPD who demonstrate exercise-induced oxygen desaturation: An analysis of test repeatability and cardiorespiratory responses.

Exercise-induced oxygen desaturation (EID) is prevalent in people with chronic obstructive pulmonary disease (COPD). This article reports a sub-analysis from a randomized controlled trial (RCT) in people with COPD and EID (COPD/EID). The primary aim, in people with COPD/ EID, was to determine the repeatability of the distance and time walked in the incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT), respectively. A secondary aim was to determine whether any participant characteristics predicted those who did not demonstrate improvements on a repeat ISWT or ESWT. Participants with nadir oxygen saturation (SpO2) < 90% on the 6-minute walk test were recruited to the RCT. Two ISWTs and two ESWTs were then performed as part of the baseline assessments, and participants were included in this sub-analysis if their nadir SpO2 was <90% during the better of two ISWTs. Repeatability of the tests was analysed using Bland-Altman plots and paired t-tests. Participant characteristics of age, lung function, level of nadir SpO2 and end-test dyspnoea were used to predict those who were not likely to demonstrate improvements on a repeat test using receiver operating curves. Eighty-seven participants (mean age (standard deviation, SD) 70 (7) years; forced expiratory volume in one second (FEV1) 47 (17)% predicted) were included. The mean differences (coefficient of repeatability) for the ISWTs and ESWTs were 9 m (55 m) and 19 seconds (142 seconds) respectively ( p < 0.05). No participant characteristic predicted the absence of improvement on the second ISWT (area under the curve (AUC) ranged from 0.49 to 0.58, all p > 0.2) or the second ESWT (AUC ranged from 0.43 to 0.52, all p > 0.3). Although repeating the tests showed only small improvements in distance (ISWT) and time (ESWT) walked in people with COPD/EID, the variability was large making definite conclusions about test repeatability in these individuals difficult.

Gas exchange responses during 6-min walk test in patients with pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: The 6-min walk test (6MWT) is the most widely utilized method of assessing exercise capacity in pulmonary arterial hypertension (PAH). Cardiopulmonary exercise testing has the advantage of providing additional physiological information over 6MWT. The goals of our study were to describe the addition of gas exchange measurements to 6MWT and to determine how these parameters were related to the severity of PAH in three major subgroups of PAH (idiopathic (IPAH), connective tissue disease-related (CTPAH) and congenital heart disease-related (CHPAH)). METHODS: Seventy-six PAH patients (IPAH, n = 28; CTPAH, n = 24; CHPAH, n = 24) completed the 6MWT with simultaneous gas exchange measurements. The 6-min walk distance (6MWD), oxygen uptake ( V ˙ O2 ), carbon dioxide production ( V ˙ CO2 ), oxygen saturation, minute ventilation to carbon dioxide output ( V ˙ E / V ˙ CO2 ) and end-tidal partial pressure for carbon dioxide (PET CO2 ) were compared between subgroups, different functional classes (FCs) and pharmacotherapy. RESULTS: Whilst no significant difference in 6MWT was observed, absolute V ˙ O2 and V ˙ CO2 were higher for IPAH (P < 0.05). Differences were removed when V ˙ O2 and V ˙ CO2 were expressed relative to body mass (i.e. mL/kg/min). CHPAH had the most significant desaturation during 6MWT (CPAH: 73 ± 15%; CTPAH: 90 ± 8%, IPAH: 92 ± 8%, P < 0.01). There was no difference in V ˙ E / V ˙ CO2 and PET CO2 between groups; however, New York Health Association (NYHA) FC II performed better than FC III subjects in 6MWT with lower V ˙ E / V ˙ CO2 and higher end-exercise PET CO2 . Similarly, individuals on more advanced pharmacotherapy (triple therapy vs monotherapy) had poorer gas exchange during exercise. CONCLUSION: Whilst 6MWT and gas exchange did not differentiate between PAH groups, individuals with more severe disease and on more advanced pharmacotherapy had poorer gas exchange during exercise.

A randomised controlled trial of supplemental oxygen versus medical air during exercise training in people with chronic obstructive pulmonary disease: supplemental oxygen in pulmonary rehabilitation trial (SuppORT) (Protocol).

BACKGROUND: Oxygen desaturation during exercise is common in people with chronic obstructive pulmonary disease (COPD). The aim of the study is to determine, in people with COPD who desaturate during exercise, whether supplemental oxygen during an eight-week exercise training program is more effective than medical air (sham intervention) in improving exercise capacity and health-related quality of life both at the completion of training and at six-month follow up. METHODS/DESIGN: This is a multi-centre randomised controlled trial with concealed allocation, blinding of participants, exercise trainers and assessors, and intention-to-treat analysis. 110 people with chronic obstructive pulmonary disease who demonstrate oxygen desaturation lower than 90 % during the six-minute walk test will be recruited from pulmonary rehabilitation programs in seven teaching hospitals in Australia. People with chronic obstructive pulmonary disease on long term oxygen therapy will be excluded. After confirmation of eligibility and baseline assessment, participants will be randomised to receive either supplemental oxygen or medical air during an eight-week supervised treadmill and cycle exercise training program, three times per week for eight weeks, in hospital outpatient settings. Primary outcome measures will be endurance walking capacity assessed by the endurance shuttle walk test and health-related quality of life assessed by the Chronic Respiratory Disease Questionnaire. Secondary outcomes will include peak walking capacity measured by the incremental shuttle walk test, dyspnoea via the Dyspnoea-12 questionnaire and physical activity levels measured over seven days using an activity monitor. All outcomes will be measured at baseline, completion of training and at six-month follow up. DISCUSSION: Exercise training is an essential component of pulmonary rehabilitation for people with COPD. This study will determine whether supplemental oxygen during exercise training is more effective than medical air in improving exercise capacity and health-related quality of life in people with COPD who desaturate during exercise. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000395831, 5th Jan,2012.

Impaired exercise capacity after lung transplantation is related to delayed recovery of muscle strength.

Lung transplant recipients report reduced exercise capacity despite satisfactory graft function. We analysed changes in lung function, six-min walk distance (6MWD), and quadriceps strength in the first 26-wk post-transplant and examined what factors predict 6MWD recovery. All lung transplant recipients at a single institution between June 2007 and January 2011 were considered for inclusion. Lung function, 6MWD, and quadriceps strength corrected for body weight (QS%) were recorded pre- and two-, six-, 13-, and 26-wk post-transplant. Fifty recipients, of mean (± SD) age 42 (± 13) yr, were studied. Mean FEV1 % and 6MWD improved from 26.4% to 88.9% and from 397 to 549 m at 26 wk, respectively (both p < 0.001). QS% declined in the first two wk but had improved to above pre-transplant levels by 26 wk (p = 0.027). On multivariate analysis (n = 35), lower pre-transplant exercise capacity and greater recovery in muscle strength explained most of the improvement in exercise capacity. Delayed recovery of exercise capacity after lung transplantation is unrelated to delay in improvement in graft function, but occurs secondary to the slow recovery of muscle strength. Our findings show that additional controlled trials are needed to better understand the influence of exercise rehabilitation on improvement in exercise capacity post-transplantation.

Metabolic disease and participant age are independent predictors of response to pulmonary rehabilitation.

PURPOSE: The study aims were (1) to determine whether baseline measures-including the Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index; Age, Dyspnea, and Airflow Obstruction (ADO) index; physical activity; comorbidities (cardiac, metabolic, or musculoskeletal disease); and the number of hospitalizations over the previous 12 months-can predict responders in 6-minute walk distance (6MWD) following pulmonary rehabilitation (PR) and (2) to determine whether different methods in defining improvement in 6MWD affected identifying responders to PR. METHODS: All participants with chronic obstructive pulmonary disease who attended PR at our institution between 2004 and 2009 were evaluated. A participant was classified as a responder with improvement in 6MWD (≥25 m or ≥2 SD of this dataset coefficient of repeatability). RESULTS: A total of 203 participants (mean age, 68.2 ± 8.7 years; mean predicted forced expiratory volume in 1 second, 52.5 ± 22.4%) were analyzed. One hundred twenty participants (59.1%) had a comorbidity categorized as cardiac, metabolic, or musculoskeletal disease. The binary logistic regression models showed that younger participants (P ≤ .015) and, when using the coefficient of repeatability method (≥60.9 m), participants with metabolic disease (P = .040) were the only independent predictors of response. No other measure, including participant BODE or ADO index scores, contributed to either model. CONCLUSION: Identifying responders in exercise capacity following PR remains difficult, with only age and participants with metabolic disease identified as independent predictors.

Balance is impaired in people with chronic obstructive pulmonary disease.

BACKGROUND: It has recently been suggested that people with chronic obstructive pulmonary disease have an increased risk of falls. Although falls risk is multifactorial, impaired balance may contribute. The primary aim of this study was to compare balance between people with and without chronic obstructive pulmonary disease and the secondary aim was to determine if balance deteriorates when respiratory demand is increased by upper limb exercise. METHODS: Twelve people with chronic obstructive pulmonary disease and 12 healthy control subjects participated in this study. Participants stood on a force plate to record centre of pressure displacement during a range of conditions that challenge balance. Lumbar spine and hip motion were measured with inclinometers. Balance trials were performed before and after participation in upper limb exercise that increased respiratory demand in those with chronic obstructive pulmonary disease. FINDINGS: People with chronic obstructive pulmonary disease had increased mediolateral centre of pressure displacement and increased angular motion of the hip compared to healthy controls. Mediolateral centre of pressure displacement was further increased in people with chronic obstructive pulmonary disease following exercise, but unchanged in controls. Anteroposterior centre of pressure displacement did not differ between groups. INTERPRETATION: People with chronic obstructive pulmonary disease have reduced control of balance in the mediolateral direction. This may contribute to an increased risk of falls in this population.

Predictive utility of the 6-minute walk distance on survival in patients awaiting lung transplantation.

BACKGROUND: The 6-minute walk distance (6MWD) is a widely used clinical indicator of exercise capacity. Although used as part of the assessment process in determining a candidate's suitability for lung transplantation (LT), the literature describing the impact of the 6MWD in predicting survival on LT waiting lists is limited. This study aimed to determine the hazard function associated with the 6MWD, and its utility relative to other prognostic variables. METHODS: A retrospective chart review was conducted on 163 patients who were listed for single or double LT, and either survived to transplant or died while on the waiting list. A Cox regression for survival analysis, stratified by diagnostic group, was conducted utilizing the 6MWD, demographic variables and measures of cardiopulmonary function. RESULTS: The 6MWD proved to be the only significant covariate in the Cox regression for survival analysis (p < 0.001), with all other variables eliminated as non-significant. Furthermore, there was a protective effect for each unit increase in the 6MWD [Exp (B) = 0.994, 95% confidence interval 0.990 to 0.997]. CONCLUSIONS: This research demonstrates that the 6MWD is useful for stratifying patients on the LT waiting list by identifying those patients with a significantly higher risk of mortality.

Muscle stretching technique increases vital capacity and range of motion in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To determine if a specific hold and relax stretching technique was capable of (1) reversing the effect of tight chest wall muscles by increasing chest expansion, vital capacity, and shoulder range of motion and (2) decreasing perceived dyspnea and respiratory rate in persons with chronic obstructive pulmonary disease (COPD). DESIGN: Double-blind crossover trial. SETTING: A physiotherapy department at a major metropolitan hospital. PARTICIPANTS: Fourteen stable patients with COPD who had recently completed a pulmonary rehabilitation program were enrolled, with 10 patients completing the study. INTERVENTION: A hold and relax stretching technique of the pectoralis major and a sham technique each for 2 days. MAIN OUTCOME MEASURES: The primary outcome measure was vital capacity (VC), with secondary outcome measures being perceived dyspnea, axillary (ACE) and xiphisternal chest expansion (XCE), right and left shoulder horizontal extension, and respiratory rate. RESULTS: The hold and relax technique to the pectoralis major compared with the sham technique produced significant effects on VC (P<.01), and right (P<.01) and left (P<.05) upper-limb range of motion. There was no significant effect on ACE, XCE, perceived dyspnea, or respiratory rate. There was no order effect for either technique. CONCLUSIONS: The hold and relax technique produces short-term benefits in patients with COPD and should be investigated further.

Static balance is affected following an exercise task in chronic obstructive pulmonary disease.

PURPOSE: To investigate balance following a submaximal exercise task (6-minute walk test [6MWT]) in patients with chronic obstructive pulmonary disease (COPD). METHODS: A consecutive sample of 19 patients with COPD from an institutional pulmonary rehabilitation program served as participants. The following measures were recorded before and following a 6MWT: (1) timed-up and go (TUG) test, (2) step-up test, and (3) quiet standing for 30 seconds with eyes open and closed in a narrow and semi-tandem stance. Displacement of the body at the level of the waist was recorded using a swaymeter. Data were analyzed using a linear mixed model. RESULTS: In the semi-tandem stance with eyes closed post-6MWT, increases in total sway (165.9 mm vs 240.0 mm, P = .043) and mediolateral sway (45.8 mm vs 66.6 mm, P = .011) were found in comparison with pre-6MWT measures. The exercise task did not affect the TUG test performance (8.3 seconds vs 9.0 seconds, P = .213), number of steps completed during the step-up test (10 vs 10, P = .233), or sway during the semi-tandem stance with eyes open; narrow base, eyes open or closed (P > .05). CONCLUSIONS: A submaximal exercise task in patients with COPD affects balance during static standing tasks in the absence of visual input. This may have implications for functional performance following exercise in patients with chronic respiratory disease.