Project description:Cystic fibrosis (CF) is a debilitating chronic condition, which requires complex and expensive disease management. Exercise has now been recognised as a critical factor in improving health and quality of life in patients with CF. Hence, cardiopulmonary exercise testing (CPET) is used to determine aerobic fitness of young patients as part of the clinical management of CF. However, at present there is a lack of conclusive evidence for one limiting system of aerobic fitness for CF patients at individual patient level. Here, we perform detailed data analysis that allows us to identify important systems-level factors that affect aerobic fitness. We use patients' data and principal component analysis to confirm the dependence of CPET performance on variables associated with ventilation and metabolic rates of oxygen consumption. We find that the time at which participants cross the gas exchange threshold (GET) is well correlated with their overall performance. Furthermore, we propose a predictive modelling framework that captures the relationship between ventilatory dynamics, lung capacity and function and performance in CPET within a group of children and adolescents with CF. Specifically, we show that using Gaussian processes (GP) we can predict GET at the individual patient level with reasonable accuracy given the small sample size of the available group of patients. We conclude by presenting an example and future perspectives for improving and extending the proposed framework. The modelling and analysis have the potential to pave the way to designing personalised exercise programmes that are tailored to specific individual needs relative to patient's treatment therapies.
Project description:Cardiopulmonary exercise testing (CPET) has become an important clinical tool to evaluate exercise capacity and predict outcome in patients with heart failure and other cardiac conditions. It provides assessment of the integrative exercise responses involving the pulmonary, cardiovascular and skeletal muscle systems, which are not adequately reflected through the measurement of individual organ system function. CPET is being used increasingly in a wide spectrum of clinical applications for evaluation of undiagnosed exercise intolerance and for objective determination of functional capacity and impairment. This review focuses on the exercise physiology and physiological basis for functional exercise testing and discusses the methodology, indications, contraindications and interpretation of CPET in normal people and in patients with heart failure.
Project description:BackgroundNew therapies with prognostic benefits have been recently introduced in heart failure with reduced ejection fraction (HFrEF) management. The aim of this study was to evaluate the prognostic power of current listing criteria for heart transplantation (HT) in an HFrEF cohort submitted to cardiopulmonary exercise testing (CPET) between 2009 and 2014 (group A) and between 2015 and 2018 (group B).MethodsConsecutive patients with HFrEF who underwent CPET were followed-up for cardiac death and urgent HT.ResultsCPET was performed in 487 patients. The composite endpoint occurred in 19.4% of group A vs. 7.4% of group B in a 36-month follow-up. Peak VO2 (pVO2) and VE/VCO2 slope were the strongest independent predictors of mortality. International Society for Heart and Lung Transplantation (ISHLT) thresholds of pVO2 ≤ 12 mL/kg/min (≤14 if intolerant to β-blockers) and VE/VCO2 slope > 35 presented a similar and lower Youden index, respectively, in group B compared to group A, and a lower positive predictive value. pVO2 ≤ 10 mL/kg/min and VE/VCO2 slope > 40 outperformed the traditional cut-offs. An ischemic etiology subanalysis showed similar results.ConclusionISHLT thresholds showed a lower overall prognostic effectiveness in a contemporary HFrEF population. Novel parameters may be needed to improve risk stratification.
Project description:Accurate prediction of survival for cystic fibrosis (CF) patients is instrumental in establishing the optimal timing for referring patients with terminal respiratory failure for lung transplantation (LT). Current practice considers referring patients for LT evaluation once the forced expiratory volume (FEV1) drops below 30% of its predicted nominal value. While FEV1 is indeed a strong predictor of CF-related mortality, we hypothesized that the survival behavior of CF patients exhibits a lot more heterogeneity. To this end, we developed an algorithmic framework, which we call AutoPrognosis, that leverages the power of machine learning to automate the process of constructing clinical prognostic models, and used it to build a prognostic model for CF using data from a contemporary cohort that involved 99% of the CF population in the UK. AutoPrognosis uses Bayesian optimization techniques to automate the process of configuring ensembles of machine learning pipelines, which involve imputation, feature processing, classification and calibration algorithms. Because it is automated, it can be used by clinical researchers to build prognostic models without the need for in-depth knowledge of machine learning. Our experiments revealed that the accuracy of the model learned by AutoPrognosis is superior to that of existing guidelines and other competing models.
Project description:BackgroundCardiopulmonary exercise testing is an increasingly common test and is considered the accepted standard for assessing exercise capacity. Quantifying variability is important to assess the instrument for quality control purposes. Though guidelines recommend biologic control testing, there are minimal data on how to do it. We sought to describe variability for oxygen consumption (V̇O2 ), carbon dioxide production (V̇CO2 ), and minute ventilation (V̇E) at various work rates under steady-state conditions in multiple subjects over a 1-y period to provide a practical approach to assess and perform biologic control testing.MethodsWe performed a single-center, prospective study with 4 healthy subjects, 2 men and 2 women. Subjects performed constant work rate exercise tests for 6 min each at 25-100 W intervals on a computer-controlled cycle ergometer. Data were averaged over the last 120 s at each work rate to reflect stepwise steady-state conditions. Descriptive statistics, including the mean, median, range, SD, and coefficient of variation (CoV) are reported for each individual across the 4 work rates and all repetitions. As these data were normative, z-scores were utilized, and a value greater than ± 1.96 z-scores was used to define significant test variability.ResultsSubjects performed 16-39 biocontrol studies over 1-y. The mean CoV for all subjects in V̇O2 was 6.59%, V̇CO2 was 6.41%, and V̇E was 6.32%. The ± 1.96 z-scores corresponded to a 9.4-18.1% change in V̇O2 , a 9.6-18.1% change in V̇CO2 , and a 9-21.5% change in V̇E across the 4 workloads.ConclusionsWe report long-term variability for steady-state measurement of V̇O2 , V̇CO2 , and V̇E obtained during biocontrol testing. Utilizing ± 1.96 z-scores allows one to determine if a result exceeds expected variability, which may warrant investigation of the instrument.
Project description:BackgroundBronchiectasis is associated with morbidity, low exercise capacity and poor quality of life. There is a paucity of data on exercise capacity using cardiopulmonary exercise test (CPET) in non-cystic fibrosis (CF) bronchiectasis. Our aim was to compare exercise capacity using CPET in CF and non-CF bronchiectasis patients.MethodsCross-sectional retrospective/prospective controlled study assessing CPET using cycle ergometer. Exercise parameters and computed tomography (CT) findings were compared. Results: Hundred two patients with bronchiectasis and 88 controls were evaluated; 49 CF (age 19.7 ± 9.7 y/o, FEV1%predicted 70.9 ± 20.5%) and 53 non-CF (18.6 ± 10.6 y/o, FEV1%predicted 68.7 ± 21.5%). Peak oxygen uptake (peak [Formula: see text]) was similar and relatively preserved in both groups (CF 1915.5±702.0; non-CF 1740±568; control 2111.0±748.3 mL/min). Breathing limitation was found in the two groups vs. control; low breathing reserve (49% in CF; 43% non-CF; 5% control) and increased [Formula: see text] (CF 31.4±4.1, non-CF 31.7±4.1 and control 27.2 ± 2.8). Oxygen pulse was lower in the non-CF; whereas a linear relationship between peak [Formula: see text] vs. FEV1 and vs. FVC was found only for CF. CT score correlated with [Formula: see text] and negatively correlated with [Formula: see text] and post exercise oxygen saturation (SpO2).ConclusionsCPET parameters may differ between CF and non-CF bronchiectasis. However, normal exercise capacity may be found unrelated to the etiology of the bronchiectasis. Anatomical changes in CT are associated with functional finding of increased [Formula: see text] and decreased SpO2. Larger longitudinal studies including cardiac assessment are needed to better study exercise capacity in different etiologies of non-CF bronchiectasis.Trial registrationClinicalTrials.gov, registration number: NCT03147651.
Project description:Unexplained exertional dyspnoea or fatigue can arise from a number of underlying disorders and shows only a weak correlation with resting functional or imaging tests. Noninvasive cardiopulmonary exercise testing (CPET) offers a unique, but still under-utilised and unrecognised, opportunity to study cardiopulmonary and metabolic changes simultaneously. CPET can distinguish between a normal and an abnormal exercise response and usually identifies which of multiple pathophysiological conditions alone or in combination is the leading cause of exercise intolerance. Therefore, it improves diagnostic accuracy and patient health care by directing more targeted diagnostics and facilitating treatment decisions. Consequently, CPET should be one of the early tests used to assess exercise intolerance. However, this test requires specific knowledge and there is still a major information gap for those physicians primarily interested in learning how to systematically analyse and interpret CPET findings. This article describes the underlying principles of exercise physiology and provides a practical guide to performing CPET and interpreting the results in adults.
Project description:Cystic fibrosis (CF) transmembrane conductance regulator is expressed in myocardium, but cardiac involvement in CF remains poorly understood. The recent development of a combined cardiopulmonary magnetic resonance imaging technology allows for a simultaneous interrogation of cardiac and pulmonary structure and function. The aim of this study was to investigate myocardial manifestations in adults with CF, both in a stable state and during an acute respiratory exacerbation, and to investigate the relationship between cardiac and pulmonary disease. Healthy adult volunteers (n = 12) and adults with CF (n = 10) were studied using a multiparametric cardiopulmonary magnetic resonance protocol. CF patients were scanned during an acute respiratory exacerbation and re-scanned when stable. Stable CF was associated with left ventricular dilatation and hypertrophy (LVH; left ventricular mass: CF 59 ± 9 g/m2 vs. control 50 ± 8 g/m2; p = 0.028). LVH was predominantly driven by extracellular myocardial matrix expansion (extracellular matrix mass: CF 27.5 ± 3.4 g vs. control 23.6 ± 5.2 g; p = 0.006; extracellular volume [ECV]: CF 27.6 [24.7-29.8]% vs. control 24.8 [22.9-26.0]%; p = 0.030). Acute CF was associated with an acute reduction in left ventricular function (ejection fraction: acute 57 ± 3% vs. stable 61 ± 5%; p = 0.025) and there was a suggestion of myocardial oedema. Myocardial oedema severity was strongly associated with the severity of airflow limitation (r = - 0.726, p = 0.017). Multiparametric cardiopulmonary magnetic resonance technology allows for a simultaneous interrogation of cardiac and pulmonary structure and function. Stable CF is associated with adverse myocardial remodelling, including left ventricular systolic dilatation and hypertrophy, driven by myocardial fibrosis. CF exacerbation is associated with acute myocardial contractile dysfunction. There is also a suggestion of myocardial oedema in the acute period which is related to pulmonary disease severity.
Project description:PurposeThe aims of this study were to assess the feasibility of cardiopulmonary exercise testing (CPET) for the early assessment of cardiorespiratory fitness in general adult intensive care unit (ICU) survivors and to characterize the pathophysiology of exercise limitation in this population.MethodsFifty general ICU survivors (ventilated for ≥ 5 days) performed a maximal cycle ergometer CPET within 6 weeks of hospital discharge. Health-related quality of life was measured by the Medical Outcome Study Short Form 36 version 2.0 questionnaire.ResultsFifty patients (median age, 57 years; median Acute Physiology And Chronic Health Evaluation II score, 16) completed a CPET 24 ± 14 days after hospital discharge with no adverse events. Significant exercise limitation was present with peak Vo(2) 56% ± 16% predicted and anaerobic threshold (AT) 41% ± 13% of peak predicted Vo(2). Prospectively stratified subgroup comparison showed that patients ventilated for 14 days or more had a significantly lower AT and peak Vo(2) than those ventilated for 5 to 14 days (AT: 9.6 vs 11.7 mL/kg per minute O(2), P = .009; peak Vo(2): 12.9 vs 15.3 mL/kg per minute O(2), P = .022). At peak exercise, heart rate reserve was 25% ± 14%, breathing reserve was 47% ± 19%, and the respiratory exchange ratio was 0.96 ± 0.11. Ventilatory equivalents for CO(2) (Eqco(2)) were 39 ± 9.ConclusionsSignificant exercise limitation is evident in patients who have had critical illness. Etiology of exercise limitation appears multifactorial, with general deconditioning and muscle weakness as major contributory factors. Early CPET appears a practical method of assessing exercise capacity in ICU survivors. Cardiopulmonary exercise testing could be used to select patients who may benefit most from a targeted physical rehabilitation program, aid in exercise prescription, and help assess the response to intervention.