Zoe L. Saynor

Reproducibility of maximal cardiopulmonary exercise testing for young cystic fibrosis patients

BACKGROUND The reproducibility of cardiopulmonary exercise testing (CPET) has not been established in young cystic fibrosis (CF) patients using a valid protocol. METHODS Thirteen 7-18 year olds completed three CPETs, separated by 48 h and 4-6 weeks. CPET involved a ramp-incremental cycling test with supramaximal verification. RESULTS Maximal oxygen uptake was repeatedly determined with no learning effect and typical errors expressed as a coefficient of variation (TE(CV%)) of 9.3% (48 h) and 13.3% (4-6 weeks). The reproducibility of additional parameters of aerobic function [gas exchange threshold (TE(CV%): 11.2%, 16.8%); VO2 mean response time (TE(CV%): 37.8%, 89.4%); VO2 gain (TE(CV%): 17.4%, 24.5%)] and clinical utility [e.g. SaO2% (TE(CV%): 2.2%, 3.1%); ventilatory drive (V(E)/VCO2-slope) (TE(CV%): 7.8%, 17.7%)] was also established over the short- and the medium-term, respectively. CONCLUSION These results establish limits of variability to determine meaningful changes over the short- and the medium-term for CPET outcomes in young CF patients.

Cystic fibrosis and physiological responses to exercise

Cardiopulmonary exercise testing is underutilized within the clinical management of patients with cystic fibrosis. But within the last 5 years, there has been considerable interest in its implementation, which has included deliberations by the European Cystic Fibrosis Society about incorporating this method within the clinical assessment of patients. This review examines the current use of cardiopulmonary exercise testing in assessing the extent and cause(s) of exercise limitation from a pediatric perspective. Examples of the measured parameters and their interpretation are provided. Critical synthesis of recent work in the oxygen uptake (VO2) kinetics response to and following exercise is also discussed, and although identified more as a research tool, its utilization advances researchers understanding of the cardiovascular, respiratory and muscular limitations to exercise tolerance. Finally, exercise and its application in therapeutic interventions are highlighted and a number of recommendations made about the utility of exercise prescription.

Impaired Aerobic Function in Patients with Cystic Fibrosis during Ramp Exercise.

PURPOSE This study aimed to document the matching of muscle O2 delivery to O2 use in young patients with cystic fibrosis (CF) from muscle deoxygenation (HHb) dynamics during ramp exercise. METHODS Ten patients with stable, mild-to-moderate CF (12.7 ± 2.8 yr) and 10 healthy controls (CON, 12.8 ± 2.8 yr) completed a combined ramp and supramaximal cycling test to determine maximal O2 uptake (V˙O2max). Changes in gas exchange and ventilation, HR, and m. vastus lateralis HHb (near-infrared spectroscopy) were assessed. Δ[HHb]-work rate and Δ[HHb]-V˙O2 profiles were normalized and fit using a sigmoid function. RESULTS Aerobic function was impaired in CF, indicated by very likely reduced fat-free mass-normalized V˙O2max (mean difference, ±90% confidence interval: -7.9 mL·kg·min, ±6.1), very likely lower V˙O2 gain (-1.44 mL·min·W, ±1.12), and a likely slower V˙O2 mean response time (11 s, ±13). An unclear effect was found upon the absolute and relative work rate (-14 W, ±44, and -0.7% peak power output, ±12.0, respectively) and the absolute and percentage (-0.10 L·min, ±0.43, and 3.3% V˙O2max, ±6.0) V˙O2 corresponding to 50% Δ[HHb] amplitude, respectively, between groups. However, arterial oxygen saturation (SpO2) was very likely lower in CF (-1%, ±1) and demonstrated moderate-to-very large relations with parameters of aerobic function. CONCLUSIONS Young patients with mild-to-moderate CF present with impaired aerobic function during ramp incremental cycling exercise. Because the rate of fractional O2 extraction during ramp cycling exercise was not altered by CF, yet SpO2 was lower, the present findings support the notion of centrally mediated oxygen delivery to principally limit the aerobic function of pediatric patients with CF during ramp incremental cycling exercise.

The effect of ivacaftor in adolescents with cystic fibrosis (G551D mutation): an exercise physiology perspective.

Purpose: The purpose of this report was to evaluate the influence of 12 weeks of ivacaftor treatment on the aerobic function of 2 teenage patients with cystic fibrosis (CF; &Dgr;F508/G551D) using a maximal cardiopulmonary exercise test. Summary of Key Points: One patient, with relatively mild disease, demonstrated no clinically meaningful changes in maximal oxygen uptake ( O2max). However, in the second case, with more established lung disease on imaging, O2max improved by approximately 30%, an improvement out of proportion with early lung function changes. This improvement resulted from increased muscle oxygen delivery and extraction. Statement of Conclusions: Cardiopulmonary exercise testing can monitor the extent and cause(s) of change following interventions such as ivacaftor, with the potential to identify functional changes independent from spirometry indices. Recommendations for Clinical Practice: Cardiopulmonary exercise testing represents an important and comprehensive clinical assessment tool, and its use as an outcome measure in the functional assessment of patients with CF is encouraged.

Impaired pulmonary VO2 kinetics in cystic fibrosis depend on exercise intensity

PURPOSE This study aimed to investigate the effects of mild-to-moderate cystic fibrosis (CF) on the pulmonary oxygen uptake (V˙O2) kinetics of seven pediatric patients (13.5 ± 2.8 yr) versus seven healthy matched controls (CON; 13.6 ± 2.4 yr). We hypothesized that CF would slow the V˙O2 kinetic response at the onset of moderate (MOD) and very heavy (VH) intensity cycling. METHODS Changes in breath-by-breath V˙O2, near-infrared spectroscopy-derived muscle deoxygenation ([HHb]) at the vastus lateralis muscle and thoracic bioelectrical impedance-derived heart rate (HR), stroke volume index, and cardiac index were measured during repeat transitions to MOD (90% of the gas exchange threshold) and VH (Δ60%) intensity cycling exercise. RESULTS During MOD, the phase II V˙O2 τ (P = 0.84, effect size [ES] = 0.11) and the overall mean response time (MRT) (P = 0.52, ES = 0.11) were not significantly slower in CF versus CON. However, during VH exercise, the phase II V˙O2 τ (P = 0.02, ES = 1.28) and MRT (P = 0.01, ES = 1.40) were significantly slower in CF. Cardiac function, central O2 delivery (stroke volume index and cardiac index), and muscle [HHb] kinetics were unaltered in CF. However, the arteriovenous O2 content difference ((Equation is included in full-text article.)) was reduced during VH at 30 s (P = 0.03, ES = 0.37), with a trend for reduced levels at 0 s (P = 0.07, ES = 0.25), 60 s (P = 0.05, ES = 0.28), and 120 s (P = 0.07, ES = 0.25) in CF. Furthermore, (Equation is included in full-text article.)significantly correlated with the VH phase II V˙O2 τ (r = -0.85, P = 0.02) and MRT (r = -0.79, P = 0.03) in CF only. CONCLUSION Impairments in muscle oxidative metabolism during constant work rate exercise are intensity dependent in young people with mild-to-moderate CF. Specifically, V˙O2 kinetics are slowed during VH but not MOD cycling and appear to be mechanistically linked to impaired muscle O2 extraction and utilization.

The oxygen uptake efficiency slope is not a valid surrogate of aerobic fitness in cystic fibrosis

Maximal cardiopulmonary exercise testing is recommended on an annual basis for children with cystic fibrosis (CF), due to clinically useful prognostic information provided by maximal oxygen uptake (V̇O2max). However, not all patients are able, or willing, to reach V̇O2max, and therefore submaximal alternatives are required. This study explored the validity of the oxygen uptake efficiency slope (OUES) as a submaximal measure of V̇O2max in children and adolescents with CF.

WS16.2 The reliability of maximal cardiopulmonary exercise testing for young cystic fibrosis patients

Background: Maximal cardiopulmonary exercise testing (CPET) is the most precise method for evaluating physical function of patients with mild-to-moderate cystic fibrosis (CF). This study sought to establish the between trial variation of CPET parameters across three different time points. Methods: Fourteen 7−18 year olds (10 male) completed an incremental ramp cycle test to exhaustion. Peak oxygen uptake (V˙ O2peak), power output (Wpeak), heart rate (HRpeak ) and end-exercise oxygen saturation (SaO2%) and breathlessness (RPD) were determined. Following 15-min recovery supramaximal exercise to exhaustion was performed at a work rate (WR) equal to 110% ramp Wpeak (T1). Testing was repeated 48 h (T2) and 4−6 weeks later (T3). Intra-class retest correlations, change in the mean score [V˙ O2peak] and the typical error for all measurements assessed reliability. Results: Intra-class correlations ranged from r = 0.57–0.99 and were highest for WR. No significant differences in mean (SD) V˙ O2peak were found between T1-T2; 1.91 (0.80) and 1.93 (0.66) L×min−1, p = 0.79; T2-T3 1.81 (0.48) and 1.68 (0.50) L×min−1, n = 13, p = 0.20 and T1-T3 1.77 (0.63) and 1.68 (0.50) L×min−1, n = 13, p = 0.25, respectively. The highest typical error for HRpeak (T1-T2), WR (T2-T3), RPD (T1-T2), SaO2% (T2-T3), and V˙ O2peak (T1-T2) were 12, 9.3, 1.4, 1.3 and 0.3%, respectively. Conclusion: CPET derived variables especially V˙ O2peak are highly reproducible between 1 and 42 days. Clinicians can have confidence in precisely reproducing the effect of exercise/pharmacological interventions or CF disease on parameters obtained during CPET. Acknowledgments: Supported by the Peninsula NIHR Research Facility.

Analysis of oxygen uptake efficiency parameters in young people with cystic fibrosis

PurposeThis study characterised oxygen uptake efficiency (OUE) in children with mild-to-moderate cystic fibrosis (CF). Specifically, it investigated (1) the utility of OUE parameters as potential submaximal surrogates of peak oxygen uptake (

A protocol to determine valid V˙O2max in young cystic fibrosis patients.

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