Validity and repeatability of cardiopulmonary exercise testing in interstitial lung disease

Owen W Tomlinson, Laura Markham, Rebecca L Wollerton, Bridget A Knight, Anna Duckworth, Michael A Gibbons, Chris J Scotton, Craig A Williams, Owen W Tomlinson, Laura Markham, Rebecca L Wollerton, Bridget A Knight, Anna Duckworth, Michael A Gibbons, Chris J Scotton, Craig A Williams

Abstract

Background: Cardiopulmonary exercise testing (CPET), and its primary outcome of peak oxygen uptake (VO2peak), are acknowledged as biomarkers in the diagnostic and prognostic management of interstitial lung disease (ILD). However, the validity and repeatability of CPET in those with ILD has yet to be fully characterised, and this study fills this evidence gap.

Methods: Twenty-six people with ILD were recruited, and 21 successfully completed three CPETs. Of these, 17 completed two valid CPETs within a 3-month window, and 11 completed two valid CPETs within a 6-month window. Technical standards from the European Respiratory Society established validity, and repeatability was determined using mean change, intraclass correlation coefficient and typical error.

Results: Every participant (100%) who successfully exercised to volitional exhaustion produced a maximal, and therefore valid, CPET. Approximately 20% of participants presented with a plateau in VO2, the primary criteria for establishing a maximal effort. The majority of participants otherwise presented with secondary criteria of respiratory exchange ratios in excess of 1.05, and maximal heart rates in excess of their predicted values. Repeatability analyses identified that the typical error (expressed as percent of coefficient of variation) was 20% over 3-months in those reaching volitional exhaustion.

Conclusion: This work has, for the first time, fully characterised how patients with ILD respond to CPET in terms of primary and secondary verification criteria, and generated novel repeatability data that will prove useful in the assessment of disease progression, and future evaluation of therapeutic regimens where VO2peak is used as an outcome measure.

Keywords: Aerobic fitness; Clinical physiology; Maximal exercise; Pulmonary disease.

Conflict of interest statement

M. A. Gibbons has received support to attend conferences and professional fees from Roche and Boehringer-Ingelheim. Other authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Example VO2 responses to increasing work-rate during cardiopulmonary exercise tests. A: Deceleration of VO2, producing a plateau (64-year old male with idiopathic pulmonary fibrosis); B: Linear response (70-year old male with idiopathic pulmonary fibrosis); C: Acceleration of VO2 against power (58-year old male with chronic hypersensitive pneumonitis). For all cases, the extrapolated regression line is fitted from 120 s, through to volitional exhaustion. VO2: oxygen uptake
Fig. 2
Fig. 2
Flowchart detailing participant enrolment and successful completion of cardiopulmonary exercise tests within study. CPET: cardiopulmonary exercise test; SpO2: peripheral capillary oxygen saturation
Fig. 3
Fig. 3
Frequency of VO2 profiles, and primary and secondary verification criteria, in each cardiopulmonary exercise test. 1 = All completed CPETs (CPET 1, n = 24; CPET 2, n = 22; CPET 3, n = 21). 2 = CPETs whereby participants reached volitional exhaustion (CPET 1, n = 14; CPET 2, n = 11; CPET 3, n = 17). CPET: cardiopulmonary exercise test; HRmax: maximal heart rate; RER: respiratory exchange ratio; VE/MVV: minute ventilation/maximal voluntary ventilation; VO2: oxygen uptake; VO2peak: peak oxygen uptake; WRpeak: peak work rate
Fig. 4
Fig. 4
Individual changes in absolute VO2peak over 3- and 6-months. A, B: three month changes; C, D: six-month changes. Data is provided for all participants (A, C) and for those only to reach volitional exhaustion (B, D). VO2peak: peak oxygen uptake
Fig. 5
Fig. 5
Bland Altman plots displaying mean bias and limits of agreement for absolute VO2peak obtained from cardiopulmonary exercise tests. A: CPETs performed 3 months apart for n = 17 participants. B: CPETs performed 6 months apart for n = 11 participants. C: CPETs performed 3 months apart for n = 10 participants, who reached volitional exhaustion only. D: CPETs performed 6 months apart for n = 5 participants, who reached volitional exhaustion only. In each instance, difference (y-axis) presents data from CPET 2–CPET 1 (i.e., a value above zero indicates CPET 2 was higher than CPET 1 and therefore an increase in function has occurred). CPET: cardiopulmonary exercise test

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