Structured exercise training in patients with idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease and is characterised by breathlessness and exercise limitation. Despite advances in anti-fibrotic therapies there is an unmet need for interventions which improve patient’s symptoms.

Exercise training is recommended for patients with IPF with evidence that it leads to short-term improvements in functional status. However individual responses to exercise training are variable and it is uncertain which strategies provide optimal training for each individual. In addition, the mechanisms underlying any positive effects and whether focused targeting for these could further increase clinical benefit remains uncertain.

The null hypothesis underpinning this thesis was that an individualised, 8-week, interval-based structured responsive exercise training programme (SRETP) in patients with IPF does not lead to significant improvements in either exercise capacity, symptoms, or quality of life. Further that this SRETP does not have a positive effect on the physiological and/or biochemical mechanisms limiting exercise capacity in patients with IPF.

Cardiopulmonary exercise testing (CPET) was used to prescribe exercise performed on an electromagnetically braked cycle-ergometer to patients with IPF, so facilitating the delivery of an individually prescribed SRETP. Baseline CPET identified patients with IPF exhibited significantly impaired exercise capacity. Significant and clinically meaningful improvements were identified in endurance time, peak work-rate, FVC% predicted and MRC breathlessness score following the SRETP, whilst no corresponding significant change in peak oxygen uptake or anaerobic threshold was observed. The SRETP was also found to be feasible with good adherence in this patient cohort with no serious adverse events encountered. These observations prompted further mechanistic exploration of the possible explanations for the positive training response focusing on the role of oxidative stress.

Patients with IPF had evidence of increased pre- and post-exercise oxidative stress compared to age, sex and functionally matched controls. A significant increase in post-exercise systemic antioxidant buffering capacity and reduction in oxidative stress was identified in patients with IPF following the SRETP. This is a potential mechanism which could improve muscular fatigue resistance and consequently submaximal exercise test performance. An exercise-induced fall in nitrite concentration was also observed, a response that was further enhanced on completion of the SRETP, identifying a potential mechanistic rationale to investigate nitrate/nitrite supplementation in IPF patients.

Further work is required to validate these observations and provide greater understanding of the mechanisms by which exercise exerts its positive effects in patients with IPF. Such understanding could ultimately lead to the development of individualised exercise programmes which, in addition to improving patients’ functional status, have disease modifying effects.

More information

Identifiers

ORCID for Timothy Wallis: orcid.org/0000-0001-7936-9764

ORCID for Mark Jones: orcid.org/0000-0001-6308-6014

Catalogue record

Export record