Exercise intolerance in cystic fibrosis-the role of CFTR modulator therapies

Abstract

Exercise intolerance is common in people with CF (pwCF), but not universal among all individuals. While associated with disease prognosis, exercise intolerance is not simply a reflection of the degree of lung disease. In people with severe CF, respiratory limitations may contribute more significantly to impaired exercise capacity than in those with mild-moderate CF. At all levels of disease severity, there are peripheral factors e.g., abnormal macro- and micro-vascular function that impair blood flow and reduce oxygen extraction, and mitochondrial defects that diminish metabolic efficiency. We discuss advances in understanding the central and peripheral mechanisms underlying exercise intolerance in pwCF. Exploring both the central and peripheral factors that contribute to exercise intolerance in CF can help inform the development of new therapeutic targets, as well as help define prognostic criteria.

Keywords: Cystic fibrosis; Exercise intolerance; Phosphorus magnetic resonance spectroscopy CFTR modulators.