Following the 1992 study of Nixon et al. in the New England Journal of Medicine linking aerobic fitness to survival,165 exercise testing and physical activity counseling have become part of routine care in many CF centers.169 Nixon et al. concluded, "Higher levels of aerobic fitness in patients with cystic fibrosis are associated with a significantly lower risk of dying. Although better aerobic fitness may simply be a marker for less severe illness, measurement of VO2 peak appears to be valuable for predicting prognosis."165
Since the 1992 NEJM paper, numerous publications have confirmed the clinical value of CPET in the evaluation and management of CF,166,169,170 but its use in US CF centers has historically been inconsistent; a 1991 survey found that fewer than half of US CF referral centers offered exercise testing.171 CFTR modulator medications, which partially restore the function of the defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, have produced unprecedented improvements in lung function and overall health for most people with CF.167,172
CFTR modulators, along with steady improvement in the management of nutritional and infectious disease complications over the past several decades, have led to marked increases in the health span and lifespan of people with CF.173,174 Even overweight, obesity and related cardiometabolic risk factors, once rare in CF, are emerging as longevity increases and care improves.175–177 However, peak V̇O₂ has long been known to be lower in CF than in healthy controls.178,179
This reduction in skeletal muscle function in CF is not completely understood but likely results from a combination of factors, including physical inactivity, systemic inflammation, nutritional and metabolic abnormalities, and the effects of defective CFTR, which is expressed in skeletal muscle itself.180,181 Understanding and utilizing therapeutic exercise in the age of disease modifying drugs is an exciting future avenue in CF care and research.168