Exercise Physiology Across the Lifespan in Cystic Fibrosis.

Ren-Jay Shei,Melitta A Mcnarry,Kelly A Mackintosh,Jacelyn E Peabody Lever,Stefanie Krick

doi:10.3389/fphys.2019.01382

Ren-Jay Shei, Melitta A Mcnarry + Show 3 more

Open Access

https://doi.org/10.3389/fphys.2019.01382

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Abstract

Cystic fibrosis (CF), a severe life-limiting disease, is associated with multi-organ pathologies that contribute to a reduced exercise capacity. At present, the impact of, and interaction between, disease progression and other age-related physiological changes in CF on exercise capacity from child- to adult-hood is poorly understood. Indeed, the influences of disease progression and aging are inherently linked, leading to increasingly complex interactions. Thus, when interpreting age-related differences in exercise tolerance and devising exercise-based therapies for those with CF, it is critical to consider age-specific factors. Specifically, changes in lung function, chronic airway colonization by increasingly pathogenic and drug-resistant bacteria, the frequency and severity of pulmonary exacerbations, endocrine comorbidities, nutrition-related factors, and CFTR (cystic fibrosis transmembrane conductance regulator protein) modulator therapy, duration, and age of onset are important to consider. Accounting for how these factors ultimately influence the ability to exercise is central to understanding exercise impairments in individuals with CF, especially as the expected lifespan with CF continues to increase with advancements in therapies. Further studies are required that account for these factors and the changing landscape of CF in order to better understand how the evolution of CF disease impacts exercise (in)tolerance across the lifespan and thereby identify appropriate intervention targets and strategies.

Highlights

Defects in CFTR result in airway dehydration and the production of hyperviscous and acidic mucus, which contributes to defective mucociliary clearance (Fahy and Dickey, 2010; Peabody et al, 2018; Shei et al, 2018)
Co-morbidities such as chronic infections from an ever-changing spectrum of pathogens, some of which may become multi-drug resistant [i.e., Pseudomonas aeruginosa (PsA), Burkholderia cepacia (B. cepacia), and atypical mycobacteria, Figure 1A], and more frequent and severe pulmonary exacerbations lead to a progressive lung function decline and may, increase mortality (Rowe et al, 2005, 2016; Ratjen et al, 2015; Elborn, 2016)
Understanding the differences in exercise physiology and pathophysiology in children vs. adults in Cystic fibrosis (CF) may provide insight into how disease progression affects exercise intolerance. This information may aid in designing appropriate interventions and exercise prescription to reduce the decline in exercise capacity and improve patient health

Summary

INTRODUCTION

Cystic fibrosis (CF) is the most common genetic disease in the Caucasian population, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (Rowe et al, 2005, 2016; Cutting, 2015; Ratjen et al, 2015; Elborn, 2016; Farrell et al, 2017). Co-morbidities such as chronic infections from an ever-changing spectrum of pathogens, some of which may become multi-drug resistant [i.e., Pseudomonas aeruginosa (PsA), Burkholderia cepacia (B. cepacia), and atypical mycobacteria, Figure 1A], and more frequent and severe pulmonary exacerbations lead to a progressive lung function decline and may, increase mortality (Rowe et al, 2005, 2016; Ratjen et al, 2015; Elborn, 2016) This “aging CF population” has shown an increased incidence of CF-related diabetes (CFRD), low bone mineral density, and endothelial dysfunction due to chronic inflammation. Future studies should aim to determine how and to what extent these therapies are beneficial for exercise, and control for the use of these therapies when classifying the CF population

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