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  • Active Voice: Can Exercise Capacity Predict Survival in Cystic Fibrosis?

    by User Not Found | Mar 16, 2015
    By Erik H. J. Hulzebos, P.T., M.Sc., Ph.D., and Tim Takken, M.Sc., Ph.D. 

    Life expectancy in patients with cystic fibrosis (CF) is increasing. However, since the predicted median survival is still around 50 years for individuals with CF who were born in 2000, life expectancy remains an important, clinically-relevant outcome. A number of modifiable and nonmodifiable variables, including gender, lung function decline, number of pulmonary exacerbations, nutritional status/lower muscle mass, diabetes mellitus, a positive culture for Burkholderia cepacia colonization and lower peak oxygen uptake (VO2peak), have all been associated with mortality in patients with CF. Among these variables, several studies have identified percentage of predicted forced expired volume in one second (FEV1%predicted) as being one of the best predictors of mortality in adults, children and adolescents with CF. Other common predictors of mortality in patients with CF are derived from cardiopulmonary exercise testing (CPET) including peak minute ventilation (VEpeak), peak ventilatory equivalent ratio for oxygen (VE/VO2), a marker of ventilatory efficiency and perhaps the best known predictor from CPET - the VO2peak.

    Nevertheless, exercise capacity in patients with CF is limited, which seems to have a multifactorial cause. If there is a possible relationship between CF genotype and some measures of exercise capacity, the mechanisms remain to be determined. It seems that there is an interrelationship between lung function, muscle mass, energy expenditure, respiratory and/or skeletal muscle function and exercise capacity in patients with CF. The pathophysiology of reduced lung function and reduced muscle mass are known to be the most important factors leading to exercise limitation in CF.

    Nixon et al. (1992) were the first to report a significant association between the aerobic exercise capacity of young patients with CF and survival over eight years. Patients with the highest levels of aerobic exercise capacity (VO2peak ≥ 82% of predicted) had a survival rate of 83% after eight years, as compared with rates of 51% and 28% for patients with middle (VO2peak, ranging between 59-81% of predicted) and lowest (VO2peak ≤ 58% of predicted) levels of aerobic exercise capacity respectively. Thus, higher levels of aerobic exercise capacity in patients with CF are associated with a significantly lower risk of dying. Although a better aerobic exercise capacity may simply be a marker for less severe illness, measurement of VO2peak appears to be clinical valuable for predicting prognosis.

    The debate with regards to the strongest predictor of mortality in CF is ongoing. To date, a strong focus has been on VO2peak as a biomarker for cardiorespiratory health status - for example, to assess how physical activity or exercise training might positively affect VO2peak. Yet, the question arises whether other parameters of exercise or a combination of both exercise and non-exercise parameters might yield even stronger biomarkers of health status.

    In our study, recently reported in MSSE, we found that a model consisting of BMI, FEV1%predicted and VE/VO2 is a strong predictor of mortality in adolescents with CF over a 7.5±2.7 year follow-up period. Further research is warranted to determine whether improving aerobic exercise capacity, through physical exercise programs or other interventions (e.g., nutritional supplementation) will result in a better prognosis.

    Viewpoints presented on the ACSM blog reflect opinions of the authors and do not necessarily reflect positions or policies of ACSM.

    Erik J. Hulzebos, P.T., M.Sc., Ph.D., is a clinical exercise physiologist, sports physical therapist, and assistant professor in clinical health sciences at the University Children’s Hospital of the University Medical Center Utrecht, the Netherlands. His main research and clinical interest is clinical pediatric exercise physiology. He has performed studies in many clinical populations including children with cardiorespiratory disease. Dr. Hulzebos published more than 35 peer-reviewed papers and authored five books. He is an ACSM Registered Clinical Exercise Physiologist, and member of the European Pediatric Work Physiology, European Cystic Fibrosis Society and ECFS working group “Exercise in patients with cystic fibrosis.

    Tim Takken, M.Sc., Ph.D., is a medical physiologist and associate professor in pediatrics at the Wilhemina Children’s Hospital of the University Medical Center Utrecht, the Netherlands. He has a special interest in clinical pediatric exercise physiology. He is currently director of the Clinical Exercise Testing Laboratory in Utrecht. Further, he is the chair of the Dutch chapter of CPX international. Dr. Takken has published more than 150 peer-reviewed papers and authored four books. This commentary presents Dr. Hulzebos’ and Takken’s views on the topic related to a research article that they authored with colleagues. Their article is published in the November 2014 issue of Medicine & Science in Sports & Exercise® (MSSE).

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