More Than Half of Kids in Study Show Poor Cardiorespiratory Fitness

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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More than half of children and teens with cystic fibrosis (CF) who do not show breathing difficulties during physical exercise were found to have reduced cardiorespiratory fitness (CRF), a measure of oxygen supply to the muscles, according to a single-center study in the Netherlands.

Notably, glucose intolerance and Pseudomonas aeruginosa lung infection were significantly associated with poor cardiorespiratory fitness, which has been tied to reduced survival in CF patients.

These findings highlight the reduced CRF of children and adolescents with CF, regardless of their breathing limitations during exercise, and suggest that glucose intolerance and P. aeruginosa lung infection may predict aerobic capacity in this pediatric population.

“Our study showed that 55% of our pediatric sample with CF … was classified as having ‘low CRF’. This is much higher than the 9% of healthy peers classified having ‘low CRF,’” the researchers wrote. “This is especially alarming in light of the fact that CRF is associated with survival in pwCF [people with cystic fibrosis].”

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The study, “Physiological predictors of cardiorespiratory fitness in children and adolescents with cystic fibrosis without ventilatory limitation,” was published in the journal Therapeutic Advances in Respiratory Disease.

Cardiorespiratory fitness refers to the ability of the circulatory and respiratory systems to supply oxygen to muscles involved in movement during sustained physical activity.

Reduced aerobic capacity or peak oxygen uptake (VO2peak), a measure of cardiorespiratory fitness, is associated with poorer quality of life and lesser survival in people with CF. Previous studies in CF patients have suggested that a VO2peak of less than 82% of normal represents lower-than-normal cardiorespiratory fitness.

“Given the strong link between survival and CRF in pwCF [people with CF], identifying predictors of CRF is critical for supporting optimal health in this vulnerable population,” the researchers wrote.

However, few studies have analyzed the potential predictors of cardiorespiratory fitness in CF patients with normal lung function and no breathing difficulties during exercise.

Notably, “establishing predictors of CRF in pediatric patients with CF and no ventilatory limitations will allow for optimal monitoring and treatment early in CF management, resulting in the best possible outcome for pwCF across the lifespan,” the researchers wrote.

Now, a team of researchers from the Netherlands analyzed the cardiorespiratory fitness of 60 children and adolescents — 31 boys and 29 girls, with a median age of 15.3 years — with CF who had no breathing limitations during exercise. They also assessed potential predictors of CRF.

All patients were seen at the University Medical Center Utrecht’s Wilhelmina Children’s Hospital between December 2016 and January 2019.

Cardiopulmonary fitness was assessed with cardiopulmonary exercise testing (CPET), a non-invasive assessment of the cardiopulmonary system at rest and during exercise using a stationary bicycle. Aerobic capacity, one of CPET’s parameters, was normalized to each patient’s body weight to generate a measure of CRF, which was classified as “low” when predicted percentage values were lower than 82%.

Evaluated potential predictors of CRF included sweat chloride levels (a measure of CF severity), body mass index (a measure of nutritional status), P. aeruginosa lung infection, glucose intolerance — including CF-related diabetes — CF-related liver disease, and self-reported physical activity.

P. aeruginosa is a bacterium that commonly causes lung infections in people with CF, and that is associated with resistance to standard antibiotic treatment and lung function decline.

Given that CF affects other organs besides the lungs, such as the pancreas — an organ in the abdomen that helps regulate blood sugar — and the liver, many CF patients develop glucose intolerance and/or liver disease. Glucose intolerance is an umbrella term that refers to high levels of glucose, or sugar, in the blood, which can be an early sign of diabetes.

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The lung function of patients was within the normal range, as assessed with a common measure of lung function based on how much air a person can exhale in one second.

About one-quarter of patients showed glucose intolerance, while one-third had P. aeruginosa lung infection, and 36.7% showed CF-related liver disease. A total of 10 patients (16.7%) were on CFTR modulators, a type of disease-modifying therapy approved for CF, for a mean of 15.4 months.

The children and teens had undergone physical activity four days a week. Sweat chloride data were missing for 11 patients (18%).

Results showed that the patients’ mean percentage predicted cardiorespiratory fitness was 81.4% and that 33 of them (55%) were classified as having low CRF.

According to the investigators, this percent was “much higher” than that of these patients’ healthy peers, among whom the rate is 9%. Given the association between CRF and survival prognosis, the team said these findings were “especially alarming.”

Glucose intolerance and P. aeruginosa infection were found to be significantly associated with a four to six times higher risk of having poorer CRF, while having CF-related liver disease was linked to a slightly lower risk of low CRF.

A model combining these three factors could predict the presence of low cardiorespiratory fitness among these children and adolescents and explain between 26.7% and 35.6% of differences in CRF.

The researchers hypothesized that a link between glucose intolerance and CRF may be related to the known effects of insulin on muscle growth and the presence of reduced muscle mass among CF patients with glucose intolerance.

P. aeruginosa lung infection has been previously associated with a decline in CRF regardless of lung function. Previous research also suggests that such infection may negatively affect muscle due to its associated chronic inflammation and reduced physical activity related to more frequent hospitalizations.

Notably, a potential link between CF-related liver disease and a lower likelihood of having poor cardiorespiratory fitness goes against evidence in the non-CF population, for whom liver disease is associated with low CRF.

The researchers hypothesized that the observed weak association may be related to the fact that liver disease was more frequent among boys than in girls and that boys showed significantly higher CRF relative to girls.

Given that the study looked at patients’ data only at a given time point, it remains unclear whether any of these factors influence the subsequent development of low cardiorespiratory fitness in children and adolescents with CF. Future, larger studies are needed to validate these findings and confirm whether there are causal associations, the team noted.