Study finds mild CF lung disease still linked to oxidative stress
Children and teens also showed higher inflammation and heart rate changes
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Children and adolescents with cystic fibrosis (CF) showed increased oxidative stress, which can cause cellular damage, higher inflammation, and reduced activity in the nervous system that helps regulate heart rate, even when their lung disease was mild, a study reports.
The study also found that, in the study population as a whole, reduced lung function was significantly associated with lower values on two measures of heart rate variability and with reduced total antioxidant capacity, although the correlations were weak. Oxidative stress occurs when harmful reactive oxygen species build up faster than the body’s antioxidant defenses can remove or neutralize them, causing cellular damage.
Oxidative stress seen despite mild lung disease
According to the researchers, these results are “consistent with the vulnerability of the lungs to oxidative stress in CF.”
The study, “Redox Profile, Inflammatory and Cardiac Autonomic Nervous Activity of Children and Adolescents With Cystic Fibrosis,” was published in Pediatrics International.
CF is caused by genetic mutations that result in a missing or dysfunctional CFTR protein. This disrupts the movement of salt and water in and out of cells, leading to the buildup of thick, sticky mucus in several organs and causing many CF symptoms.
Oxidative stress, chronic inflammation, and changes in autonomic nervous system activity contribute to the processes underlying CF. “However, their interplay in children and adolescents with CF remains unclear,” the researchers wrote. The autonomic nervous system regulates involuntary body functions such as heart rate and breathing.
To learn more, researchers in Brazil conducted a cross-sectional study involving 12 children and adolescents with CF, ages 5 to 18 years, treated at a university hospital, and 12 healthy participants for comparison. Both groups had a similar mean age (about 12 years).
“The main strength of this study is the simultaneous assessment of oxidative stress, inflammatory markers, and autonomic nervous activity in the same group of children and adolescents with cystic fibrosis,” the scientists wrote. “To our knowledge, no previous study has evaluated these three domains concurrently using a broad set of indicators.”
Almost half of the participants with CF (41.7%) had the F508del mutation, the most common CF-causing mutation. About one-third had a low body mass index (BMI) — a measure based on weight and height — for their age, but the majority had a normal BMI.
Lower vitamin A intake may affect antioxidant balance
While dietary intake was generally similar between the groups, both had diets high in carbohydrates and fats. However, children and adolescents with CF had significantly lower vitamin A intake. Vitamin A is involved in multiple bodily processes, including immune response, cellular communication, and vision.
Compared with healthy controls, children and adolescents with CF had significantly higher levels of malondialdehyde (MDA), a marker of oxidative stress, and lower total antioxidant capacity in blood plasma. MDA levels were 35.7% higher, and total antioxidant capacity was 27.1% lower.
These results suggest that “oxidative stress should not be considered an absolute condition in CF, and that assessment of redox balance should account for nutritional status, particularly antioxidant vitamin intake,” the researchers wrote.
Children with CF had higher levels of several inflammatory markers, including C-reactive protein, interleukin (IL)-6, and IL-17A, than healthy controls.
Heart rate variability points to autonomic changes
The researchers also assessed autonomic nervous system function by measuring heart rate variability, which reflects the natural variation in the time between consecutive heartbeats. Children with CF showed reduced activity of both the parasympathetic and sympathetic systems. The parasympathetic nervous system normally slows the heart rate, while the sympathetic nervous system has the opposite effect. Overall, the findings suggest autonomic dysfunction in children and adolescents with CF.
In the study population as a whole, two measures of heart rate variability were significantly associated with lung function. Lower pulmonary function was also associated with lower total antioxidant capacity. The correlations were weak.
As a practical clinical implication of the study, the researchers highlighted the reduced parasympathetic activity detected through heart rate variability testing. They said this finding could help establish heart rate variability “as the first domestic clinical marker of CF.”
Study limitations included the relatively small number of participants and the assessment of only two measures of oxidative stress, without measuring markers of protein or DNA damage or specific antioxidant enzymes. Because the study was cross-sectional, it could not track changes over time.
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