In Children, High Levels of Oxidative Stress Tied to Worse Lung Function

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by Steve Bryson, PhD |

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Children with cystic fibrosis (CF) who have lung infections due to CF-related bacteria, especially Pseudomonas aeruginosa, were found to have higher levels in their bloodstream of biomarkers of oxidative stress and related tissue damage.

These high levels were accompanied by reduced lung function and worse nutritional status, according to a single-center study in Brazil.

The findings suggest that oxidative stress markers may be useful for monitoring tissue damage and disease progression in children with the genetic disease, the researchers noted.

“We demonstrated that bacterial infections worsened the oxidative damage to proteins, nutritional status, and lung function” of children with cystic fibrosis, the team wrote.

The study, “Systemic oxidative stress in children with cystic fibrosis with bacterial infection including Pseudomonas Aeruginosa,” was published in The Clinical Respiratory Journal.

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Respiratory infections are common among people with CF, regularly starting during childhood. This is due to the buildup of thick mucus caused by inherited defects in CFTR, a protein that helps maintain the balance of salt and water on many surfaces in the body, including the lungs.

“Pulmonary infections can lead to the development of malnutrition, and deficiencies in antioxidant factors in CF patients,” the researchers wrote.

In CF, Pseudomonas aeruginosa — a highly antibiotic-resistant bacterium, called P. aeruginosa for short — is one of the main causes of chronic lung infections and tissue-damaging oxidative stress. Oxidative stress is an imbalance between the production of potentially harmful oxidant molecules and the cells’ ability to clear them with antioxidants.

Given the high incidence of lung infections among cystic fibrosis patients, researchers say it is important to understand their impact on biomarkers of oxidative stress and related damage. However, most studies on this subject have focused on adults with CF.

Now, a team of scientists in Brazil sought to learn more about the impact of such infections on these biomarkers in children with CF. They evaluated the effects of bacterial lung infections on biomarkers of oxidative stress and related damage in 55 children with CF, and 31 age- and sex-matched children without the disease, who were used as controls.

The researchers also examined the impact of such infections on the children’s lung function and nutritional status.

The study was carried out at the Joana de Gusmão Children’s Hospital, in Florianópolis, Brazil. The 29 girls and 26 boys with CF had a median age of 3.9 years. Meanwhile, the 19 girls and 12 boys in the control group had a median age of 4.6 years.

Throat swabs were collected for bacterial analysis, and CF patients were divided based on the presence or absence of CF-related bacteria in general, and of P. aeruginosa in particular.

A total of 28 patients (50.9%) were positive for CF-related bacteria. Among them, 19 were infected with P. aeruginosa, 19 with Staphylococcus aureus, and three with Burkholderia cepacia. Notably, 13 children were simultaneously infected with different types of bacteria.

After adjusting for potential influencing factors, including age and sex, the results showed that CF patients had significantly lower blood levels of antioxidant enzymes than controls. Specifically, that included lower levels of catalase (22.6 vs. 32.2 millimole/min/mL) and glutathione peroxidase (2 vs. 3.3 micromole/min/mL).

Children with CF also had significantly higher levels of TBARS (0.21 vs. 0.02 nanomole/mL), a marker of oxidative damage to fatty molecules, and of carbonyl levels (PC), a marker reflecting oxidative damage to proteins.

The levels of glutathione, another antioxidant molecule, were not significantly different between the CF and control groups.

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P. aeruginosa in Infancy Tied to Poor Lung Function by Preschool Age

Further analyses showed that blood catalase levels were significantly lower across all CF subgroups relative to controls, while glutathione peroxidase levels were significantly lower in CF patients with or without CF-related bacteria, and in those without P. aeruginosa.

TBARD levels were significantly higher across all CF subgroups, while PC levels were higher only in those positive for CF-related bacteria and those with P. aeruginosa, compared with the control group.

The participants’ lung function was assessed through the amount of air forced from the lungs in one second (FEV1). Results showed that FEV1 was significantly higher — which reflects better lung function — among controls (88.6%) than among the children with CF (66.8%), those with CF-related bacteria (57.9%), and those positive for P. aeruginosa (54.8%).

Children with CF, and those testing positive for CF-related bacteria, also had a reduced nutritional status relative to controls. The nutritional status was assessed via the body mass index (BMI), a ratio of weight to height.

Overall, “the present study identified higher levels of oxidative damage to proteins and lipids … [and] lower antioxidant defense activities … as well as lower lung function (FEV1) and nutritional status (BMI-z) in children with CF,” the researchers wrote.

Moreover, having bacterial infections, particularly with P. aeruginosa, was found to cause worse lung function and greater oxidative damage to proteins, nutritional status, and lung function” in these children, the team wrote.

“While similar findings have been reported in adults with CF, this study pioneered early evidence of [oxidative stress], using a diverse set of blood biomarkers, in association with bacterial infections in childhood with CF,” they concluded.