Second-hand Smoke Affects Metabolism in Infants and Children with CF, Study Finds

Exposure to second-hand smoke in infants and children with cystic fibrosis (CF) is linked to changes in levels of metabolites and activation of signaling pathways that enhance inflammation, a study has found.

The findings suggest exposure to second-hand smoke is a potentially important environmental factor in CF.

The study “Metabolomics profiling of tobacco exposure in children with cystic fibrosis” was published in the Journal of Cystic Fibrosis.

Environmental factors are known to influence the course of inflammation and infections in CF patients.

In previous studies, researchers from Nationwide Children’s Hospital in Columbus, Ohio, found that exposure to second-hand smoke was associated with worse outcomes in young patients with CF. Specifically, young patients exposed to second-hand smoke had worse respiratory function, increased inflammation, and a higher bacterial burden.

However, the underlying molecular mechanisms as to why exposure to second-hand smoke affects the tissues that lead to CF worsening remain elusive.

To address this question, researchers compared the changes in metabolites present in the blood — a metabolomics profile — of children and infants with and without CF, taking into consideration their exposure to second-hand smoke, which was evaluated by measuring the nicotine concentration in their hair.

In total, 80 participants from a larger previous study were included in the new study: 15 healthy controls an 65 infants (younger than 1 year, total of 25) and children with CF (age 1-10 years, total of 40). Infants and children were divided into three groups: non-CF, CF without second-hand smoke exposure (SHSe), and CF with SHSe.

Metabolomics analysis showed that top metabolites in children with CF and SHSe were very different from those who had not been exposed to second-hand smoke.

When researchers grouped patients according to their levels of metabolites, they observed that age played a role.

For instance, “while palmitic acid and 4-pyridoxic acid were the top metabolites identified in CF infants with SHSe, 3-sulfinoalanine and 2,4-dihydroxyacetophenone were the top altered metabolites in CF children with SHSe,” they wrote.

Accounting for patient age, the team’s model showed a clear distinct metabolic profile for CF patients with and without SHSe.

Moreover, the analysis revealed that metabolite changes were linked with specific organ/tissue location. For instance, enriched metabolites found in CF infants exposed to SHSe had changes occurring mainly in the small intestine, liver, and striatum (a region in the brain). In contrast, CF children exposed to SHSe had an alteration in metabolites located in the hypothalamus (a small region of the brain), spinal cord, and sex glands.

Biological processes that included carbohydrate metabolism, blood and nervous system function, and cellular movements were among the top biological functions affected by SHSe in CF, regardless of age.

Both CF children and infants showed alterations due to smoke in processes related to oxidative stress and cellular adhesion. Oxidative stress is a condition that gives rise to potentially harmful reactive oxygen species (ROS), also called free radicals, which can inflict damage to cellular components and is linked to inflammation.

To validate that oxidative stress and cellular adhesion were indeed influenced by SHSe, researchers analyzed biomarkers in 52 blood samples of 10 healthy controls, 19 young patients with SHSe, and 23 samples from CF children without SHSe.

They found that MMP-9 and MPO, two enzymes responsible for degradation of extracellular matrix — the mesh-like scaffold surrounding cells — were increased in the SHSe group. In addition, E-selectin, ICAM-1, and VCAM-1­­­ adhesion proteins also were increased in the CF group compared to non-CF group.

“These findings indicate that CF alterations in oxidative stress and cellular adhesion are worsened by SHSe,” the researchers wrote.

Overall, the findings suggest that “SHSe in young children and infants with CF is associated with altered global metabolomics profiles and specific biochemical pathways, including enhanced oxidative stress,” the team concluded.

“SHSe remains an important but understudied modifiable environmental variable in early CF disease that needs further study,” they added.