Browsing by Author "Antos, Nicholas J."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Impact of acid blocker therapy on growth, gut microbiome, and lung disease in young children with cystic fibrosis
    (Wiley, 2024) Liu, Cathy; Bach, Taiya R.; Farrell, Philip M.; Pavelec, Derek; Antos, Nicholas J.; Rock, Michael J.; Asfour, Fadi; Howenstine, Michelle; Gaffin, Jonathan M.; Lai, HuiChuan J.; Pediatrics, School of Medicine
    Objective: Acid blocker therapy (ABT) has become common in cystic fibrosis (CF), despite insufficient evidence for benefits and studies showing potentially negative effects. We examined associations between ABT usage and growth, gut microbiome (GM), and early-onset lung disease in young children with CF. Methods: One hundred and forty-five infants with CF born during 2012-2017, diagnosed through newborn screening by age 3 months and followed to 36 months of age at six CF centers were evaluated. Longitudinal data on growth, pancreatic functional status, pulmonary symptoms, and acid blocker medications were prospectively collected. Early-onset lung disease severity was evaluated by a clinical scoring system. GM composition was assessed by 16S rRNA methodology. Results: ABT use before age 3 years was frequent, with 81 (56%) of patients on H2 receptor antagonist (H2RA) or proton pump inhibitor (PPI), and higher among pancreatic insufficient (60%) versus pancreatic sufficient (26%) children. H2RA was commonly prescribed in infancy before transitioning to PPI. Growth improvements were not significantly greater, while GM α-diversity at 3 years of age was significantly lower and early-onset lung disease more severe, in persistent ABT users compared to nonusers of ABT. Conclusion: In our cohort of young children with CF, early and persistent ABT use was not associated with significant growth benefits and instead showed associations with reduced GM diversity and negative effects on early-onset lung disease. Consequentially, there is a critical need for systematic evaluation and comprehensive risk-benefit analysis of ABT to ensure proper guidelines for children with CF.
  • Thumbnail Image
    Item
    The Frequency and Potential Implications of HFE Genetic Variants in Children With Cystic Fibrosis
    (Wiley, 2025) Huang, Leslie; Lai, HuiChuan J.; Furuya, Katryn N.; Antos, Nicholas J.; Asfour, Fadi; Boyne, Kathleen L.; Howenstine, Michelle; Rock, Michael J.; Sawicki, Gregory S.; Gaffin, Jonathan M.; Worthey, Elizabeth A.; Farrell, Philip M.; Pediatrics, School of Medicine
    Background: Genetic modifiers have been identified that increase the risks of lung disease and other complications, such as diabetes in people with cystic fibrosis (CF). Variants in the hemochromatosis gene (HFE) were reported in a study of adults to be associated with worse lung disease. Objectives: To ascertain the frequency of HFE variants, particularly C282Y (c.845G > A) and H63D (c.187C > G) and to determine if they are associated with variations in the onset and early severity of CF lung disease as well as abnormalities in iron status. Design: We studied with whole genome sequencing and clinical outcome measures in a cohort of 104 children with CF at 5-6 years old who were previously found to show an association between aggregated genetic modifiers and an earlier onset and a more severe lung disease phenotype. Results: In our cohort, 23% have H63D and 11% have C282Y. Lung function at age 6 years and Pseudomonas aeruginosa infections did not differ by HFE variants, but having C282Y was associated with more pulmonary exacerbations in the first 6 years of life. Three patients have H63D/C282Y genotype, and all showed phenotypic expression of hemochromatosis with abnormal iron indices. Conclusion: Our study revealed that the presence of HFE variant C282Y in people with CF may lead to more severe lung disease manifestations beginning in early childhood. There is a risk of hemochromatosis in CF patients with two HFE variants, and thus they should be followed for evidence of iron overload.