Levels of Exhaled Fraction of Nitric Oxide (FeNO) and Type 2 Biomarkers in Individuals Naturally Exposed to Helminth Parasites in a Tropical Region

The exhaled fraction of nitric oxide (FeNO) is a biomarker of type 2 inflammation, reflecting the activity of inducible nitric oxide synthase (iNOS) in the bronchial epithelium in response to IL-4 and IL-13. Elevated FeNO levels support asthma diagnosis; however, it is unclear whether active helminth infections and rural environments influence this biomarker. The aim of this study was to compare FeNO levels among subjects naturally infected with helminth parasites and to evaluate their correlation with eosinophil counts and other inflammatory mediators. A total of 275 adult asthmatic patients and 161 healthy controls were involved; also, 223 asthmatic children and 114 healthy controls from the urban area of Cartagena were compared to 90 healthy children from a rural area. We found significant differences in FeNO levels between asthmatic patients and healthy controls in both adult and children's cohorts (<i>p</i> < 0.0001). There was no difference in FeNO levels between Ascaris-positive and Ascaris-negative adults nor between subjects with active helminth infection and the non-infected. However, FeNO levels were significantly lower in rural healthy children (median 7.50 ppb, [IQR 4-14 ppb]) compared to urban healthy children (median 13.5 ppb, [IQR 10-18.5 ppb], <i>p</i> < 0.0001) and asthmatic children (median 20 ppb, [IQR 11-51 ppb], <i>p</i> < 0.0001). Rural healthy children had the highest total IgE levels (median 508 kU/L, [IQR 168-1020 kU/L]), high eosinophil counts (median 550 eos/μL, [IQR 360-800 eos/μL]) and plasma IL-5 levels (median 0.276 pg/mL, [IQR 0.19-0.53 pg/mL]). In conclusion, FeNO levels are not influenced by either natural exposure to helminth parasites or active infection, which supports its usefulness as a robust asthma biomarker in the tropics. Rural children have the lowest FeNO levels together with the highest total IgE levels, IL-5, and eosinophil counts, suggesting that lung-specific mechanisms are in place controlling iNOS expression during type 2 responses in healthy children.