Fractional exhaled nitric oxide in preterm-born subjects: A systematic review and meta-analysis

Decreased lung function is common in preterm-born survivors. Increased fractional exhaled nitric oxide (FeNO) appears to be a reliable test for eosinophillic airway inflammation especially in asthma. We, systematically, reviewed the literature to compare FeNO levels in preterm-born children and adults who did or did not have chronic lung disease of prematurity (CLD) in infancy with term-born controls.

We searched eight databases up to February 2018. Studies comparing FeNO levels in preterm-born subjects (<37 weeks' gestation) in childhood and adulthood with and without (CLD) with term-born subjects were identified and extracted by two reviewers. Data were analysed using Review Manager v5.3.

From 6042 article titles, 183 full articles were screened for inclusion. Nineteen studies met the inclusion criteria. Seventeen studies compared FeNO levels in preterm- and term-born children and adults; 11 studies (preterm n = 640 and term n = 4005) were included in a meta-analysis. The mean FeNO concentration difference between the preterm-born and term-born group was -0.74 (95% CI -1.88 to 0.41) ppb. For the six studies reporting data on CLD (preterm n = 204 and term n = 211) the mean difference for FeNO levels was -2.82 (95% CI -5.87 to 0.22) ppb between the preterm-born CLD and term-born groups.

Our data suggest that preterm born children with and without CLD have similar FeNO levels to term-born children suggesting an alternative mechanism to eosinophilic inflammation for symptoms of wheezing and airway obstruction observed in preterm-born subjects.