Measurement of Fractional Exhaled Nitric Oxide (FeNO) as a Marker of Disease Activity in IBD: 1689

Purpose: Active inflammation in IBD is frequently estimated through readily available markers such as C-reactive protein, erythrocyte sedimentation rate, and the leukocyte and platelet count. Small studies have shown that levels of exhaled nitric oxide levels correlate with disease activity in patients with IBD, perhaps due to genetic polymorphisms of NOS genes unique to IBD or up-regulation of NOS activity in bronchial epithelium. Our purpose was to use data from the National Health and Nutrition Examination Survey (NHANES) to identify whether a relationship exists between fractional exhaled nitric oxide (FeNO) and IBD severity. Methods: Two years of NHANES data were combined (2009-2010) for analysis. After weighting (variable WTINT2YR) using the complex samples module of SPSS 20.0, the age range was restricted to 18-65 years. Subjects were self-identified as having Crohn's disease (CD) or ulcerative colitis (UC). FeNO was measured using the Aerocrine NIOX MINO® analyzer (Aerocrine AB, Sweden). Participants were asked to empty their lungs, then to fill their lungs to capacity with NO-free air. Participants then expired all of their air at a constant pressure while exhaled NO from the bronchial tree was measured. Technicians coached participants in proper technique. The NHANES protocol required two valid FeNO measurements that were reproducible. Overall, 89.1% of all subjects underwent FeNO testing. Normal FeNO levels are ≤ 25 ppb. Data are expressed as mean ± SEM. Results: Of a weighted sample size of 199,283,214 NHANES participants, there were 524,350 with CD (0.26%) and 1,628,605 with UC (0.82%). Mean FeNO levels in those with IBD (16.9 ± 0.01 ppb) were slightly higher than those without (15.7 ± 0.01 ppb); P <0.001. However, elevated FeNO levels occurred in 13.6% of those without IBD, but only 9.2% of IBD patients. In regression modeling, adjusting for age, gender, meal NO levels and use of inhaled steroids prior to testing, the risk of an elevated FeNO level > 25 ppb for IBD patients with some level of disease activity (either diarrhea, anemia, weight loss, or elevated CRP) was slightly increased in stratified analysis; the odds were 1.09 (1.08-1.10) for CD and 2.25 (2.24-2.27) for UC. Conclusion: FeNO levels in subjects with and without IBD were, on average, within the normal range. The adjusted risk for a FENO level ≥ 25 ppb in active IBD was slightly increased. However, for those with UC, the risk was significantly greater. Further trials assessing the value of FeNO measurement as a non-invasive marker of IBD disease activity are necessary before it can be recommended for clinical use.