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Poor Relationship Between Fractionated Exhaled Nitric Oxide and Disease Activity in Eosinophilic Esophagitis

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Abstract

Current eosinophilic esophagitis care requires monitoring with repeat endoscopy and biopsy, which has significant cost, risk, and inconvenience for patients. Fractionated exhaled nitric oxide testing (FeNO) is a standardized non-invasive test with proven utility in evaluation of asthma. Elevated FeNO has reported use in other eosinophilic inflammatory conditions; however, its use in eosinophilic esophagitis has not been fully evaluated. To assess the utility of FeNO in predicting severity of eosinophilic esophagitis activity. Fifty patients received fractionated exhaled nitric oxide testing within 1 week of endoscopic evaluation with biopsy for determination of peak eosinophil counts. Presence of furrows was also evaluated with respect to FeNO levels. Spearman correlation was calculated between FeNO and peak eosinophil counts (PEC) with subgroup analysis performed based on PPI use. Spearman correlation was performed on the change in FeNO and PEC on the patients receiving repeat testing. FeNO was poorly correlated to PEC (Spearman correlation 0.22). With a cut-off FeNO value of > 40 ppb, specificity of FeNO for detecting presence of ≥ 15 eos/hpf was 0.94 and sensitivity was 0.16. FeNO showed weak relationship to presence of furrows. Within the subgroup of patients not taking PPI, the spearman correlation was 0.21. Delta- FeNO versus Delta-PEC had spearman correlation of 0.72 for patients receiving repeat testing. FeNO likely has limited clinical utility for predicting severity of esophageal eosinophilia. In patients with FeNO levels > 40 ppb, specificity of testing was high, but very few patients reached this FeNO level.

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References

  1. Dellon ES, Liacouras CA. Advances in clinical management of eosinophilic esophagitis. Gastroenterology. 2014;147(6):1238–54. https://doi.org/10.1053/j.gastro.2014.07.055.

    Article  PubMed  Google Scholar 

  2. Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142(7):1451–9. https://doi.org/10.1053/j.gastro.2012.03.001.

    Article  PubMed  Google Scholar 

  3. Lucendo AJ, Arias A, Gonzalez-Cervera J, Yague-Compadre JL, Guagnozzi D, Angueira T, Jimenez-Contreras S, Gonzalez-Castillo S, Rodriguez-Domingez B, De Rezende LC, Tenias JM. Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease. J Allergy Clin Immunol. 2013;131(3):797–804. https://doi.org/10.1016/j.jaci.2012.12.664.

    Article  PubMed  Google Scholar 

  4. Spergel JM, Andrews T, Brown-Whitehorn TF, Beausoleil JL, Liacouras CA. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol. 2005;95(4):336–43. https://doi.org/10.1016/s1081-1206(10)61151-9.

    Article  PubMed  Google Scholar 

  5. Henderson CJ, Abonia JP, King EC, Putnam PE, Collins MH, Franciosi JP, Rothenberg ME. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012;129(6):1570–8. https://doi.org/10.1016/j.jaci.2012.03.023.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Philpott H, Nandurkar S, Royce SG, Gibson PR. Ultrathin unsedated transnasal gastroscopy in monitoring eosinophilic esophagitis. J Gastroenterol Hepatol. 2016;31(3):590–4. https://doi.org/10.1111/jgh.13173.

    Article  PubMed  Google Scholar 

  7. Katzka DA, Geno DM, Ravi A, Smyrk TC, Lao-Sirieix P, Miremadi A, Debiram I, O’Donovan M, Kita H, Kephart GM, Kryzer LA, Camilleri M, Alexander JA, Fitzgerald RC. Accuracy, safety, and tolerability of tissue collection by Cytosponge vs endoscopy for evaluation of eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2015;13(1):77–83. https://doi.org/10.1016/j.cgh.2014.06.026.

    Article  PubMed  Google Scholar 

  8. Dellon ES, Rusin S, Gebhart JH, Covey S, Higgins LL, Beitia R, Speck O, Woodward K, Woosley JT, Shaheen NJ. Utility of a noninvasive serum biomarker panel for diagnosis and monitoring of eosinophilic esophagitis: a prospective study. Am J Gastroenterol. 2015;110(6):821–7. https://doi.org/10.1038/ajg.2015.57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mummadi SR, Hahn PY. Update on exhaled nitric oxide in clinical practice. Chest. 2016;149(5):1340–4. https://doi.org/10.1016/j.chest.2015.11.020.

    Article  PubMed  Google Scholar 

  10. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602–15. https://doi.org/10.1164/rccm.9120-11ST.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lanz MJ, Guerrero RA, Gonzalez-Vallina R. Measurement of exhaled nitric oxide in the evaluation for eosinophilic esophagitis in children. Ann Allergy Asthma Immunol. 2012;109(1):81–2. https://doi.org/10.1016/j.anai.2012.05.009.

    Article  CAS  PubMed  Google Scholar 

  12. Leung J, Nguyen-Traxler A, Lee EM, Yip JS, Weinstock JV, Chan WW, Ngo P, Weinstein BJ, Bonis PA. Assessment of fractionated exhaled nitric oxide as a biomarker for the treatment of eosinophilic esophagitis. Allergy Asthma Proc. 2012;33(6):519–24. https://doi.org/10.2500/aap.2012.33.3606.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut. 2013;62(4):489–95. https://doi.org/10.1136/gutjnl-2011-301817.

    Article  CAS  PubMed  Google Scholar 

  14. R core team (2017) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.

  15. Olin AC, Rosengren A, Thelle DS, Lissner L, Bake B, Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample. Chest. 2006;130(5):1319–25. https://doi.org/10.1378/chest.130.5.1319.

    Article  PubMed  Google Scholar 

  16. Scott M, Raza A, Karmaus W, Mitchell F, Grundy J, Kurukulaaratchy RJ, Arshad SH, Roberts G. Influence of atopy and asthma on exhaled nitric oxide in an unselected birth cohort study. Thorax. 2010;65(3):258–62. https://doi.org/10.1136/thx.2009.125443.

    Article  PubMed  Google Scholar 

  17. Rees DC, Satsangi J, Cornelissen PL, Travis SP, White J, Jewell DP. Are serum concentrations of nitric oxide metabolites useful for predicting the clinical outcome of severe ulcerative colitis? Eur J Gastroenterol Hepatol. 1995;7(3):227–30.

    CAS  PubMed  Google Scholar 

  18. Oudkerk Pool M, Bouma G, Visser JJ, Kolkman JJ, Tran DD, Meuwissen SG, Pena AS. Serum nitrate levels in ulcerative colitis and Crohn’s disease. Scand J Gastroenterol. 1995;30(8):784–8.

    Article  CAS  PubMed  Google Scholar 

  19. Kimura H, Miura S, Shigematsu T, Ohkubo N, Tsuzuki Y, Kurose I, Higuchi H, Akiba Y, Hokari R, Hirokawa M, Serizawa H, Ishii H. Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn’s disease. Dig Dis Sci. 1997;42(5):1047–54.

    Article  CAS  PubMed  Google Scholar 

  20. Rachmilewitz D, Eliakim R, Ackerman Z, Karmeli F. Direct determination of colonic nitric oxide level–a sensitive marker of disease activity in ulcerative colitis. Am J Gastroenterol. 1998;93(3):409–12. https://doi.org/10.1111/j.1572-0241.1998.00409.x.

    Article  CAS  PubMed  Google Scholar 

  21. Goggins MG, Shah SA, Goh J, Cherukuri A, Weir DG, Kelleher D, Mahmud N. Increased urinary nitrite, a marker of nitric oxide, in active inflammatory bowel disease. Mediat Inflamm. 2001;10(2):69–73. https://doi.org/10.1080/09629350120054536.

    Article  CAS  Google Scholar 

  22. Koek GH, Verleden GM, Evenepoel P, Rutgeerts P. Activity related increase of exhaled nitric oxide in Crohn’s disease and ulcerative colitis: a manifestation of systemic involvement? Respir Med. 2002;96(7):530–5.

    Article  CAS  PubMed  Google Scholar 

  23. Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. Inflamm Bowel Dis. 2003;9(3):179–89.

    Article  PubMed  Google Scholar 

  24. Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, Leiper J, Cooke JP. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation. 2013;128(8):845–53. https://doi.org/10.1161/circulationaha.113.003602.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

All authors approved of the final version to be published. We thank the Mayo Gastroenterology fellows who work in the EoE clinic and help care for the patients participating in this study. We also thank our expert pathologists who reviewed the biopsy samples. This publication was made possible by the Mayo Clinic CTSA through Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH).

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Correspondence to Jeffrey Alexander.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Johnson, K., Iyer, V., Katzka, D. et al. Poor Relationship Between Fractionated Exhaled Nitric Oxide and Disease Activity in Eosinophilic Esophagitis. Dysphagia 34, 138–144 (2019). https://doi.org/10.1007/s00455-018-9925-4

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