Assessment of fractionated exhaled nitric oxide as a biomarker for the treatment of eosinophilic esophagitis.

Diagnosis of eosinophilic esophagitis (EoE) and determination of response to therapy is based on histological assessment of the esophagus, which requires upper endoscopy. In children, in whom a dietary approach is commonly used, multiple endoscopies are needed, because foods are eliminated and then gradually reintroduced. Ideally, noninvasive methods could supplement or replace upper endoscopy to facilitate management. Fractionated exhaled nitric oxide (FeNO) has been proposed as a useful measure for monitoring disease activity in studies of patients with eosinophil-predominant asthma and in other atopic disorders. Thus, we evaluated whether FeNO levels could be a useful biomarker to assess the response to therapy in EoE patients. This study was designed to determine whether there is a change in FeNO levels during treatment with topical corticosteroids and whether changes correlated with clinical response. This was a prospective, multicenter study that enrolled nonasthmatic patients with established EoE. FeNO levels and symptom scores were measured at baseline, biweekly during 6-week swallowed fluticasone treatment, and 4 weeks posttreatment. Twelve patients completed the trial. We found a statistically significant difference between median pre- and posttreatment FeNO levels [20.3 ppb (16.0 -29.0 ppb) vs 17.6 ppb (11.7 -27.3 ppb), [corrected] p=0.009]. However, neither the pretreatment FeNO level, a change of FeNO level after 2 weeks of treatment, nor the FeNO level at the end of treatment confidently predicted a clinical or histological response. Although our findings suggest nitric oxide possibly has a physiological role in EoE, our observations do not support a role of FeNo determination for management of EoE.

How are Azathioprine and 6-mercaptopurine dosed by gastroenterologists? Results of a survey of clinical practice.

BACKGROUND: Azathioprine (AZA) and 6-mercaptopurine (6-MP) are accepted as effective therapy for Crohn's disease and ulcerative colitis. Although general guidelines have been suggested for weight-based dosing of thiopurines, no standard of care has been established. Clinical trials have demonstrated efficacy for weight-based dosing of AZA at 2.5 mg/kg/day and 6-MP at 1.5 mg/kg/day. Escalation of dosing is recommended within 2 weeks of initiating therapy. The aim was to determine the prescribing practices of community practice gastroenterologists with respect to 6-MP/AZA dosing. METHODS: Questionnaires were distributed via a mail database or during gastroenterology society meetings to gastroenterologists in NY, NJ, and CT. Questionnaires ascertained starting doses of AZA/6-MP, use of thiopurine methyltransferase (TPMT) enzyme testing, and strategy for dose optimization. RESULTS: A total of 145 questionnaires were collected. Twenty-four percent of gastroenterologists escalated the dose within 2 weeks after initiating therapy. The majority used weight-based dosing as their target of therapy. Thirty-five percent reported measuring TPMT levels and 46% used metabolite monitoring. CONCLUSIONS: Most gastroenterologists take longer than recommended to raise the dose of AZA/6-MP. Although the majority of gastroenterologists reported maximal dosages based on weight, there may be a delay in achieving this goal. Optimizing dosing of AZA/6-MP may improve efficacy and reduce the need to use additional therapy.