Fractional Exhaled Nitric Oxide (FENO Sample Clauses

Fractional Exhaled Nitric Oxide (FENO. Nitric Oxide (NO) is a complex signaling molecule produced by airway cells that regulates several processes including ciliary activity, ion transport, inflammation, and vascular tone.27, 28 The fraction of exhaled nitric oxide (FENO) is an established test to monitor the concentration of NO derived from the lung. It is commonly used to monitor disease status in asthma, where it is typically elevated in the context of eosinophilic inflammation. Exhaled NO is extremely low in patients with primary ciliary dyskinesia (PCD), and nasal eNO is a recently validated biomarker of ciliary activity for the diagnosis of PCD.27, 28 FENO is also reduced in CF patients with normal lung function compared to non-CF controls, and it demonstrates an inverse correlation with the lung function tests such as FEV1 and the lung clearance index.29, 30 It is unclear why FENO is reduced in CF, but hypotheses include trapping of locally produced NO in the thick mucus blanket characteristic of the CF airway, decreased production by deficient nitric oxide synthase, increased NO consumption, or defects in ciliary function.27-32 Thus, exhaled NO may serve as a marker of ciliary function and secondarily mucociliary clearance in the context of CF. Recently we examined the fraction of exhaled nitric oxide (FENO) in a cohort of CF patients admitted for treatment of pulmonary exacerbations, and in a second cohort of CF patients with gating mutations who were candidates for ivacaftor therapy. We examined FENO reproducibility, intra-subject and intersubject variability, correlations with lung function, and relationships to concomitant therapies. In the second cohort we examined FENO, FEV1, weight and body mass index before and after four weeks of ivacaftor treatment (150 mg every twelve hours). The results support the hypothesis that changes in FENO can reflect restored CFTR function in CF patients, and due to its ease of measurement, availability of standardized equipment and procedures, and its direct relationship to ciliary function in PCD, we hypothesize that FENO could potentially serve as a novel biomarker reflecting restored CFTR activity in the lower airways. FENO testing will be performed in a subset of subjects enrolled in the Part B CORE Study to evaluate the suitability of FENO as an outcome measure to detect and track treatment effects in patients receiving CFTR directed pharmacotherapy.
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