Reference Ranges for Exhaled Nitric Oxide Derived from a Random Community Survey of Adults

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Abstract
Measurement of the fraction of nitric oxide in exhaled breath (Fe(NO)) has been proposed as a noninvasive marker of airway inflammation. Before the widespread use of this test, there is a need to develop reference ranges to allow clinicians to interpret Fe(NO) measurements. To derive reference ranges for Fe(NO) and to determine which factors in health and disease influence Fe(NO) levels. Subjects aged between 25 and 75 years were drawn from a random sample of the predominantly white population of Wellington, New Zealand. Fe(NO) was measured using an online nitric oxide monitor in accordance with international guidelines. A detailed respiratory questionnaire and pulmonary function tests were performed. The geometric mean Fe(NO) was 17.9 parts per billion (ppb) with a 90% confidence interval for an individual prediction (reference range) for normal subjects of 7.8 to 41.1 ppb. Sex, atopy, and smoking status significantly affected Fe(NO) levels, and several reference ranges are presented adjusting for these factors. Asthma and allergic rhinitis were associated with higher Fe(NO). Measurement of Fe(NO) had poor discriminant ability to identify steroid-naive subjects with asthma. The reference ranges presented may be used to assist in the interpretation of Fe(NO) measurements in white adults.