Association of Fractional Exhaled Nitric Oxide With Pulmonary Health and All-Cause Mortality in a Population Without Airflow Limitation.

OBJECTIVES

The association between fractional exhaled nitric oxide (FeNO) and airway inflammation is evident. However, the precise relationship of FeNO with pulmonary health and all-cause mortality among participants without airflow limitation remains undisclosed. We investigated the association of FeNO with respiratory symptoms, lung function, and all-cause mortality in this population.

METHODS

Participants included in the 2007–2012 National Health and Nutrition Examination Survey cycles with complete questionnaire information, quality-controlled prebronchodilator spirometry data, acceptable FeNO data, and full follow-up records until December 31, 2019, were included. The skewed distribution of FeNO was addressed by applying natural logarithmic transformation. Multivariable linear regression, logistic regression, and Cox proportional-hazards regression analyses were used to investigate the relationship of FeNO with spirometry, respiratory symptoms, and all-cause mortality. Subgroup analyses were performed based on sex, age, body mass index, smoking status, and blood eosinophil count to validate the robustness of the results.

RESULTS

The data of 5842 eligible participants were analyzed. After adjusting for confounding factors, for each 1-unit increment in natural logarithm (ln) (FeNO), the risk of chronic cough and wheezing decreased by 28% and 22%, respectively. Additionally, forced vital capacity increased by 27.9mL, and forced expiratory volume in 1 second increased by 27.8mL. During the average follow-up of 10 years, 255 participants experienced mortality. There was a nonlinear relationship between FeNO and all-cause mortality. Specifically, when ln (FeNO) was <2.6 (FeNO<13.5ppb), the hazard ratio was 0.45 (95% confidence interval 0.29–0.70; p<0.001). The subgroup analyses demonstrated consistent results.

CONCLUSIONS

Elevated FeNO was closely associated with fewer respiratory symptoms and improved lung function in a population without airflow limitation. A nonlinear relationship existed between FeNO and all-cause mortality, with mortality initially decreasing as FeNO increased, followed by stabilization.