Exhaled NO reference limits in a large population-based sample using the Lambda-Mu-Sigma method

The Third National Health and Nutrition Examination Survey (NHANES III) reference is currently recommended for interpreting spirometry results, but it is limited by the lack of subjects younger than 8 years and does not continuously model spirometry across all ages. By collating pediatric data from other large-population surveys, we have investigated ways of developing reference ranges that more accurately describe the relationship between spirometric lung function and height and age within the pediatric age range, and allow a seamless transition to adulthood. Data were obtained from four surveys and included 3,598 subjects aged 4-80 years. The original analyses were sex specific and limited to non-Hispanic white subjects. An extension of the LMS (lambda, mu, sigma) method, widely used to construct growth reference charts, was applied. The extended models have four important advantages over the original NHANES III analysis as follows: (1) they extend the reference data down to 4 years of age, (2) they incorporate the relationship between height and age in a way that is biologically plausible, (3) they provide smoothly changing curves to describe the transition between childhood and adulthood, and (4) they highlight the fact that the range of normal values is highly dependent on age. The modeling technique provides an elegant solution to a complex and longstanding problem. Furthermore, it provides a biologically plausible and statistically robust means of developing continuous reference ranges from early childhood to old age. These dynamic models provide a platform from which future studies can be developed to continue to improve the accuracy of reference data for pulmonary function tests.

Reliable interpretation of pulmonary function results relies on the availability of appropriate reference data to help distinguish between health and disease and to assess the severity and nature of any functional impairment. The overwhelming number of published reference equations, with at least 15 published for spirometry alone in the past 3 yrs, complicates the selection of an appropriate reference. The use of inappropriate reference equations and misinterpretation, even when potentially appropriate equations are used, can lead to serious errors in both under and over diagnosis, with its associated burden in terms of financial and human costs. Further misdiagnosis occurs when fixed cut-offs, such as 80% predicted forced expiratory volume in 1 s (FEV(1)) or 0.70 FEV(1)/forced vital capacity, are used; particularly in young children and elderly adults. While per cent predicted has historically been used to interpret lung function results, z-scores are more appropriate as they take into account the predicted value, as well as the between-subject variability of measurements. We aim to highlight some of the main issues in selecting and using reference equations and discuss how recent developments may improve interpretation of pulmonary function results.

The fraction of exhaled nitric oxide (Feno) is elevated in subjects with asthma and atopy, and it has been proposed to be a noninvasive marker of airway inflammation. In addition to asthma and atopy, there is limited information about the determinants of Feno in a general population. Cross-sectional. A random adult general population sample. A total of 2,200 subjects, 1,111 women and 1,089 men, aged 25 to 75 years. The subjects were examined with regard to Feno, pulmonary function, anthropometric variables, and blood samples for Ig E, and completed a respiratory questionnaire. The associations between different determinants and Feno were analyzed with multiple linear regression models. The median value of Feno was 16.0 parts per billion (ppb), ranging from 2.4 to 199 ppb. Height, age, atopy, reporting of asthma symptoms in the last month, and reported use of inhaled steroids were positively associated with Feno. Current smokers had lower values of Feno. Gender was not associated with Feno. In this random adult population sample, height, but not gender, was associated with Feno. Furthermore, asthma symptoms in the last month, reported use of inhaled steroids, and atopy were positively and independently associated with Feno, while there was a negative association with smoking.