Reference ranges for spirometry across all ages: a new approach

Abstract

Rationale: 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.

Objectives: 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.

Methods: 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.

Measurements and main results: 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.

Conclusions: 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.

Figures

Figure 1.

The median volumes for each outcome, smoothed by age. Note the relatively higher FEF25–75 compared with FVC and FEV1 in females compared with males.

Figure 2.

Height trends in FEV1 at eight specific ages demonstrate that, for any given height, age is as important to consider in determining the reference range, especially during puberty. In contrast to adulthood, where there is a decline with age, throughout childhood at any given height an older subject can be expected to have higher values of lung function. This effect is most marked during puberty.

Figure 3.

Between-subject variability, expressed as the coefficient of variantion (CV) for each of the three spirometric outcomes. A CV of 10% corresponds to a normal range of 80 to 120% predicted. As can be seen, the CV for FVC and FEV1 is near 10% only over the age range of 15 to 35 years. The variability at other ages and for FEF25–75 at all ages is considerably greater.

Figure 4.

Median curves for FEV1/FVC in males and females and their corresponding fifth percentile lower limit of normal. Females have greater FEV1/FVC ratios than males at all ages.

Figure 5.

Comparison of z scores (as determined by the current model developed in non-Hispanic white subjects) among non-Hispanic whites, African-American females (A-AF, n = 1,481), African-American males (A-AM, n = 1,481), Mexican-American females (M-AF, n = 1,523), and Mexican-American males (M-AM, n = 1,116) from the original NHANES III dataset. As expected, non-Hispanic white subjects had a mean ± SD z score of 0 (±1). African-American subjects had lower FEV1 and FVC, but similar FEV/FVC ratios and flows compared with non-Hispanic white subjects. With the exception of Mexican-American females who had somewhat lower FVC, Mexican-American subjects had similar values to non-Hispanic white subjects.

Figure 6.

(A) Median FEV1 in males determined by the current model compared with the original NHANES III equations with the lower limit of normal. (B) The pediatric age range is expanded and demonstrates where the current models improve fit and how the use of the original NHANES III would underpredict true values in those younger than 8 years.