Pulmonary Function Reference Equations: A Brief History to Explain All the Confusion

Predicted values for pulmonary function tests differ significantly from the reference values used for many other diagnostic tests. Historically, simple equations using age, height, and sex were used to "predict" normal lung function. However, these multiple factors interact in complex ways to determine what the expected lung function values are in healthy subjects. Healthy individuals exhibit a wide range of variability for most pulmonary function variables, and this variability is not consistent across all age ranges. Recent analysis of large groups of healthy subjects has allowed the development of sophisticated prediction models that take into account not only variability but also skew that occurs as the lungs develop and mature. These modern reference equations provide uninterrupted expected values from early childhood, through adolescence and adulthood, and extending into the ninth decade. Modern equations use upper and lower limits of normal to offer a statistically robust means of defining who is within normal limits. Despite these advances, interpretation of pulmonary function test results has not been highly standardized, largely because interpretation depends on the reference equations used and, more importantly, how they are applied. This review discusses the strengths and limitations of using reference equations to interpret pulmonary function data in the context of research and clinical practice.