A Comparison of Global Lung Initiative 2012 with Third National Health and Nutrition Examination Survey Spirometry Reference Values. Implications in Defining Obstruction

Rationale: Obstructive lung disease is diagnosed by a decreased ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity (FVC); however, there is no universally accepted lower limit of normal for the FEV₁/FVC ratio. Current established reference values use the Third National Health and Nutrition Examination Survey (NHANES III) database. In 2012, the Global Lung Initiative (GLI) introduced GLI12, which is a compilation reference set that uses standard deviation values to define normal spirometry.

Objectives: To evaluate the changes in classification of obstructive spirometry with use of GLI12 compared with NHANES III in a heterogeneous, multiracial population.

Methods: We evaluated the spirometry studies conducted in our pulmonary function laboratory between January 2005 and December 2015. NHANES III reference equations were calculated to predict lower limits of normal for FEV₁, FVC, and FEV₁/FVC. GLI12 values were established using European Respiratory Society published computer software. FEV₁ severity was graded using 2005 American Thoracic Society guidelines for NHANES III and using z-score-based criteria for GLI12. Asymmetric partition analysis evaluated agreement between the reference sets.

Results: A total of 11,888 studies were evaluated. Obstruction was diagnosed in 2,857 studies using NHANES III versus 2,489 studies using GLI12. Agreement regarding the presence or absence of obstruction occurred in 2,483 of studies with obstruction and 9,025 studies without obstruction (agreement, 96.8%; κ = 0.91). Of the studies with obstruction, 1,595 had agreement in severity grading. Overall, agreement regarding obstruction and severity grading occurred in 10,620 studies, representing 89.3% of all studies. A total of 380 studies (3.2%) had discordance regarding the presence or absence of obstruction, 34.0% (844 of the 2,483 obstruction studies) had a one-degree of change in FEV₁ disease severity scoring, with 44 cases (1.8%) that had changes of two categories in FEV₁ severity scores. No studies had greater than two degrees of change. Asymmetric partition analysis suggested that the highest clinically significant changes were seen in older individuals, particularly African American men older than 65.

Conclusions: Our evaluation suggests that there is moderate overall agreement between NHANES III and GLI12. We found a 3.2% change in classification of obstruction when transitioning from NHANES III to GLI12. When incorporating a z-score-based FEV₁ and GLI12 reference set, 10.7% of the spirometry studies had a change in their categorization. The disagreement between the two datasets was most pronounced in elderly subjects. Although we cannot endorse one reference set over the other, we highlight the potential implications of adopting the GLI12 reference sets and suggest caution when interpreting spirometry in the elderly.