A Comparison of GLI12 with NHANES III Spirometry Reference Values: The Implications in Defining Obstruction

Nikhil A Huprikar, Aaron B Holley, Andrew J Skabelund, Jackie A Hayes, Paul D Hiles, James K Aden, Michael J Morris, Andrew M Hersh
Annals of the American Thoracic Society 2018 November 14

RATIONALE: Obstructive lung disease is diagnosed by a decreased ratio of forced expiratory volume in the first second (FEV1) to forced vital capacity (FVC); however, there is no universally accepted lower limit of normal (LLN) for the FEV1/FVC ratio. Current established reference values use the NHANES III database. In 2012, the Global Lung Initiative (GLI) introduced GLI12: 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 to NHANES III in a heterogenous, multiracial population.

METHODS: We evaluated the spirometric studies conducted in our pulmonary function laboratory between January 2005 and December 2015. NHANES III reference equations were calculated to predict LLN for FEV1, FVC, and FEV1/FVC. GLI12 values were established using ERS published computer software. FEV1 severity was graded using 2005 ATS Guidelines for NHANES III and using z-scoring based criteria for GLI12. Asymmetric partition analysis evaluated agreement between the reference sets.

RESULTS: 11,888 studies were evaluated. Obstruction was diagnosed in 2,857 studies using NHANES III versus 2,489 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%, kappa 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. 380 studies (3.2%) had discordance regarding presence or absence of obstruction, 34.0% (844 of the 2,483 obstructed studies) had one-degree of change in FEV1 disease severity scoring, with 44 cases (1.8%) had changes of two categories FEV1 severity scores. No studies had greater than two degrees of change. Asymmetric partition analysis suggested the highest clinically significant changes were seen in older individuals, particularly African-American males older than 65.

CONCLUSION: Our evaluation suggests 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-based FEV1 and GLI12 reference set, 10.7% of the spirometric studies had a change in their categorization. The disagreement between the two data sets was most pronounced in elderly subjects. Although we cannot endorse one reference set over the other, we highlight the potential implications from adopting the GLI12 reference sets and suggest caution when interpreting spirometry in the elderly.

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