Spirometry, Static Lung Volumes, and Diffusing Capacity

Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity).

We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry (n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver (n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity (n = 2,508). Using multivariable linear regression, adjusted least-squares means (adj_LSMeans) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adj_LSMeans were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal (n = 1,251), restrictive pattern (n = 663), and air-flow obstruction (mild, [n = 128]; moderate, [n = 150]; and severe, [n = 394]).

Relative to normal spirometry, restrictive-pattern had lower adj_LSMeans for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity (P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adj_LSMeans for FRC and RV (P < .001). However, only mild and moderate air-flow obstruction had higher adj_LSMeans for TLC (P < .001), while only moderate and severe air-flow obstruction had higher adj_LSMeans for RV/TLC (P < .001) and lower adj_LSMeans for hemoglobin-adjusted single-breath diffusing capacity (P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction (P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction (P < .001), thus opposing the increased FRC (P < .001). Finally, P values were similar whether adj_LSMeans were height-cubed standardized.

A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity).