Diffusing capacity in normal-for-age spirometry and spirometric impairments, using reference equations from the global lung function initiative.

BACKGROUND: Reference equations from the Global Lung Function Initiative (GLI) are now available for both spirometry and diffusion. However, respiratory phenotypes defined by GLI-based measures of diffusion have not yet been evaluated in GLI-based normal-for-age spirometry or spirometric impairments. METHODS: We evaluated cross-sectional data from 2100 Caucasians, aged 40-85 years. GLI-based spirometric categories included normal-for-age and the impairments of restrictive-pattern and three-level severity of airflow-obstruction (mild, moderate, severe). GLI-based diffusion included diffusing capacity of the lung for carbon monoxide (D(LCO)) and measured components of alveolar volume (V(A)) and transfer coefficient (K(CO)): D(LCO) = [V(A)]x[K(CO)]. Using multivariable regression models, adjusted odds ratios (adjORs) for D(LCO), V(A), and K(CO) < lower limit of normal (LLN) were calculated for spirometric impairments, relative to normal-for-age spirometry. RESULTS: Relative to normal-for-age spirometry, the restrictive-pattern increased the adjORs (95% confidence intervals) for D(LCO) and V(A) < LLN-4.61 (3.62, 5.85) and 15.53 (11.8, 20.4), respectively, but not for K(CO) < LLN-1.02 (0.79, 1.33). Also relative to normal-for-age spirometry, airflow-obstruction from mild to severe increased the adjORs for D(LCO) < LLN-from 1.22 (0.80, 1.86) to 6.63 (4.91, 8.95), for V(A) < LLN-from 1.37 (0.85, 2.18) to 7.01 (5.20, 9.43), and for K(CO) < LLN-from 2.04 (1.33, 3.14) to 3.03 (2.29, 3.99). Notably, in normal-for-age spirometry, 34.5%, 19.7%, and 25.3% of participants had D(LCO), V(A), or K(CO) < LLN, respectively. CONCLUSION: Abnormal diffusion is most prevalent in spirometric impairments but also occurs in normal-for-age spirometry. These results further inform the respiratory phenotypes of GLI-based spirometric categories and, in turn, the spirometric evaluation of respiratory disease.