Implications of the 2022 lung function update and GLI global reference equations among patients with interstitial lung disease

Abstract

Background: Lung function testing remains a cornerstone in the assessment and management of interstitial lung disease (ILD) patients. The clinical implications of the Global Lung function Initiative (GLI) reference equations and the updated interpretation strategies remain uncertain.

Methods: Adult patients with ILD with baseline forced vital capacity (FVC) were included from the Australasian ILD registry and the National Healthcare Group ILD registry, Singapore.The European Coal and Steel Community and Miller reference equations were compared with the GLI reference equations to assess (a) differences in lung function percent predicted values; (b) ILD risk prediction models and (c) eligibility for ILD clinical trial enrolment.

Results: Among 2219 patients with ILD, 1712 (77.2%) were white individuals. Idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD and unclassifiable ILD predominated.Median FVC was 2.60 (2.01-3.36) L, forced expiratory volume in 1 s was 2.09 (1.67-2.66) L and diffusing capacity of the lungs for carbon monoxide (DLCO) was 13.60 (10.16-17.60) mL/min/mm Hg. When applying the GLI reference equations, the mean FVC percentage predicted was 8.8% lower (87.7% vs 78.9%, p<0.01) while the mean DLCO percentage predicted was 4.9% higher (58.5% vs 63.4%, p<0.01). There was a decrease in 19 IPF and 119 non-IPF patients who qualified for the nintedanib clinical trials when the GLI reference equations were applied. Risk prediction models performed similarly in predicting mortality using both reference equations.

Conclusion: Applying the GLI reference equations in patients with ILD leads to higher DLCO percentage predicted values and smaller lung volume percentage predicted values. While applying the GLI reference equations did not impact on prognostication, fewer patients met the clinical trial criteria for antifibrotic agents.

Keywords: Connective tissue disease associated lung disease; Idiopathic pulmonary fibrosis; Interstitial Fibrosis; Pulmonary vasculitis; Rare lung diseases.

Figure 1. Kaplan-Meier survival curve for ILD-GAP index (GLI). GAP, Gender, Age, Physiology; GLI, Global Lung function Initiative; ILD, interstitial lung disease.

Figure 2. (A) Kaplan-Meier survival curve with CPI (GLI) cut-off of 40. (B) Kaplan-Meier survival curve with CPI (ECSC) cut-off of 40. (C) Kaplan-Meier survival curve with CPI (GLI) cut-off of 50. (D) Kaplan-Meier survival curve with CPI (ECSC) cut-off of 50. CPI, Composite Physiologic Index; ECSC, European Coal and Steel Community; GLI, Global Lung function Initiative.

Figure 3. Area under the curve of ILD-GAP index comparing ECSC and z-scores severity values. AUC, area under the curve; ECSC, European Coal and Steel Community; GAP, Gender, Age, Physiology; ILD, interstitial lung disease.