Incidence and Prognostic Significance of Hypoxemia in Fibrotic Interstitial Lung Disease: An International Cohort Study.

Background: Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD currently is unknown.
Research Question: What are the epidemiologic features of hypoxemia and its additive prognostic value in a current risk prediction model of fibrotic ILD?
Methods: We identified 848 patients with fibrotic ILD (258 with idiopathic pulmonary fibrosis [IPF]) in five prospective ILD registries from Australia, Canada, and Switzerland. Cumulative incidence of exertional and resting hypoxemia from the time of diagnosis was estimated at 1-year intervals in patients with baseline 6-min walk tests, adjusted for competing risks of death and lung transplantation. Likelihood ratio tests were used to determine the prognostic significance of exertional and resting hypoxemia for 1-year mortality or transplantation when added to the ILD-GAP model. The cohort was divided into derivation and validation subsets to evaluate performance characteristics of the extended model (the ILD-GAP-O ₂ model), which included oxygenation status as a predictor.
Results: The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1%, respectively, for exertional hypoxemia and 2.4%, 5.6%, and 16.5%, respectively, for resting hypoxemia, which were significantly higher in patients with IPF compared with patients without IPF (P < .001 for both). Addition of exertional or resting hypoxemia to the ILD-GAP model improved 1-year mortality and transplantation prediction (P < .001 for both). The ILD-GAP-O ₂ model showed improved discrimination (C-index, 0.80 vs 0.75) and model fit (Akaike information criteria, 400 vs 422) in the validation cohort, with comparable calibration.
Interpretation: Patients with IPF have higher cumulative incidence of exertional and resting hypoxemia than patients without IPF. The extended ILD-GAP-O ₂ model provides additional risk stratification for 1-year prognosis in fibrotic ILD.
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