Incidence and prognostic significance of hypoxemia in fibrotic interstitial lung disease: an international cohort study.

Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD is currently unknown.What are the epidemiology of hypoxemia and its additive prognostic value in current risk prediction model in fibrotic ILD?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-minute 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/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-O2" model), which included oxygenation status as a predictor.The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1% for exertional hypoxemia, and 2.4%, 5.6%, and 16.5% for resting hypoxemia, which were significantly higher in IPF patients compared to non-IPF patients (p<0.001 for both). Addition of exertional or resting hypoxemia to the ILD-GAP model improved 1-year mortality/transplantation prediction (p<0.001 for both). The ILD-GAP-O2 model had improved discrimination (C-index of 0.80 vs 0.75) and model fit (Akaike information criteria of 400 vs 422) in the validation cohort, with comparable calibration.IPF patients have higher cumulative incidence of exertional and resting hypoxemia than non-IPF patients. The extended ILD-GAP-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD.

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Authors: Yet H Khor, Lawrence Gutman, Nebal Abu Hussein, Kerri A Johannson, Ian N Glaspole, Sabina A Guler, Manuela Funke-Chambour, Thomas Geiser, Nicole Sl Goh, Christopher J Ryerson