Yet H Khor1, Lawrence Gutman2, Nebal Abu Hussein3, Kerri A Johannson4, Ian N Glaspole5, Sabina A Guler3, Manuela Funke-Chambour3, Thomas Geiser3, Nicole S L Goh6, Christopher J Ryerson7. 1. Department of Respiratory and Sleep Medicine/Institute for Breathing and Sleep, Austin Health, Heidelberg, VIC, Australia; Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Respiratory Medicine, Alfred Health, Melbourne, VIC, Australia; Centre for Heart Lung Innovation, Providence Health Care, Vancouver, BC, Canada. Electronic address: yethong.khor@austin.org.au. 2. Department of Medicine, University of Calgary, Calgary, AB, Canada. 3. Department of Pulmonary Medicine, Inselspital Bern University Hospital, University of Bern, Bern, Switzerland. 4. Department of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada. 5. Department of Respiratory Medicine, Alfred Health, Melbourne, VIC, Australia; Department of Medicine, Monash University, Melbourne, VIC, Australia. 6. Department of Respiratory and Sleep Medicine/Institute for Breathing and Sleep, Austin Health, Heidelberg, VIC, Australia; Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia; Centre for Heart Lung Innovation, Providence Health Care, Vancouver, BC, Canada. 7. Centre for Heart Lung Innovation, Providence Health Care, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Abstract
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-O2 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-O2 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-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD.
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-O2 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-O2 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-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD.