Development of exertional, resting hypoxemia common in patients with IPF

Patients with idiopathic pulmonary fibrosis appear to have higher cumulative incidences of exertional and resting hypoxemia compared with patients with non-IPF fibrotic interstitial lung disease, researchers reported in Chest.

“The incidence, progression and prognostic significance of hypoxemia in patients with fibrotic interstitial lung disease is unknown,” Yet H. Khor, MBBS, PhD, of the department of medicine at the University of Melbourne, Australia, and colleagues wrote. “A better understanding of the natural course of hypoxemia in fibrotic ILD is needed to aid discussion regarding patient expectations and guide management decisions.”

The international, multicenter cohort study included 848 participants (mean age, 63 years; 50% men) from five prospective ILD registries from Australia, Canada and Switzerland. Of these patients, 258 had IPF. Researchers evaluated the cumulative incidence of exertional and resting hypoxemia from time of diagnosis to years 1, 2 and 5 in patients with baseline 6-minute walk tests.

Patients were categorized into derivation and validation subsets to assess performance characteristics of the extended ILD-GAP-O₂ model, which included oxygenation status.

At baseline, 57.8% of patients were normoxemic, 39.6% had isolated exertional hypoxemia and 2.6% had resting hypoxemia. In those who were normoxemic, 38% developed exertional hypoxemia during follow-up. The overall cumulative incidence of exertional hypoxemia was 6.1% for year 1, 17.3% for year 2 and 40.1% for year 5. Among those who were normoxemic or had isolated exertional hypoxemia at baseline, 17% developed resting hypoxemia. The overall cumulative incidence of resting hypoxemia was 2.4% for year 1, 5.6% for year 2 and 16.5% for year 5. The cumulative incidence of exertional and resting hypoxemia was significantly higher among patients with IPF compared with those with non-IPF fibrotic ILD (P < .001).

The addition of exertional or resting hypoxemia to the ILD-GAP model was associated with improved prediction of 1-year mortality and transplantation (P < .001 for both). This model also had improved discrimination with a C-index of 0.8 vs. 0.75 and model fit with 400 vs. 422 in the validation cohort.

“To our knowledge, this is the first longitudinal study of a large international cohort of patients with well-defined fibrotic ILD to evaluate the cumulative incidence and prognosis of exertional and resting hypoxemia. We show that exertional hypoxemia is a common early feature in fibrotic ILD, with 17.3% of patients developing it within 2 years of the first objective evidence of lung fibrosis. Conversely, resting hypoxemia is a late feature that signifies end-stage disease with similar poor prognosis in both IPF and non-IPF patients, with 42% of patients having died or received lung transplantation within a year of developing resting hypoxemia.

“Additional studies are needed to evaluate the effects of ambulatory and long-term oxygen therapy in altering the natural history of hypoxemia in patients with fibrotic ILD,” the researchers wrote.