Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test

Abstract

Rationale and hypothesis: Idiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide.

Methods: One hundred ninety-seven patients with idiopathic pulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation < or = 88% during a baseline 6MWT. For patients with a baseline saturation < or = 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation > 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequent mortality, whereas decreases in walk distance and in diffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients.

Conclusion: These data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.

Figure 1.

Desaturation area (DA) was defined as the total area above the curve created using desaturation percentage values observed at baseline and at each subsequent minute of the six-min-walk test (6MWT; i.e., summing up the differences between an Sa_O2 of 100% and the patient's Sa_O2 at each minute). For example, a patient with an Sa_O2 of 98% at each minute during the 6MWT would have a DA of 12. For safety, we stopped the 6MWT when patients reached an Sa_O2 of 86%, and a desaturation score of 14% was assigned for that minute and all subsequent minutes of the 6MWT. A higher DA indicates higher overall quantity of desaturation during the 6MWT.

Figure 2.

Kaplan-Meier survival curves for 197 patients with idiopathic pulmonary fibrosis stratified by baseline walk distance (circles = censored, solid line = walked 1–599 ft, continuous dashed line = walked 600–1199 ft, broken dashed line = walked at least 1,200 ft).

Figure 3.

Graphic representation of how the predictive ability of serial changes in FVC, diffusion capacity of carbon monoxide (Dl_CO), change in walk distance, and change in desaturation varies by the presence/absence of desaturation to ⩽ 88% during a baseline 6MWT. These data suggest that decline in Dl_CO over 6 mo is the sole predictor of increased risk of subsequent mortality and that declines in Dl_CO, FVC, walk distance, and worsening desaturation can be used to follow patients who do not desaturate ⩽ 88% during a baseline 6MWT.