Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline

Abstract

Background: Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage.

Methods: Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage.

Results: Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1).

Conclusions: Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation.

Keywords: idiopathic pulmonary fibrosis; interstitial lung disease; lung function.

Figure 1

Kaplan-Meier transplant-free survival according to GAP stage. Transplant-free survival, defined as time from first pulmonary function test to death or lung transplantation, is displayed with patients grouped according to their GAP Index stage at the time of the baseline pulmonary function test. Patients with GAP stage 1 experienced the lowest event rates, and patients with GAP stage 3 had the highest event rates; GAP stage 2 was intermediate over 3 years of follow-up (P < .0001). Figure 1 Table shows the number at risk each year according to GAP stage. GAP = Gender-Age-Physiology.

Figure 2

Relative FVC decline according to GAP stage. The percent-predicted FVC trajectory is assessed by using the mixed models method with splines at yearly intervals. The relative decline from baseline at years 1 and 2 is shown with patients stratified according to baseline GAP stage. The point estimates for relative decline from baseline at years 1 and 2 for each GAP stage group are shown in Figure 2 Table. Although patients with GAP stage 2 declined significantly more compared with patients with GAP stage 1 during year 1 (P = .04), no significant difference was seen between groups by year 2 (P ≥ .31). See Figure 1 legend for expansion of abbreviation.

Figure 3

Relative Dlco decline according to GAP stage. The percent-predicted Dlco trajectory was assessed by using the mixed models method with splines at yearly intervals. The relative decline from baseline at years 1 and 2 with patients stratified according to baseline GAP stage is shown. The point estimates for relative decline from baseline at years 1 and 2 for each GAP stage group are shown in Figure 3 Table. There is no accelerated decline seen for any GAP stage, with no significant difference in the relative decline from baseline at year 1 or 2 of follow-up (P ≥ .07). Dlco = diffusing capacity of the lung for CO₂. See Figure 1 legend for expansion of other abbreviation.

Figure 4

A-C, Kaplan-Meier transplant-free survival according to GAP stage in those experiencing a 10% decline in FVC, Dlco, both, or neither. Kaplan-Meier transplant-free survival, defined as time from the follow-up pulmonary function test (PFT) to death or lung transplantation, is shown for patients with (A) GAP stage 1, (B) GAP stage 2, and (C) GAP stage 3. Patients were grouped based on whether they experienced a ≥ 10% decline in FVC, Dlco, both FVC and Dlco, or neither during the first 6 months of follow-up. Patients with GAP stage 1 and 2 with a decline in both FVC and Dlco experienced higher event rates compared with those experiencing no change in either parameter. In GAP stage 3, only 6 patients experienced no decline in pulmonary function over 6 months, and the power was low to find differences between groups. See Figure 1 and 3 legends for expansion of abbreviations.