Chest
Volume 149, Issue 2, February 2016, Pages 491-498
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Original Research: Diffuse Lung Disease
Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline

This work was presented in part at the ATS International Conference, May 18, 2015, Denver, CO (Abstract ID59201).
https://doi.org/10.1378/chest.15-0530Get rights and content

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.

Section snippets

Patients

We identified subjects with IPF (diagnosed according to results of lung biopsy or CT scan [as previously described])1, 21 through review of interstitial lung disease databases at the Royal Brompton and Harefield National Health Service Foundation Trust, National Jewish Health, and the University of Michigan Health System from 1981 to 2008. For each patient, age, sex, and each pulmonary function test (PFT) were captured, with PFTs performed as described.22, 23, 24, 25 Patients with missing

Patient Population and Survival Comparisons

From the interstitial lung disease databases, 734 patients with IPF were identified; 657 had FVC and Dlco data available at baseline and were included in the present analysis. Patient characteristics for the included group as a whole and according to GAP stage are shown in Table 1. Overall, 70% were men, and the mean age was 62.9 years at the time of the baseline PFT. The mean ± SD percent-predicted baseline FVC was 68.0 ± 17.0, and for Dlco it was 45.7 ± 16.0.

For the combined end point of

Discussion

Pulmonary function trajectories were modeled in a large retrospective cohort of patients with IPF seen at 3 referral centers to determine if the GAP Index stage, a validated estimate of mortality risk, was also predictive of the future rate of decline in pulmonary function. Our findings are most notable for the lack of a consistently larger absolute or relative decline in FVC or Dlco for a particular GAP stage over 2 years of follow-up. Several modestly significant P values were reported

Conclusions

Our findings showed that pulmonary function trajectory does not vary based on disease severity as defined according to the GAP Index. We also found that 6-month declines in pulmonary function may add prognostic value to the baseline GAP stage. Further validation of our findings in additional cohorts is warranted, as well as a search for novel markers of future disease progression not tied to pulmonary function variables.

Acknowledgments

Author contributions: M. L. S. and K. R. F conceived and designed the study, had full access to all of the data, and take responsibility for the integrity of the data and the accuracy of the data analysis. M. L. S., M. X., and Y. Z. analyzed the data with supervision and assistance from S. M. and K. R.; F. N. T., K. K. B., A. U. W., S. L. S., and F. J. M. contributed data; and M. L. S. and K. R. F. prepared the manuscript. All other authors revised the manuscript and approved the final draft.

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    FUNDING/SUPPORT: This study was funded by the National Institutes of Health [Grant K24 HL111316 to Dr Flaherty and Grant T32 HL007749-22].

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