Chest
Volume 145, Issue 3, March 2014, Pages 579-585
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Original Research: Diffuse Lung Disease
Predicting Pulmonary Fibrosis Disease Course From Past Trends in Pulmonary Function

https://doi.org/10.1378/chest.13-0844Get rights and content

Background

The clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by progressive decline in lung function and eventual mortality. We sought to determine if future declines in pulmonary function, mortality, or both can be predicted from prior trends in pulmonary function tests (PFTs).

Methods

Data from 1981 to 2008 on 4,431 PFTs and mortality were analyzed from 734 subjects with IPF. The Kaplan-Meier method was used for mortality analyses. Mixed models were used to describe longitudinal pulmonary function dynamics, since PFTs were observed at varying time points from baseline.

Results

During the first year of follow-up, 135 subjects (73%) had stable FVC while 50 subjects (37%) showed a decline in FVC. During months 12 to 24 (1-2 years after diagnosis), a stable FVC occurred with the same frequency among both subjects whose FVC had declined during year 1 and whose FVC had remained stable (84.0% and 80.7%, respectively; P = .59). Among subjects alive at the end of year 1, those with a stable FVC were more likely to be alive at the end of year 2 than those whose FVC declined (hazard ratio [HR], 0.91 [95% CI, 0.87-0.94] and HR, 0.71 [95% CI, 0.62-0.78], respectively).

Conclusions

PFT decline predicts early mortality, but not future declines in physiology, regardless of time since diagnosis.

Section snippets

Materials and Methods

We identified pulmonary function tests (PFTs) for patients with IPF through interstitial lung disease databases from the Royal Brompton and Harefield National Health Service Foundation Trust, National Jewish Health, and the University of Michigan Health System from 1981 through 2008. Patients were diagnosed with IPF either through surgical lung biopsy or characteristic chest CT scan.1, 24 For each patient, sex, age, and every PFT they had performed at their home center were captured for

Patient Population

A total of 4,431 PFTs were analyzed from 734 patients (characteristics are in Table 1). Fewer patients had baseline Dlco measurement performed than FVC: 657 vs 730, respectively. If a patient had subsequent Dlco measured, their data would return to the analysis for later years. An aggregate mean FVC and Dlco were recorded for each year of the analysis and were remarkably consistent between the years: within 5% predicted for FVC and 4% predicted for Dlco.

Due to losses to follow-up, we compared

Discussion

In a large, multicenter, retrospective cohort of patients with IPF, we report (1) the change in pulmonary function in the prior year does not predict the change in pulmonary function in the subsequent year, (2) declines in the pulmonary function in the prior year predicts mortality in the following year, and (3) commonly used study end points such as mortality and decline in pulmonary function occur with greatest frequency the first year after presentation.

Attempts to enrich study populations

Conclusions

In summary, short-term, clinically significant declines in FVC or Dlco correlate with an increased risk of mortality in the following 12 months. However, declines in these measures do not predict subsequent declines in pulmonary physiology. These data should help inform the next generation of treatment trials in IPF.

Acknowledgments

Author contributions: Dr Flaherty had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Schmidt: contributed to study conception and design; data acquisition, analysis, and interpretation; and preparation and final approval of the manuscript and served as principal author.

Ms Tayob: contributed to data analysis and revision and final approval of the manuscript.

Dr Han: contributed to data analysis and

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  • Cited by (0)

    Part of this article was presented at the American Thoracic Society International Conference, May 13-18, 2011, Denver, CO, and in abstract form (Schmidt SL, Han MK, Tayob N, et al. Am J Respir Crit Care Med. 2011;183:A5299).

    Funding/Support: This study was supported by National Institutes of Health [Grant HL093351 to Dr Han and Grants K24HL11316, R01HL19743 and HL007749 to Dr Flaherty].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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