Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis

PLoS One. 2016 Mar 29;11(3):e0151425. doi: 10.1371/journal.pone.0151425. eCollection 2016.


Introduction: Comorbidities significantly influence the clinical course of idiopathic pulmonary fibrosis (IPF). However, their prognostic impact is not fully understood. We therefore aimed to determine the impact of comorbidities, as individual and as whole, on survival in IPF.

Methods: The database of a tertiary referral centre for interstitial lung diseases was reviewed for comorbidities, their treatments, their frequency and survival in IPF patients.

Results: 272 patients were identified of which 12% had no, 58% 1-3 and 30% 4-7 comorbidities, mainly cardiovascular, pulmonary and oncologic comorbidities. Median survival according to the frequency of comorbidities differed significantly with 66 months for patients without comorbidities, 48 months when 1-3 comorbidities were reported and 35 months when 4-7 comorbidities were prevalent (p = 0.004). A multivariate Cox proportional hazard analyses identified other cardiac diseases and lung cancer as significant predictors of death, gastro-oesophageal reflux disease (GERD) and diastolic dysfunction had a significant positive impact on survival. A significant impact of comorbidities associated therapies on survival was not discovered. This included the use of proton pump inhibitors at baseline, which was not associated with a survival benefit (p = 0.718). We also established a predictive tool for highly prevalent comorbidities, termed IPF comorbidome which demonstrates a new relationship of IPF and comorbidities.

Conclusion: Comorbidities are frequent in IPF patients. Some comorbidities, especially lung cancer, mainly influence survival in IPF, while others such as GERD may inherit a more favourable effect. Moreover, their cumulative incidence impacts survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Comorbidity*
  • Demography
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / mortality*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Kaplan-Meier Estimate
  • Male
  • Proportional Hazards Models
  • Proton Pump Inhibitors / therapeutic use
  • Survival Analysis


  • Proton Pump Inhibitors

Grants and funding

This work was supported by the German Centre for Lung research and by an unrestricted grant from InterMune which is now F. Hoffmann-La Roche Ltd. The funder provided support in the form of funding the statistical analyses, which were performed by Jacques Bruhwyler who is an employee of CRO ECSOR, Belgium and for further research material. The funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the 'author contributions' section. Furthermore, we acknowledge financial support by Deutsche Forschungsgemeinschaft and Ruprecht-Karls-Universität Heidelberg within the funding programme Open Access Publishing