What Are the Outcomes of Combined Pulmonary Fibrosis and Emphysema in Patients with IPF?

Background

Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by substantial smoking history, exercise hypoxemia, upper lobe emphysema and lower lobe fibrosis, unexpected subnormal lung volumes, and severe reduction of carbon monoxide transfer.1 CPFE has a poor prognosis and is frequently complicated by pulmonary hypertension, acute lung injury, and lung cancer. The prevalence of CPFE in IPF and its impact on prognosis is not known. To address these questions, the authors conducted an IPF-specific multicenter study using both a standardized definition of CPFE and rigorous statistical methods to determine differences in clinical features and outcomes.2

What They Did

Patients with high-resolution computed tomography (HRCT)- confirmed IPF were identified through the University of California San Francisco (n=192) and Mayo Clinic Rochester (n=173) interstitial lung disease databases between January 2000 and July 2010.2 Two experienced thoracic radiologists who were blinded to other patient data independently reviewed the HRCT scans. The percent of reticular change and honeycombing were used to determine a fibrosis score for each scan. An emphysema score was calculated in a similar manner. Emphysema was defined as a hyperlucent area of lung that lacked a distinct wall. A threshold of ≥10% was chosen to define patients with CPFE as this amount of emphysema is expected to have symptomatic and physiologic consequences.

What They Found

Criteria for CPFE were met in 29 of 365 patients (8%).2 Compared with patients without CPFE, patients with CPFE had a more extensive smoking history, greater oxygen requirements, higher pulmonary artery pressure, less restrictive physiology, lower diffusing capacity, and a lower total fibrosis score. Patients with CPFE were more likely to have a diagnosis of chronic obstructive pulmonary disease (COPD) and were managed more frequently with short-acting bronchodilators and long-acting anticholinergics. On unadjusted analysis, patients with CPFE had a similar risk of death compared with IPF patients using a competing risk analysis (HR, 1.08; 95% CI, 0.67-1.73; P=.75). The risk of death was also similar after adjustment for baseline fibrosis score (HR, 1.14; 95% CI, 0.61-2.13; P=.69). During the initial 12 months of follow-up, disease progression occurred in 135 patients (71%). No association between the diagnosis of CPFE and disease progression on unadjusted or adjusted analyses was found.

What It Means

Despite significantly less fibrosis in patients with CPFE vs patients with IPF without emphysema, there was no clear difference in survival.2 The similar mortality in the 2 groups may be due to the approximately balanced mortality risk factors in CPFE (ie, worse oxygenation and pulmonary hypertension) and IPF without emphysema (ie, more fibrosis). Whether CPFE is a biologically distinct condition or is simply IPF and emphysema in the same patient remains an unanswered question. To address this question, future research will be needed, evaluating underlying biologic pathways and clarifying why some smokers develop emphysema, some IPF, and some CPFE.



References

  1. Lin H, Jiang S. Combined pulmonary fibrosis and emphysema (CPFE): an entity different from emphysema or pulmonary fibrosis alone. J Thorac Dis. 2015;7:767-779.
  2. Ryerson CJ, Hartman T, Elicker BM, et al. Clinical features and outcomes in combined pulmonary fibrosis and emphysema in idiopathic pulmonary fibrosis. Chest. 2013;144:234-240.