Mortality in combined pulmonary fibrosis and emphysema patients is determined by the sum of pulmonary fibrosis and emphysema

Abstract

Emphysema is one of the most common pulmonary comorbidities of idiopathic pulmonary fibrosis (IPF), presenting in about one-third of IPF patients [1]. The term combined pulmonary fibrosis and emphysema (CPFE) has been used to describe a potential phenotype characterised by the coexistence of upper lobe-predominant emphysema, lower lobe-predominant fibrosis and relative preservation of lung volumes (forced vital capacity; FVC) in the context of a disproportionately reduced gas transfer (diffusing capacity of the lung for carbon monoxide; D LCO ) [1–3]. With regard to patient survival, it remains unclear whether mortality in patients with CPFE reflects the cumulative effects of two disease processes (emphysema and fibrosis), or whether CPFE represents a distinct disease phenotype where outcome is worse than the sum of disease parts (emphysema and fibrosis).

Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement

“…Patients with CPFE have worse survival than patients with emphysema alone on HRCT 42 . As compared to patients with IPF alone, patients with CPFE were reported to have worse 32,38,49,55,56 , comparable 24,26,35,37,39,47,[57][58][59]119,[210][211][212] , or better survival 31,120,147 . Possible explanations for this discrepancy include diagnostic contamination (with a higher proportion of non-IPF cases in CPFE populations with better survival), attrition bias 26,60 , differences in the relative extent of emphysema versus fibrosis in different cohorts 24,59,213 , and a 'healthy smoker' effect 214 .…”

“…A positive correlation was found in some series between the extent of emphysema and the extent of fibrosis 32 , however a negative correlation was found in others 29,129,215 . In some series, an attempt was made to examine CPFE specifically in sub-groups mostly or wholly made up of IPF 24,32,36,42,55,120,146,212 . However, this goal is complicated by the lack of histologic confirmation of UIP in most CPFE patients with suspected IPF, and difficulties discriminating between true honeycomb change (required for an HRCT pattern of UIP) and the admixture of emphysema and pulmonary fibrosis ("pseudohoneycomb change") on HRCT 216,217 .…”

“…Prognostic evaluation of CPFE, with particular reference to comparisons between CPFE and isolated IPF, requires quantification of both pulmonary fibrosis and emphysema. This was conducted in two retrospective cohorts of patients with IPF 58,212 , using both visual analysis to the nearest 5% 58,212 and computer-based analysis with the CALIPER software 58 . The global disease extent on HRCT (i.e.…”

“…The global disease extent on HRCT (i.e. the combined extent of fibrosis and of emphysema) and the baseline DLco both predicted mortality, reflecting the overall severity of parenchymal lung destruction 58,212 . After correction for baseline severity using DLco, the presence or extent of emphysema did not impact on survival 58 .…”

Chronic Obstructive Pulmonary Disease and Small Airways Diseases

“…63 In these cases, the IPF tends to drive prognosis and mortality. 64 From an imaging perspective, the findings of IPF in CPFE are identical to those in patients without emphysema. Subpleural and basilar fibrosis with honeycombing are the typical CT findings.…”