Combined Pulmonary Fibrosis and Emphysema (CPFE) Clinical Features and Management

Abstract

Background Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47–90% of the patients and lung cancer in 46.8% of the patients. Objective Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE. Methods We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data. Results Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers. Conclusion CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients.

Differential Genomic Profile in TERT, DSP, and FAM13A Between COPD Patients With Emphysema, IPF, and CPFE Syndrome

“…Regarding clinical and demographic variables of patients' groups and control subjects, we observed that the CPFE patients are the group that presents the lowest DL CO , FEV 1 , and FVC values when were compared with the IPF patients and the PAC subjects. Interestingly, despite the decrease in FEV 1 and FVC, the FEV 1 /FVC ratio was maintained at >70%, another characteristic previously reported in CPFE patients (9,13,25).…”

“…The CPFE is a recently described entity in which emphysema is predominantly in the upper and fibrosis in the basal lung lobes and subpleural regions ( 9 , 12 ). The etiology and pathogenesis of this disease remain unknown and result in a diagnostic challenge with poor prognosis and high mortality ( 4 , 12 , 13 ). In 2020, Kinjo et al reported that the minor allele of the AGER rs2070600 was associated with CPFE related with COPD patients in the dominant model in a Japanese cohort ( 14 ).…”

COPD, Pulmonary Fibrosis and ILAs in Aging Smokers: The Paradox of Striking Different Responses to the Major Risk Factors

“…CPFE is usually not included in the ILAs; we propose its inclusion here to avoid a separate section. CPFE is a syndrome occurring in smokers or ex-smokers characterized by dyspnea that is often severe, with relatively preserved lung volumes, severely impaired gas exchange, and an increased risk of pulmonary hypertension, and is associated with a very poor prognosis, including an increased risk of lung cancer [18][19][20][21]. It is also encountered in the setting of connective tissue diseases, especially rheumatoid arthritis, which has similar features to 'idiopathic' (tobacco-related) CPFE [18].…”

“…CPFE may be associated with a higher risk of pulmonary hypertension and death (although this is controversial) [22]. Despite the publication of several papers since the first description by Wiggins et al [21], the pathophysiology and mechanisms of CPFE largely remain obscure [18,20].…”

“…Patients with CPFE may experience exacerbations that can be attributed to the emphysema component (COPD-type) or the fibrosis component of the lung (IPF-type) [116]. COPD types of AE-CPFE are defined in the same way as severe exacerbations of COPD (i.e., acute worsening of respiratory symptoms that result in hospitalization) and show clinical and physiological features comparable to ECOPD: airflow obstruction, increased airway resistance, and dynamic hyperinflation [20]. IPF types of AE-CPFE are defined according to the criteria established by the International Working Group for AE-IPF and are associated with higher morbidity and need for ICU management compared to the COPD type [104,116].…”