Chest
Recent Advances In Chest MedicineCombined Pulmonary Fibrosis and Emphysema Syndrome: A Review
Section snippets
Diagnosis of the CPFE Syndrome
The diagnosis of the CPFE syndrome is established after HRCT imaging, sometimes in conjunction with pathology. A consensus definition of CPFE syndrome does not currently exist. In the broadest sense, this term should include all patients with coexistent emphysema and pulmonary fibrosis pathology, although current methods of detection, such as HRCT scanning, likely allow identification of a portion of this larger group. The combination of emphysema and pulmonary fibrosis detectable on HRCT scan
Cigarette Smoking
Recent studies of CPFE consistently have revealed a strong association with cigarette smoking. Of the 607 total patients with CPFE for whom smoking status was recorded in the published studies summarized in Table 2, 592 (98%) were either current or former smokers. These results are not surprising given the relationships between emphysema/COPD35 and IPF36 and smoking. Interstitial lung abnormalities visible by HRCT scan have been observed in 8% of HRCT scans in a cohort of 2,416 smokers.37 In
Pathogenesis
A single gene defect responsible for most cases of CPFE has not been established in humans. The best established environmental insult in the CPFE syndrome is cigarette smoking, which is associated with the majority of reported cases. Cigarette smoking exposure induced a combination of pulmonary fibrosis and emphysema in a canine model.58 A variety of genetically altered animal models have demonstrated incidental lung morphologic changes, including both pulmonary emphysema and fibrosis, thus
Physiologic Consequences
The physiologic consequences of the CPFE syndrome include preservation of spirometric values and lung volumes despite extensive radiographic evidence of lung disease as well as marked impairment of gas exchange manifested as a reduction in Dlco.4, 12 Mean values for vital capacity and total lung capacity frequently are in the normal range, whereas values for gas exchange are nearly always abnormal (Table 2). To account for the effects of emphysema on lung function parameters in the setting of
Radiology
Characteristic radiologic findings in the CPFE syndrome include upper-lobe emphysema and lower-lobe interstitial fibrotic changes (Fig 1). The emphysema in CPFE includes bullous, paraseptal, and centrilobular changes7, 13, 25 and is typically distributed in the upper lobes.7, 25 Kitaguchi et al25 found that paraseptal emphysema was more common in the CPFE population than in a control group of patients with COPD (33.3% vs 8.5%, respectively). Honeycombing and reticular abnormalities are
Pathology
A variety of pathologic patterns of pulmonary fibrosis have been reported in conjunction with emphysema in the CPFE syndrome, including usual interstitial pneumonia,7 airspace enlargement with fibrosis,69 nonspecific interstitial pneumonia,7 respiratory bronchiolitis-associated interstitial lung disease with alveolar septal fibrosis,70 desquamative interstitial pneumonia with extensive fibrosis,9 and unclassifiable smoking-related interstitial fibrosis.2
Natural History and Mortality
The significance of changes in lung function over time appears to differ in patients with isolated IPF compared with patients with CPFE syndrome. Akagi et al18 reported that patients with CPFE experience a slower decline in FVC and Dlco over time than do patients with isolated IPF. Because decline in FVC and Dlco are important prognostic factors in IPF, lack of recognition of concomitant emphysema in these patients may result in errors in prognostication. This has been highlighted by Schmidt et
Pulmonary Hypertension
Pulmonary hypertension is a well-described complication of advanced lung disease in patients with CPFE syndrome. Pulmonary hypertension appears to be more frequent and more severe in the CPFE population than in patients with IPF alone.15 Cottin et al21 reported right heart catheterization findings in 40 patients with CPFE and pulmonary hypertension, with a mean pulmonary artery pressure of 40 ± 9 mm Hg. In this cohort, a reduced cardiac index (< 2.4 L/min/m2) or elevated pulmonary vascular
Treatment of CPFE
There is no specific treatment of the CPFE syndrome. Smoking cessation, of course, should be encouraged and supported. Immunosuppressive therapy in conjunction with smoking cessation may be reasonable in select patients with evidence of active inflammation, such as ground glass infiltrates,9 but is unlikely to be helpful in the setting of emphysema plus end-stage usual interstial pneumonia/IPF. Oxygen therapy is appropriate for management of hypoxemia. However, use of specific pulmonary
Conclusions
The CPFE syndrome illustrates the limitations of a simplistic diagnostic dichotomy between lung emphysema and fibrosis. Tobacco smoking may cause emphysema-dominant, fibrosis-dominant, or CPFE pathology, with differing implications for treatment, complications, and prognosis. We should take a broad view of the mixture of lung pathologies in patients and avoid single-minded application of classification schemes that have great usefulness in categorizing large groups of patients for clinical
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Role of sponsors: The opinions expressed by the authors do not necessarily reflect the opinions of the Department of Veterans Affairs. The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.
Other contributions:
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Funding/Support: This publication is the result of work supported with resources and facilities from the Providence VA Medical Center. Dr Jankowich is funded by a Chairman's Developmental Research Grant from the Department of Medicine, Alpert Medical School of Brown University. Dr Rounds is funded by a VA Merit Review grant and the National Heart, Lung, and Blood Institute [Grant R01 HL64936].
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