The Syndrome of Combined Pulmonary Fibrosis and Emphysema

Abstract

Combined pulmonary fibrosis and emphysema (CPFE) is a recently identified syndrome occurring almost exclusively in smokers or ex-smokers, characterized by severe dyspnea and limitation to exercise capacity. Tobacco smoking is the main etiologic factor. However, it may occur in the context of connective tissue disease especially rheumatoid arthritis and systemic sclerosis. Velcro-crackles are present at lung auscultation. CPFE may be overlooked due to preserved lung volumes and subnormal spirometry, however gas exchange is severely impaired, with hypoxemia at exercise. The diagnosis is based on the presence at HRCT of both emphysema predominating in the upper lobes and frequently paraseptal, and interstitial abnormalities suggesting pulmonary fibrosis in the lower zones of the lungs, with especially reticulation, traction bronchiectasis, honeycombing, and possible ground glass opacities. Thick-walled large cysts are another distinctive feature at imaging. Pathologic radiological correlations are difficult owing to various pathology and difficulties in identifying honeycombing at chest HRCT in the setting of coexistent emphysema. Lung pathology when available may show a pattern of usual interstitial pneumonia, however other patterns can also be found. Survival is generally comparable to that of idiopathic pulmonary fibrosis (without emphysema), however with an increased risk of precapillary pulmonary hypertension associated with a dismal prognosis. Lung cancer and acute exacerbation of pulmonary fibrosis may further hamper the prognosis. The CPFE syndrome impacts modalities of follow-up with a relative lack of restrictive physiology despite progression of disease, and the need to monitor for pulmonary hypertension. Management is mostly supportive, with smoking cessation, inhaled bronchodilators, and long-term oxygen therapy or lung transplantation when appropriate. Drug therapy with pirfenidone or nintedanib, which reduce the decline in lung function in idiopathic pulmonary fibrosis, might be used pending further evaluation. There are no data to support treatment specific for pulmonary hypertension in CPFE outside clinical studies or prospective registries.