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The Syndrome of Combined Pulmonary Fibrosis and Emphysema

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Orphan Lung Diseases

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Abstract

Combined pulmonary fibrosis and emphysema (CPFE) is a recently identified syndrome occurring generally in smokers or ex-smokers, characterized by severe dyspnea and exercise limitation. Tobacco smoking is the main etiologic factor. However, CPFE may also occur in the context of connective tissue disease, especially rheumatoid arthritis and systemic sclerosis, even in lifelong nonsmokers. Velcro-crackles are present on lung auscultation. CPFE may be overlooked due to preserved lung volumes and subnormal spirometry, however, gas exchange is severely impaired, often with profound exercise induced desaturation. The diagnosis is based on HRCT evidence of emphysema predominating in the upper lobes and paraseptal regions, involving up to 5% of total lung volume or more, and pulmonary fibrosis in the lower zones of the lungs, with reticulation, traction bronchiectasis, honeycombing, and ground-glass opacities. Thick-walled, large cysts are often another distinctive feature at imaging. Pathologic, radiologic, and physiologic correlations are difficult owing to the opposing effects of emphysema and fibrosis on lung mechanics and difficulties in identifying interstitial infiltrates and honeycombing on chest HRCT in the setting of coexistent emphysema. Lung pathology when available may show a pattern of usual interstitial pneumonia, although other patterns can also be found, including nonspecific interstitial pneumonitis and smoking-related interstitial fibrosis. Outcomes are impacted by the increased risk of precapillary pulmonary hypertension, lung cancer, acute exacerbation of pulmonary fibrosis, and mortality. CPFE syndrome can be difficult to follow because restrictive physiology may not track linearly with progression of disease, and pulmonary hypertension can intervene and cause worsening symptoms. Management is mostly supportive, with smoking cessation, inhaled bronchodilators, and long-term oxygen therapy or lung transplantation when appropriate. Treatment with antifibrotic drugs is warranted in patients with idiopathic pulmonary fibrosis combined with emphysema, and in those with fibrosing interstitial lung disease with a progressive phenotype. There are no data to support treatment specific for pulmonary hypertension in CPFE outside of clinical studies or prospective registries.

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  1. Department of Respiratory Medicine, National Coordinating Reference Centre for Rare Pulmonary Diseases (OrphaLung), Louis Pradel Hospital, University of Lyon, Lyon, France

    Vincent Cottin

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  1. Department of Respiratory Medicine, National Coordinating Reference Centre for Rare Pulmonary Diseases (OrphaLung), Louis Pradel Hospital, University of Lyon, Lyon, France

    Vincent Cottin

  2. Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

    Luca Richeldi

  3. National Jewish Health, Denver, CO, USA

    Kevin Brown

  4. Division of Pulmonary, Critical Care, and Sleep Medicine Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Francis X. McCormack

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Cottin, V. (2023). The Syndrome of Combined Pulmonary Fibrosis and Emphysema. In: Cottin, V., Richeldi, L., Brown, K., McCormack, F.X. (eds) Orphan Lung Diseases. Springer, Cham. https://doi.org/10.1007/978-3-031-12950-6_33

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