DESTIN, FLA. – A 2010 study by Dr. Anna-Luise A. Katzenstein and her colleagues was the first to show that interstitial fibrosis is remarkably common and often severe in cigarette smokers, including those with no clinical evidence of interstitial lung disease.
Pathologic specimens showed that interstitial fibrosis occurred in 12 of 20 smokers (60%) but in none of 3 nonsmokers; three of the smokers with fibrosis had well-defined smoking-related disorders such as respiratory bronchiolitis–interstitial lung disease (RB-ILD), but 9 had pathology showing more than 10% fibrosis on their lung biopsies (Hum. Pathol. 2010;41:316-25). They were considered to have smoking-related interstitial lung disease, Dr. David Moller said at the Congress of Clinical Rheumatology.
"More recently this has been described as [combined pulmonary fibrosis and emphysema, or CPFE syndrome], and it’s largely with the advent of high resolution computed tomography scanning that it has been appreciated how common fibrosis is in association with emphysema," said Dr. Moller, professor of medicine and director of the sarcoidosis clinic at Johns Hopkins University, Baltimore.
Typically, patients with CPFE syndrome have upper-lobe emphysema and lower-lobe fibrosis, he said.
"Because of that, you can get relatively normalized lung volumes and spirometry, but what characterizes these patients is a severe reduction in diffusing capacity. This is often associated with a pulmonary hypertension, which can be a major determinant of survival," he added.
CPFE syndrome is more common in males than females, and is found in 19%-51% of smokers with emphysema on chest CT who have no defined underlying interstitial lung disease. On biopsy, a number of pathological patterns may be seen, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonia, and RB-ILD, Dr. Moller said.
Mortality is increased in patients with this syndrome, compared with those who smoke and have chronic obstructive pulmonary disease, and survival ranges from 35% to 80% at 5 years, he added, noting that the mortality rate is unclear in patients who may have underlying idiopathic pulmonary fibrosis.
The syndrome is strongly associated with smoking but is also associated with lung cancer, asbestos and mineral dust exposures, and pulmonary hypertension. A 2011 study demonstrated that CPFE is also associated with connective tissue disease.
In that retrospective study of 34 patients with both connective tissue disease and CPFE syndrome who were followed for about 8 years, 18 had rheumatoid arthritis, 10 had systemic sclerosis, 2 had mixed connective tissues disease, 2 had overlapping connective tissue disease, 1 had Sjögren’s syndrome, and 1 had polymyositis.
High resolution CT showed emphysema of the upper lobes of the lungs and pulmonary fibrosis of the lower lobes in all patients, and all experienced dyspnea during exercise. Pulmonary hypertension was present in five of the systemic sclerosis patients, and four of these patients died during follow-up (Arthritis Rheum. 2011;63:295-304).
The patients in this study were significantly younger than a historical control group of patients with idiopathic CPFE syndrome, and were more frequently female than male, Dr. Moller noted.
Compared with patients with connective tissue disease and lung fibrosis without emphysema, however, the study patients with connective tissue disease and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures and were more frequently male than female.
There was also some suggestion that those with connective tissue disease and CPFE syndrome may have less severe outcomes than did those with idiopathic CPFE syndrome, but again, pulmonary hypertension is the key to the clinical course, Dr. Moller said.
The authors of this study concluded that CPFE syndrome should be included as a novel, distinct pulmonary manifestation within the spectrum of connective tissue disease–associated lung diseases in smokers and former smokers – particularly those with rheumatoid arthritis or systemic sclerosis.
Treatment for CPFE syndrome includes smoking cessation and treating the underlying cause when it is apparent, Dr. Moller said.
Dr. Moller reported having no financial disclosures.