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Early Interstitial Lung Disease in Familial Pulmonary Fibrosis

¹ Pulmonary–Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; ² Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; ³ Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC; ⁴ Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; ⁵ Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and ⁶ Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland

Correspondence and requests for reprints should be addressed to Bernadette R. Gochuico, M.D., Pulmonary–Critical Care Medicine Branch, 10 Center Drive, MSC 1590, Bethesda, MD 20892-1590. E-mail: gochuicb{at}mail.nih.gov

Rationale: Identification of early, asymptomatic interstitial lung disease (ILD) in populations at risk of developing idiopathic pulmonary fibrosis (IPF) may improve the understanding of the natural history of IPF.

Objectives: To determine clinical, radiographic, physiologic, and pathologic features of asymptomatic ILD in family members of patients with familial IPF.

Methods: One hundred sixty-four subjects from 18 kindreds affected with familial IPF were evaluated for ILD. Bronchoalveolar lavage fluid cells were analyzed using flow cytometry. Lung biopsies were performed in six subjects with asymptomatic ILD.

Measurements and Main Results: High-resolution computed tomography abnormalities suggesting ILD were identified in 31 (22%) of 143 asymptomatic subjects. Subjects with asymptomatic ILD were significantly younger than subjects with known familial IPF (P < 0.001) and significantly older than related subjects without lung disease (P < 0.001). A history of smoking was identified in 45% of subjects with asymptomatic ILD and in 67% of subjects with familial IPF; these percentages were significantly higher than that of related subjects without lung disease (23%) (P = 0.02 and P < 0.001, respectively). Percentages of activated CD4⁺ lymphocytes were significantly higher in bronchoalveolar lavage fluid cells from subjects with asymptomatic ILD compared with related subjects without lung disease (P < 0.001). Lung biopsies performed in subjects with asymptomatic ILD revealed diverse histologic subtypes.

Conclusions: Asymptomatic ILD in individuals at risk of developing familial IPF can be identified using high-resolution computed tomography scan of the chest, especially in those with a history of smoking. Lung biopsies from individuals in this cohort with early asymptomatic lung disease demonstrate various histologic subtypes of ILD.

Key Words: idiopathic pulmonary fibrosis • interstitial lung disease • high-resolution computed tomography • bronchoalveolar lavage • asymptomatic interstitial lung disease

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Despite significant progress in understanding the mechanisms involved in lung fibrosis, the natural history of the disease is still not well understood. There is evidence that a period of asymptomatic disease may precede the clinical diagnosis of interstitial lung disease (ILD). What This Study Adds to the Field A study on familial interstitial pneumonia demonstrated that some subjects without symptoms of lung disease had high-resolution computed tomography scan findings of ILD. Lung biopsies performed in subjects with familial interstitial pneumonia within the same family showed heterogeneous types of ILD.

 

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