Chest
Selected ReportNatural History of Pulmonary Fibrosis in Two Subjects With the Same Telomerase Mutation
Section snippets
Subjects
Two subjects, who were previously part of a familial pulmonary fibrosis research study,6 provided written consent to participate in protocols approved by the Institutional Review Board of the National Human Genome Research Institute (04-HG-0211) and/or the National Heart, Lung, and Blood Institute (04-H-0012). The two subjects were initially evaluated in 1982, and they were subsequently studied in 2009. Bronchoscopy and BAL were performed as previously described.9 Cytospins from BAL fluid cells
Progressive Natural History of Familial Pulmonary Fibrosis
Two white sisters were initially evaluated at the National Institutes of Health in 1982 to 1983 as part of a familial pulmonary fibrosis study.6 Their father, paternal aunt, and cousin died of biopsy-proven IPF, but they were asymptomatic for lung disease (Fig 1A). (Subjects 1 and 2 were previously reported as B4 and B5 [family B in Reference 6], respectively.)6 Their clinical examination, chest radiographs, and pulmonary function tests were normal (Table 2), but they had alveolar inflammation
Discussion
This work defines the natural history of preclinical pulmonary fibrosis and demonstrates for the first time that alveolar inflammation in familial pulmonary fibrosis progresses to clinical disease over two to three decades. It also provides evidence that immune-cell dysregulation in the lung is a characteristic of early fibrotic lung disease. Furthermore, siblings at risk for familial pulmonary fibrosis, despite having an identical genetic mutation, can manifest variable long-term 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.
Other contributions: We thank Irina Maric, MD, Department of Laboratory Medicine, Clinical Center, for reviewing the bone marrow biopsy and the patients who participated in this study for their contributions.
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2020, Presse MedicaleCitation Excerpt :The mean survival for symptomatic patients is 2.8 to 5.2 years after diagnosis. However, the evolution can be longer, particularly in asymptomatic patients [70]. Transplant-free survival could be lower for carriers of TERT or TERC mutations than patients with familial ILD without TERT or TERC mutation [58].
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2015, Revue des Maladies RespiratoiresCitation Excerpt :However, the evolution can be longer and a very long evolution was described in two sisters presenting asymptomatic ILD associated with TERT mutation. After 30 years of follow-up, one patient still presented a normal DLCO, whereas the other decreased the DLCO from 101% to 54% of the predicted value [29]. There is no specific treatment for pulmonary fibrosis associated with TERT mutation and there are no guidelines on this topic.
Funding/Support: This research was sponsored in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute, National Institutes of Health.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).