Beyond cystic fibrosis: Genetics of PF and other lung diseases


The remarkable story of cystic fibrosis (CF) – from gene discovery in 1989 to highly effective precision-medicine therapies today – inspires Christine Kim Garcia, MD, PhD, as she searches for rare mutations in genes linked to inherited forms of lung fibrosis, termed familial pulmonary fibrosis (FPF).

“Cystic fibrosis has provided a framework for approaching the genetics of lung fibrosis,” said Dr. Garcia, Frode Jensen Professor of Medicine and chief of the pulmonology, allergy, and critical care medicine division at Columbia University, and director of the Columbia Precision Medicine Initiative, both in New York.

Christine Kim Garcia, MD, PhD,

Dr. Christine Kim Garcia

Pulmonary fibrosis is more complicated than CF. “Mutations in more than 10 different genes can lead to the increased heritable risk of pulmonary fibrosis that we find in families. Different mutations exist for each gene. Sometimes the mutations are so rare that they are only found in a single family,” she said. “In addition, different subtypes of fibrotic interstitial lung disease can be linked to the same mutation and found in the same family.”

Despite these complexities, genetic discoveries in PF have illuminated pathophysiologic pathways and are driving the research that Dr. Garcia and other experts hope will lead to helpful prognostic tools and to precision therapies. And already, at institutions like Columbia, genetic discoveries are changing clinical care, driving treatment decisions and spurring family screening.

Thomas Ferkol, MD, whose research focuses on genetic factors that contribute to suppurative airway diseases such as CF and primary ciliary dyskinesia (PCD), similarly regards CF as a road map for genetics research and genetic testing in practice.

“The treatments we’re doing now for CF are increasingly based on the genetics of the individual,” said Dr. Ferkol, professor and division chief for pediatric pulmonology at the University of North Carolina at Chapel Hill, where the UNC Children’s Hospital hosts a rare and genetic lung disease program. For PCD, genetic testing has become a front-line diagnostic tool. But in the future, he hopes, it will also become a determinant for personalized treatment for children with PCD.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene was the first lung disease gene to be discovered using gene-mapping techniques. Since then, and especially in the last 15-20 years, “there’s been a lot of progress in the identification of genes for which mutations and variations cause specific forms of pulmonary disease, many of which can now establish a firm diagnosis, and some of which lead to very directed changes in management. There has also been great progress in the availability of genetic testing,” said Benjamin A. Raby, MD, MPH, director of the Pulmonary Genetics Center at Brigham and Women’s Hospital, Boston, which sees patients with a host of cystic lung diseases, bronchiectasic lung diseases, fibrotic lung diseases, and other conditions, including pulmonary fibrosis and PCD.

Pulmonary fibrosis in adults and PCD in children are two examples of lung diseases for which genetic discoveries have exploded in recent years, with important implications for care now and in the future.


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