Genetics and Early Detection in Idiopathic Pulmonary Fibrosis

Abstract

Genetic studies hold promise in helping to identify patients with early idiopathic pulmonary fibrosis (IPF). Recent studies using chest computed tomograms (CTs) in smokers and in the general population have demonstrated that imaging abnormalities suggestive of an early stage of pulmonary fibrosis are not uncommon and are associated with respiratory symptoms, physical examination abnormalities, and physiologic decrements expected, but less severe than those noted in patients with IPF. Similarly, recent genetic studies have demonstrated strong and replicable associations between a common promoter polymorphism in the mucin 5B gene (MUC5B) and both IPF and the presence of abnormal imaging findings in the general population. Despite these findings, it is important to note that the definition of early-stage IPF remains unclear, limited data exist to definitively connect abnormal imaging findings to IPF, and genetic studies assessing early-stage pulmonary fibrosis remain in their infancy. In this perspective we provide updated information on interstitial lung abnormalities and their connection to IPF. We summarize information on the genetics of pulmonary fibrosis by focusing on the recent genetic findings of MUC5B. Finally, we discuss the implications of these findings and suggest a roadmap for the use of genetics in the detection of early IPF.

Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study

“…The association between MUC5B promoter genotype and progressive imaging abnormalities is worth further discussion. The association between the minor allele of the MUC5B promoter polymorphism (rs35705950) and IPF is among the most well-replicated findings of genetic association in pulmonary medicine (18). Somewhat unexpectedly, increasing copies of the minor allele of rs35705950 have also been associated with reduced mortality among patients with IPF, suggesting that the MUC5B variant defines a mild subtype of IPF (19).…”

Clinical characteristics of idiopathic pulmonary fibrosis patients according to their smoking status

“…Steele, et al described approximately 309 familial interstitial pneumonia (FIP) patients and they found that patient age, male sex, and smoking history were important risk factors of FIP (20). Therefore, individual susceptibility to fibrosis may partly explain the development of IPF (21)(22)(23). In addition, a quarter of these patients had a history of exposure to passive smoking.…”

A First Glimpse at the Early Origins of Idiopathic Pulmonary Fibrosis

“…Accumulating evidence suggests that early stages of sporadic IPF that are comparable to these findings in FPF (5) may be also detectable (23). However, we should be cautious in extrapolating the findings of early disease detection in FPF to sporadic IPF.…”