Genetics in Idiopathic Pulmonary Fibrosis: A Clinical Perspective

Abstract

Background: Unraveling the genetic background in a significant proportion of patients with both sporadic and familial IPF provided new insights into the pathogenic pathways of pulmonary fibrosis. Aim: The aim of the present study is to overview the clinical significance of genetics in IPF. Perspective: It is fascinating to realize the so-far underestimated but dynamically increasing impact that genetics has on aspects related to the pathophysiology, accurate and early diagnosis, and treatment and prevention of this devastating disease. Genetics in IPF have contributed as no other in unchaining the disease from the dogma of a “a sporadic entity of the elderly, limited to the lungs” and allowed all scientists, but mostly clinicians, all over the world to consider its many aspects and “faces” in all age groups, including its co-existence with several extra pulmonary conditions from cutaneous albinism to bone-marrow and liver failure. Conclusion: By providing additional evidence for unsuspected characteristics such as immunodeficiency, impaired mucus, and surfactant and telomere maintenance that very often co-exist through the interaction of common and rare genetic variants in the same patient, genetics have created a generous and pluralistic yet unifying platform that could lead to the understanding of the injurious and pro-fibrotic effects of many seemingly unrelated extrinsic and intrinsic offending factors. The same platform constantly instructs us about our limitations as well as about the heritability, the knowledge and the wisdom that is still missing.

Russian Registry of Idiopathic Pulmonary Fibrosis: Clinical Features, Treatment Management, and Outcomes

“…On the one hand, heterogeneity of the patients in different registries should be regarded as one of registries’ strengths [ 9 ]. The variability in the characteristics of IPF patients from different parts of the world may be associated with genetic differences [ 36 ], environmental factors [ 37 ], additionally, differences in geographic and ethnic populations may also play a role. On the other hand, it is necessary to understand the limitations of our registry, which, in addition to patients with IPF, presumably also included patients with other fibrotic ILDs.…”

NAD metabolism: Role in senescence regulation and aging

“…One of the hallmarks of aging is telomere shortening (López‐Otín et al, 2023 ). Diseases characterized by telomeres attritions, such as telomere syndromes, include dyskeratosis congenita (DC), aplastic anemia, and idiopathic pulmonary fibrosis (Kam et al, 2021 ; Papiris et al, 2022 ; Shin et al, 2022 ). Emerging evidence indicates that short telomere‐induced DNA damage response (DDR) plays a crucial role in the cellular dysfunction in DC (Sun et al, 2020 ).…”

Prognostic Value of Serum Biomarkers in Patients with Idiopathic Pulmonary Fibrosis in Relation to Disease Progression

“…However, there is great variability in the clinical course of IPF patients, including long periods of stability, a steady, gradual decline, and/or periods of acute deterioration. Recently, studies highlighted the increasing impact of genetics on aspects related to pathophysiology, accurate and early diagnosis, and the treatment and prevention of IPF, though this requires further investigation [ 5 , 6 , 7 ]. Thus, predictors of survival in everyday clinical practice are needed for physicians and patients.…”