Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2015

Open Access 01-12-2015 | Opinion

Incorporating genetics into the identification and treatment of Idiopathic Pulmonary Fibrosis

Authors: Susan K. Mathai, Ivana V. Yang, Marvin I. Schwarz, David A. Schwartz

Published in: BMC Medicine | Issue 1/2015

Login to get access

Abstract

Background

Idiopathic pulmonary fibrosis, the most common form of idiopathic interstitial pneumonia, is characterized by progressive, irreversible scarring of the lung parenchyma. Idiopathic pulmonary fibrosis has a poor prognosis, and there are no medical therapies available that have been shown to improve survival. It is usually sporadic, but there is evidence of familial clustering of pulmonary fibrosis, suggesting a genetic basis for this disease. More recently, studies have confirmed that specific genetic variants are associated with both familial and sporadic forms of pulmonary fibrosis.

Discussion

Although there are common and rare genetic variants that have been associated with the risk of developing pulmonary fibrosis, the genotyping of patients is not a generally accepted strategy. Better understanding of the interplay between genetic risk and environmental exposure is likely needed to inform both treatment and disease prevention. Several identified disease-associated genetic variants have implications for disease progression and survival, but systematic studies of known genetic variants and their influence on therapeutic efficacy are lacking. Future investigations should focus on understanding phenotypic differences between patients carrying different risk alleles, and clinical studies should be designed to control for the influence of different genetic risk variants on patient outcomes.

Summary

Inherited genetic factors play a significant role in the risk of developing pulmonary fibrosis. Future studies will be needed to characterize patient phenotypes and to understand how these genetic factors will influence clinical decision-making for both diagnosis and treatment of idiopathic pulmonary fibrosis.
Literature
1.
Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174:810–6.CrossRefPubMed
2.
Olson AL, Swigris JJ, Lezotte DC, Norris JM, Wilson CG, Brown KK. Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003. Am J Respir Crit Care Med. 2007;176:277–84.CrossRefPubMed
3.
4.
Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45:613–20.CrossRefPubMedPubMedCentral
5.
García-Sancho C, Buendía-Roldán I, Fernández-Plata MR, Navarro C, Pérez-Padilla R, Vargas MH, et al. Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis. Respir Med. 2011;105:1902–7.CrossRefPubMed
6.
Seibold MA, Wise A, Speer M, Steele M, Brown K, Lloyd JE, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364:1503–12.CrossRefPubMedPubMedCentral
7.
Bonanni PP, Frymoyer JW, Jacox RF. A family study of idiopathic pulmonary fibrosis. A possible dysproteinemic and genetically determined disease. Am J Med. 1965;39:411–21.CrossRefPubMed
8.
Bitterman PB, Rennard SI, Keogh BA, Wewers MD, Adelberg S, Crystal RG. Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members. N Engl J Med. 1986;314:1343–7.CrossRefPubMed
9.
Javaheri S, Lederer DH, Pella JA, Mark GJ, Levine BW. Idiopathic pulmonary fibrosis in monozygotic twins: the importance of genetic predisposition. Chest. 1980;78:591–4.CrossRefPubMed
10.
Solliday N, Williams J, Gaensler E, Coutu R, Carringon C. Familial chronic interstitial pneumonia. Am Rev Respir Dis. 1973;108:193–204.PubMed
11.
Nogee LM, Dunbar AE, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med. 2001;344:573–9.CrossRefPubMed
12.
Lawson WE, Grant SW, Ambrosini V, Womble KE, Dawson EP, Lane KB, et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax. 2004;59:977–80.CrossRefPubMedPubMedCentral
13.
Fernandez BA, Fox G, Bhatia R, Sala E, Noble B, Denic N, et al. A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features. Respir Res. 2012;13:64.CrossRefPubMedPubMedCentral
14.
Maitra M, Wang Y, Gerard RD, Mendelson CR, Garcia CK. Surfactant protein A2 mutations associated with pulmonary fibrosis lead to protein instability and endoplasmic reticulum stress. J Biol Chem. 2010;285:22103–13.CrossRefPubMedPubMedCentral
15.
Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009;84:52–9.CrossRefPubMedPubMedCentral
16.
Gochuico BR, Huizing M, Golas GA, Scher CD, Tsokos M, Denver SD, et al. Interstitial lung disease and pulmonary fibrosis in Hermansky-Pudlak syndrome type 2, an adaptor protein-3 complex disease. Mol Med. 2012;18:56–64.CrossRefPubMed
17.
Wei ML. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res. 2006;19:19–42.CrossRefPubMed
18.
Vulliamy TJ, Marrone A, Knight SW, Walne A, Mason PJ, Dokal I. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. 2011;107:2680–5.CrossRef
19.
Armanios M, Chen J-L, Chang Y-PC, Brodsky RA, Hawkins A, Griffin CA, et al. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci U S A. 2005;102:15960–4.CrossRefPubMedPubMedCentral
20.
Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356:1317–26.CrossRefPubMed
21.
22.
Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A. 2007;104:7552–7.CrossRefPubMedPubMedCentral
23.
Cogan JD, Kropski JA, Zhao M, Mitchell DB, Rives L, Markin C, et al. Rare variants in RTEL1 are associated with familial interstitial pneumonia. Am J Respir Crit Care Med. 2015;191:646–55.CrossRefPubMedPubMedCentral
24.
Stuart BD, Choi J, Zaidi S, Xing C, Holohan B, Chen R, et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat Genet. 2015;47:512–7.CrossRefPubMedPubMedCentral
25.
Seibold MA, Smith RW, Urbanek C, Groshong SD, Cosgrove GP, Brown KK, et al. The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium. PLoS One. 2013;8:e58658.CrossRefPubMedPubMedCentral
26.
Zhang Y, Noth I, Garcia JGN, Kaminski N. A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis NT5E mutations and arterial calcifications. N Engl J Med. 2011;364:1576–7.CrossRefPubMedPubMedCentral
27.
Stock CJ, Sato H, Fonseca C, Banya WAS, Molyneaux PL, Adamali H, et al. Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis. Thorax. 2013;68:436–41.CrossRefPubMed
28.
Noth I, Zhang Y, Ma S-F, Flores C, Barber M, Huang Y, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1:309–17.CrossRefPubMedPubMedCentral
29.
Borie R, Crestani B, Dieude P, Nunes H, Allanore Y, Kannengiesser C, et al. The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population. PLoS One. 2013;8:e70621.CrossRefPubMedPubMedCentral
30.
Wei R, Li C, Zhang M, Jones-Hall YL, Myers JL, Noth I, et al. Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes. Transl Res. 2014;163:494–502.CrossRefPubMed
31.
Horimasu Y, Ohshimo S, Bonella F, Tanaka S, Ishikawa N, Hattori N, et al. MUC 5 B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis. Respirology. 2015;20:439–44.CrossRefPubMed
32.
Hunninghake GM, Hatabu H, Okajima Y, Gao W, Dupuis J, Latourelle JC, et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med. 2013;368:2192–200.CrossRefPubMedPubMedCentral
33.
Peljto AL, Zhang Y, Fingerlin TE, Ma S-F, Garcia JGN, Richards TJ, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA. 2013;309:2232–9.CrossRefPubMedPubMedCentral
34.
Yang I V, Fingerlin TE, Evans CM, Schwarz MI, Schwartz DA. Genetic variants and outcome of idiopathic pulmonary fibrosis. Ann Am Thorac Soc. 2015; in press.
35.
Peljto AL, Selman M, Kim DS, Murphy E, Tucker L, Pardo A, et al. The muc5b promoter polymorphism is associated with idiopathic pulmonary fibrosis in a Mexican cohort but is rare among Asian ancestries. Chest. 2015;147:460–4.CrossRefPubMed
36.
Wang C, Zhuang Y, Guo W, Cao L, Zhang H, Xu L, et al. Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males. PLoS One. 2014;9:e104919.CrossRefPubMedPubMedCentral
37.
38.
39.
40.
Armanios M. Telomerase and idiopathic pulmonary fibrosis. Mutat Res. 2013;730:52–8.CrossRef
41.
De Leon AD, Cronkhite JT, Katzenstein ALA, Godwin JD, Raghu G, Glazer CS, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One. 2010;5:e10680.CrossRef
42.
Silhan LL, Shah PD, Chambers DC, Snyder LD, Riise GC, Wagner CL, et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. Eur Respir J. 2014;44:178–87.CrossRefPubMedPubMedCentral
43.
O’Dwyer DN, Armstrong ME, Trujillo G, Cooke G, Keane MP, Fallon PG, et al. The Toll-like receptor 3 L412F polymorphism and disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2013;188:1442–50.CrossRefPubMed
44.
Stuart BD, Lee JS, Kozlitina J, Noth I, Devine MS, Glazer CS, et al. Effect of telomere length on survival in patients with idiopathic pulmonary fibrosis: an observational cohort study with independent validation. Lancet Respir Med. 2014;2:557–65.CrossRefPubMedPubMedCentral
45.
King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–92.CrossRefPubMed
46.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.CrossRefPubMed
47.
Schaffer JM, Singh SK, Reitz BA, Zamanian RT, Mallidi HR. Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need. JAMA. 2015;313:936.CrossRefPubMed
48.
King TE, Albera C, Bradford WZ, Costabel U, Du Bois RM, Leff JA, et al. All-cause mortality rate in patients with idiopathic pulmonary fibrosis: implications for the design and execution of clinical trials. Am J Respir Crit Care Med. 2014;189:825–31.CrossRefPubMed
49.
50.
El-Chemaly S, Ziegler SG, Calado RT, Wilson KA, Wu HP, Haughey M, et al. Natural history of pulmonary fibrosis in two subjects with the same telomerase mutation. Chest. 2011;139:1203–9.CrossRefPubMed
51.
Kropski JA, Pritchett JM, Zoz DF, Crossno PF, Markin C, Garnett ET, et al. Extensive phenotyping of individuals at risk for familial interstitial pneumonia reveals clues to the pathogenesis of interstitial lung disease. Am J Respir Crit Care Med. 2015;191:417–26.CrossRefPubMedPubMedCentral
52.
Steele MP, Speer MC, Loyd JE, Brown KK, Herron A, Slifer SH, et al. Clinical and pathologic features of familial interstitial pneumonia. Am J Respir Crit Care Med. 2005;172:1146–52.CrossRefPubMedPubMedCentral
53.
Antonarakis SE, Chakravarti A, Cohen JC, Hardy J. Mendelian disorders and multifactorial traits: the big divide or one for all? Nat Rev Genet. 2010;11:380–4.CrossRefPubMed
Metadata
Title
Incorporating genetics into the identification and treatment of Idiopathic Pulmonary Fibrosis
Authors
Susan K. Mathai
Ivana V. Yang
Marvin I. Schwarz
David A. Schwartz
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2015
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-015-0434-0

Other articles of this Issue 1/2015

BMC Medicine 1/2015 Go to the issue

Question and Answer

Lifestyle factors in preventing mental health disorders: an interview with Felice Jacka

Research article

Delays in the post-marketing withdrawal of drugs to which deaths have been attributed: a systematic investigation and analysis

Research article

The Brief Memory and Executive Test (BMET) for detecting vascular cognitive impairment in small vessel disease: a validation study

Research article

Catastrophic health expenditure and 12-month mortality associated with cancer in Southeast Asia: results from a longitudinal study in eight countries

Commentary

Making sense of technology adoption in healthcare: meso-level considerations

Research article

Early goal-directed therapy in the management of severe sepsis or septic shock in adults: a meta-analysis of randomized controlled trials