Familial pulmonary fibrosis –⁠ guidelines for diagnostics and treatment

Czech version

Authors: Martina Šterclová ^1,2; Michael Doubek ^3,4; Martina Doubková ⁵
Authors‘ workplace: Pneumologická klinika 2. LF a FN Motol, Praha ¹; Interní oddělení Nemocnice na Homolce, Praha ²; Interní hematologická a onkologická klinika FN Brno a LF Brno 4Středoevropský technologický institut, Masarykova univerzita, Brno ³; Klinika nemocí plicních a tuberkulózy FN Brno a LF Masarykovy univerzity Brno ⁵
Published in: Vnitř Lék 2020; 66(6): 365-370
Category:

Overview

Familial pulmonary fibrosis (FPF) is defined as interstitial lung involvement in at least two members of the same biological family. Pathogenesis of FPF involves background of genetic risk factors further modified by environmental exposures and aging. Manifesta ‑⁠ tion of FPF mirrors manifestation of interstitial lung diseases generally. Patients may present also with involvement of other organs, as seen usually in those affected by complex syndromes or telomeropaties. Described mutations concern telomeres homeostasis genes (TERT, TERC, RTEL1, PARN, DKC1, TINF, NAF1), surfactant genes (SFTPC, ABCA3, NFKX2‑1) or genes associated with complex syndromes (COPA, TMEM173, HPS‑1‑8, NF1, FAM111B, NDUFAF6, GATA 2). Genetic tests are indicated by specialist in clinical genetics, optimaly after consultation with respiratory specialist involved in interstitial lung diseases. Treatment of FPF is currently unknown. In patients with multiorgan involvement growing number of organs may be affected in time and sometimes dysfunction of mostly severe affected organ may manifest before interstitial lung involvement.

Keywords:

Genetics – treatment – familial pulmonary fibrosis – telomer – surfaktant

Sources

1. Borie R, Crestani B. Familial pulmonary fibrosis: a world without frontiers. J Bras Pneumol 2019; 45: e20190303.

2. Kaur A, Mathai S, Schwartz DA. Genetics in idiopathic pulmonary fibrosis pathogenesis, prognosis and treatment. Front Med 2017; 4 : 154.

3. Doubková M, Trizuljak J, Vzralová Z, et al. Novel genetic variant of HPS1 gene in Hermansky‑Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report. BMC Pulm Med 2019; 19 : 178.

4. Krauss E, Gehrken G, Drakopanagiotakis F, et al. Clinical characteristics of patients with familial idiopathic pulmonary fibrosis. BMC Pulmonay Medicine 2019; 19 : 130.

5. Hortense AB, Santos MK, Wada D, et al. Familial pulmonary fibrosis: a heterogenous spectrum of presentations. J Bras Pneumol 2019; 45: e20180079.

6. Borie R, Kannengiesser C, Fontbrune FS, et al. Management of suspected monogenic lung fibrosis in a specialised center. Eur Respir Rev 2017; 26 : 160122.

7. Armanious MY, Chen JJ ‑L, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med2007; 356 : 1317–1326.

8. Tsakiri KD, Cronkhite JT, Kuan PJ, et al. Adult –⁠ onset pulmonary fibrosis cause by mutations in telomerase. Proc Natl Acad Sci USA 2007; 104 : 7552–7557.

9. Fingerlin TE, Murphy E, Zhang W, et al. Genomewide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 2013; 45 : 613–620.

10. Roy MG, Livraghi ‑Butrico A, Fletcher AA, et al. Muc5b is required for airway defence. Nature 2014; 505 : 412–416.

11. Kropski JA, Young LR, Cogan JD, et al. Genetic Evaluation and Testing of Patients and Families with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Me. 2017; 195 : 1423–1428.

12. Společnost lékařské genetiky a genomiky. http://www.slg.cz. Navštíveno dne 27. 2. 2020.

13. Doubková M, Staňo Kozubík K, Radová L, et al. A novel germline mutation of the SFT ‑⁠ PA1 gene in familial interstitial pneumonia. Hum Genome Var 2019; 6 : 12.

14. Borie R, Kannengiesser C, Gouya L, et al. Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis. Orphanet Journal of Rare Diseases 2019; 14 : 280.

15. Hartmannová H, Piherová L, Tauchmannová K, et al. Acadian variant of Fanconi syndrome is caused by mitochondrial respiratory chain complex I deficiency due to a noncoding mutation in complex I assembly factor NDUFAF6. Hum Mol Genet 2016; 25 : 4062–4079.

16. Donadieu J, Lamant M, Fieschi C, et al. Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients. Haematologica 2018; 103 : 1278–1287.

17. Kazzi B, Lederer D, Arteaga ‑Solis E, et al. Recurrent diffuse lung disease due to surfactant protein C deficiency. Respir Med Case Rep 2018; 25 : 91–95.

18. Silhan LL, Shah PD, Chambers DC, et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. Eur Respir J 2014; 44 : 178–187.

19. Bennett D, Refini RM, Valentini ML,et al. Pirfenidone Therapy for Familial Pulmonary Fibrosis: A Real‑Life Study. Lung 2019; 197 : 147–153.

20. Mangaonkar AA, Ferrer A, Pinto E Vairo F, et al. Clinical Correlates and Treatment Outcomes for Patients With Short Telomere Syndromes. Mayo Clin Proc 2018; 93 : 834–839.