Cited by 17Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisOccupational and environmental lung diseasesPulmonary Hypertension Research and Treatments

Idiopathic Pulmonary Fibrosis: Where do We Stand and How Far to Go?

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Singh, Vaishali, Ulasov, Ilya, Gupta, Sachin, Singh, Anita, Roy, Vikas Kumar, Kharwar, Rajesh Kumar·2024·Discovery Medicine

Abstract

Idiopathic pulmonary fibrosis is a progressive and incurable lung disease characterized by collagen deposition, alveolar inflammation, fibroblast proliferation, and the destruction of lung tissue structures. It is a rare yet severe condition with a high mortality rate, typically leading to death within 3-5 years of diagnosis. The clinical presentation of idiopathic pulmonary fibrosis (IPF) involves a gradual and substantial loss of lung function, ultimately resulting in respiratory failure. Despite more than half a century of intensive research, the origin of IPF remains a mystery. Despite its unknown etiology, several genetic and non-genetic factors have been linked to IPF. Recent significant advancements have been made in the field of IPF diagnosis and treatment. Two oral small-molecule drugs, pirfenidone and nintedanib, have recently gained approval for the treatment of IPF. Pirfenidone exhibits antifibrotic, antioxidant, and anti-inflammatory properties, while nintedanib is a tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF) receptors, prostaglandin F (PGF) receptors, and fibroblast growth factor (FGF) receptors. Both of these compounds are capable of slowing down the progression of the disease with an acceptable safety profile. This review provides a brief introduction, historical background, epidemiological insights, and an exploration of various environmental risk factors that may influence the lung microenvironment and contribute to the advancement of IPF. The review also delves into the diagnosis, signaling pathways, and ongoing clinical trials worldwide. A thorough review of the literature was conducted using PubMed and Google Scholar to gather information on various aspects of IPF. Numerous potential drugs are currently under investigation in clinical trials, and the completion of this process is crucial to the ultimate goal of finding a cure for IPF patients. The investigation of the role of genes, surfactant proteins, infectious agents, biomarkers, and epigenetic changes holds the promise of offering earlier and more accurate understanding and diagnosis of IPF. This information could be instrumental in the development of new therapeutic approaches for treating IPF and is expected to be of great interest to researchers.

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References 295 · Cited by 17

Research works printed but not linked: 35

  1. [2]2. Wolters PJ, Blackwell TS, Eickelberg O, Loyd JE, Kaminski N, Jenkins G, et al. Time for a change: is idiopathic pulmonary fi- brosis still idiopathic and only fibrotic? The Lancet. Respiratory Medicine. 2018; 6: 154-160.
  2. [8]8. Meyer C, Nathan SD. Idiopathic Pulmonary Fibrosis: a Com- prehensive Clinical Guide. Humana Press: Totowa, NJ. 2013.
  3. [40]40. Scadding JG. FIBROSING ALVEOLITIS. British Medical Jour- nal. 1964; 2: 686.
  4. [41]41. Kondoh Y, Taniguchi H, Kawabata Y, Yokoi T, Suzuki K, Takagi K. Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases. Chest. 1993; 103: 1808-1812.
  5. [42]42. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clin- ical relevance of pathologic classification. American Journal of Respiratory and Critical Care Medicine. 1998; 157: 1301-1315.
  6. [45]45. American Thoracic Society. Idiopathic pulmonary fibrosis: di- agnosis and treatment. International consensus statement. Amer- ican Thoracic Society (ATS), and the European Respiratory So- ciety (ERS). American Journal of Respiratory and Critical Care Medicine. 2000; 161: 646-664.
  7. [58]58. Khosla N, Valdez R. A compilation of national plans, policies and government actions for rare diseases in 23 countries. In- tractable & Rare Diseases Research. 2018; 7: 213-222.
  8. [72]72. Fernández Pérez ER, Daniels CE, Schroeder DR, St Sauver J, Hartman TE, Bartholmai BJ, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population- based study. Chest. 2010; 137: 129-137.
  9. [80]80. Bellou V, Belbasis L, Evangelou E. Tobacco Smoking and Risk for Pulmonary Fibrosis: A Prospective Cohort Study From the UK Biobank. Chest. 2021; 160: 983-993.
  10. [91]91. Park JH, Shin JM, Yang HW, Kim TH, Lee SH, Lee HM, et al. Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways. Antioxidants. 2020; 9: 739.
  11. [99]99. Hartelius H, Gaub J, Ingemann Jensen L, Jensen J, Faber V. Computed tomography of the lungs in acquired immunodefi- ciency syndrome. An early indicator of interstitial pneumonia. Acta Radiologica. 1988; 29: 641-644.
  12. [100]100. Siegel C, Johnston S, Adair S. Isolation of measles virus in primary rhesus monkey cells from a child with acute interstitial pneumonia who cytologically had giant-cell pneumonia without a rash. American Journal of Clinical Pathology. 1990; 94: 464- 469.
  13. [112]112. Borie R, Bouvry D, Cottin V, Gauvain C, Cazes A, Debray MP, et al. Regulator of telomere length 1 (RTEL1) mutations are associated with heterogeneous pulmonary and extra-pulmonary phenotypes. The European Respiratory Journal. 2019; 53: 1800508.
  14. [146]146. Renzoni EA. Neovascularization in idiopathic pulmonary fi- brosis: too much or too little? American Journal of Respiratory and Critical Care Medicine. 2004; 169: 1179-1180.
  15. [147]147. Frangogiannis N. Transforming growth factor-β in tissue fi- brosis. The Journal of Experimental Medicine. 2020; 217: e20190103.
  16. [152]152. Aumiller V, Balsara N, Wilhelm J, Günther A, Königshoff M. WNT/β-catenin signaling induces IL-1β expression by alveolar epithelial cells in pulmonary fibrosis. American Journal of Res- piratory Cell and Molecular Biology. 2013; 49: 96-104.
  17. [153]153. Epstein Shochet G, Brook E, Bardenstein-Wald B, Shitrit D. TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling. Respiratory Research. 2020; 21: 56.
  18. [157]157. Shi X, Young CD, Zhou H, Wang X. Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts. Biomolecules. 2020; 10: 1666.
  19. [158]158. Saito A, Horie M, Nagase T. TGF-β Signaling in Lung Health and Disease. International Journal of Molecular Sciences. 2018; 19: 2460.
  20. [163]163. Vallée A, Lecarpentier Y. TGF-β in fibrosis by acting as a con- ductor for contractile properties of myofibroblasts. Cell & Bio- science. 2019; 9: 98.
  21. [165]165. Treviño-Villarreal JH, Reynolds JS, Langston PK, Thompson A, Mitchell JR, Franco RA, Jr. Down-Regulation of a Profibrotic Transforming Growth Factor-β1/Cellular Communication Net- work Factor 2/Matrix Metalloprotease 9 Axis by Triamcinolone Improves Idiopathic Subglottic Stenosis. The American Journal of Pathology. 2021; 191: 1412-1430.
  22. [167]167. Robertson IB, Rifkin DB. Regulation of the Bioavailability of TGF-β and TGF-β-Related Proteins. Cold Spring Harbor Per- spectives in Biology. 2016; 8: a021907.
  23. [173]173. Walsh SLF. Multidisciplinary evaluation of interstitial lung dis- eases: current insights: Number 1 in the Series "Radiology" Edited by Nicola Sverzellati and Sujal Desai. European Respi- ratory Review. 2017; 26: 170002.
  24. [192]192. Sarmiento-Monroy JC, Perez-Isidro A, Castellanos Moreira R, Ruiz V, Frade-Sosa B, Azuaga A, et al. POS0452 Diagnostic and prognostic role of serum KL-6 in rheumatoid arthritis-associated interstitial disease. Annals of the Rheumatic Diseases. 2023; 82: 482-483.
  25. [199]199. Elhai M, Avouac J, Allanore Y. Circulating lung biomarkers in idiopathic lung fibrosis and interstitial lung diseases associated with connective tissue diseases: Where do we stand? Seminars in Arthritis and Rheumatism. 2020; 50: 480-491.
  26. [215]215. Oh K, Seo MW, Kim YW, Lee DS. Osteopontin Potenti- ates Pulmonary Inflammation and Fibrosis by Modulating IL- 17/IFN-γ-secreting T-cell Ratios in Bleomycin-treated Mice. Immune Network. 2015; 15: 142-149.
  27. [237]237. van Geffen C, Deißler A, Quante M, Renz H, Hartl D, Kolahian S. Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes? Frontiers in Immunology. 2021; 12: 663203.
  28. [256]256. Somogyi V, Chaudhuri N, Torrisi SE, Kahn N, Müller V, Kreuter M. The therapy of idiopathic pulmonary fibrosis: what is next? European Respiratory Review. 2019; 28: 190021.
  29. [259]259. Bonella F, Long X, He X, Ohshimo S, Griese M, Guzman J, et al. Serum YKL-40 is a reliable biomarker for pulmonary alveo- lar proteinosis. Respirology. 2017; 22: 1371-1378.
  30. [260]260. Kokosi MA, Margaritopoulos GA, Wells AU. Personalised medicine in interstitial lung diseases: Number 6 in the Series "Personalised medicine in respiratory diseases" Edited by Re- naud Louis and Nicolas Roche. European Respiratory Review. 2018; 27: 170117.
  31. [272]272. Papiris SA, Tomos IP, Karakatsani A, Spathis A, Korbila I, Analitis A, et al. High levels of IL-6 and 8 characterize early- on idiopathic pulmonary fibrosis acute exacerbations. Cytokine. 2018; 102: 168-172.
  32. [279]279. Jin J, Togo S, Kadoya K, Tulafu M, Namba Y, Iwai M, et al. Pirfenidone attenuates lung fibrotic fibroblast responses to trans- forming growth factor-β1. Respiratory Research. 2019; 20: 119.
  33. [282]282. Conte E, Gili E, Fagone E, Fruciano M, Iemmolo M, Vancheri C. Effect of pirfenidone on proliferation, TGF-β-induced myofi- broblast differentiation and fibrogenic activity of primary human lung fibroblasts. European Journal of Pharmaceutical Sciences. 2014; 58: 13-19.
  34. [303]303. Olschewski H, Eber E, Bucher B, Hackner K, Handzhiev S, Hoetzenecker K, et al. Management of patients with SARS- CoV-2 infections with focus on patients with chronic lung dis- eases (as of 10 January 2022): Updated statement of the Aus- trian Society of Pneumology (ASP). Wiener Klinische Wochen- schrift. 2022; 134: 399-419.
  35. [317]317. Hadda V, Guleria R. Antifibrotic drugs for idiopathic pul- monary fibrosis: What we should know? The Indian Journal of Medical Research. 2020; 152: 177-180.

Authors
Singh, V., Ulasov, I., Gupta, S., Singh, A., Roy, V. K., & Kharwar, R. K.
Affiliations
  • University of Lucknow (IN)
  • Sechenov University (RU)
  • Mizoram University (IN)
Venue
Discovery Medicine
Published
2024
Volume
36
Issue
180
Pages
22
ISSN
1539-6509 (ISSN-L)
OpenAlex
W4391028071
Cited by
17
References
295
Citations by year
2026: 7 · 2025: 4 · 2024: 6
FWCI
1.26
Type
journal article
Language
en
Open access
Locations
  • Discovery Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
Science and Engineering Research Board
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Keywords
idiopathic pulmonary fibrosis, pirfenidone, nintedanib, antifibrotic therapy, tyrosine kinase inhibitors, VEGF receptor inhibition, disease progression, environmental risk factors, genetic susceptibility, surfactant proteins, biomarkers, epigenetics, lung microenvironment, signaling pathways, clinical trials, pulmonary fibrosis
MeSH terms
Humans, Inflammation, Lung, Pyridones, Vascular Endothelial Growth Factor A, Protein Kinase Inhibitors, Idiopathic Pulmonary Fibrosis

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