Research Progress in Progressive Pulmonary Fibrosis

doi:10.3870/j.issn.1672-0741.25.11.006

Abstract

Abstract: Progressive pulmonary fibrosis （PPF） is a group of interstitial lung diseases （ILD） characterized by a progressive phenotype and poor prognosis. It is based on a comprehensive assessment of symptoms, lung function and imaging findings. PPF is not limited to specific etiologies, but encompasses patients with ILD presenting with progressive fibrosis, with the exception of idiopathic pulmonary fibrosis.Currently, it remains difficult to identify early-stage patients at risk of progression and provide timely intervention. Existing antifibrotic treatments only slow disease progression without reversing it, and some patients exhibit poor tolerability. Therefore, this article reviews the pathogenesis, clinical identification, and treatment strategies for PPF, aiming to provide new insights into early prediction and precision-targeted therapy for patients with PPF.

Key words: progressive pulmonary fibrosis, pathogenesis, early identification, antifibrotic treatment

CLC Number:

R563.13

Chen Danni, Xiang Fei. Research Progress in Progressive Pulmonary Fibrosis[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(5): 742-751.

References

[1] Raghu G,Remy-Jardin M,Richeldi L,et al.Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults:An official ATS/ERS/JRS/ALAT clinical practice guideline[J].Am J Respir Crit Care Med,2022,205(9):e18-e47.
[2] Spagnolo P,Kropski J A,Jones M G,et al.Idiopathic pulmonary fibrosis:Disease mechanisms and drug development[J].Pharmacol Ther,2021,222:107798.
[3] Gandhi S,Tonelli R,Murray M,et al.Environmental causes of idiopathic pulmonary fibrosis[J].Int J Mol Sci,2023,24(22):16481.
[4] Zhang Y,Huang W,Zheng Z,et al.Cigarette smoke-inac-tivated SIRT1 promotes autophagy-dependent senescence of alveolar epithelial type 2 cells to induce pulmonary fibrosis[J].Free Radic Biol Med,2021,166:116-127.
[5] Chen L,Sun R,Lei C,et al.Alcohol-mediated susceptibility to lung fibrosis is associated with group 2 innate lymphoid cells in mice[J].Front Immunol,2023,14:1178498.
[6] Leuschner G,Klotsche J,Kreuter M,et al.Idiopathic pulmonary fibrosis in elderly patients:Analysis of the INSIGHTS-IPF observational study[J].Front Med,2020,7:601279.
[7] Ruaro B,Pozzan R,Confalonieri P,et al.Gastroesophageal reflux disease in idiopathic pulmonary fibrosis:Viewer or actor? To treat or not to treat?[J].Pharmaceuticals,2022,15(8):1033.
[8] Huang W J,Tang X X.Virus infection induced pulmonary fibrosis[J].J Transl Med,2021,19(1):496.
[9] Liu G Y,Budinger G R S,Dematte J E.Advances in the management of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis[J].BMJ,2022,377:e066354.
[10] Sullivan D I,Jiang M,Hinchie A M,et al.Transcriptional and proteomic characterization of telomere-induced senescence in a human alveolar epithelial cell line[J].Front Med,2021,8:600626.
[11] Tirelli C,Pesenti C,Miozzo M,et al.The genetic and epigenetic footprint in idiopathic pulmonary fibrosis and familial pulmonary fibrosis:A state-of-the-art review[J].Diagnostics (Basel),2022,12(12):3107.
[12] Moll M,Peljto A L,Kim J S,et al.A polygenic risk score for idiopathic pulmonary fibrosis and interstitial lung abnormalities[J].Am J Respir Crit Care Med,2023,208(7):791-801.
[13] Helling B A,Gerber A N,Kadiyala V,et al.Regulation of MUC5B expression in idiopathic pulmonary fibrosis[J].Am J Respir Cell Mol Biol,2017,57(1):91-99.
[14] Garcia C K.Idiopathic pulmonary fibrosis:Update on genetic discoveries[J].Proc Am Thorac Soc,2011,8(2):158-162.
[15] Oldham J M,Ma S F,Martinez F J,et al.TOLLIP,MUC5B,and the response to N-acetylcysteine among individuals with idiopathic pulmonary fibrosis[J].Am J Respir Crit Care Med,2015,192(12):1475-1482.
[16] Singh P,Edjah S,Shi W,et al.Emerging concepts in fibroblast biology and progressive pulmonary fibrosis[J].Semin Respir Crit Care Med,2025,46(4):322-329.
[17] Hecker L,Logsdon N J,Kurundkar D,et al.Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance[J].Sci Transl Med,2014,6(231):231ra47.
[18] Wynes M W,Edelman B L,Kostyk A G,et al.Increased cell surface Fas expression is necessary and sufficient to sensitize lung fibroblasts to Fas ligation-induced apoptosis:Implications for fibroblast accumulation in idiopathic pulmonary fibrosis[J].J Immunol,2011,187(1):527-537.
[19] Ajayi I O,Sisson T H,Higgins P D,et al.X-linked inhibitor of apoptosis regulates lung fibroblast resistance to Fas-mediated apoptosis[J].Am J Respir Cell Mol Biol,2013,49(1):86-95.
[20] Zhou Y,Huang X,Hecker L,et al.Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis[J].J Clin Invest,2013,123(3):1096-1108.
[21] Bamberg A,Redente E F,Groshong S D,et al.Protein tyrosine phosphatase-N13 promotes myofibroblast resistance to apoptosis in idiopathic pulmonary fibrosis[J].Am J Respir Crit Care Med,2018,198(7):914-927.
[22] Golan-Gerstl R,Wallach-Dayan S B,Zisman P,et al.Cellular FLICE-like inhibitory protein deviates myofibroblast fas-induced apoptosis toward proliferation during lung fibrosis[J].Am J Respir Cell Mol Biol,2012,47(3):271-279.
[23] Redente E F,Chakraborty S,Sajuthi S,et al.Loss of Fas signaling in fibroblasts impairs homeostatic fibrosis resolution and promotes persistent pulmonary fibrosis[J].JCI Insight,2020,6(1):e141618.
[24] Hanson K M,Hernady E B,Reed C K,et al.Apoptosis resistance in fibroblasts precedes progressive scarring in pulmonary fibrosis and is partially mediated by toll-like receptor 4 activation[J].Toxicol Sci,2019,170(2):489-498.
[25] Ediga H H,Vemulapalli C P,Sontake V,et al.Wilms tumor 1 impairs apoptotic clearance of fibroblasts in distal fibrotic lung lesions[J].J Clin Investig,2025,135(15):e188819.
[26] Luis-García E R,Becerril C,Salgado-Aguayo A,et al.Mitochondrial dysfunction and alterations in mitochondrial permeability transition pore (mPTP) contribute to apoptosis resistance in idiopathic pulmonary fibrosis fibroblasts[J].Int J Mol Sci,2021,22(15):7870.
[27] Lin Y,Xu Z.Fibroblast senescence in idiopathic pulmonary fibrosis[J].Front Cell Dev Biol,2020,8:593283.
[28] Álvarez D,Cárdenes N,Sellarés J,et al.IPF lung fibroblasts have a senescent phenotype[J].Am J Physiol Lung Cell Mol Physiol,2017,313(6):L1164-L1173.
[29] Schafer M J,White T A,Iijima K,et al.Cellular senescence mediates fibrotic pulmonary disease[J].Nat Commun,2017,8:14532.
[30] Han D,Gong H,Wei Y,et al.Hesperidin inhibits lung fibroblast senescence via IL-6/STAT3 signaling pathway to suppress pulmonary fibrosis[J].Phytomedicine,2023,112:154680.
[31] Zhou S,Peng L,Wang Y,et al.Bazibushen attenuates fibroblast senescence in silica-induced pulmonary fibrosis via FOXO1/PINK1/Parkin Axis[J].Phytomedicine,2025,141:156714.
[32] Sanders Y Y,Liu H,Zhang X,et al.Histone modifications in senescence-associated resistance to apoptosis by oxidative stress[J].Redox Biol,2013,1(1):8-16.
[33] Blokland K E C,Waters D W,Schuliga M,et al.Senescence of IPF lung fibroblasts disrupt alveolar epithelial cell proliferation and promote migration in wound healing[J].Pharmaceutics,2020,12(4):389.
[34] Hernandez-Gonzalez F,Prats N,Ramponi V,et al.Human senescent fibroblasts trigger progressive lung fibrosis in mice[J].Aging,2023,15(14):6641-6657.
[35] Rana T,Jiang C,Liu G,et al.PAI-1 regulation of TGF-β1-induced alveolar type Ⅱ cell senescence,SASP secretion,and SASP-mediated activation of alveolar macrophages[J].Am J Respir Cell Mol Biol,2020,62(3):319-330.
[36] Probst C K,Montesi S B,Medoff B D,et al.Vascular permeability in the fibrotic lung[J].Eur Respir J,2020,56(1):1900100.
[37] Caporarello N,Meridew J A,Aravamudhan A,et al.Vascular dysfunction in aged mice contributes to persistent lung fibrosis[J].Aging Cell,2020,19(8):e13196.
[38] Gaikwad A V,Lu W,Dey S,et al.Endothelial-to-mes-enchymal transition:A precursor to pulmonary arterial remodelling in patients with idiopathic pulmonary fibrosis[J].ERJ Open Res,2023,9(2):00487-02022.
[39] Zhou J,Xia X,An X,et al.New perspectives on the progression of pulmonary fibrosis:The cascade from aberrant microvascular endothelial cell activation to fibrosis[J].Front Med,2025,12:1639043.
[40] Panda B,Chilvery S,Devi P,et al.Inhibition of peptidyl arginine deiminase-4 ameliorated pulmonary fibrosis via modulating M1/M2 polarisation of macrophages[J].Life Sci,2025,362:123354.
[41] Li S,Xu H,Liu S,et al.Targeting Lp-PLA2 inhibits profibrotic monocyte-derived macrophages in silicosis through restoring cardiolipin-mediated mitophagy[J].Cell Mol Immunol,2025,22(7):776-790.
[42] Crowley L E,Stockley R A,Thickett D R,et al.Neutrophil dynamics in pulmonary fibrosis:Pathophysiological and therapeutic perspectives[J].Eur Respir Rev,2024,33(174):240139.
[43] Suzuki M,Ikari J,Anazawa R,et al.PAD4 deficiency improves bleomycin-induced neutrophil extracellular traps and fibrosis in mouse lung[J].Am J Respir Cell Mol Biol,2020,63(6):806-818.
[44] Huaux F.Interpreting immunoregulation in lung fibrosis:A new branch of the immune model[J].Front Immunol,2021,12:690375.
[45] Kamiya M,Carter H,Espindola M S,et al.Immune mechanisms in fibrotic interstitial lung disease[J].Cell,2024,187(14):3506-3530.
[46] Tsukui T,Wolters P J,Sheppard D.Alveolar fibroblast lineage orchestrates lung inflammation and fibrosis[J].Nature,2024,631(8021):627-634.
[47] Ganzleben I,Medoff B D.Mechanobiology and the extracellular matrix in pulmonary fibrosis[J].iScience,2025,28(12):113993.
[48] Liu F,Lagares D,Choi K M,et al.Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis[J].Am J Physiol Lung Cell Mol Physiol,2015,308(4):L344-L357.
[49] Yang J,Ma Y,Zhang R,et al.Fibrotic extracellular matrix microenvironment induces alveolar type Ⅱ epithelial cell senescence via integrin-β1/FAK/YAP signaling pathway[J].Int Immunopharmacol,2025,162:115169.
[50] Parimon T,Yao C,Stripp B R,et al.Alveolar epithelial type Ⅱ cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis[J].Int J Mol Sci,2020,21(7):2269.
[51] Cohen M L,Brumwell A N,Ho T C,et al.A fibroblast-dependent TGF-β1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis[J].J Clin Invest,2024,134(18):e174598.
[52] Liang D,Wang Y,Zhu Z,et al.BMP-7 attenuated silica-induced pulmonary fibrosis through modulation of the balance between TGF-β/Smad and BMP-7/Smad signaling pathway[J].Chem Biol Interact,2016,243:72-81.
[53] Ramos C,Becerril C,Montaño M,et al.FGF-1 reverts epithelial-mesenchymal transition induced by TGF-β₁ through MAPK/ERK kinase pathway[J].Am J Physiol Lung Cell Mol Physiol,2010,299(2):L222-L231.
[54] Ong C H,Tham C L,Harith H H,et al.TGF-β-induced fibrosis:A review on the underlying mechanism and potential therapeutic strategies[J].Eur J Pharmacol,2021,911:174510.
[55] Klingberg F,Hinz B,White E S.The myofibroblast matrix:Implications for tissue repair and fibrosis[J].J Pathol,2013,229(2):298-309.
[56] Cen Z,Cen T,Ding Q,et al.Outcomes and predictors of progression in progressive pulmonary fibrosis[J].Ann Med,2024,56(1):2406439.
[57] Ghuman A,Khanna D,Lin C J F,et al.Prognostic and predictive markers of systemic sclerosis-associated interstitial lung disease in a clinical trial and long-term observational cohort[J].Rheumatology (Oxford),2024,63(2):472-481.
[58] Chan C,Ryerson C J,Dunne J V,et al.Demographic and clinical predictors of progression and mortality in connective tissue disease-associated interstitial lung disease:A retrospective cohort study[J].BMC Pulm Med,2019,19(1):192.
[59] Mira-Avendano I,Kaye M.Key learnings from the INBUILD trial in patients with progressive pulmonary fibrosis[J].Ther Adv Respir Dis,2024,18:17534666241266343.
[60] Kim M J,Yang J,Song J W.Acute exacerbation of progressive pulmonary fibrosis:Incidence and outcomes[J].Respir Res,2024,25(1):415.
[61] Solomon J J,Chung J H,Cosgrove G P,et al.Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease[J].Eur Respir J,2016,47(2):588-596.
[62] Fan J J,Gu J M,Xiao S Y,et al.Risk factors for progression of pulmonary fibrosis:A single-centered,retrospective study[J].Front Med,2024,11:1335758.
[63] Lee S M,Seo J B,Oh S Y,et al.Prediction of survival by texture-based automated quantitative assessment of regional disease patterns on CT in idiopathic pulmonary fibrosis[J].Eur Radiol,2018,28(3):1293-1300.
[64] Chen Y H,Lee T J,Hsieh H J,et al.Clinical outcomes and risk factors of progressive pulmonary fibrosis in primary Sjögren’s syndrome-associated interstitial lung disease[J].BMC Pulm Med,2023,23(1):268.
[65] Hambly N,Farooqi M M,Dvorkin-Gheva A,et al.Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry[J].Eur Respir J,2022,60(4):2102571.
[66] Choi B,Kawut S M,Raghu G,et al.Regional distribution of high-attenuation areas on chest computed tomography in the Multi-Ethnic Study of Atherosclerosis[J].ERJ Open Res,2020,6(1):00115-02019.
[67] Barnes H,Humphries S M,George P M,et al.Machine learning in radiology:The new frontier in interstitial lung diseases[J].Lancet Digit Heal,2023,5(1):e41-e50.
[68] Guiot J,Henket M,Gester F,et al.Automated AI-based image analysis for quantification and prediction of interstitial lung disease in systemic sclerosis patients[J].Respir Res,2025,26(1):39.
[69] Chelala L,Brixey A G,Hobbs S B,et al.Current state of fibrotic interstitial lung disease imaging[J].Radiology,2025,316:e242531.
[70] Zhu W,Liu C,Tan C,et al.Predictive biomarkers of disease progression in idiopathic pulmonary fibrosis[J].Heliyon,2024,10(1):e23543.
[71] Li X,Lin Q,Guan B,et al.Multi-omics analysis links mitochondrial-related genes to idiopathic pulmonary fibrosis and in vivo transcriptome validation[J].Transl Res,2025,278:10-21.
[72] Karampitsakos T,Jia M,Tourki B,et al.The transcriptome of CD14+CD163-HLA-DR^low monocytes predicts mortality in idiopathic pulmonary fibrosis[J].Eur Respir J,2026,67(5):2500804.
[73] Zhumagaliyeva A,Chorostowska-Wynimko J,Jezela-Stanek A.Genetic determinants of progressive pulmonary fibrosis:A comprehensive review[J].Int J Mol Sci,2025,26(24):11846.
[74] Wollin L,Wex E,Pautsch A,et al.Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis[J].Eur Respir J,2015,45(5):1434-1445.
[75] Flaherty K R,Wells A U,Cottin V,et al.Nintedanib in progressive fibrosing interstitial lung diseases[J].N Engl J Med,2019,381(18):1718-1727.
[76] Au W,Kr F,Kk B,et al.Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial:A randomised,double-blind,placebo-controlled,parallel-group trial[J].Lancet Respir Med,2020,8(5):453-460.
[77] Distler O,Highland K B,Gahlemann M,et al.Nintedanib for systemic sclerosis-associated interstitial lung disease[J].N Engl J Med,2019,380(26):2518-2528.
[78] Dixon G,Hague S,Mulholland S,et al.Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK[J].ERJ Open Res,2024,10(1):00529-2023.
[79] Ocal N,Cilli A,Mogulkoc N,et al.Analysis of treatment efficacy,tolerability,and survival of patients receiving antifibrotic therapy for progressive nonidiopathic pulmonary fibrosis[J].Ann Thorac Med,2025,20(2):98-107.
[80] Mondoni M,Varone F,Luppi F,et al.Effectiveness of nintedanib in progressive pulmonary fibrosis assessed by progression criteria:An Italian,observational,multicenter study[J].Lung,2025,203(1):77.
[81] Chianese M,Screm G,Salton F,et al.Pirfenidone and nintedanib in pulmonary fibrosis:Lights and shadows[J].Pharmaceuticals,2024,17(6):709.
[82] Bargagli E,Piccioli C,Rosi E,et al.Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis:Real-life experience in an Italian referral centre[J].Pulmonology,2019,25(3):149-153.
[83] Westerink L,Nicolai J L J,Postma M J,et al.Cost-eff-ectiveness of nintedanib for patients with progressive fibrosing interstitial lung disease (PF-ILD)[J].Pharmacoecon Open,2022,6(5):647-656.
[84] Chaudhuri N,Azuma A,Sroka-Saidi K,et al.Safety and tolerability of nintedanib in patients with fibrosing interstitial lung diseases:Post-marketing data[J].Adv Ther,2024,41(12):4581-4590.
[85] Lv Q,Wang J,Xu C,et al.Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways[J].Mol Med,2020,26(1):49.
[86] Ruwanpura S M,Thomas B J,Bardin P G.Pirfenidone:Molecular mechanisms and potential clinical applications in lung disease[J].Am J Respir Cell Mol Biol,2020,62(4):413-422.
[87] Maher T M,Corte T J,Fischer A,et al.Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease:A double-blind,randomised,placebo-controlled,phase 2 trial[J].Lancet Respir Med,2020,8(2):147-157.
[88] Behr J,Prasse A,Kreuter M,et al.Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF):A double-blind,randomised,placebo-controlled,phase 2b trial[J].Lancet Respir Med,2021,9(5):476-486.
[89] Nieto M A,Vadillo C,Pernaute O S,et al.Role of antifibrotics in progressive pulmonary fibrosis associated to autoimmune diseases:Multicenter study from NEREA registry[J].Respir Res,2025,26(1):234.
[90] Aimo A,Spitaleri G,Nieri D,et al.Pirfenidone for idiopathic pulmonary fibrosis and beyond[J].Card Fail Rev,2022,8:e12.
[91] 中华人民共和国国家卫生健康委员会.国家卫生健康委办公厅关于印发软骨发育不全等86个罕见病病种诊疗指南(2025年版)的通知[EB/OL].(2025-07-10)[2026-01-07].https://www.nhc.gov.cn/yzygj/c100068/202507/5b3f41180a42465eb9eec34597bacaf2.shtml
[92] Li H,Zuo J,Tang W.Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases[J].Front Pharmacol,2018,9:1048.
[93] Kolb M,Crestani B,Maher T M.Phosphodiesterase 4B inhibition:A potential novel strategy for treating pulmonary fibrosis[J].Eur Respir Rev,2023,32(167):220206.
[94] Matsuhira T,Nishiyama O,Tabata Y,et al.A novel phosphodiesterase 4 inhibitor,AA6216,reduces macrophage activity and fibrosis in the lung[J].Eur J Pharmacol,2020,885:173508.
[95] Sisson T H,Christensen P J,Muraki Y,et al.Phosphodiesterase 4 inhibition reduces lung fibrosis following targeted type II alveolar epithelial cell injury[J].Physiol Rep,2018,6(12):e13753.
[96] Jin S L,Goya S,Nakae S,et al.Phosphodiesterase 4B is essential for T(H)₂-cell function and development of airway hyperresponsiveness in allergic asthma[J].J Allergy Clin Immunol,2010,126(6):1252-1259.e12.
[97] Hansen G,Jin S,Umetsu D T,et al.Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D[J].Proc Natl Acad Sci U S A,2000,97(12):6751-6756.
[98] Selige J,Hatzelmann A,Dunkern T.The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion[J].J Cell Physiol,2011,226(8):1970-1980.
[99] Herrmann F,Hesslinger C,Wollin L,et al.BI 1015550 is a PDE4B inhibitor and a clinical drug candidate for the oral treatment of idiopathic pulmonary fibrosis[J].Front Pharmacol,2022,13:838449.
[100] Maher T M,Assassi S,Azuma A,et al.Nerandomilast in patients with progressive pulmonary fibrosis[J].N Engl J Med,2025,392(22):2203-2214.
[101] Decaris M L,Schaub J R,Chen C,et al.Dual inhibition of α_vβ₆ and α_vβ₁ reduces fibrogenesis in lung tissue explants from patients with IPF[J].Respir Res,2021,22(1):265.
[102] Lancaster L,Cottin V,Ramaswamy M,et al.Bexotegrast in patients with idiopathic pulmonary fibrosis:The INTEGRIS-IPF clinical trial[J].Am J Respir Crit Care Med,2024,210(4):424-434.
[103] Montesi S B,Cosgrove G P,Turner S M,et al.Dual αvβ6 and αvβ1 inhibition over 12 weeks reduces active type I collagen deposition in individuals with idiopathic pulmonary fibrosis:A phase 2,double-blind,placebo-controlled clinical trial[J].Am J Respir Crit Care Med,2025,211(7):1229-1240.
[104] Denis A,Tsiri P,Guiot J,et al.A new era in the treatment of progressive fibrosing interstitial lung diseases[J].Breathe (Sheff),2025,21(2):240259.
[105] Shea B S,Tager A M.Role of the lysophospholipid mediators lysophosphatidic acid and sphingosine 1-phosphate in lung fibrosis[J].Proc Am Thorac Soc,2012,9(3):102-110.
[106] Corte T J,Behr J,Cottin V,et al.Efficacy and safety of admilparant,an LPA1 antagonist,in pulmonary fibrosis:A phase 2 randomized clinical trial[J].Am J Respir Crit Care Med,2025,211(2):230-238.
[107] Kolb M,Orfanos S E,Lambers C,et al.The antifibrotic effects of inhaled treprostinil:An emerging option for ILD[J].Adv Ther,2022,39(9):3881-3895.
[108] Nikitopoulou I,Manitsopoulos N,Kotanidou A,et al.Orotracheal treprostinil administration attenuates bleomycin-induced lung injury,vascular remodeling,and fibrosis in mice[J].Pulm Circ,2019,9(4):2045894019881954.
[109] Fang L,Chen W C,Jaksch P,et al.Treprostinil reconstitutes mitochondrial organisation and structure in idiopathic pulmonary fibrosis cells[J].Int J Mol Sci,2023,24(15):12148.
[110] Lambers C,Roth M,Jaksch P,et al.Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation[J].Sci Rep,2018,8(1):1087.
[111] Kolodsick J E,Peters-Golden M,Larios J,et al.Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E.Prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation[J].Am J Respir Cell Mol Biol,2003,29(5):537-544.
[112] Ayabe S,Kida T,Hori M,et al.Prostaglandin D2 inhibits collagen secretion from lung fibroblasts by activating the DP receptor[J].J Pharmacol Sci,2013,121(4):312-317.
[113] White E S,Atrasz R G,Dickie E G,et al.Prostaglandin E(2) inhibits fibroblast migration by E-prostanoid 2 receptor-mediated increase in PTEN activity[J].Am J Respir Cell Mol Biol,2005,32(2):135-141.
[114] Ali F Y,Egan K,FitzGerald G A,et al.Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts[J].Am J Respir Cell Mol Biol,2006,34(2):242-246.
[115] Nathan S D,Waxman A,Rajagopal S,et al.Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension:A post-hoc analysis of the INCREASE study[J].Lancet Respir Med,2021,9(11):1266-1274.
[116] Effendi W I,Nagano T.The hedgehog signaling pathway in idiopathic pulmonary fibrosis:Resurrection time[J].Int J Mol Sci,2021,23(1):171.
[117] Maher T M,Goldin J G,Hood J,et al.Taladegib for the treatment of idiopathic pulmonary fibrosis (ENV-IPF-101):A multicentre,randomised,double-blind,placebo-controlled,phase 2a trial[J].Lancet Respir Med,2025,13(11):1001-1010.
[118] Huang H,Wang Q,Xu Z.Advances in the identification and management of progressive pulmonary fibrosis:Perspective from Chinese experts[J].Ther Adv Respir Dis,2024,18:17534666241288417.
[119] Tashkin D P,Elashoff R,Clements P J,et al.Cyclophosphamide versus placebo in scleroderma lung disease[J].N Engl J Med,2006,354(25):2655-2666.
[120] Tashkin D P,Roth M D,Clements P J,et al.Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS Ⅱ):A randomised controlled,double-blind,parallel group trial[J].Lancet Respir Med,2016,4(9):708-719.
[121] Johnson S R,Bernstein E J,Bolster M B,et al.2023 American college of rheumatology (ACR)/American college of chest physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases[J].Arthritis Rheumatol,2024,76(8):1182-1200.
[122] Calaras D,David A,Vasarmidi E,et al.Hypersensitivity pneumonitis:Challenges of a complex disease[J].Can Respir J,2024,2024(1):4919951.
[123] Morisset J,Johannson K A,Vittinghoff E,et al.Use of mycophenolate mofetil or azathioprine for the management of chronic hypersensitivity pneumonitis[J].Chest,2017,151(3):619-625.
[124] Adegunsoye A,Oldham J M,Fernández Pérez E R,et al.Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis[J].ERJ Open Res,2017,3(3):00016-02017.
[125] Kang H K,Song J W.Progressive pulmonary fibrosis:Where are we now?[J].Tuberc Respir Dis,2024,87(2):123-133.
[126] Kreuter M,Belloli E A,Bendstrup E,et al.Acute exacerbations in patients with progressive pulmonary fibrosis[J].ERJ Open Res,2024,10(6):00403-02024.
[127] Rajan S K,Cottin V,Dhar R,et al.Progressive pulmonary fibrosis:An expert group consensus statement[J].Eur Respir J,2023,61(3):2103187.
[128] Nici L,Donner C,Wouters E,et al.American thoracic society/European respiratory society statement on pulmonary rehabilitation[J].Am J Respir Crit Care Med,2006,173(12):1390-1413.
[129] Jacobs S S,Krishnan J A,Lederer D J,et al.Home oxygen therapy for adults with chronic lung disease.An official American thoracic society clinical practice guideline[J].Am J Respir Crit Care Med,2020,202(10):e121-e141.
[130] Oliveira A,Fabbri G,Gille T,et al.Holistic management of patients with progressive pulmonary fibrosis[J].Breathe (Sheff),2023,19(3):230101.