Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention
Abstract
1. Introduction
2. Molecular Mechanisms of Pulmonary Fibrosis
3. Serum Biomarkers for Diagnosing and Monitoring Pulmonary Fibrosis
3.1. Idiopathic Pulmonary Fibrosis (IPF)
3.2. CTD-ILDs
3.3. Other Fibrosing ILDs
4. Therapeutic Strategies in PPF
4.1. Idiopathic Pulmonary Fibrosis (IPF)
4.2. CTD-ILDs
4.3. Sarcoidosis
4.4. Fibrotic HP
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Biomarker | Population | Findings | References |
---|---|---|---|
Anti-CXCR3/CXCR4 | SSc (n = 327) |
| Weigold et al. [55] |
Anti-Scl 70 | SSc (n = 117) |
| Wangkaew et al. [56] |
Anti-SS-A/Ro52+ | CTD/IPAF (n = 107) |
| Nagy et al. [57] |
CCL15 | HP (n = 51) |
| Watanabe [58] |
CCL18 | IPF (n = 72) |
| Prasse et al. [59] |
SSc (n = 83) | Tiev et al. [60] | ||
SSc (n = 87) |
| Khanna et al. [61] | |
| |||
| |||
IL-6 | SSc (n = 286) |
| De Lauretis [62] |
KL-6 | IPF (n = 89) |
| Wakamatsu et al. [63] |
Early-SSc (n = 50) |
| Kuwana et al. [64] | |
RA-ILD (n = 84) |
| Kim et al. [65] | |
HP (n = 49) |
| Sánchez-Díez [66] | |
f-HP (n = 185) |
| Ejima et al. [67] | |
MMP7 | IPF (n = 97) |
| Tzouvelekis et al. [68] |
Monocytes | IPF (n = 37) |
| Fraser et al. [69] |
IPF (n = 2067) |
| Kreuter et al. [70] | |
IPF (n = 128) |
| Achaiah et al. [71] | |
Periostin | IPF (n = 54) |
| Naik et al. [72] |
RF | RA (n = 60) |
| Chen et al. [73] |
SP-D | IPF (n = 52) |
| Takahasi et al. [74] |
| |||
|
Molecule | Route of Administration | Mechanism of Action | Key Trials | Status |
---|---|---|---|---|
BI 1015550 | Oral | ↓ PDE4b ↓ TNF-α ↓ IL-2 ↓ FGF ↓ myofibroblast transformation | FIBRONEER-IPF NCT05321069 NCT04419506 (Phase 2) | Under evaluation |
BMS 986278 | Oral | LPAR1 antagonist ↓ myofibroblast activation | NCT04308681—Phase 2 | Under evaluation |
Pirfenidone | Oral | ↓ TGF-β ↓ PDGF ↓ TNF-α ↓ IL-13 ↓ IL-4 ↑ MMPs | ASCEND—NCT01366209 Capacity 1—NCT00287729 Capacity 2—NCT00287716 SP3—Japanese | Approved |
Nintedanib | Oral | FGFR inhibitor PDGFR inhibitor VGFR inhibitor | INPULSIS-1—NCT01335464 INPULSIS-2—NCT01335477 | Approved |
Pamrevlumab | Intravenous | ↓ CTGF | ZEPHYRUS 2—NCT04419558 | Not approved |
PRM-151 (rhPTX-2) | Intravenous | ↓ Inflammation ↓ Fibrosis | WA42404—NCT02550873 STARSCAPE—NCT04552899 | Not approved |
Treprostinil | Inhaled | ↑ EP2 ↑ DP1 ↑ PPAR ↓ Cell proliferation ↓ Collagen synthesis ↓ Inflammation ↓ Fibroblast proliferation | INCREASE—NCT02630316 TETON—NCT04708782 | Under evaluation |
Ziritaxestat | Oral | ↓ Autotaxin ↓ LPA | ISABELLA 1—NCT03711162 ISABELLA 2—NCT03733444 | Not approved |
RA-ILD | |||
---|---|---|---|
Molecule | Key Trials | Recommendation | |
BI 1015550 (PDE4Bi) | NCT05321082 | Under evaluation as per PPF | |
Nintedanib | INBUILD—NCT02999178 | Recommended for ILD progression despite first-line treatment | |
Pirfenidone | TRAIL 1—NCT02808871 | Not recommended | |
SSc-ILD | |||
Molecule | Key Trials | Recommendation | |
BI 1015550 (PDE4Bi) | NCT05321082 | Under evaluation as per PPF | |
Nintedanib | INBUILD—NCT02999178 SENSCIS—NCT02597933 | Recommended as additional first-line ILD option | |
Pirfenidone | NCT03856853 SLSIII—NCT03221257 | Not recommended | |
Tacrolimus | INSIST—CTRI/2021/11/037864 | Under evaluation | |
Tocilizumab | focuSSced—NCT02453256 | Recommended as first-line preferred ILD option | |
Other CTD-ILDs (Myositis, MCTD, Sjogren) | |||
Molecule | Key Trial | Recommendation | |
BI 1015550 (PDE4Bi) | NCT05321082 | Under evaluation as per PPF | |
Nintedanib | INBUILD—NCT02999178 | Recommended for ILD progression despite first-line treatment |
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D’Agnano, V.; Mariniello, D.F.; Ruotolo, M.; Quarcio, G.; Moriello, A.; Conte, S.; Sorrentino, A.; Sanduzzi Zamparelli, S.; Bianco, A.; Perrotta, F. Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention. Life 2024, 14, 229. https://doi.org/10.3390/life14020229
D’Agnano V, Mariniello DF, Ruotolo M, Quarcio G, Moriello A, Conte S, Sorrentino A, Sanduzzi Zamparelli S, Bianco A, Perrotta F. Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention. Life. 2024; 14(2):229. https://doi.org/10.3390/life14020229
Chicago/Turabian StyleD’Agnano, Vito, Domenica Francesca Mariniello, Michela Ruotolo, Gianluca Quarcio, Alessandro Moriello, Stefano Conte, Antonio Sorrentino, Stefano Sanduzzi Zamparelli, Andrea Bianco, and Fabio Perrotta. 2024. "Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention" Life 14, no. 2: 229. https://doi.org/10.3390/life14020229
APA StyleD’Agnano, V., Mariniello, D. F., Ruotolo, M., Quarcio, G., Moriello, A., Conte, S., Sorrentino, A., Sanduzzi Zamparelli, S., Bianco, A., & Perrotta, F. (2024). Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention. Life, 14(2), 229. https://doi.org/10.3390/life14020229