Biomarker Distinction
CAN BIOMARKERS HELP DISTINGUISH COMBINED IPF AND EMPHYSEMA FROM IPF ALONE OR EMPHYSEMA ALONE?
Emphysema and IPF have been considered two independent pathologies, but reports of coexisting disease are increasing.1 Emphysema impacts both lung function and molecular markers (particularly VEGF and TGF-β1) in an opposite manner to IPF.2-6 In emphysema, lung volumes tend to be higher than normal, while lung volumes are reduced in IPF.2,6
Conversely, FEV1 is lower in emphysema, while in IPF, FEV1 increases, resulting in relatively normal lung volumes and spirometry readings but significantly compromised gas exchange.2,6 On a molecular level, emphysema is characterized by lower TGF-β1 expression, while IPF is driven by excess production of TGF-β1.1
On high-resolution computed tomography (HRCT) scans, features of both emphysema and IPF are evident in patients with combined pulmonary fibrosis and emphysema (CPFE).7 This study was designed to ascertain how certain molecular markers of emphysema and/or IPF are distinct in CPFE compared with IPF or emphysema alone.
WHAT THEY DID
This study included 38 patients with CPFE, 50 patients with only emphysema (first control group), and 34 patients with only IPF (second control group).1 Peripheral blood was collected to assess circulating levels of VEGF, TGF-β1, KL-6, MMP-9, TIMP-1, SCC, and CYFRA21-1, as well as the activity of telomerase.
WHAT THEY FOUND
The IPF-only group showed significantly higher levels of VEGF, TGF-β1, KL-6, and CYFRA21-1 than the emphysema-only group, while only KL-6 and CYFRA21-1 were significantly higher in IPF-only than in CPFE.1 In the CPFE group, the levels of VEGF and TGF-β1 were numerically higher than in emphysema and numerically lower than in IPF, but neither comparison was statistically significant. No significant differences were found between the CPFE group and the emphysema-only group with regard to any of the molecular markers.
| Emphysema | CPFE | IPF | |
|---|---|---|---|
| VEGF | * | † | |
| TGF-β1 | * | † | |
| KL-6 | * | * | † |
| MMP-9 | |||
| TIMP-1 | |||
| CYFRA21-1 | * | † | |
| SCC | |||
| Telomerase |
Gray indicates no statistically significant difference compared with other groups. Dark blue indicates significantly higher value; light blue indicates significantly lower values.
*indicates statistical significance vs IPF.
†indicates statistical significance vs emphysema.
WHAT IT MEANS
The molecular markers assessed in this study have been implicated in one or both of these distinct disease states.1 In particular, TGF-β1 show decreased expression in emphysema, while TGF-β1 expression is essential to the pathology of pulmonary fibrosis.1
The intermediate levels of VEGF and TGF-β1 seen in CPFE suggest that the molecular profile of CPFE may exist as a hybrid between those of emphysema and IPF. Further studies need to be performed to tease out whether a unique molecular profile exists that could be used to screen for the presence of CPFE.
Link to Abstract: http://www.ncbi.nlm.nih.gov/pubmed/28128990.
REFERENCES
- Xu L, Bian W, Gu X-H, Shen C. Differing expression of cytokines and tumor markers in combined pulmonary fibrosis and emphysema compared to emphysema and pulmonary fibrosis. COPD. 201714(2):245-250. doi: 10.1080/15412555.2017.1278753.
- Jankowich MD, Rounds SI. Combined pulmonary fibrosis and emphysema syndrome: a review. Chest. 2012;141(1):222-231. doi: 10.1378/chest.11-1062.
- Kanazawa H, Hirata K, Yoshikawa J. Imbalance between vascular endothelial growth factor and endostatin in emphysema. Eur Respir J. 2003;22(4):609-612. doi: 10.1183/09031936.03.00030403.
- Konigshoff M, Kneidinger N, Eickelberg O. TGF-beta signaling in copd: Deciphering genetic and cellular susceptibilities for future therapeutic regimen. Swiss Med Wkly. 2009;139(39-40):554-563.
- Lee CG, Cho S, Homer RJ, Elias JA. Genetic control of transforming growth factor-beta1-induced emphysema and fibrosis in the murine lung. Proc Am Thorac Soc. 2006;3(6):476-477. doi: 10.1513/pats.200603-040MS.
- Lin H, Jiang S. Combined pulmonary fibrosis and emphysema (CPFE): An entity different from emphysema or pulmonary fibrosis alone. J Thorac Dis. 2015;7(4):767-779. doi: 10.3978/j.issn.2072-1439.2015.04.17.
- Mitchell PD, Das JP, Murphy DJ, et al. Idiopathic pulmonary fibrosis with emphysema: evidence of synergy among emphysema and idiopathic pulmonary fibrosis in smokers. Respir Care. 2015;60(2):259-268. doi: 10.4187/respcare.03389.
