Tags

Type your tag names separated by a space and hit enter

A Sputum Proteomic Signature That Associates with Increased IL-1β Levels and Bacterial Exacerbations of COPD.
Lung 2016; 194(3):363-9LUNG

Abstract

PURPOSE

Activation of the interleukin-1β (IL-1β) signaling pathway has been implicated in COPD, but the proportion of COPD subjects whose disease is principally driven by activation of this pathway is poorly understood. In this study, we sought to differentiate an IL-1β-associated sputum signature from other inflammation-associated COPD phenotypes.

METHODS

Luminex-multiplex assays were used to study IL-1β-mediated signature proteins within airway epithelium, smooth muscle, and vascular endothelial cell cultures. The IL-1β-mediated signature was tested in a longitudinal study comprising of 35 paired stable-COPD and acute exacerbation (AECOPD) sputum samples. The presence of respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae, and P. aeruginosa) was evaluated by sputum cultures.

RESULTS

Five proteins namely TNF-α, GCSF, IL-6, CD-40L, and MIP-1β were found to be IL-1β-regulated across all donors and cell types. All five of these IL-1β-mediated proteins were significantly increased (p < 0.05) in sputum corresponding to AECOPD events showing at least a twofold increase in IL-1β (IL-1β(+) events, 18 of 35 total events), relative to preceding stable-COPD state. Sputum IL-1β levels showed no significant association (p > 0.05, spearman) with known markers of other major COPD inflammation phenotypes. In addition, there was a significant association with bacterial presence in sputum culture with an odds ratio of 9 (95 % CI 1.56, 51.9) in IL-1β(+) events versus IL-1β(-) events.

CONCLUSION

Our findings provide insights into potential markers of IL-1β-associated AECOPD, and reaffirm association between IL-1β pathway activation and airway bacterial infection in COPD. Taken together, our findings could help identify COPD patient subsets who may benefit from therapies targeting IL-1β pathway.

Authors+Show Affiliations

Translational Medicine - Respiratory, Inflammation, Autoimmunity, MedImmune LLC, One Medimmune Way, Gaithersburg, MD, 20878, USA. DameraG@medimmune.com.Translational Medicine - Respiratory, Inflammation, Autoimmunity, MedImmune LLC, One Medimmune Way, Gaithersburg, MD, 20878, USA.Nonclinical Statistics, MedImmune LLC, One Medimmune Way, Gaithersburg, MD, 20878, USA.Translational Medicine - Respiratory, Inflammation, Autoimmunity, MedImmune LLC, One Medimmune Way, Gaithersburg, MD, 20878, USA.Translational Medicine - Respiratory, Inflammation, Autoimmunity, MedImmune LLC, One Medimmune Way, Gaithersburg, MD, 20878, USA.Translational Medicine - Respiratory, Inflammation, Autoimmunity, MedImmune LLC, One Medimmune Way, Gaithersburg, MD, 20878, USA.VA WNY Healthcare System and University at Buffalo, State University of New York, Buffalo, NY, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27083436

Citation

Damera, Gautam, et al. "A Sputum Proteomic Signature That Associates With Increased IL-1β Levels and Bacterial Exacerbations of COPD." Lung, vol. 194, no. 3, 2016, pp. 363-9.
Damera G, Pham TH, Zhang J, et al. A Sputum Proteomic Signature That Associates with Increased IL-1β Levels and Bacterial Exacerbations of COPD. Lung. 2016;194(3):363-9.
Damera, G., Pham, T. H., Zhang, J., Ward, C. K., Newbold, P., Ranade, K., & Sethi, S. (2016). A Sputum Proteomic Signature That Associates with Increased IL-1β Levels and Bacterial Exacerbations of COPD. Lung, 194(3), pp. 363-9. doi:10.1007/s00408-016-9877-0.
Damera G, et al. A Sputum Proteomic Signature That Associates With Increased IL-1β Levels and Bacterial Exacerbations of COPD. Lung. 2016;194(3):363-9. PubMed PMID: 27083436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Sputum Proteomic Signature That Associates with Increased IL-1β Levels and Bacterial Exacerbations of COPD. AU - Damera,Gautam, AU - Pham,Tuyet-Hang, AU - Zhang,Jianchun, AU - Ward,Christine K, AU - Newbold,Paul, AU - Ranade,Koustubh, AU - Sethi,Sanjay, Y1 - 2016/04/15/ PY - 2016/01/08/received PY - 2016/04/04/accepted PY - 2016/4/17/entrez PY - 2016/4/17/pubmed PY - 2017/12/30/medline KW - Airway inflammation KW - COPD KW - IL-1β KW - Sputum biomarkers SP - 363 EP - 9 JF - Lung JO - Lung VL - 194 IS - 3 N2 - PURPOSE: Activation of the interleukin-1β (IL-1β) signaling pathway has been implicated in COPD, but the proportion of COPD subjects whose disease is principally driven by activation of this pathway is poorly understood. In this study, we sought to differentiate an IL-1β-associated sputum signature from other inflammation-associated COPD phenotypes. METHODS: Luminex-multiplex assays were used to study IL-1β-mediated signature proteins within airway epithelium, smooth muscle, and vascular endothelial cell cultures. The IL-1β-mediated signature was tested in a longitudinal study comprising of 35 paired stable-COPD and acute exacerbation (AECOPD) sputum samples. The presence of respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae, and P. aeruginosa) was evaluated by sputum cultures. RESULTS: Five proteins namely TNF-α, GCSF, IL-6, CD-40L, and MIP-1β were found to be IL-1β-regulated across all donors and cell types. All five of these IL-1β-mediated proteins were significantly increased (p < 0.05) in sputum corresponding to AECOPD events showing at least a twofold increase in IL-1β (IL-1β(+) events, 18 of 35 total events), relative to preceding stable-COPD state. Sputum IL-1β levels showed no significant association (p > 0.05, spearman) with known markers of other major COPD inflammation phenotypes. In addition, there was a significant association with bacterial presence in sputum culture with an odds ratio of 9 (95 % CI 1.56, 51.9) in IL-1β(+) events versus IL-1β(-) events. CONCLUSION: Our findings provide insights into potential markers of IL-1β-associated AECOPD, and reaffirm association between IL-1β pathway activation and airway bacterial infection in COPD. Taken together, our findings could help identify COPD patient subsets who may benefit from therapies targeting IL-1β pathway. SN - 1432-1750 UR - https://www.unboundmedicine.com/medline/citation/27083436/A_Sputum_Proteomic_Signature_That_Associates_with_Increased_IL_1β_Levels_and_Bacterial_Exacerbations_of_COPD_ L2 - https://dx.doi.org/10.1007/s00408-016-9877-0 DB - PRIME DP - Unbound Medicine ER -