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Original Research: Obstructive Lung Diseases |

Airway IL-1β and Systemic Inflammation as Predictors of Future Exacerbation Risk in Asthma and COPDInflammatory Predictors of Exacerbation

Juan-juan Fu, MD, PhD; Vanessa M. McDonald, PhD; Katherine J. Baines, PhD; Peter G. Gibson, MBBS
Author and Funding Information

From the Respiratory Group (Dr Fu), Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Sichuan, China; the Priority Research Centre for Asthma and Respiratory Diseases (Drs Fu, McDonald, Baines, and Gibson) and the School of Nursing and Midwifery (Dr McDonald), Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; and Hunter Medical Research Institute (Drs Baines and Gibson), Newcastle, NSW, Australia.

CORRESPONDENCE TO: Peter G. Gibson, MBBS, Department of Respiratory and Sleep Medicine, John Hunter Hospital, Lookout Rd, New Lambton 2305, NSW, Australia; e-mail: Peter.Gibson@hnehealth.nsw.gov.au


A subset of the data in this study has been presented in abstract form (Fu JJ, McDonald VM, Baines KJ, et al. Airway IL-1 pathway activation and systemic inflammation predict future exacerbation risk in asthma and COPD. D12. Exacerbation of lung disease: shared mechanisms. Am Thorac Soc. 2014:A5357) and as an oral presentation at the 2014 American Thoracic Society Conference in, May 21, 2014, San Diego, CA.

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(3):618-629. doi:10.1378/chest.14-2337
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BACKGROUND:  The innate inflammatory pathways involved in the frequent exacerbator phenotypes of asthma and COPD are not well understood. This study aimed to investigate airway innate immune activation and systemic inflammation as predictors of exacerbations in asthma and COPD.

METHODS:  In this prospective cohort study, baseline airway IL-1β, serum C-reactive protein, and IL-6 were assessed in 152 participants with stable asthma (n = 63) or COPD (n = 89) and were related to exacerbations over the following 12 months. Clinical characteristics and inflammatory biomarkers were compared between the frequent (two or more exacerbations in the follow-up) and infrequent exacerbators. The frequent exacerbation phenotype and exacerbation frequency were analyzed with multivariable modeling. The relationships among airway inflammation, systemic inflammation, and future exacerbations were examined using path analysis.

RESULTS:  Ninety-four participants experienced a total of 201 exacerbations, and 36.4% had two or more exacerbations. Serum IL-6 and sputum gene expression of IL-1β at baseline were higher in the frequent exacerbators with COPD. Significant pathways initiated by previous exacerbations were identified as occurring through activation of the IL-1β-systemic inflammatory axis leading to future exacerbations in COPD. Systemic inflammation was also associated with increased exacerbation risk in asthma.

CONCLUSIONS:  Airway IL-1β and systemic inflammation are associated with frequent exacerbations and may mediate a vicious cycle between previous and future exacerbations in COPD. Treatment strategies aimed at attenuating these inflammatory pathways to reduce COPD exacerbations deserve further investigation.

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