Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV₁ for COPD in Chinese Population: A Prospective Cohort Study

Abstract

Background

In China, the high prevalence and mortality rate of Chronic Obstructive Pulmonary Disease (COPD) and the poor intervention effect makes it into a heavy social burden. The main reason is that the current diagnosis of COPD mainly based on the static lung function, which is difficult for early intervention. Through matching a predictive model for high-risk groups of COPD that rewards FEV₁ rapid decline as the core, we will establish the early warning model and prove its validity and socio-economic value.

Methods

This is a multi-center, prospective, cohort study. A total of 10,000 people aged 40∼75 without lung disease will be recruited and followed for 3 years. Some questionnaires such as St George’s Respiratory Questionnaire (SGRQ), income class, educational level, comorbidity, smoking habit, and biomass smoke exposure history will be collected. The baseline level of Interleukin 6 (IL-6), high-sensitivity C-reactive Protein (hs-CRP), microRNAs-23a (miR-23a) in peripheral blood and pH value in exhaled breath condensate (EBC) will be measured, lung spirometry will be tested in the first, second, and fourth years. Primary outcome is the incidence of COPD, multivariate regression analysis will be used to establish the predictive model for COPD in China.

Discussion

With the rapid decline of lung function as the core and the baseline inflammatory biomarkers in peripheral blood and pH of the exhaled breath condensate as affecting factors, a predictive model to achieve early detection of high-risk COPD groups will be established and promoted.

Trial registration

This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT3532893) on 21 May 2018, https://register.clinicaltrials.gov.

Keywords:

• COPD
• decline in FEV1
• inflammatory biomarkers
• EBC
• microRNA-23a

Acknowledgments

The authors thank Dr Chengli Que, Dr Shixuan Wang, Dr Haiyan Tang, as well as nurse Liping Feng from the Department of Respiratory and Critical Care Medicine and Lina Zhang from Shichahai Community Health Service Center for their help in investigator training. The authors feel really appreciative for the cooperation in enrolling the subjects and advancing the research to Dr Ruiying Wang from Department of Respiratory Medicine, Shanxi Dayi Hospital, Dr Jinzhi Yin from Department of Respiratory and Critical Care Medicine, the Second Hospital of Jilin University, Dr Xixin Yan from Department of Respiratory Medicine, the Second Hospital of Hebei Medical University, Dr Xiaomin Dang from Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Dr Limin Zhao from Department of Respiratory Medicine, Henan Provincial People’s Hospital, Dr Xiuhua Fu from Department of Respiratory Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Dr Lixia Dong from Department of Respiratory Medicine, Tianjin Medical University General Hospital, Dr Shujuan Jiang from Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Dr Hua Qiao from Department of Respiratory Medicine, The First Hospital of Qinhuangdao.

Abbreviations

COPD, chronic obstructive pulmonary disease; SGRQ, St George’s Respiratory Questionnaire; IL-6, Interleukin 6; hs-CRP, high-sensitivity C-reactive protein; miR, microRNAs; EBC, exhaled breath condensate; FEV1, forced expiratory volume in 1s; FEC, forced vital capacity; ALF, airway lining fluid; EMT, epithelial–mesenchymal transition.

Trial Status

The trial is currently at the stage of patient recruitment and data collection.

Ethics Approval and Consent to Participate

The first version study protocol has been approved by the Peking University First Hospital Institutional Review Board (IRB) (2018[31]) on 7 March 2018. Any protocol modifications will be submitted for the IRB review and approval. The study will be conducted in accordance with Good Clinical Practice (GCP) requirements and ethical principles of the Declaration of Helsinki. The purposes, procedures, as well as potential benefits and risks of the study, will be explained carefully by investigators with a written informed consent. Written informed consent will be obtained from each participant or from the surrogate of the participant who cannot provide informed consent. Personal information and related documents of all participants will be kept strictly. Every participant will be identified by a subject number and a name acronym in the Case Report Form. Results of the study will be submitted to peer-reviewed journals and academic conferences and until now not any result of this study has already been published or been submitted to any journal.

Data Sharing Statement

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Author Contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Dr Guangfa Wang reports grants from the National Science and Technology Ministry Project of Chronic Diseases, during the conduct of the study. The authors report no other conflicts of interest in this work.