Potential pre-COPD indicators in association with COPD development and COPD prediction models in Chinese: a prospective cohort studyResearch in context

Abstract

Summary: Background: Lung injury might take place before chronic obstructive pulmonary disease (COPD) occurs. A clearer definition of “pre-COPD” based on the effects of potential indicators on increasing risk of COPD development and a prediction model involving them are lacking. Methods: A total of 3526 Chinese residents without COPD aged 40 years or older derived from the national cross-sectional survey of COPD surveillance in 2014–2015 were followed up for a mean of 3.59 years. We examined the associations of chronic bronchitis, preserved ratio impaired spirometry (PRISm), low peak expiratory flow (PEF), spirometric small airway dysfunction (sSAD), low maximal mid-expiratory flow (MMEF), low forced expiratory flow 50% of pulmonary volume (FEF50), and low FEF75 with subsequent COPD and constructed a prediction model with LASSO-Cox regression. Findings: 235 subjects in the cohort developed COPD during the follow-up. Subjects with PRISm, low PEF, sSAD, low MMEF, low FEF50, and low FEF75 had an increased risk of developing COPD (adjusted hazard ratio [HR] ranging from 1.57 to 3.01). Only chronic bronchitis (HR 2.84 [95% CI 1.38–5.84] and 2.94 [1.43–6.04]) and sSAD/low MMEF (HR 2.74 [2.07–3.61] and 2.38 [1.65–3.43]) showed effects independent of the other indicators and their concurrence had the strongest effect (HR 5.89 and 4.80). The prediction model including age, sex, low MMEF, low FEF50, and indoor exposure to biomass had good performance both internally and temporally. The corrected C-index was 0.77 (0.72–0.81) for discrimination in internal validation. For temporal validation, the area under the receiver operating characteristic curve was 0.73 (0.63–0.83). Good calibration was indicated in plot for internal validation and by Hosmer–Lemeshow test for temporal validation. Interpretation: Individuals with concurrent chronic bronchitis and sSAD/low MMEF indicating pre-COPD optimally require more high attention from physicians. Our prediction model could serve as a multi-dimension tool to predict COPD comprehensively. Funding: The Ministry of Finance and the Ministry of Science and Technology of the People's Republic of China and the National Natural Science Foundation of China. 摘要: 背景: 在慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)出现前, 肺损伤可能已经发生。目前尚缺乏依据潜在指标对升高COPD发生风险的影响而产生的更明确的''慢阻肺前期''的定义, 以及包含这些潜在指标的慢阻肺发病预测模型。 方法: 本研究基于2014–2015年中国居民慢阻肺监测横断面调查, 对3526名40岁及以上的非慢阻肺居民进行了平均3.59年的随访；旨在分析慢性支气管炎、保留比值的肺功能损伤 (preserved ratio impaired spirometry, PRISm)、低呼气峰流速 (peak expiratory flow, PEF)、小气道功能障碍 (spirometric small airway dysfunction, sSAD)、低最大呼气中期流速 (maximal mid-expiratory flow, MMEF)、低呼出50%用力肺活量时的最大呼气流速 (forced expiratory flow 50% of pulmonary volume, FEF50)、低FEF75与COPD发生的关系, 并采用LASSO-Cox回归构建预测模型。 结果: 本前瞻性队列中共有235名研究对象在随访期间发展为COPD患者。PRISm、低PEF、sSAD、低MMEF、低FEF50和低FEF75者发生COPD的风险增加(调整后的风险比 [hazard ratio, HR] 在1.57至3.01之间)。只有慢性支气管炎 (HR 2.84 [95% CI 1.38–5.84] 和2.94 [1.43–6.04]) 和sSAD/低MMEF (HR 2.74 [2.07–3.61] 和2.38 [1.65–3.43]) 的效应独立于其他指标, 且慢性支气管炎和sSAD共存或慢性支气管炎和低MMEF共存的效应最强 (HR 5.89和4.80)。本研究构建的预测模型因子包括年龄、性别、低MMEF、低FEF50和室内生物燃料暴露。该模型在内部验证和外部验证中均表现出良好的预测性能。内部验证中该模型的区分度即校正后C-index为0.77 (0.72–0.81)。外部验证中受试者工作特征曲线下面积为0.73 (0.63–0.83)。该模型在内部验证的校准图和外部验证的Hosmer-Lemeshow检验中均显示出良好的校准度。 解读: 慢性支气管炎和sSAD/低MMEF是提示COPD前期的最佳指标, 同时存在这两种表现的个体需引起临床医生的高度重视。本研究构建的预测模型可以作为一个多维度的综合预测COPD的工具。 资助: 中华人民共和国财政部、科学技术部和国家自然科学基金。

Keywords

• COPD
• Pre-COPD
• Prediction model