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Background <p>Several digestive diseases have been reported as comorbidities of COPD. However, consistent evidence supporting their associations is limited. Our study aims to investigate the associations between prevalent COPD and incident digestive diseases in the Chinese population.</p> Methods <p>We used data from the China Kadoorie Biobank (CKB), enrolling 512,724 participants aged 30–79 years at baseline from 10 areas in China. COPD was defined by spirometry (without bronchodilator) and self-reported emphysema/chronic bronchitis at baseline. We employed stratified Cox proportional regression models to assess the prospective associations of prevalent COPD and airflow obstruction severity with the risks of incident digestive diseases. A total of 31 digestive diseases were included, including the overall digestive diseases, 15 major disease categories, and 15 specific subtypes nested within the major categories. We further conducted one-sample Mendelian randomization analyses to assess the associations of genetically predicted COPD with digestive diseases.</p> Results <p>During a median follow-up of 15.3 years, a total of 131,993 participants experienced at least one hospitalization or death due to the included digestive diseases. For the composite outcome and major categories, prevalent COPD at baseline was significantly associated with a higher risk of overall digestive diseases (hazard ratio and 95% confidence interval: 1.05 [1.03–1.08]), gastrointestinal inflammation (1.11 [1.07–1.15]) and abdominal pain (1.20 [1.12–1.28]). Dose–response associations of airflow obstruction severity with the overall digestive diseases (<i>P</i> value for trend: &lt; 0.001) and six other disease types were identified. In MR analyses, a genetically predicted higher probability of COPD was significantly associated with overall digestive diseases (OR per doubling of genetically-predicted COPD prevalence: 3.21 [1.71–6.03]) and three other disease types.</p> Conclusions <p>Prevalent COPD is associated with various digestive diseases in the Chinese population, with MR analyses further supporting a potential causal link. These findings underscore the importance of considering disease severity when managing COPD-related digestive diseases. While COPD was defined based on baseline spirometry in this study, future research incorporating post-bronchodilator assessment could further refine these associations and help distinguish COPD from other reversible airflow limitations.</p>

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Chronic obstructive pulmonary disease and risk of digestive diseases: observational and mendelian randomization analyses in the China Kadoorie Biobank

  • 期刊论文

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  • 发表日期：

    2026年7月17日

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  • Yuxuan Zhao,
  • Yalei Ke,
  • Dianjianyi Sun,
  • Pei Pei,
  • Ling Yang,
  • Iona Y. Millwood,
  • Robin G. Walters,
  • Yiping Chen,
  • Huaidong Du,
  • Junshi Chen,
  • Zhengming Chen,
  • Jun Lv,
  • Liming Li,
  • Canqing Yu,
  • Robert Clarke,
  • Rory Collins,
  • Richard Peto,
  • Daniel Avery,
  • Maxim Barnard,
  • Derrick Bennett,
  • Ruth Boxall,
  • Zhengming Chen,
  • Johnathan Clarke,
  • Ahmed Edris Mohamed,
  • Hannah Fry,
  • Prapthi Harish,
  • Pek Kei Im,
  • Andri Iona,
  • Christiana Kartsonaki,
  • Kshitij Kolhe,
  • Hubert Lam,
  • Kuang Lin,
  • James Liu,
  • Sam Morris,
  • Qunhua Nie,
  • Alfred Pozarickij,
  • Maryanm Rahmati,
  • Paul Ryder,
  • Maruf Sarder,
  • Dan Schmidt,
  • Becky Stevens,
  • Iain Turnbull,
  • Baihan Wang,
  • Lin Wang,
  • Neil Wright,
  • Xiaoming Yang,
  • Pang Yao,
  • Dianjianyi Sun,
  • Yuanjie Pang,
  • Yuting Han,
  • Can Hou,
  • Qingmei Xia,
  • Chao Liu,
  • Lang Pan,
  • Xiao Han,
  • Honglu Bian,
  • Xinxin Chen,
  • Zengchang Pang,
  • Ruqin Gao,
  • Kunzheng Lv,
  • Shanpeng Li,
  • Haiping Duan,
  • Shaojie Wang,
  • Yongmei Liu,
  • Ranran Du,
  • Liang Cheng,
  • Xiaocao Tian,
  • Hua Zhang,
  • Dan Hu,
  • Xiaoyan Zheng,
  • Yujie Wan,
  • Wei Sun,
  • Shichun Yan,
  • Yong Zhou,
  • Chi Wang,
  • Zhenyuan Wu,
  • Lishun Zhai,
  • Zhaoxi Pang,
  • Shiwen Dong,
  • Li Liu,
  • Dapeng Yin,
  • Bin He,
  • Ying Liu,
  • Xingren Wang,
  • Tingting Ou,
  • Xiangyang Zheng,
  • Dewei Zheng,
  • Shuai Yang,
  • Lihui Li,
  • Xingjiao Chen,
  • Yan Xu,
  • Jinyi Zhou,
  • Ran Tao,
  • Jian Su,
  • Xikang Fan,
  • Xuejia Chen,
  • Yuxiao Huang,
  • Yan Lu,
  • Yujie Hua,
  • Li Xing,
  • Shuxian Wang,
  • Jianrong Jin,
  • Juping Ma,
  • Kaifei Zhu,
  • Hongfu Ren,
  • Xingfeng Shen,
  • Ge Zhong,
  • Wei Mao,
  • Zhenzhen Lu,
  • Yanxu Zhong,
  • Lifang Zhou,
  • Rong Pan,
  • Jian Lan,
  • Xiaoping Tan,
  • Jinxue Tan,
  • Yishan Xie,
  • Liuping Wei,
  • Liyuan Zhou,
  • Sisi Wang,
  • Xianping Wu,
  • Ningmei Zhang,
  • Xiaofang Chen,
  • Xiaoyu Chang,
  • Zhuo Wang,
  • Yujin He,
  • Mingqiang Yuan,
  • Ling Wang,
  • Zhaodong Wang,
  • Qiang Sun,
  • Yang Lin,
  • Faqing Chen,
  • Xiaolan Ren,
  • Lijun Chang,
  • Feiming Zhong,
  • Jianjun Feng,
  • Weijie Hu,
  • Xiaofang Zhang,
  • Yalin Chen,
  • Honghong Wang,
  • Jun Wang,
  • Linqi Diao,
  • Zhiwei Han,
  • Dengjun Zhu,
  • Kai Kang,
  • Shixian Feng,
  • Wenjie Yang,
  • Huizi Tian,
  • Yali Yan,
  • Bing Han,
  • Li Gao,
  • Shaofang Li,
  • Tianfang Xing,
  • Wei Tang,
  • Xiaolin Li,
  • Huarong Sun,
  • Xiaocong Zhao,
  • Chen Hu,
  • Pan He,
  • Xukui Zhang,
  • Jin Yuanyuan,
  • Lan Luo,
  • Min Yu,
  • Ruying Hu,
  • Hao Wang,
  • Weiwei Gong,
  • Jieming Zhong,
  • Meng Wang,
  • Chunxiao Xu,
  • Keqing Gong,
  • Hao Xu,
  • Yuan Cao,
  • Kaixu Xie,
  • Lingli Chen,
  • Xiaomei Tu,
  • Junlong Pan,
  • Xiaojun Li,
  • Li Yin,
  • Huilin Liu,
  • Yuan Liu,
  • Lei Yin,
  • Xian Xie,
  • Jing Wang,
  • Bo Xiao,
  • Zongwei Deng,
  • Yuan Peng,
  • Libo Zhang,
  • Chan Qu,
  • Li Deng,
  • Qili Jiang,
  • Yanling Chen,
  • Junshi Chen,
  • Zhengming Chen,
  • Liming Li,
  • Jun Lv,
  • Robin Walters,
  • Yiping Chen,
  • Huaidong Du,
  • Iona Millwood,
  • Ling Yang,
  • Pei Pei,
  • Canqing Yu,
  • Ying Li

摘要

Background

Several digestive diseases have been reported as comorbidities of COPD. However, consistent evidence supporting their associations is limited. Our study aims to investigate the associations between prevalent COPD and incident digestive diseases in the Chinese population.

Methods

We used data from the China Kadoorie Biobank (CKB), enrolling 512,724 participants aged 30–79 years at baseline from 10 areas in China. COPD was defined by spirometry (without bronchodilator) and self-reported emphysema/chronic bronchitis at baseline. We employed stratified Cox proportional regression models to assess the prospective associations of prevalent COPD and airflow obstruction severity with the risks of incident digestive diseases. A total of 31 digestive diseases were included, including the overall digestive diseases, 15 major disease categories, and 15 specific subtypes nested within the major categories. We further conducted one-sample Mendelian randomization analyses to assess the associations of genetically predicted COPD with digestive diseases.

Results

During a median follow-up of 15.3 years, a total of 131,993 participants experienced at least one hospitalization or death due to the included digestive diseases. For the composite outcome and major categories, prevalent COPD at baseline was significantly associated with a higher risk of overall digestive diseases (hazard ratio and 95% confidence interval: 1.05 [1.03–1.08]), gastrointestinal inflammation (1.11 [1.07–1.15]) and abdominal pain (1.20 [1.12–1.28]). Dose–response associations of airflow obstruction severity with the overall digestive diseases (P value for trend: < 0.001) and six other disease types were identified. In MR analyses, a genetically predicted higher probability of COPD was significantly associated with overall digestive diseases (OR per doubling of genetically-predicted COPD prevalence: 3.21 [1.71–6.03]) and three other disease types.

Conclusions

Prevalent COPD is associated with various digestive diseases in the Chinese population, with MR analyses further supporting a potential causal link. These findings underscore the importance of considering disease severity when managing COPD-related digestive diseases. While COPD was defined based on baseline spirometry in this study, future research incorporating post-bronchodilator assessment could further refine these associations and help distinguish COPD from other reversible airflow limitations.