合并糖尿病及其病情严重程度与支气管扩张患者菌群变化：EMBARC、印度 EMBARC、澳大利亚及中国支气管扩张登记库联合
2026/06/01
摘要
背景：支气管扩张与糖尿病常合并发病，二者均会造成免疫功能异常，使机体感染易感性升高。糖尿病会加剧囊性纤维化相关支气管扩张患者的不良预后，但目前尚无充足证据阐明其对非囊性纤维化型支气管扩张的影响。
目的：本研究旨在探究糖尿病对支气管扩张患者临床结局、菌群特征及炎症指标的作用。
方法：整合欧洲支气管扩张登记库、印度呼吸研究网络、中国支气管扩张登记库与澳大利亚支气管扩张登记库数据，共纳入 33 个国家 30263 例经胸部 CT 确诊的支气管扩张患者。其中欧洲库纳入 16963 例，收集时段 2015 年 1 月 12 日至 2022 年 4 月 12 日；印度及其他亚洲地区纳入 2361 例，收集时段 2015 年 6 月 1 日至 2017 年 9 月 1 日；中国库纳入 10324 例，收集时段 2020 年 1 月 10 日至 2024 年 3 月 31 日；澳大利亚库纳入 615 例，收集时段 2016 年 3 月 7 日至 2018 年 9 月 11 日。对比合并与未合并糖尿病患者的临床资料，远期结局数据取自欧洲及印度登记库。选取欧洲库部分患者开展亚组分析，通过痰液 16S 核糖体核糖核酸测序检测菌群构成（433 例），采用奥灵蛋白检测技术分析血清炎症因子水平（479 例）。
结果：30263 例支气管扩张患者中，2487 例合并糖尿病，占比 8.2%。合并糖尿病患者合并症发生率显著更高，心血管疾病 53.5% 对比 21.8%、哮喘 27.5% 对比 21.0%、慢性阻塞性肺疾病 34.3% 对比 19.0%，组间差异均具有统计学意义。合并糖尿病患者病情程度更重，支气管扩张严重指数评分、英国医学研究委员会呼吸困难评分更高，近一年住院次数也明显增多。校正混杂因素后，该类患者临床结局显著变差，急性发作发生率比 1.18，95% 置信区间 1.09~1.28；住院发生率比 1.57，95% 置信区间 1.40~1.76；5 年死亡风险比 1.80，95% 置信区间 1.53~2.12。合并糖尿病患者痰液菌群结构发生明显改变，肠杆菌科、卡他莫拉菌、流感嗜血杆菌检出率显著上升。血清中半乳糖凝集素 4、生长分化因子 15 水平明显升高，二者均为评估糖尿病病情严重程度及心血管风险的标志物。
结论：相较于无糖尿病患者，合并糖尿病的支气管扩张人群病情更重、合并症更多、感染风险更高，整体预后更差。该结果提示，临床开展支气管扩张个体化风险评估时，需将糖尿病列为重要危险因素。
Comorbid diabetes disease severity and microbial changes in patients with bronchiectasis: a combined analysis of data from the EMBARC, EMBARC-India, Australian, and BE-China registries.
Hull RC, Liu Y, Cao Z, Xuan KTL, de Lima Headley DA, Richardson H, Hennayake C, Lind H, McIntosh E, Pollock J, Hughes C, Viligorska K, Choi H, Gao Y, Chotirmall SH, Shoemark A, Robertson K, Burgel PR, Vendrell M, Xu X, Qu JM, Song Y, Guan WJ, Chen R, Singh S, Talwar D, Mohan BVM, Tripathi SK, Swarnakar R, Trivedi S, Goeminne PC, Shteinberg M, De Soyza A, Altenburg J, Haworth CS, Sibila O, Polverino E, Loebinger MR, Ringshausen FC, Mertsch P, Lorent N, Dimakou K, Mendez R, Mclaughlin AM, Borrill Z, Lord R, Finch S, Blasi F, Burr L, Crisafulli M, Keating R, Middleton PG, Long MB, Aliberti S, Morgan L, Dhar R, Chalmers JD, Xu JF; EMBARC, EMBARC India, Australian bronchiectasis registry and BE-China.
Abstract
BACKGROUND:Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis.
OBJECTIVE:This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis.
METHODS:This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479).
RESULTS:2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and more hospital admissions in the previous year (p<0·0001). After adjustment for confounders, outcomes were significantly worse in patients with diabetes than in those without diabetes, including more frequent exacerbations (incidence rate ratio [IRR] 1·18 [95% CI 1·09-1·28], p<0·0001), hospital admissions (IRR 1·57 [1·40-1·76], p<0·0001), and higher 5-year mortality (hazard ratio 1·80 [1·53-2·12], p<0·0001). The sputum microbiome was significantly altered in patients with diabetes compared to those without diabetes, with increased isolation of Enterobacteriaceae (p<0·0001), Moraxella catarrhalis (p=0·0035), and Haemophilus influenzae (p=0·046). In serum, Gal-4 and GDF-15, established biomarkers of disease severity and cardiovascular risk in diabetes, were significantly increased in patients with diabetes (Gal-4, p<0·0001; GDF-15, p=0·0019).
CONCLUSION:Patients with diabetes and bronchiectasis are a high-risk population with more severe disease, worse outcomes, increased comorbidities, and increased risk of infections compared with patients without diabetes. These findings support inclusion of diabetes as a risk factor in individualised risk assessments for bronchiectasis.
背景：支气管扩张与糖尿病常合并发病，二者均会造成免疫功能异常，使机体感染易感性升高。糖尿病会加剧囊性纤维化相关支气管扩张患者的不良预后，但目前尚无充足证据阐明其对非囊性纤维化型支气管扩张的影响。
目的：本研究旨在探究糖尿病对支气管扩张患者临床结局、菌群特征及炎症指标的作用。
方法：整合欧洲支气管扩张登记库、印度呼吸研究网络、中国支气管扩张登记库与澳大利亚支气管扩张登记库数据，共纳入 33 个国家 30263 例经胸部 CT 确诊的支气管扩张患者。其中欧洲库纳入 16963 例，收集时段 2015 年 1 月 12 日至 2022 年 4 月 12 日；印度及其他亚洲地区纳入 2361 例，收集时段 2015 年 6 月 1 日至 2017 年 9 月 1 日；中国库纳入 10324 例，收集时段 2020 年 1 月 10 日至 2024 年 3 月 31 日；澳大利亚库纳入 615 例，收集时段 2016 年 3 月 7 日至 2018 年 9 月 11 日。对比合并与未合并糖尿病患者的临床资料，远期结局数据取自欧洲及印度登记库。选取欧洲库部分患者开展亚组分析，通过痰液 16S 核糖体核糖核酸测序检测菌群构成（433 例），采用奥灵蛋白检测技术分析血清炎症因子水平（479 例）。
结果：30263 例支气管扩张患者中，2487 例合并糖尿病，占比 8.2%。合并糖尿病患者合并症发生率显著更高，心血管疾病 53.5% 对比 21.8%、哮喘 27.5% 对比 21.0%、慢性阻塞性肺疾病 34.3% 对比 19.0%，组间差异均具有统计学意义。合并糖尿病患者病情程度更重，支气管扩张严重指数评分、英国医学研究委员会呼吸困难评分更高，近一年住院次数也明显增多。校正混杂因素后，该类患者临床结局显著变差，急性发作发生率比 1.18，95% 置信区间 1.09~1.28；住院发生率比 1.57，95% 置信区间 1.40~1.76；5 年死亡风险比 1.80，95% 置信区间 1.53~2.12。合并糖尿病患者痰液菌群结构发生明显改变，肠杆菌科、卡他莫拉菌、流感嗜血杆菌检出率显著上升。血清中半乳糖凝集素 4、生长分化因子 15 水平明显升高，二者均为评估糖尿病病情严重程度及心血管风险的标志物。
结论：相较于无糖尿病患者，合并糖尿病的支气管扩张人群病情更重、合并症更多、感染风险更高，整体预后更差。该结果提示，临床开展支气管扩张个体化风险评估时，需将糖尿病列为重要危险因素。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（Lancet Respir Med. 2026 May 19:S2213-2600(26)00057-3. doi: 10.1016/S2213-2600(26)00057-3.）
（Lancet Respir Med. 2026 May 19:S2213-2600(26)00057-3. doi: 10.1016/S2213-2600(26)00057-3.）
Comorbid diabetes disease severity and microbial changes in patients with bronchiectasis: a combined analysis of data from the EMBARC, EMBARC-India, Australian, and BE-China registries.
Hull RC, Liu Y, Cao Z, Xuan KTL, de Lima Headley DA, Richardson H, Hennayake C, Lind H, McIntosh E, Pollock J, Hughes C, Viligorska K, Choi H, Gao Y, Chotirmall SH, Shoemark A, Robertson K, Burgel PR, Vendrell M, Xu X, Qu JM, Song Y, Guan WJ, Chen R, Singh S, Talwar D, Mohan BVM, Tripathi SK, Swarnakar R, Trivedi S, Goeminne PC, Shteinberg M, De Soyza A, Altenburg J, Haworth CS, Sibila O, Polverino E, Loebinger MR, Ringshausen FC, Mertsch P, Lorent N, Dimakou K, Mendez R, Mclaughlin AM, Borrill Z, Lord R, Finch S, Blasi F, Burr L, Crisafulli M, Keating R, Middleton PG, Long MB, Aliberti S, Morgan L, Dhar R, Chalmers JD, Xu JF; EMBARC, EMBARC India, Australian bronchiectasis registry and BE-China.
Abstract
BACKGROUND:Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis.
OBJECTIVE:This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis.
METHODS:This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479).
RESULTS:2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and more hospital admissions in the previous year (p<0·0001). After adjustment for confounders, outcomes were significantly worse in patients with diabetes than in those without diabetes, including more frequent exacerbations (incidence rate ratio [IRR] 1·18 [95% CI 1·09-1·28], p<0·0001), hospital admissions (IRR 1·57 [1·40-1·76], p<0·0001), and higher 5-year mortality (hazard ratio 1·80 [1·53-2·12], p<0·0001). The sputum microbiome was significantly altered in patients with diabetes compared to those without diabetes, with increased isolation of Enterobacteriaceae (p<0·0001), Moraxella catarrhalis (p=0·0035), and Haemophilus influenzae (p=0·046). In serum, Gal-4 and GDF-15, established biomarkers of disease severity and cardiovascular risk in diabetes, were significantly increased in patients with diabetes (Gal-4, p<0·0001; GDF-15, p=0·0019).
CONCLUSION:Patients with diabetes and bronchiectasis are a high-risk population with more severe disease, worse outcomes, increased comorbidities, and increased risk of infections compared with patients without diabetes. These findings support inclusion of diabetes as a risk factor in individualised risk assessments for bronchiectasis.
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