阻塞性肺疾病患者长期使用质子泵抑制剂的病情恶化风险
2026/02/02
摘要
背景：先前的研究在质子泵抑制剂（PPIs）的使用与慢性阻塞性气道疾病患者病情恶化风险之间的关联上得出了不一致的结果。
研究问题：长期使用PPI是否与病情恶化风险相关？
方法：我们利用比利时全国范围内2017 - 2022年间使用慢性药物治疗阻塞性气道疾病（COAD）的成年患者索赔数据，采用多变量Cox模型研究了PPI使用与病情恶化风险之间的关联。根据前一年发放的限定日剂量（DDD），通过治疗逆概率加权（IPTW）Cox回归模型评估了剂量依赖性关联。
结果：在纳入的932,135例COAD患者中，416,087例（44.6%）使用PPI，其中57,540（例13.8%）前一年的PPI服用剂量为1 - 28 DDD，128,017例（30.8%）为29 - 180 DDD，127,981例（30.8%）为181 - 365 DDD，102,549例（24.6%）超过365 DDD。除年龄、性别、吸烟状况、社会经济地位、病情恶化史、短效支气管扩张剂使用情况、身体虚弱程度和合并症外，PPI的使用与病情恶化风险增加相关（调整后风险比[aHR] 1.18，95%置信区间[CI] 1.17 - 1.19）。此外，与未使用者相比，病情恶化的风险随累积DDD增加而升高（剂量≤28 DDD时风险比[HR] 1.09，95%CI 1.07 - 1.10；剂量≤180 DDD时HR 1.15，95%CI 1.14 - 1.16；剂量≤365 DDD时HR 1.19，95%CI 1.18 - 1.20；剂量＞365 DDD时HR 1.24，95%CI 1.23 - 1.26）。敏感性分析表明，在无胃食管反流病（GERD）、哮喘患者、50岁以下患者、非身体虚弱患者以及PPI血浆浓度升高的患者中，PPI使用与病情恶化风险的关联最为显著。
结论：阻塞性肺疾病患者累积使用PPI与病情恶化风险增加相关。这凸显了在临床呼吸实践中应谨慎考虑使用PPI。
Exacerbation Risk by Chronic Proton Pump Inhibitor use in Obstructive Lung Diseases
Valerie Dehondt, Frauke Van Vaerenbergh, Katia Verhamme, Lies Lahousse
Abstract
Background: Previous studies have shown inconsistent results regarding the use of proton pump inhibitor (PPIs) and the risk on exacerbations in patients with chronic obstructive airway diseases.
Research question: Is chronic PPI use associated with exacerbation risk?
Methods: Using Belgian nationwide claims-based data of adult patients on chronic medication for obstructive airway diseases (COAD) between 2017 and 2022, we investigated the association between PPI use and exacerbation risk using multivariable Cox models. Based on defined daily doses (DDDs) dispensed during the prior year, dose-dependent associations were assessed by inverse probability of treatment weighted (IPTW) Cox regression models.
Results: Among 932,135 included COAD patients, 416,087 (44.6%) were PPI-users, of whom 57,540 (13.8%) had 1-28 DDDs of PPIs, 128,017 (30.8%) 29-180 DDDs, 127,981 (30.8%) 181-365 DDDs, and 102,549 (24.6%) >365 DDDs in the previous year. Beyond age, sex, smoking, socio-economic status, exacerbation history, short-acting bronchodilator use, frailty and comorbidities, PPI use was associated with an increased risk of exacerbations (aHR 1.18, 95%CI 1.17-1.19). Moreover, compared to non-users, the risk of exacerbations increased with cumulative DDD (HR≤28DDDs 1.09, 95%CI 1.07-1.10; HR≤180DDDs 1.15, 95%CI 1.14-1.16; HR≤365DDDs 1.19, 95%CI 1.18-1.20; and HR>365DDDs 1.24, 95%CI 1.23-1.26). Sensitivity analyses indicated that the association with exacerbation risk was most pronounced in patients without gastroesophageal reflux disease (GERD), with asthma, under 50 years, non-frail patients, and those with increased PPI plasma concentrations.
Conclusion: Cumulative PPI use in patients with obstructive lung diseases was associated with an increase in exacerbation risk. This highlights to carefully consider PPI use in clinical respiratory practice.
背景：先前的研究在质子泵抑制剂（PPIs）的使用与慢性阻塞性气道疾病患者病情恶化风险之间的关联上得出了不一致的结果。
研究问题：长期使用PPI是否与病情恶化风险相关？
方法：我们利用比利时全国范围内2017 - 2022年间使用慢性药物治疗阻塞性气道疾病（COAD）的成年患者索赔数据，采用多变量Cox模型研究了PPI使用与病情恶化风险之间的关联。根据前一年发放的限定日剂量（DDD），通过治疗逆概率加权（IPTW）Cox回归模型评估了剂量依赖性关联。
结果：在纳入的932,135例COAD患者中，416,087例（44.6%）使用PPI，其中57,540（例13.8%）前一年的PPI服用剂量为1 - 28 DDD，128,017例（30.8%）为29 - 180 DDD，127,981例（30.8%）为181 - 365 DDD，102,549例（24.6%）超过365 DDD。除年龄、性别、吸烟状况、社会经济地位、病情恶化史、短效支气管扩张剂使用情况、身体虚弱程度和合并症外，PPI的使用与病情恶化风险增加相关（调整后风险比[aHR] 1.18，95%置信区间[CI] 1.17 - 1.19）。此外，与未使用者相比，病情恶化的风险随累积DDD增加而升高（剂量≤28 DDD时风险比[HR] 1.09，95%CI 1.07 - 1.10；剂量≤180 DDD时HR 1.15，95%CI 1.14 - 1.16；剂量≤365 DDD时HR 1.19，95%CI 1.18 - 1.20；剂量＞365 DDD时HR 1.24，95%CI 1.23 - 1.26）。敏感性分析表明，在无胃食管反流病（GERD）、哮喘患者、50岁以下患者、非身体虚弱患者以及PPI血浆浓度升高的患者中，PPI使用与病情恶化风险的关联最为显著。
结论：阻塞性肺疾病患者累积使用PPI与病情恶化风险增加相关。这凸显了在临床呼吸实践中应谨慎考虑使用PPI。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Chest. 2026 Jan 16:S0012-3692(26)00021-8. doi: 10.1016/j.chest.2026.01.002.）
Exacerbation Risk by Chronic Proton Pump Inhibitor use in Obstructive Lung Diseases
Valerie Dehondt, Frauke Van Vaerenbergh, Katia Verhamme, Lies Lahousse
Abstract
Background: Previous studies have shown inconsistent results regarding the use of proton pump inhibitor (PPIs) and the risk on exacerbations in patients with chronic obstructive airway diseases.
Research question: Is chronic PPI use associated with exacerbation risk?
Methods: Using Belgian nationwide claims-based data of adult patients on chronic medication for obstructive airway diseases (COAD) between 2017 and 2022, we investigated the association between PPI use and exacerbation risk using multivariable Cox models. Based on defined daily doses (DDDs) dispensed during the prior year, dose-dependent associations were assessed by inverse probability of treatment weighted (IPTW) Cox regression models.
Results: Among 932,135 included COAD patients, 416,087 (44.6%) were PPI-users, of whom 57,540 (13.8%) had 1-28 DDDs of PPIs, 128,017 (30.8%) 29-180 DDDs, 127,981 (30.8%) 181-365 DDDs, and 102,549 (24.6%) >365 DDDs in the previous year. Beyond age, sex, smoking, socio-economic status, exacerbation history, short-acting bronchodilator use, frailty and comorbidities, PPI use was associated with an increased risk of exacerbations (aHR 1.18, 95%CI 1.17-1.19). Moreover, compared to non-users, the risk of exacerbations increased with cumulative DDD (HR≤28DDDs 1.09, 95%CI 1.07-1.10; HR≤180DDDs 1.15, 95%CI 1.14-1.16; HR≤365DDDs 1.19, 95%CI 1.18-1.20; and HR>365DDDs 1.24, 95%CI 1.23-1.26). Sensitivity analyses indicated that the association with exacerbation risk was most pronounced in patients without gastroesophageal reflux disease (GERD), with asthma, under 50 years, non-frail patients, and those with increased PPI plasma concentrations.
Conclusion: Cumulative PPI use in patients with obstructive lung diseases was associated with an increase in exacerbation risk. This highlights to carefully consider PPI use in clinical respiratory practice.
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哮喘相关焦虑的在线认知行为疗法：一项随机对照试验
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