Abstract：
BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination, primarily administered to prevent tuberculosis, exhibits nonspecific immune effects and could play a role in inflammatory bowel disease prevention. We investigated the associations of BCG with Crohn\'s disease and ulcerative colitis, and assessed sex-differences.
METHODS: This two-stage study included 365,206 Canadians from the Quebec Birth Cohort on Immunity and Health (1970-2014; stage 1). Vaccination status was registry-based and inflammatory bowel disease cases were identified from health services with validated algorithms. We documented additional factors among 2644 participants in a nested case-control study in 2021 (stage 2). A two-stage logistic regression analysis was applied to estimate the odds ratios (OR), corrected for sampling fractions and adjusted for confounding factors. We used interaction terms to assess sex-differences on the multiplicative scale.
RESULTS: In the stage 1 sample, 2419 cases of Crohn\'s disease and 1079 of ulcerative colitis were included. Forty-six percent of non-cases received the BCG vaccine as compared to 47% for Crohn\'s disease and 49% for ulcerative colitis. Associations differed by sex. BCG vaccination was not associated with Crohn\'s disease among men (OR = 0.91; 95% CI: 0.79-1.04) but was related to an increased risk among women (OR = 1.13; 95% CI: 1.00-1.28, P interaction: 0.001). For ulcerative colitis, there was a tendency toward a slightly elevated risk among men (OR = 1.09; 95%CI: 0.90-1.32), whereas the risk was more substantial for women (OR = 1.17; 95% CI:0.99-1.39, P interaction: <0.001).
CONCLUSIONS: BCG vaccination does not play a preventive role in inflammatory bowel disease. Our results point to distinct associations between men and women.
METHODS: This two-stage study included 365,206 Canadians from the Quebec Birth Cohort on Immunity and Health (1970-2014; stage 1). Vaccination status was registry-based and inflammatory bowel disease cases were identified from health services with validated algorithms. We documented additional factors among 2644 participants in a nested case-control study in 2021 (stage 2). A two-stage logistic regression analysis was applied to estimate the odds ratios (OR), corrected for sampling fractions and adjusted for confounding factors. We used interaction terms to assess sex-differences on the multiplicative scale.
RESULTS: In the stage 1 sample, 2419 cases of Crohn\'s disease and 1079 of ulcerative colitis were included. Forty-six percent of non-cases received the BCG vaccine as compared to 47% for Crohn\'s disease and 49% for ulcerative colitis. Associations differed by sex. BCG vaccination was not associated with Crohn\'s disease among men (OR = 0.91; 95% CI: 0.79-1.04) but was related to an increased risk among women (OR = 1.13; 95% CI: 1.00-1.28, P interaction: 0.001). For ulcerative colitis, there was a tendency toward a slightly elevated risk among men (OR = 1.09; 95%CI: 0.90-1.32), whereas the risk was more substantial for women (OR = 1.17; 95% CI:0.99-1.39, P interaction: <0.001).
CONCLUSIONS: BCG vaccination does not play a preventive role in inflammatory bowel disease. Our results point to distinct associations between men and women.
摘要：
背景：卡介苗（BCG）疫苗接种，主要用于预防结核病，表现出非特异性免疫效应，并可能在炎症性肠病的预防中发挥作用。我们调查了卡介苗与克罗恩病和溃疡性结肠炎的关系。并评估性别差异。
方法：这项两阶段研究包括来自魁北克出生队列免疫和健康（1970-2014年；阶段1）的365,206名加拿大人。疫苗接种状态是基于注册的，并且使用经过验证的算法从卫生服务中识别出炎症性肠病病例。我们在一项巢式病例对照研究中记录了2644名参与者的其他因素，2021年（第二阶段）。采用两阶段逻辑回归分析估计比值比(OR)，针对采样分数进行校正，并针对混杂因素进行调整。我们使用交互术语在乘法量表上评估性别差异。
结果：在第1阶段样本中，纳入2419例克罗恩病和1079例溃疡性结肠炎。46％的非病例接种了卡介苗，而克罗恩病的比例为47％，溃疡性结肠炎的比例为49％。协会因性别而异。卡介苗接种与男性克罗恩病无关（OR=0.91；95%CI：0.79-1.04），但与女性风险增加有关（OR=1.13；95%CI：1.00-1.28，P交互作用：0.001）。对于溃疡性结肠炎，男性风险有轻微升高的趋势(OR=1.09;95CI:0.90-1.32)，而女性的风险更大（OR=1.17;95％CI：0.99-1.39，P交互作用：<0.001）。
结论：卡介苗接种对炎症性肠病没有预防作用。我们的结果指出了男女之间的明显关联。
方法：这项两阶段研究包括来自魁北克出生队列免疫和健康（1970-2014年；阶段1）的365,206名加拿大人。疫苗接种状态是基于注册的，并且使用经过验证的算法从卫生服务中识别出炎症性肠病病例。我们在一项巢式病例对照研究中记录了2644名参与者的其他因素，2021年（第二阶段）。采用两阶段逻辑回归分析估计比值比(OR)，针对采样分数进行校正，并针对混杂因素进行调整。我们使用交互术语在乘法量表上评估性别差异。
结果：在第1阶段样本中，纳入2419例克罗恩病和1079例溃疡性结肠炎。46％的非病例接种了卡介苗，而克罗恩病的比例为47％，溃疡性结肠炎的比例为49％。协会因性别而异。卡介苗接种与男性克罗恩病无关（OR=0.91；95%CI：0.79-1.04），但与女性风险增加有关（OR=1.13；95%CI：1.00-1.28，P交互作用：0.001）。对于溃疡性结肠炎，男性风险有轻微升高的趋势(OR=1.09;95CI:0.90-1.32)，而女性的风险更大（OR=1.17;95％CI：0.99-1.39，P交互作用：<0.001）。
结论：卡介苗接种对炎症性肠病没有预防作用。我们的结果指出了男女之间的明显关联。
