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在一项大型基于登记的队列研究中抗生素和哮喘药物-混杂、因果关系。

Antibiotics and asthma medication in a large register-based cohort study - confounding, cause and effect.

机构信息

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

出版信息

Clin Exp Allergy. 2012 Jan;42(1):104-11. doi: 10.1111/j.1365-2222.2011.03850.x. Epub 2011 Sep 23.

Abstract

BACKGROUND

An association between asthma and antibiotic usage has been demonstrated, and the issue of reverse causation and confounding by indication is much debated.

OBJECTIVE

Our aim was to study the association between different classes of antibiotics and prescription of asthma medication in a register-based cohort of all Swedish children, born between July 2005 and June 2009, ever treated with antibiotics.

METHODS

Data on dispensed prescriptions of antibiotics (ATC-codes J01) and asthma medication (ATC-codes R03A-D) were requested from the Prescribed Drug Register. The association between dispensed prescriptions of different classes of antibiotics and asthma medication was analysed with Cox regression and a descriptive sequence symmetry analysis.

RESULTS

In total, 211 192 children had received prescriptions of antibiotics. There was a strong association between prescription of antibiotics and prescription of asthma medication. The hazard ratios (HRs) for asthma medication associated with prescription of amoxicillin, penicillin, cephalosporin and macrolides (Gram-positive infections) were stronger than HRs associated with prescription of sulphonamides, trimethoprim and quinolones (urinary tract infections) and flucloxacillin (skin and soft tissue infections), e.g. first year HR = 2.27 (95% confidence intervals 2.17-2.37) as compared with HR = 1.04 (0.78-1.40). The HR associated with broad spectrum antibiotics was significantly higher than the narrow spectrum.

CONCLUSIONS AND CLINICAL RELEVANCE

Our data suggest that the association between antibiotics and asthma is subject to either reverse causation or confounding by indication due to respiratory tract infections. This implies that careful consideration is required as to whether or not symptoms from the respiratory tract in early childhood should be treated with antibiotics or asthma medication.

摘要

背景

已经证明哮喘与抗生素使用之间存在关联,而因果关系的反向和指示性混杂问题存在很大争议。

目的

我们旨在研究不同类别的抗生素与在所有瑞典儿童(2005 年 7 月至 2009 年 6 月之间出生,曾接受过抗生素治疗)登记队列中开具哮喘药物之间的关联。

方法

从处方药物登记处请求有关抗生素(ATC 代码 J01)和哮喘药物(ATC 代码 R03A-D)的配药数据。使用 Cox 回归和描述性序列对称分析来分析不同类别的抗生素与哮喘药物之间的关联。

结果

共有 211 192 名儿童接受了抗生素处方。抗生素处方与哮喘药物处方之间存在很强的关联。与处方阿莫西林、青霉素、头孢菌素和大环内酯类药物(针对革兰氏阳性感染)相关的哮喘药物的风险比(HR)高于与处方磺胺类药物、甲氧苄啶和喹诺酮类药物(尿路感染)和氟氯西林(皮肤和软组织感染)相关的 HR,例如第一年的 HR 为 2.27(95%置信区间 2.17-2.37),而 HR 为 1.04(0.78-1.40)。与广谱抗生素相关的 HR 明显高于窄谱抗生素。

结论和临床相关性

我们的数据表明,抗生素和哮喘之间的关联可能是由于呼吸道感染导致的因果关系的反向或指示性混杂。这意味着需要仔细考虑是否应使用抗生素或哮喘药物治疗儿童早期呼吸道症状。

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