2014年5月20日讯 /生物谷BIOON/--婴儿在他们第一个生日前接受抗生素治疗可能导致患哮喘的风险上升。然而，英国曼彻斯特大学的新研究表明，针对病毒的免疫系统受损和17号染色体遗传变异，增加了早期使用抗生素治疗后哮喘发展的风险，而不是之前认为的是因为抗生素使用而导致的。
重要的是，这项研究，没有发现早期抗生素处方的使用和过敏性疾病发展之间的联系。结果，发表在The Lancet Respiratory Medicine杂志上，这与早期研究学说相矛盾：抗生素的用量能够改变肠道菌群，改变了儿童免疫系统的发育，导致过敏性哮喘的发病率增加。
在儿童中，抗生素通常用于治疗呼吸道感染，耳部感染和支气管炎，以及一些研究报告说，幼儿期抗生素的使用和后续发展哮喘之间的联系。然而，系统评价报告了相互矛盾的结果，这呼吁更多的纵向研究以提供明确的答案。
在这项研究中，英国研究人员检查从曼彻斯特哮喘和过敏研究（MAAS）报告中的数据，此研究收集了1000多名儿童从出生到11岁的数据。抗生素处方，喘鸣和哮喘发作信息取自病历。在3岁，5，8和11岁时，进行皮肤反应测试是否有引起该儿童过敏的过敏原。
在11岁时，收集在1岁之前接受抗生素至少一疗程或未用抗生素治疗的孩子的血液，以比较他们的免疫系统细胞对病毒（如鼻病毒，呼吸道合胞病毒）和细菌（流感嗜血杆菌和肺炎链球菌）的免疫反应。为了研究17号染色体（17q21）遗传变异与抗生素处方之间的联系，基因检测了17号染色体。
这项研究的结果被认为是第一次证明，哮喘儿童在1岁之前使用抗生素治疗，比未经治疗的儿童面临严重哮喘或哮喘发作的可能性达两倍以上。同样的，这些孩子也表现出细胞因子应答能力显著降低，这是身体免受病毒感染如普通感冒的关键防线。但是，在抗菌反应中没有差异。
研究人员还发现17q21区域的两个基因与早期生命抗生素处方治疗风险增加有关联。主要作者教授Adnan Custovic说：我们推测，增加早期抗生素处方使用以后哮喘发病的隐性因素是由于抗病毒免疫受损和17q21遗传变异，导致病毒性感染的易感性增加。然而，进一步的研究将需要确认免疫力受损是存在于幼儿呼吸道疾病中和抗生素处方使用之后，而不是抗生素使用的后果。（生物谷Bioon.com）
doi:10.1016/S2213-2600(14)70096-7
PMC:
PMID:
Assessing the association of early life antibiotic prescription with asthma exacerbations, impaired antiviral immunity, and genetic variants in 17q21: a population-based birth cohort study.
Aida Semic-Jusufagic, Danielle Belgrave, Andrew Pickles, Aurica G Telcian, Eteri Bakhsoliani, Annemarie Sykes, Angela Simpson, Sebastian L Johnston, Adnan Custovic.
Background
The relationship between early-life antibiotic use and the development of wheeze and asthma has been reported in several studies but might arise as a consequence of bias rather than causal relationship. We investigated the association between antibiotic prescription and subsequent development of atopy, wheeze, and asthma exacerbations, and the relation of early life antibiotic prescription with anti-infective immunity and genetic variants on asthma susceptibility locus 17q21.
Methods
Children in a population-based birth cohort were followed from birth to age 11 years. Information on antibiotic prescription, wheeze, and asthma exacerbations was extracted from medical records, and the effect of antibiotic prescription assessed with longitudinal analyses. We assessed immune responses of peripheral blood mononuclear cells, taken at age 11 years, to viruses (rhinovirus and respiratory syncytial virus; RSV) and bacteria (Haemophilus influenzae and Streptococcus pneumoniae) in children who either received at least one or no antibiotic prescriptions in infancy. Finally, we assessed the association of 17q21 polymorphisms with antibiotic prescription.
Findings
Of 984 families who gave consent, we extracted data for 916 children. We noted significantly higher risk of physician-confirmed wheezing after antibiotic prescription (hazard ratio [HR] 1·71, 95% CI 1·32—2·23; p<0·0001) and severe wheeze or asthma exacerbation after antibiotic prescription (HR 2·26, 95% CI 1·03—4·94; p=0·041). In children who wheezed, the hazards of exacerbations (2·09, 1·51—2·90; p<0·0001) and admissions to hospital (2·64, 1·49—4·70; p=0·0009) were significantly increased in the 2 years after the first antibiotic prescription. Children who received antibiotics in infancy had significantly lower induction of cytokines, which are important in host defence against virus infections to both RSV and rhinovirus; there were no differences in antibacterial responses. Variants in 17q21 were associated with an increased risk of early life antibiotic prescription.
Interpretation
The association between antibiotics and asthma might arise through a complex confounding by indication. Hidden factors that may increase the likelihood of both early life antibiotic prescription and later asthma are an increased susceptibility to viral infections consequent upon impaired antiviral immunity and genetic variants on 17q21.
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