Smith Kelsi A, Hiyoshi Ayako, Burkill Sarah, Bahmanyar Shahram, Öckinger Johan, Alfredsson Lars, Olsson Tomas, Montgomery Scott
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
BMJ Neurol Open. 2020 Jun 16;2(1):e000044. doi: 10.1136/bmjno-2020-000044. eCollection 2020.
Respiratory inflammation has been proposed as a risk factor for MS. This study aims to determine if hospital-diagnosed pneumonia in adolescence (before age 20 years) is associated with subsequent multiple sclerosis (MS).
This case-control study included incident MS cases after age 20 years identified using the Swedish national registers. Cases were matched with 10 general population controls by age, sex and region. Pneumonia diagnoses were identified between 0-5, 6-10, 11-15 and 16-20 years of age. Conditional logistic regression models adjusted for infectious mononucleosis (IM) and education calculated ORs with 95% CIs. Urinary tract infections (UTIs), a common complication of MS, before age 20 years were included as a control diagnosis for reverse causation.
There were 6109 cases and 49 479 controls included. Pneumonia diagnosed between age 11-15 years was associated with subsequent MS (adj OR 2.00, 95% CI 1.22 to 3.27). Although not statistically significant, sensitivity analyses showed similar magnitude associations of pneumonia between age 11-15 years and MS. No statistically significant associations with MS for pneumonia at other age groups were observed. Adjustment for IM had no notable effect on associations, but was statistically significantly associated with MS. UTIs were not associated with MS.
Pneumonia at 11-15 years of age was associated with MS, suggesting a possible role for inflammation of the respiratory system in the aetiology of MS during a period of susceptibility in adolescence. Further research on respiratory infections prior to MS onset should be conducted to replicate this finding and determine explanatory causal mechanisms.
呼吸道炎症被认为是多发性硬化症（MS）的一个风险因素。本研究旨在确定青少年期（20岁之前）医院诊断的肺炎是否与随后发生的多发性硬化症（MS）相关。
本病例对照研究纳入了使用瑞典国家登记册确定的20岁以后发病的MS病例。病例按年龄、性别和地区与10名普通人群对照进行匹配。在0至5岁、6至10岁、11至15岁和16至20岁之间确定肺炎诊断。采用条件逻辑回归模型，对传染性单核细胞增多症（IM）和教育程度进行调整，计算比值比（OR）及95%可信区间（CI）。将20岁之前MS的常见并发症尿路感染（UTIs）作为反向因果关系的对照诊断纳入研究。
共纳入6109例病例和49479名对照。11至15岁之间诊断的肺炎与随后发生的MS相关（校正OR为2.00，95%CI为1.22至3.27）。尽管无统计学意义，但敏感性分析显示11至15岁之间的肺炎与MS的关联程度相似。在其他年龄组未观察到肺炎与MS有统计学意义的关联。对IM进行调整对关联无显著影响，但IM与MS有统计学显著关联。UTIs与MS无关。
11至15岁时的肺炎与MS相关，提示在青少年易患期，呼吸系统炎症在MS病因学中可能起作用。应进一步开展MS发病前呼吸道感染的研究，以重复这一发现并确定解释性因果机制。
