To the Editors:
众所周知,肺结核(TB)会导致肺部损伤导致慢性阻塞性肺疾病(COPD)1, but less is known to what extent impaired lung function increases the risk of TB. A case–control study from the UK found patients with emphysema to have a three-fold increased risk of TB, adjusted for smoking and the use of corticosteroids2。丹麦的一项队列研究发现,中度至重度COPD与结核病的住院风险增加了两到三倍3。我们以前已经表明,与人口对照相比,患有COPD住院的患者有活性结核病风险增加了三倍。4。In the present study, we examine the risk of active TB in relation to lung function in a cohort who underwent spirometry in 1974–1992.
Between 1974 and 1992, 22,444 males and 10,902 females, born 1921–1949, participated in a health screening programme, the Malmö Preventive Project. Complete birth cohorts, born in pre-specified years, from the city of Malmö were invited; the overall participation proportion was ∼70%5。The screening included physical examination, spirometry, blood samples and assessment of lifestyle factors by means of a self-administered questionnaire. Some questions varied between the cohorts. We excluded 4,413 individuals because of missing spirometry data; 26 individuals were excluded because of missing data on either body mass index (BMI), smoking or immigration status, leaving a total of 28,907 individuals in final analysis (21,174 males and 7,733 females).
BMI计算为质量/高度2(在kg·m中−2). Individuals were regarded as having diabetes mellitus if they answered positively to the question “Do you have diabetes mellitus?” or their fasting blood glucose level was ≥6.1 mmol·L−1。
Around 96% of the cohort (n = 27,789) answered questions on alcohol. Individuals were regarded as having “problematic drinking” if they answered affirmatively to four or more questions on drinking habits and were regarded as having chronic bronchitis if reporting episodes of chronic productive cough lasting >3 months for more than two consecutive years. Individuals were categorised as current smokers if they answered affirmatively to the question “Are you a smoker?”
57% of the cohort was presented a question regarding precedent TB: “Have you had TB?”
在筛查前和随访期间,通过国家数据库之间的记录联系评估了住院评估和随访期间的移民状况,社会经济状况和事件癌症viaa unique, lifelong personal identity number assigned to each person living in Sweden.
Forced vital capacity and forced expiratory volume in 1 s (FEV1)在筛查检查时通过肺活量测定法测量;FEV1values were analysed as % predicted. The predicted values were obtained using equations derived from linear regression of 3,467 male and 2,961 female never-smokers in the present cohort and classified according to Global Initiative for Obstructive Lung Disease (GOLD) staging, as described previously6,7。
自1989年以来,社交疾病控制区域中心(Malmö,瑞典)一直持有结核病登记册。在瑞典法律应注意主动结核病,并由微生物实验室和临床医生并行进行报告。结果被定义为本地结核病寄存器中通知的第一集。随访结束于结核病的第一集,移民日期,死亡日期或2008年12月31日,以第一位为准。
卡方检验和单向方差分析用于评估具有不同肺功能水平的组之间结核病的危险因素的分布。COX比例危害模型用于估计随后的结核病的危害比(HRS)。FEV1% pred was modelled as a continuous variable; GOLD stage was modelled as categorical. Potential confounders were selecteda priori: smoking status, screening age, sex, bronchitis, immigration status, socioeconomic status, BMI, diabetes mellitus, previous TB, alcohol consumption, cancer, HIV and silicosis were considered. Effect modification by smoking, immigration status, sex and birth cohort was assessed by examining incidence rates of TB in different strata of the covariates and by entering an interaction term to the fully adjusted Cox models.
Proportionalities of hazards were assessed graphically and by testing for a non-zero slope in a generalised linear regression of the scaled Schoenfeld residuals as a function of time. All analyses were performed using STATA SE (version 10.1 for Windows; StataCorp LP, College Station, TX, USA).
A total of 26 TB cases (5.2 per 100,000 person-yrs, 95% CI 3.6–7.7) were notified in the TB register during the follow-up in 1989–2008. TB incidence was inversely correlated with FEV1%PRED(HR每10%单位增加0.71,95%CI 0.59–0.86)。FEV1–TB association persisted after adjustment for current smoking and age at screening (HR per 10%-unit increase 0.75, 95% CI 0.61–0.91). Although the stratified analyses were based on small numbers, the results were largely consistent in different strata of the covariates and all p-values from likelihood ratio tests for interaction were >0.05.
24 cases of TB occurred among 25,869 participants, classified according to the GOLD criteria. The incidence of TB increased with GOLD stage (stage I crude HR 1.9, 95% CI 0.5–6.7; stage II HR 5.64, 95% CI 2.2–14.7; and stage III–IV HR 6.9, 95% CI 0.9–52.6; p<0.001 for linear trend), although only one case of TB was GOLD stage III–IV.
The limited number of TB cases restricted the number of covariates in the final multivariate model. Smoking and screening age were included by forced entry. Additional confounders were examined separately in univariate Cox models (表格1) and in Cox models including FEV1,筛查年龄和吸烟。FEV混淆1- 与FEV模型中的TB关联1,筛查年龄和吸烟(FEV1estimates changed 0.3–2.3%), and were therefore not included in the final model (表格1). None of the participants had a hospital discharge diagnosis listing silicosis or HIV prior to screening. During follow-up, there were 24 cases of HIV and five cases of silicosis. None of these developed TB, nor did any of the 1,109 participants with diabetes at baseline. Seven individuals developed both cancer and active TB during follow-up, but only one of the episodes of cancer occurred within a year from the TB diagnosis.
所有的81参与者医院说charge listing TB or TB sequelae (International Classification of Diseases (ICD) 8: 011–019; ICD 9: 010–018 and 131; ICD 10: A15–A19 and B90) in the in-patient register prior to screening developed TB during follow-up. A stratified analysis in the subgroup who stated no history of TB in the baseline questionnaire (n = 16,291) was performed: 10 cases of TB occurred during follow-up (crude HR per 10%-unit increase in FEV10.68, 95% CI 0.50–0.92).
目前和以前的吸烟状况的数据可在85%的参与者中获得。重新调整该子体系中的分析(n = 25,804),调整了吸烟状态(当前,以前或从未)和筛查年龄的结果相似(HR的结果相似(HR,FEV的10%单位增加了1%PRED 0.74,95%CI 0.61–0.91)。
In this population-based cohort study from a low TB-incidence region, we show that decreased lung function is associated with an increased risk of active TB.
Mycobacterium tuberculosisinfects phagocytic cells in the lung; the clearance rate is not known, but infection is in many cases chronic. Antigen presentation by infected macrophages and subsequent induction of a T-cell response is crucial for controlling infection8。
In COPD, innate defence mechanisms in the airways are impaired, mainly by decreased mucociliary clearance, but additional mechanisms (例如已经描述了巨噬细胞功能的降低)9,10。Factors conferring vulnerability to respiratory infection in COPD might also play a role in increasing the risk of TB infection and/or progression to active TB disease. However, it should be noted that the relationships between FEV1and TB were seen over the entire range of FEV1in this population study, and was not limited to subjects with COPD.
A limitation of the present study is the small number of TB cases. Another limitation is the lack of data on previous TB for a large proportion of the cohort. Residual confounding from other factors, such as medication with corticosteroids, cannot be ruled out. Due to the epidemiological situation in Sweden, we believe that most cases of TB in this study are reactivations from latent TB; however, it was not possible to identify individuals with latent TB infection at baseline. The spirometry in the health screening did not meet modern standards. However, previous studies from this cohort have shown that the validity is acceptable in the context of an epidemiological study6。
尽管存在这些局限性,但似乎越来越多的证据表明肺功能和COPD损害与活性结核病的发生率增加有关。需要进一步的研究,尤其是在高结核病构成区域,以解除基本的因素,并判断是否应将肺功能受损的个体视为保证靶向针对性结核病预防措施的风险群体。
Footnotes
Statement of Interest
A statement of interest for G. Engstro¨m can be found atwww.www.qdcxjkg.com/site/misc/statements.xhtml
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