RESEARCH REPORT
doi:10.1111/add.13926
Heavy alcohol consumption increases the risk of active tuberculosis in Taiwanese adults: a nation-wide population-based cohort study Yung-Feng Yen1,2,3* , Hsiao-Yun Hu4,5, Ya-Ling Lee6,7*, Po-Wen Ku8, Pei-Hung Chuang9,10, Yun-Ju Lai2,11,12 & Dachen Chu2,13,14 Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei, Taiwan,1 School of Medicine, National Yang-Ming University, Taipei, Taiwan,2 Department of Health and Welfare, College of City Management, University of Taipei, Taiwan,3 Department of Education and Research, Taipei City Hospital, Taipei, Taiwan,4 Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan,5 Department of Dentistry, Taipei City Hospital, Taipei, Taiwan,6 School of Dentistry, National Yang-Ming University, Taipei, Taiwan,7 Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan,8 Center for Prevention and Treatment of Occupational Injury and Diseases, Taipei Veterans General Hospital, Taiwan,9 Division of Clinical Toxicology and Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taiwan,10 Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan,11 Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan,12 Department of Neurosurgery, Taipei City Hospital, Taipei, Taiwan13 and Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan14
ABSTRACT
Aims To investigate the impact of alcohol exposure on tuberculosis (TB) development in Taiwanese adults. Design Participants from the Taiwan National Health Interview Survey. Alcohol consumption and other covariates were collected by in-person interviews at baseline. Incident cases of active TB were identified from the National Health Insurance database. A multivariable Cox regression model was used to estimate the association between alcohol consumption and active TB, with adjustment for age, sex, smoking, socio-economic status and other covariates. Setting Taiwan National Health Interview Survey. Participants A total of 46 196 adult participants aged ≥ 18 years from three rounds (2001, 2005, 2009) of the Taiwan National Health Interview Survey. Measurements Alcohol consumption was classified into never, social, regular or heavy alcohol use. Heavy alcohol consumption was defined as intoxication at least once/week. Findings Of the 46 196 study subjects, 61.8, 24.2, 13.5 and 0.5% were classified as never, social, regular and heavy alcohol users, respectively. During the 398 443 person-years of follow-up, 279 (0.60%) subjects developed new-onset active TB. After adjusting for the subject demographics and comorbidities, heavy [hazard ratio (HR) = 5.27; 95% confidence interval (CI) = 2.51–11.09] and regular alcohol users (HR = 1.80; 95% CI = 1.32–2.45) had increased risks of incident TB compared to never users. Moreover, a positive trend between increasing levels of alcohol consumption and the risk of active TB was noted (P < 0.001). Conclusions In Taiwan, heavy and regular alcohol consumption are associated with higher risks of active tuberculosis. Keywords
Alcohol consumption, cohort study, epidemiology, risk, Taiwan, tuberculosis.
Correspondence to: Dachen Chu, Department of Neurosurgery, Taipei City Hospital, No. 145, Zhengzhou Rd., Datong Dist., Taipei City 103, Taiwan. E-mail:
[email protected]; Yun-Ju Lai, Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, No. 1, Rongguang Road, Puli Township, Nantou County 545, Taiwan. E-mail:
[email protected] Submitted 24 January 2017; initial review completed 22 March 2017; final version accepted 23 June 2017 *These authors contributed equally to this paper.
INTRODUCTION Alcohol consumption is socially accepted across many cultures world-wide. However, heavy alcohol consumption leads not only to devastating long-term health consequences such as cancer and diabetes [1,2], but might also cause suppression of the immune system. Prior animal
© 2017 Society for the Study of Addiction
studies have shown that alcohol exposure could cause impairment of macrophage function and reduction of T cell lymphocytes [3,4] which, in turn, may increase the susceptibility to tuberculosis (TB) infection. TB remains a common disease throughout large parts of the world [5]. Approximately one-third of the world’s population is latently infected with TB. In 2013,
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there were an estimated 9 million incident cases of TB world-wide [6]. In Taiwan, of all notified infectious diseases, TB has had the highest annual number of incident cases for decades [7]. In 2006, the Taiwan Centres for Disease Control adopted a directly observed short-course therapy programme, with the aim of halving TB incidence by 2015. As a result, the TB incidence decreased from 72.5/ 100 000 in 2005 to 49.4/100 000 in 2013. However, there were still 11 528 new TB cases in 2013 in Taiwan [7]. A relationship between alcohol consumption and TB has been reported previously. Previous studies have shown that TB patients have a high prevalence of alcohol consumption at the time of TB diagnosis, ranging from 10 to 50% [8–10]. Furthermore, a prior meta-analysis also showed a positive association between alcohol consumption and TB risk [11]. However, most of the evidence regarding the relationship between alcohol consumption and TB development comes from cross-sectional or case–control studies [11]. Such studies measuring alcohol consumption at the time of TB diagnosis are not able to estimate the precise effect of alcohol consumption on TB development. Moreover, although two previous animal studies, published in 2000 and 2005, showed that alcohol consumption can cause suppression of the immune function [3,4], few longitudinal studies have determined the temporality of alcohol consumption with subsequent TB development. A US cohort study, that had enrolled 908 adults with human immunodeficiency virus (HIV) infection, showed that alcohol consumption increased the risk of active TB after the treatment of latent TB [hazard ratio (HR) = 2.08; 95% confidence interval (CI) = 1.14–3.78] [12]. However, a UK cohort study using the Clinical Practice Research Datalink, which followed 222 731 patients with diabetes and 1 218 616 controls without diabetes, found that heavy alcohol consumption was not associated significantly with active TB (HR = 1.04; 95% CI = 0.69–1.59) [13]. Moreover, a Finnish cohort study that had enrolled 26 975 subjects showed that male smokers with alcohol consumption ≧30 g/day did not have a higher risk of TB compared to those with alcohol consumption < 30 g/day (HR = 1.03; 95% CI = 0.70–1.53) [14]. However, these previous studies of the association between alcohol consumption and incident TB enrolled either only HIV patients [13] or male smokers [14] and/or were controlled inadequately for potential confounders such as chronic lung disease [12–14]. TB prevention should focus particularly on high-risk groups. Understanding of the impact of alcohol consumption on TB development would provide important information for future TB prevention programmes. Thus, we conducted this nation-wide population-based cohort study to investigate the impact of alcohol consumption on TB development in Taiwanese adults. © 2017 Society for the Study of Addiction
METHODS Setting and study subjects Our study population for this investigation was derived from three rounds of a large national survey in Taiwan, namely the National Health Interview Survey (NHIS), conducted in 2001, 2005 and 2009. The NHIS is a periodical, crosssectional health survey carried out jointly by the Bureau of Health Promotion, Department of Health and the National Health Research Institutes in Taiwan [15]. The NHIS includes a representative sample of the general Taiwanese population, selected using a multi-stage stratified systematic sampling design, based on the degree of urbanization, geographic location and local administrative boundaries [15]. The NHIS collects baseline information on the participants’ socio-demographic (e.g. alcohol consumption) and behavioural factors using in-person interviews. This study selected all subjects aged ≥ 18 years from the 2001, 2005 and 2009 NHIS data. Subjects who had received a TB diagnosis [International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes 010–018] before enrolment were excluded. All study subjects were followed from the time of the NHIS interview until a diagnosis of TB, death or 31 December 2013. Deaths were confirmed by examining the death certificate database of Taiwan. This project was approved by the Institutional Review Board of Taipei City Hospital (TCHIRB-10404118-W).
Outcome variable This study identified incident cases of active TB from the cohort by linking the NHIS database to the National Health Insurance Research database (NHIRD) to December 2013. New-onset TB during the follow-up period was defined as the presence of the appropriate ICD-9-CM codes (010– 018) [16] and the prescription of at least two anti-TB drugs (e.g. isoniazid, ethambutol, rifampin or pyrazinamide) for 4 weeks.
Main explanatory variable The main explanatory variable was alcohol consumption. Detailed information on alcohol consumption was collected by in-person interviews at baseline. The questionnaire regarding alcohol consumption included the following questions: ‘How often did you drink alcohol in the last year? (every day/every two or three days/once per week/once or twice per month/less than once per month)’ and ‘Did you drink alcohol to the extent of being intoxicated?’ (yes/no) The level of alcohol consumption was classified into never, social (less than once per week), regular (at least once per week but not to the extent of being intoxicated) or heavy alcohol use (at least once per week and to the extent of being intoxicated) [17]. Addiction
Alcohol consumption and active tuberculosis
Potentially confounding variables Covariates identified in previous studies as risk factors [18] for TB were assessed in our analyses; these included the individuals’ socio-demographic characteristics (age, sex, marital status, educational level and smoking status) and comorbidities. Marital status was categorized as unmarried, married/cohabiting or others (e.g. widowed, divorced, separated or single parent). Educational level was classified into elementary or lower, high school and university or higher education. Smoking status included never, former and current smokers. The presence of chronic comorbidities in the study participants was determined from the NHIRD according to the ICD-9-CM codes. The comorbidities included diabetes (ICD-9 code 250), hypertension (ICD-9 codes 401–405), chronic kidney disease (ICD-9 codes 580–587), chronic obstructive pulmonary disease (COPD; ICD-9 codes 491, 492 and 496), asthma (ICD-9 code 493), cancer (ICD-9 codes 140–208) and alcoholic liver damage (ICD-9 codes 571.0–571.3). A person was considered to have a comorbidity only if the condition occurred in an in-patient setting or required three or more out-patient visits [19].
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After excluding those with antecedent TB (n = 273), unknown sex (n = 1) and unknown alcohol consumption (n = 2134), the remaining 46 196 patients were included in the analysis. The overall mean (standard deviation) age was 43.2 (16.9) years, 49.1% of the subjects were male and mean (standard deviation) follow-up time was 8.6 (3.5) years. Table 1 shows the baseline characteristics and comorbidities of the study population. According to the definition of alcohol consumption, 61.8, 24.2, 13.5 and 0.5% of the study subjects were classified as never, social, regular and heavy alcohol users, respectively. The proportion of male subjects increased as the level of alcohol consumption increased. Further, the higher the level of alcohol consumption, the more likely the individuals were to have alcoholic liver damage.
TB incidence rate During the 398 443 person-years of follow-up, 279 subjects developed new-onset active TB, including 154 (0.54%), 154 (0.54%), 76 (1.22%), and 8 (3.54%) new TB cases occurred in individuals with never, social, regular, and heavy alcohol consumption, respectively.
Statistical analysis The baseline characteristics of the study population are presented according to the level of alcohol consumption. The normality was tested for continuous data. The Cochran Armitage trend test was used to determine the trend in TB incidence and subjects’ characteristics according to the different levels of alcohol consumption. The incidences of TB per 100 000 person-years (PY) were calculated according to the different levels of alcohol consumption. The univariable Cox regression model was used to assess the crude associations of alcohol consumption and other covariates with the outcome (active TB) by computing the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). A multivariable Cox regression model was used to estimate the independent association between different levels of alcohol consumption and active TB after adjusting for potential confounders. Individuals with ‘never alcohol consumption’ were used as the reference. Adjusted HRs (AHRs) with 95% CIs are reported to indicate the strength and direction of these associations. The data management and all analyses were performed using SAS software version 9.4 (SAS Institute, Cary, NC).
RESULTS Characteristics of the study subjects A total of 48 604 adult individuals participated in the three rounds of the National Health Interview Survey in Taiwan. © 2017 Society for the Study of Addiction
Factors associated with incident TB among subjects with and without alcohol consumption A Cox proportional hazards model was used to identify the independent risk and protective factors for incident TB. After controlling for demographics and comorbidities, heavy (HR = 5.27; 95% CI = 2.51–11.09; P < 0.001) and regular alcohol users (HR = 1.80; 95% CI = 1.32–2.45; P < 0.001) had increased risks of incident TB compared to never users (Table 2). The independent risk factors for incident TB were older age, male sex, current smoking, COPD and malignancy. Moreover, a university or higher education and hypertension were associated significantly with a lower risk of incident TB. Furthermore, a positive trend was noted between increasing levels of alcohol consumption and the risk of active TB (P < 0.001).
Factors associated with incident TB among subjects with alcohol consumption Multivariable Cox regression showed that, compared with individuals with social alcohol consumption, individuals with heavy (HR = 5.53; 95% CI = 2.51–12.17; P < 0.001) or regular alcohol consumption (HR = 1.91; 95% CI = 1.28–2.87; P < 0.001) had higher risks of incident TB (Supporting information, Table S1). Moreover, the risk of developing active TB increased as the level of alcohol consumption increased (P
