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BACKGROUND: Although asthma is associated with impaired lung immunity, it is unclear whether asthma affects the risk of active tuberculosis (TB). Because the upper and lower airways are immunologically related, sinonasal disease may also modify susceptibility to TB disease. OBJECTIVES: To evaluate whether asthma and sinonasal disease prospectively modulate the risk of active TB in the Singapore Chinese Health Study. METHODS: In this population-based prospective cohort, we recruited 63,257 Chinese adults aged 45 to 74 years from 1993 to 1998 in Singapore, and conducted follow-up I interviews among 52,325 surviving participants from 1999 to 2004. Data on self-reported history of physician-diagnosed sinonasal disease were collected at baseline, and data on asthma and chronic bronchitis were collected at follow-up I interviews. Active TB cases were identified by linkage with the National TB Notification Registry through December 2014. Multivariable Cox proportional hazards regression models were used to estimate the risk of active TB. RESULTS: During a mean follow-up of 17 years from recruitment, there were 1249 cases of active TB, and among them, 678 cases were diagnosed in the 12-year period from follow-up I interviews. We observed reduced risk of active TB in those with a history of asthma at follow-up I (hazard ratio [HR], 0.55; 95% CI, 0.32-0.93) or sinonasal disease at baseline (HR, 0.59; 95% CI, 0.36-0.95). Conversely, history of chronic bronchitis was not associated with risk of TB (HR, 0.95; 95% CI, 0.68-1.31). CONCLUSIONS: Asthma or sinonasal disease may modulate immunological response to reduce the incidence of active TB in the adult population.

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Meta-analyses of studies conducted among Western populations suggest that coffee consumption does not affect osteoporotic fracture risk. However, experimental studies have shown that the effect of caffeine on bone health may depend on dosage. We examined the associations between consumption of coffee, tea and caffeine and risk of hip fracture in an Asian cohort. In a population-based prospective cohort of 63,257 Chinese men and women aged 45-74 years in Singapore, a validated semi-quantitative food frequency questionnaire was used to assess habitual consumption of coffee and tea at baseline. Cox proportional hazards regression models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) for risk of hip fracture with adjustment for potential confounders. During a mean follow-up of 16.7 years, 2502 incident hip fracture cases were identified. Compared to coffee drinkers <1 cup/week, those who drank ≥4 cups/day had a statistically significant higher risk to develop hip fractures, the HR (95% CI) was 1.32 (1.07, 1.63) in the whole cohort analysis, 1.46 (1.01, 2.10) for men and 1.33 (1.02, 1.72) for women. Among postmenopausal women, compared to those who drank coffee <1 cup/week, drinking 2-3 cups/day was associated with the lowest risk [HR: 0.88 (0.76, 1.01)] and drinking ≥4 cups/day was associated with the highest risk [HR: 1.31 (1.00, 1.71)]. Similar associations with caffeine intake were found among postmenopausal women. Restricted spline analyses suggested a non-linear association between coffee/caffeine consumption and hip fracture risk in postmenopausal women (p for non-linearity ≤ 0.05). No association was found with tea consumption in either sex. These data suggest that drinking coffee ≥4 cups/day is associated with a higher hip fracture risk, while a moderate intake may alleviate risk in postmenopausal women. Future studies should corroborate these results to determine levels of optimal coffee consumption in relation to bone health.

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Study Objectives: Epidemiological evidence indicates that both short and long sleep at midlife increase mortality risk, but few studies have examined how change in sleep duration between midlife and later life affects this risk. We examined the association between change in sleep duration and mortality risk. Methods: The Singapore Chinese Health Study is a prospective cohort of 63257 Chinese in Singapore aged 45-74 years at recruitment (1993-1998). Self-reported sleep duration was collected from 39523 participants who completed both baseline (mean age 54.8 years) and follow-up II (mean age 67.9 years; 2006-2010) interviews, which were on average 12.7 years apart. Mortality data were obtained via linkage with national death registry up to December 31, 2015. Results: Compared with participants who reported sleeping the recommended duration (7 hr) at both interviews, those with persistently short sleep (≤5 hr) had increased risk of all-cause mortality (hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.06-1.53). Similarly, those with persistently long sleep (≥9 hr) had increased risk of all-cause (HR 1.47, 95% CI 1.24-1.73) and cardiovascular (HR 1.40, 95% CI 1.04-1.89) mortality. The proportion of long-sleepers increased with aging (6%-23.7%). Progression to long sleep from short (HR 1.50, 95% CI 1.24-1.81) or recommended (HR 1.43, 95% CI 1.25-1.64) duration was associated with increased all-cause mortality, especially for cardiovascular mortality. Change in sleep duration was not linked to cancer mortality. Conclusions: Persistent short or long sleep or increasing sleep duration in late adulthood was associated with increased risk of all-cause mortality, especially from cardiovascular causes.

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PURPOSE: The relationship between coffee and tea, and risk of hypertension remains controversial in Western populations. We investigated these associations in an Asian population. METHODS: The Singapore Chinese Health Study is a population-based prospective cohort that recruited 63,257 Chinese aged 45-74 years and residing in Singapore from 1993 to 1998. Information on consumption of coffee, tea, and other lifestyle factors was collected at baseline, and self-reported physician-diagnosed hypertension was assessed during two follow-up interviews (1999-2004, 2006-2010). RESULTS: We identified 13,658 cases of incident hypertension after average 9.5 years. Compared to those who drank one cup of coffee/day, the hazard ratios (HR) and 95% confidence intervals (CI) were 0.87 (0.83-0.91) for

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INTRODUCTION: Heavy alcohol consumption increases the risk of active tuberculosis (TB). However, the relation between lower levels of alcohol intake and TB risk remains unclear. We aimed to evaluate the association between alcohol intake and risk of active TB and assess whether the associations were modified by smoking status, which is another risk factor for active TB. METHODS: The Singapore Chinese Health Study is a prospective cohort of 63 257 adults aged 45-74 years recruited from 1993 to 1998. Information on alcohol intake and smoking history was collected at recruitment. Active TB cases were identified via linkage with National TB Notification Registry. RESULTS: During a mean follow-up of 16.8 years, 1249 incident cases of active TB were identified. Among non-smokers, compared with total abstinence, participants who had monthly to weekly intake of alcohol had reduced TB risk (HR 0.70, 95% CI 0.55 to 0.89), but this reduction in risk with low-dose drinking was not observed among current smokers (HR 0.96, 95% CI 0.77 to 1.18; p for interaction=0.02). Comparatively, drinking 2+ drinks daily was associated with increased TB risk among current smokers (HR 1.51, 95% CI 1.11 to 2.05). This increased risk was not observed among non-smokers (HR 0.93, 95% CI 0.49 to 1.77) and the interaction between alcohol intake and smoking status was of borderline significance (p for interaction=0.08). In joint effect, compared with those who neither smoked nor drank, the risk of active TB increased from 1.82 (95% CI 1.57 to 2.10) in current smokers who were non-drinkers to 3.16 (95% CI 2.35 to 4.24) in current smokers who also drank 2+ drinks daily. CONCLUSION: While low intake of alcohol may protect against active TB among non-smokers, drinking 2+ drinks daily could act synergistically with smoking to increase the risk of active TB in current smokers.

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Experimental studies showed that tea polyphenols may inhibit growth of Mycobacterium tuberculosis. However, no prospective epidemiologic study has investigated tea drinking and the risk of active tuberculosis. We investigated this association in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese aged 45-74 years recruited between 1993 and 1998 in Singapore. Information on habitual drinking of tea (including black and green tea) and coffee was collected via structured questionnaires. Incident cases of active tuberculosis were identified via linkage with the nationwide tuberculosis registry up to 31 December 2014. Cox proportional hazard models were used to estimate the relation of tea and coffee consumption with tuberculosis risk. Over a mean 16.8 years of follow-up, we identified 1249 incident cases of active tuberculosis. Drinking either black or green tea was associated with a dose-dependent reduction in tuberculosis risk. Compared to non-drinkers, the hazard ratio (HR) (95% confidence interval (CI)) was 1.01 (0.85-1.21) in monthly tea drinkers, 0.84 (0.73-0.98) in weekly drinkers, and 0.82 (0.71-0.96) in daily drinkers (p for trend = 0.003). Coffee or caffeine intake was not significantly associated with tuberculosis risk. In conclusion, regular tea drinking was associated with a reduced risk of active tuberculosis.

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Antioxidants may protect against oxidative stress, which is associated with tuberculosis (TB) disease. However, direct evidence for a protective association between dietary antioxidants and TB incidence in humans has been lacking. The relationship between intake of antioxidant vitamins (vitamins A, C, D, and E) and individual carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein) and TB incidence was examined in the Singapore Chinese Health Study, a prospective cohort study of 63,257 adults aged 45-74 years enrolled during 1993-1998. Baseline intake of these antioxidants was estimated using a validated semiquantitative food frequency questionnaire including questions on use of dietary supplements. After an average of 16.9 years of follow-up, 1,186 incident active TB cases were identified among cohort participants. Compared with the lowest quartile, reduced risk of active TB was observed for the highest quartile of vitamin A intake (hazard ratio = 0.71, 95% confidence interval: 0.59, 0.85; P-trend < 0.01) and ß-carotene intake (hazard ratio = 0.76, 95% confidence interval: 0.63, 0.91; P-trend < 0.01), regardless of smoking status. Lower TB risk was seen for vitamin C intake among current smokers only. Other vitamins and carotenoids were not associated with TB risk. These results suggest that vitamin C may reduce TB risk among current smokers by ameliorating oxidative stress, while vitamin A and ß-carotene may have additional antimycobacterial properties.

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BACKGROUND: Experimental studies suggest that cholesterol enhances the intracellular survival of Mycobacterium tuberculosis, whereas marine ω-3 (n-3) and ω-6 (n-6) fatty acids (FAs) may modulate responses to M. tuberculosis in macrophage and animal models. However, there are no epidemiologic data from prospective studies of the relation between dietary cholesterol and FAs and the risk of developing active tuberculosis. OBJECTIVE: We aimed to investigate the relation between dietary intake of cholesterol and FAs and the risk of active tuberculosis in a prospective cohort in Singapore. METHODS: We analyzed data from the Singapore Chinese Health Study, a cohort of 63,257 Chinese men and women aged 45-74 y recruited between 1993 and 1998. Dietary intake of cholesterol and FAs was determined with the use of a validated food-frequency questionnaire. Incident cases of active tuberculosis were identified via linkage with the nationwide tuberculosis registry. Analysis was performed with the use of Cox proportional hazards models. RESULTS: As of 31 December 2013, 1136 incident cases of active tuberculosis were identified. Dietary cholesterol was positively associated with an increased risk of active tuberculosis in a dose-dependent manner. Compared with the lowest intake quartile, the HR was 1.22 (95% CI: 1.00, 1.47) for the highest quartile (P-trend = 0.04). Conversely, dietary marine n-3 and n-6 FAs were associated with a reduced risk of active tuberculosis in a dose-dependent manner. Compared with the lowest quartile, the HR for the highest intake quartile was 0.77 (95% CI: 0.62, 0.95) for marine n-3 FAs (P-trend = 0.01) and 0.82 (95% CI: 0.68, 0.98) for n-6 FAs (P-trend = 0.03). There was no association with saturated, monounsaturated, or plant-based n-3 FA intake. CONCLUSION: Dietary intake of cholesterol may increase the risk of active tuberculosis, whereas marine n-3 and n-6 FAs may reduce the risk of active tuberculosis in the Chinese population.

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