Background: While the association between occupational inhalation of silica dust and pulmonary tuberculosis has been known for over a century, there has never been a published systematic review, particularly of experience in the current era of less severe silicosis and treatable tuberculosis. We undertook a systematic review of the evidence for the association between (1) silicosis and pulmonary tuberculosis, and (2) silica exposure and pulmonary tuberculosis controlling for silicosis, and their respective exposure-response gradients. Methods: We searched PUBMED and EMBASE, and selected studies according to a priori inclusion criteria. We extracted, summarised and pooled the results of published case-control and cohort studies of silica exposure and/or silicosis and incident active tuberculosis. Study quality was assessed on the Newcastle-Ottawa Scale. Where meta-analysis was possible, effect estimates were pooled using inverse-variance weighted random-effects models. Otherwise narrative and graphic synthesis was undertaken. Confidence regarding overall effect estimates was assessed using the GRADE schema. Results: Nine studies met the inclusion criteria. Meta-analysis of eight studies of silicosis and tuberculosis yielded a pooled relative risk of 4.01 (95% confidence interval (CI) 2.88, 5.58). Exposure-response gradients were strong with a low silicosis severity threshold for increased risk. Our GRADE assessment was high confidence in a strong association. Meta-analysis of five studies of silica exposure controlling for or excluding silicosis yielded a pooled relative risk of 1.92 (95% CI 1.36, 2.73). Exposure-response gradients were observable in individual studies but not finely stratified enough to infer an exposure threshold. Our GRADE assessment was low confidence in the estimated effect owing to inconsistency and use of proxies for silica exposure. Conclusions: The evidence is robust for a strongly elevated risk of tuberculosis with radiological silicosis, with a low disease severity threshold. The effect estimate is more uncertain for silica exposure without radiological silicosis. Research is needed, particularly cohort studies measuring silica exposure in different settings, to characterise the effect more accurately as well as the silica exposure threshold that could be used to prevent excess tuberculosis risk.

To identify modifiable risk factors for wheezing illness in childhood, the associations between current asthma or wheezing and factors such as household smoking, damp and dietary salt preference were measured in a questionnaire-based prevalence study of schoolchildren 7 to 9 yr of age in Cape Town. In a random sample of 15 schools, questionnaires were completed by parents of 1,955 children, from which 368 cases and 294 controls were selected on the basis of reported asthma diagnosis or symptoms. Urinary cotinine concentrations were measured, and the parents were interviewed. An exposure-response relationship between the urinary cotinine creatinine ratio and asthma/wheeze was observed. In multivariate analysis, predictors of asthma/wheeze were hay fever (odds ratio [OR] - 5.30; 95% confidence interval [CI] = 3.16 to 8.89), eczema (OR = 2.19; 95% CI = 1.33-3.62), parental asthma (OR = 1.77; 95% CI = 1.11 to 2.84), absence of paternal contribution to income (OR = 1.72; 95% CI = 1.17 to 2.54), maternal smoking in pregnancy (OR = 1.87; 95% CI = 1.25 to 2.81), and each additional household smoker (OR = 1.15; 95% CI = 1.01 to 1.30). Findings were similar, with higher odds ratios for most variables, except number of household smokers, when the group was restricted to children with parent-reported asthma. The findings confirm that household smoking is an important modifiable risk factor in asthma/wheeze among young schoolchildren, and they suggest that maternal smoking in pregnancy and current household exposure are independent contributors to this effect.

This study was conducted in a high tuberculosis (TB) burden area in Worcester, South Africa, with a notified all TB incidence rate of 1,400/100,000. To compare the predictive value of a baseline tuberculin skin test (TST) with that of the QuantiFERON TB Gold (In-tube) assay (QFT) for subsequent microbiologically confirmed TB disease among adolescents. Adolescents aged 12–18 years were recruited from high schools in the study area. At baseline, blood was drawn for QFT and a TST administered. Participants were followed up for up to 3.8 years for incident TB disease (median 2.4 years). After exclusions, 5244 (82.4%) of 6,363 adolescents enrolled, were analysed. The TB incidence rate was 0.60 cases per 100 person years (pyrs) (95% CI 0.43–0.82) for baseline TST positive (≥5 mm) participants and 0.64 cases per 100 pyrs (95% CI 0.45–0.87) for baseline QFT positive participants. TB incidence rates were 0.22 per 100 pyrs (0.11–0.39) and 0.22 per 100 pyrs (0.12–0.38) among those with a negative baseline TST and QFT respectively. Sensitivity for incident TB disease was 76.9% for TST and 75.0% for QFT (p = 0.81). Positive predictive value was 1.4% for TST and 1.5% for QFT. Positive TST and QFT tests were moderately sensitive predictors of progression to microbiologically confirmed TB disease. There was no significant difference in the predictive ability of these tests for TB disease amongst adolescents in this high burden setting. Therefore, these findings do not support use of QFT in preference to TST to predict the risk of TB disease in this study population.