Background
Methods
Systematic review and selection criteria
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Population - populations in which individuals were or had been exposed to crystalline silica dust and in which incident tuberculosis was recorded;
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Exposures - studies of individuals with silicosis; and/or with respiratory exposure to silica dust, explicitly measured or inferred from occupation or industry;
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Comparators - studies reporting comparative effect estimates, specifically case-control or cohort studies reporting risk, rate or odds across groups exposed to different levels of silica (including binary comparisons of exposed/unexposed), and across groups with silicosis (including different grades) and without;
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Outcome - studies reporting incident active pulmonary tuberculosis, with or without extrapulmonary tuberculosis. Diagnosis must have been made on histological or microbiological grounds, or an explicit combination of clinical assessment, radiology and/or response to treatment. Tuberculosis must have been diagnosed after the onset of silica exposure or silicosis diagnosis;
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English-language full-text available;
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Publication 1970 to April 2020 inclusive.
Search terms, sources and strategy
Study selection
Data extraction
Study quality assessment
Standardisation of results and summary presentation
Evidence synthesis and assessment of certainty
Results
Study selection
Study characteristics
First author, publication year. Countrya, study dates | Study design (effect measure), study population and data sources for comparison groups | Sample size | Tuberculosis (TB) diagnosis | Silica exposure/silicosis b categories compared, diagnostic/exposure assessment |
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Westerholm 1986 [46]. Sweden, 1959–1977. | • Matched retrospective cohort (risk ratio) • Male silicosis cases reported 1959–1977 to the National Swedish Pneumoconiosis Register from mining, quarrying and tunneling industries, and iron and steel foundries. Controls from silica exposed persons undergoing periodic health examinations recorded in same register. • TB identified from the Swedish Tuberculosis Index 1971–1980. | 712 silicosis, 810 no silicosis, matched for occupation, age and calendar year at first silica exposure. | Verified by microscopy or by guinea pig or bacteriological culture. | • Silicosis versus no silicosis. • Diagnostic criteria for silicosis not reported. |
Sherson 1990 [47]. Denmark, 1967–1986. | • Retrospective cohort (standardized incidence ratio) • Male foundry workers in the Foundry Worker Registry of the Danish Labour Inspectorate • Registry populated with data from two national silicosis surveys, 1967–1969 and 1972–1974. • Pulmonary TB identified from the Danish TB Registry though 1986. | 155 silicosis, 5424 no silicosis. | 19/21 cases had positive cultures. Diagnostic criteria not stated for the other two. | • (1) Silicosis versus no silicosis. (2) Years of metal foundry work. • Diagnostic criteria for silicosis not reported. |
Cowie 1994 [48]. South Africa, 1984–1991. | • Retrospective cohort (annual incidence rate; risk ratio) • Medical surveillance database of 90,000 black male gold miners from 24 mines in the Orange Free State Province. • Silicosis and controls ascertained prospectively. • TB identified from a central TB registry. | 818 silicosis, 335 no silicosis, matched for day of CXR and age. | Positive sputum cultures in all pulmonary TB subjects. 30 cases of extrapulmonary TB (24 intrathoracic). | • (1) Silicosis vs no silicosis; (2) increasing ILO profusion of radiologic silicosis: 0, 1, 2, 3. • Silicosis read on full size CXR using ILO Classification. |
Hnizdo 1998 [49]. South Africa, 1968/71–1995. | • Prospective cohort (rate ratio, relative risk) c • White male gold miners aged 45–54 years with ≥10 yr underground experience who attended state examination bureau for compulsory medical surveillance 1968–1971. • Silicosis identified from ongoing surveillance CXRs and/or at autopsy in decedents. TB identified from medical and/or autopsy records through 1995. | 2255 miners; 321 radiological silicosis, 719 autopsy silicosis (of whom 546 autopsy silicosis only). | Positive sputum test (76), positive histology (36), and positive CXR (5). | • Silicosis vs no silicosis; (2) Quartiles of cumulative dust exposure (mg-yr/m3); (3) Degree of silicosis at autopsy. • Radiological silicosis ILO > 1/1, 1990 - re-reading of all previous CXRs. • Autopsy silicosis on microscopy by pathologist: none, negligible, slight, moderate/marked. |
Corbett 1999 [50]. South Africa, 1993–1996. | • Case-control (odds ratio) • Silicosis cases and controls (trauma, surgical) from medical and personnel records of gold miners attending a company hospital, the sole source of tertiary care for this population. • TB cases: random sample of central database. | 381 TB cases; 180 non-TB controls. | First episode of culture positive TB. | • (1) Silicosis grade d (none, “possible” = ILO 0/1, “probable =1/0, “early” =1/1, “high grade” = 1/1); (2) years of gold mining: < 10; 10–14; 15–19: ≥ 20; (3) dusty job at diagnosis. • Silicosis consensus by 2 readers on mini-CXRs in 93.4% of subjects, standard size films in the rest. |
Corbett 2000 [51]. South Africa, 1991–1996. | • Retrospective cohort (rate ratio) • Medical and personnel records of male gold miners attending peripheral clinics and company hospital of a single gold mining company. • TB cases identified from a centralized TB database. • No overlap with Corbett 1999. | 4022 miners 1025 silicosis (including ILO 0/1). | Pulmonary TB (80.8% of TB cases): smear or culture positive (88.4%) or compatible radiologic changes plus clinical and laboratory features consistent with TB.e | • Silicosis grade (none, ILO 0/1, 1/0, 1/1, > 1/1); (2) years of employment 0–4; 5–9; 10–19; ≥ 20; (3) main job underground vs surface. • Silicosis consensus read by 2 readers on mini-CXRs. |
Chang 2001 [52]. Hong Kong, 1988–1999. | • Retrospective cohort (relative risk; standardized risk ratio) • Silicosis diagnosed at Pneumoconiosis Medical Board 1988–1993, followed for TB through records until death or end of 1999. • Supplementary information from TB Notifications Register. | 707 silicosis | Bacteriologically confirmed cases. | • (1) Cohort vs general population; (2) within cohort: (a) years of occupational dust exposure; (b) Caisson construction work; f (c) ILO profusion > grade 1; (e) progressive massive fibrosis (PMF). • Diagnostic criteria for silicosis not stated. |
Li 2011 [53]. Taiwan, 1998–2006. | • Retrospective cohort (hazard ratio) • Incident end stage renal disease (ESRD) patients recorded in National Health Insurance Research (NIHR) Database 1998–2004. • Incident TB identified from the Taiwan Centers for Disease Control TB database through 2006. • Silicosis recorded from co-morbidity information on NHIR database. | 49,983 ESRD. 52 silicosis. | “ICD-9 code (010–018) in at least three ambulatory visits and insurance claims for anti-TB drugs … for more than 90 days.” | • Silicosis vs no silicosis. • Diagnostic criteria for silicosis not given. |
Yarahmadi 2013 [54]. Iran, 2006–2011. | • Case-control g (odds ratio) • TB cases and controls (individuals investigated for TB and found to be negative) at the Infectious Disease Control Center of the Health Deputy of Khoramabad City, Lorestan. | 871 TB cases (55.5% female); 429 non-TB controls (56.1% female). | Microscopy of 3 sputum samples of people coughing for 2 weeks or longer. | • Silica exposure (based on interview) without silicosis vs no silica exposure; • Silicosis: pulmonologist assessment of subjects with suggestive CXR, with HRCT if required. |
Risk of bias assessment
Studies of the association between silicosis and tuberculosis
First author, year of publication | Study Design | Study /control population(s) | N | Controlling for | Estimate (95% CI) (silicosis vs no silicosis) |
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Low or intermediate TB burden countries | |||||
Westerholm 1986 [46] | Cohort | Mining, quarrying and tunneling industries and iron and steel foundries. | 1522 | Occupation, age, calendar year at first silica exposure. | OR 32.99 (4.50, 241.58) a |
Sherson 1990 [47] | Cohort | Foundry workers, general population | 5579 | (i)None (ii)Age | (i) RR 8.25 (2.81, 24.25) b (ii) SIR 10.00 (2.72, 25.61) |
Chang 2001 [52] | Cohort | Silicosis register / general population | 707 | Age, gender | SIR 4.9 c |
Li 2011 [53] | Cohort | End-stage renal disease patients | 49,983 | Age, gender, income,COPD | HR 5.82 (2.17, 15.6) |
Yarahmadi 2013 [54] | Case control | Community | None | OR 4.08 (2.63, 3.62) | |
High TB burden countries | |||||
Cowie 1994 [48] | Cohort | Gold miners | 1153 | Age, date of CXR | RR 2.8 (1.9, 4.1) |
Hnizdo 1998 [49] | Cohort | Gold miners | 2255 | Age, smoking, cumulative dust exposure | RR 4.18 (2.75, 6.36) |
Corbett 1999 [50] | Case control | Gold miners | 561 | Age, HIV, duration, employed, dusty job | OR 4.90 (2.32,10.58) |
Corbett 2000 [51] | Cohort | Gold miners | 4022 | Age, HIV, duration employed, surface/underground | RR 2.2 (1.3, 3.7) d |
Study by date of publication (effect measure) | Cowie 1994 (IR) [48] | Hnizdo 1998 (RR) [49] (Autopsy grading) | Corbett 1999 (OR) [50] | Corbett 2000 (RR) [51] | Chang 2001 (RR) [52] |
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Adjusted/controlled for. N | Age, date of CXR. N = 1153 | Age, smoking. N = 2255 | Age, HIV, duration employed, dusty job. N = 561 | Age, HIV, duration employed, underground/surface job. N = 4022 | Age, sex, smoking. N = 707 |
Grades or markers of extent of silicosis | None (n = 335): 1.0 (0, 2.0) ILO 1 (n = 418): 2.2 (0.7, 3.6) ILO 2 (n = 355): 2.9 (1.1, 4.6) ILO 3 (n = 45): 6.3 (0, 13.4) | None (n = 577): 1.00 Negligible (n = 310): 1.86 (0.97, 3.58) Slight (n = 196): 2.62 (1.36, 5.03) Moderate/ marked(n = 213): 2.71 (1.41, 5.20) | None (n = 340): 1.00 ILO 0/1 (n = 69): 1.6 (0.86, 2.90) ILO 1/0 (n = 48): 2.8 (1.24, 6.46) ILO > 1/1 (n = 90): 4.9 (2.32, 10.58) | None (n = 2924): 1.00 ILO 0/1 (n = 460): 1.4 (1.0, 2.2) ILO 1/0 (n = 212): 1.8 (1.0, 3.0) ILO 1/1 (n = 156): 2.2 (1.3, 3.7) ILO > 1/1 (n = 197): 2.5 (1.6, 4.0) | PMF (n = 141) vs no PMF (n = 566): 3.78 (2.24, 6.35) |
Certainty assessment | No. of participants | Effect | Certainty | ||||||
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Country TB burden. No. of studies | Study design | Risk of bias a | Inconsistency b | Indirectness c | Imprecision d | Other considerations e | Pooled relative risk (95% CI) | ||
All 8 | Observational | Not serious | Not serious | Not serious | Not serious | Strong association, dose response gradient | 66,982 | 3.65 (2.79, 4.78) | ⨁⨁⨁⨁ HIGH |
Low/intermediate 4 | Observational | Not serious | Not serious | Not serious | Not serious | Strong association, dose response gradient | 59,091 | 4.68 (3.22, 6.80) | ⨁⨁⨁⨁HIGH |
High 4 | Observational | Not serious | Not serious | Not serious | No serious | Strong association, dose response gradient | 7891 | 3.16 (2.31, 4.32) | ⨁⨁⨁⨁ HIGH |
Studies of the association between silica exposure and tuberculosis, controlling for silicosis
Sherson 1990 [47] | Hnizdo 1998 [49] | Corbett 1999 [50] | Corbett 2000 [51] | Yarahmadi 2013 [54] |
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SIR or RR a (95% CI) | RR (95% CI) | OR 95%CI) | RR (95%CI) | OR (95% CI) |
Silicotics excluded. | White miners, > 10 years’ exposure; adjusted for silicosis b, age, smoking. | Adjusted for silicosis, age, HIV. | Adjusted for silicosis, age, HIV. | Silicotics excluded. No other adjustment. |
Binary or summary effect measures | ||||
Duration of employment (yr), (RR) < 15: 1.00 > 15: 2.39 (0.96, 6.44) | Per 8 mg-yr/m3 c 1.95 (1.58, 2.2) | Occupation (dusty job at diagnosis) No: 1.00 Yes 1.00 (0.62, 1.63) | Occupation (underground vs surface) No: 1.00 Yes: 2.00 (1.11, 3.33) | Silica exposure None: 1.00 Any: 2.85 (1.13, 3.42) |
Dose-response | ||||
Duration of employment (yr), SIR General male population: 100 0.15–14.5: 133 (57, 262) 15.0–24.5: 128 (26, 375) > 25: 353 (130, 768) | Cumulative dust (mg-yr/m3) quartile 1: 1.00 2: 1.51 (0.78, 2.91) 3: 2.35 (1.28, 4.32) 4: 3.22 (1.75, 5.90) | Duration of employment (yr) < 10: 1.00 10–14: 1.9 (1.07, 3.36) 15–19: 4.4 (2.45, 7.75) > 20: 3.6 (1.84, 7.12) | Duration of exposure (yr) 0–4: 1.8 (0.9, 3.5) 5–9: 1.00 10–19: 1.6 (1.0, 2.5) > 20: 1.3 (0.8, 2.3) | |
Duration of employment (yr), (RR) 0.05–14.5: 1.00 15–24.5: 1.44 (0.38, 5.43) > 25: 3.9 (1.36, 11.23)a |
Certainty assessment | No. of participants | Effect | Certainty | ||||||
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Country TB burden No. of studies | Study design | Risk of bias a | Inconsistency b | Indirectness c | Imprecision d | Other considerations | Pooled relative risk (95% CI) | ||
All 5 | Observational | Not serious | Not serious | Not serious | Not serious | None | 13,617 | 1.92 (1.36, 2.73) | ⨁⨁◯◯LOW |
Low/intermediate 2 | Observational | Not serious | not serious | Not serious | Not serious | None | 6879 | 2.75 (1.70, 4.45) | ⨁⨁◯◯LOW |
High 3 | Observational | Not serious | not serious | Not serious | Not serious | None | 6738 | 1.66 (1.04, 2.66) | ⨁⨁◯◯LOW |