Main features and findings of meta-analyses reporting on tuberculosis (TB) incidence among individuals with selected risk factors: use of inhaled corticosteroids (ICS) in obstructive lung diseases (n=2), diabetes (n=3) and malignancies (n=1)
| First author, year [reference] | Inclusion criteria for studies | Exclusion criteria for review | Number of studies and study types, where relevant | Pooled estimates of active TB (95% CI) versus reference groups |
| Inhaled corticosteroid use in obstructive lung diseases | ||||
| Castellana, 2019 [27] | Design: nonrandomised studies Exposure: patients with obstructive lung diseases, including asthma, using ICS Comparators: patients with obstructive lung diseases not using ICS Search period: up to September 2018 | Randomised trials Studies without data on ICS use | RC with medical record review (2 studies) | Pooled OR of active TB in people with obstructive lung diseases using ICS versus those not using ICS: 4.48 (1.85–10.86) (Current users of ICS defined as those using inhalers in the 3 months leading up to TB diagnosis date, or those with a prescription for ICS in the 30 days leading up to the date), I2=0% |
| RC with nested CC (7 studies) | Pooled OR of active TB in people with obstructive lung diseases using ICS versus those not using ICS: 1.31 (0.94–1.82), I2=97% | |||
| RC with nested CC (3 studies) | Pooled OR of active TB in people with obstructive lung diseases using ICS versus those not using ICS, with simultaneous oral corticosteroid use: 1.22 (0.92–1.62), I2=38% | |||
| RC with nested CC (4 studies) | Pooled OR of active TB in people with obstructive lung diseases using ICS versus those not using ICS, without simultaneous oral corticosteroid use: 1.63 (1.05–2.52), I2=94% | |||
| Dong, 2014 [28] | Design: RCTs lasting ≥6 months Exposure: patients with COPD of any severity using ICS Comparators: RCT control groups Search period: up to July 2013 | Trials that included patients with asthma Trials that did not involve pre-defined intervention or control treatments | 5 studies | Pooled OR of active TB in people with COPD using ICS versus those not using ICS: 2.29 (1.04–5.03), I2=0.4% |
| Diabetes mellitus | ||||
| Jeon, 2008 [25] | Design: cohort, CC or CS studies Exposure: adults with diabetes mellitus Comparators: general population Search period: up to March 2007 | Studies that did not adjust for age Studies that employed different methods for assessing TB among individuals with and without diabetes mellitus or for assessing diabetes mellitus among TB patients and controls Studies that investigated the reverse association of the impact of TB disease or TB treatment on diabetes mellitus | RC (3 studies) | Pooled risk ratio of active TB: 3.11 (2.27–4.26), I2=39% |
| CC (8 studies) | Authors did not calculate a pooled estimate as they felt the between-study heterogeneity (I2=68%) was too high. Risk ratios of active TB varied from 1.61 (0.58–2.32) to 7.83 (2.37–25.9) | |||
| Al-Rifai, 2017 [24] | Design: studies that provided or allowed computation of an estimate of the association between active TB and diabetes mellitus Exposure: adults with diabetes mellitus Comparators: “control arm or comparator group”, not specified Search period: up to December 2015 | Studies where TB patients with diabetes mellitus were not separated from those with other comorbidities Studies that did not report adjusted estimates of the TB–diabetes mellitus association | 44 studies | Pooled OR/IRR/risk ratio/HR of active TB: 2.00 (1.78–2.24), I2=90.5% |
| Foe-Essomba, 2021 [26] | Design: cohort, CC or CS studies Exposure: patients with diabetes mellitus Comparators: “controls”, not specified Search period: up to October 2020 | Studies with other designs | Overall (49 studies) | Pooled OR of active TB 2.33 (2.00–2.71), I2=94.2% |
| RC (10 studies) | Pooled OR of active TB 1.92 (1.53–2.40), I2=94.3% | |||
| CC (23 studies) | Pooled OR of active TB 2.38 (1.96–2.89), I2=93% | |||
| CS (16 studies) | Pooled OR of active TB 2.51 (1.82–3.47), I2=95.2% | |||
| Malignancies | ||||
| Dobler, 2017 [29] | Design: varied designs Exposure: patients with cancer Comparators: control group specified for the study or general population with or without adjustment for potential confounders Search period: up to December 2016 | CS studies Studies that used cumulative incidence without adjustment for time at risk Studies in which TB diagnosis preceded cancer diagnosis or the temporal relationship was not specified Studies only reporting TB risk in subgroups of cancer patients considered to have an increased pre-test probability of TB infection (e.g. because of abnormal chest radiographs) | 11 studies | Pooled IRR of active TB in adults with cancer 2.61 (2.12–3.22), I2=91% |
| 2 studies | Pooled IRR of active TB in adults with haematological malignancies 3.53 (1.63–7.64), I2=96% | |||
| 4 studies | Pooled IRR of active TB in adults with lung cancer 6.14 (1.97–19.20), I2=76% | |||
| 3 studies | Pooled IRR of active TB in adults with gastric cancer 2.63 (1.96–3.52), I2=93% | |||
| 8 studies | Pooled IRR of active TB in adults with breast cancer 2.17 (1.98–2.38), I2=0% | |||
| 3 studies | Pooled IRR of active TB in adults with liver cancer 2.02 (0.83–4.91), I2=83% | |||
| 3 studies | Pooled IRR of active TB in adults with colon cancer 2.00 (1.16–3.43), I2=75% | |||
| 3 studies | Pooled IRR in children with cancer 16.82 (8.81–32.12), I2=79% | |||
RC: retrospective cohort study; CC: case–control study; RCT: randomised control trial; IRR: incidence rate ratio; HR: hazard ratio; CS: cross-sectional study.