A systematic review and meta-analysis on the association between air pollution and pulmonary tuberculosis

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Review descriptive statistics

Figure 1 summarizes the study selection process.

illustration 1

The search returned a total of 12,652 records. After removal of duplicates, screening of titles and abstracts, inclusion of studies from the reference list of relevant studies, full-text reviews, 24 eligible studies were retained. Figure 1 summarizes the PRISMA flow chart of the study selection process. The studies excluded after a full text check and the reasons for the exclusion are shown in additional file 4.

Narrative synthesis including study validity assessment

Most of the studies were from Asian countries and a total of 437,255 tuberculosis cases were reported across the 22 studies reporting the number of tuberculosis cases during their study periods (1996-2019).7,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46. Of the 24 studies included in the review, 10 were time series, 5 cohort studies (3 retrospective, 2 prospective), 5 ecological, 2 case-control studies (1 nested, 1 retrospective), 1 retrospective case-cross-over and 1 was cross-sectional. The average male participation was 64.9% (N=13 studies)7,27,29,30,31,32,33,34,35,37,40,43,46Mean age 46.3 years (N=7 studies)27,30,31,32,37,40,43 and the mean annual tuberculosis incidence was 45.3 per 100,000 population (N=10 studies)7,27,29,32,35,36,45,46,47,48. Study and participant characteristics are summarized in Table 1.

Table 1 Study and participant characteristics of the eligible studies (N = 22 datasets).

The mean values ​​of the annual mean concentrations of the various air pollutants are shown in Table 2.

Table 2 Average annual mean and median concentrations of air pollutants.

Twelve studies were of good quality, eleven of moderate quality and one of poor quality (Supplementary File 6). The overall quality of the evidence for the association of all 6 air pollutants with the incidence of PTB was rated as low due to study limitations affecting the generalizability of the results and some inter-study discrepancies due to significantly increased inter-study heterogeneity (Supplement File 7).

data synthesis

Association between air pollutants and pulmonary tuberculosis incidence

pm2.5

There was a significant association between PM exposure2.5 and incidence of pulmonary tuberculosis (PTB), pooled adjusted RR = 1.12 (95% CI: 1.06-1.19), p 2= 72.4%7,29,38,39,43,49 . There was no evidence of publication bias (Begg’s test, p = 0.133 and Egger’s test, p = 0.203). Begg’s test, p=1. Likewise, Xiong et al.46 reported an association (RR = 3.10, 95% CI: 1.10-8.79) for 50 µg/m3 increase in PM2.5 Concentration. The study by Lai et al.32 (RR = 1.39, 95% CI: 0.95-2.03), which was cohort-like in design, found no significant association. Jassal et al.28reported an odds ratio of 25.3 (95% CI: 3.38-29.1).

pm10

There was a significant association between PM exposure10 and PTB incidence, pooled adjusted RR = 1.06 (95% CI: 1.01-1.12), p = 0.022, N = 8, I2 = 97.6% (Begg’s test, p = 0.536 and Egger’s test, p = 0.204)7,29,35,39,40,43,44,49 . The studies by Lai et al.32(HR=0.95, 95% CI: 0.78-1.17) and Hwang et al.27(RR=1.00 for males, 95% CI: 0.96-1.05 and RR for females=1.01, 95% CI: 0.98-1.05) found no significant association. Likewise, the pooled adjusted OR was 1.03 (95% CI: 1.01-1.04), p=0.001, N=3, I2 = 0% (Begg’s test, p = 1 and Egger’s test, p = 0.211) (Fig. 2)31,34,37 .

figure 2
figure 2

Forest plot showing the individual and pooled risk ratios and odds ratios for occurrence of pulmonary tuberculosis for PM2.5 and PM10. The dashed line in the forest plot represents the overall pooled estimate. The gray squares and horizontal lines represent each study’s vaccine acceptance rate and its 95% confidence intervals. The size of the gray square represents the weight that each study in contributed to the meta-analysis. The diamond represents the pooled vaccine acceptance rate and its 95% confidence intervals.

CO

There was no significant association between exposure to CO and incidence of PTB, pooled adjusted RR = 1.04 (95% CI: 0.98-1.11), p = 0.211, N = 4, I2= 87.4% (Begg’s test, p = 0.734 and Egger’s test, p = 0.355)39,43,47,49 . The studies by Lai et al.32 (HR=1.89, 95% CI: 0.78-4.58) and Hwang et al.27(RR=0.99 for males, 95% CI: 0.95-1.03 and RR for females=1.01, 95% CI: 0.98-1.04) had similar results. The pooled adjusted OR was 1.22 (95% CI: 0.84-1.76), p=0.305, N=3, I2 = 78.5% (Begg’s test, p = 1 and Egger’s test, p = 0.364) (Fig. 3)31,34,37 . Xiong et al.46(RR = 1.436, 95% CI: 1.004-2.053) reported a significant association at 100 µg/m3 Increase in CO concentration.

figure 3
figure 3

Forest plot showing the individual and pooled risk ratios and likelihood ratios for pulmonary tuberculosis occurrence for CO and NO2. The dashed line in the forest plot represents the pooled overall estimate. The gray squares and horizontal lines represent the odds ratios of each study and their 95% confidence intervals. The size of the gray square represents the weight contributed by each study in the meta-analysis. The diamond represents the pooled odds ratio and its 95% confidence intervals.

NO2

There was no association between NO exposure2 and the incidence of PTB, pooled adjusted RR = 1.08 (95% CI: 0.99-1.17), p = 0.057, N = 7, I2 = 98% (Begg’s test, p = 1 and Egger’s test, p = 0.437) (Fig. 3)7,35,39,40,43,48,49. Lai et al.32 (HR = 1.33, 95% CI: 1.04-1.70) found a significant association, while Hwang et al.27 (RR=1.00 for males, 95% CI: 0.96-1.05 and RR for females=1.01, 95% CI: 0.98-1.05) did not. Likewise, the pooled adjusted OR was 1.05 (95% CI: 0.95-1.17), p=0.322, N=3, I2 = 72.4% (Begg’s test, p = 0.296 and Egger’s test, p = 0.145) (Fig. 3)31,34,37. Xiong et al.46 (RR = 1.8, 95% CI: 1.11-2.91) reported a significant association for 5 µg/m3 increase of NO2 Concentration.

SO2

There was an association between exposure to SO2 and PTB incidence, pooled adjusted RR = 1.08 (95% CI: 1.04-1.12), p 2 = 94.4% (Begg’s test, p = 0.517 and Egger’s test, p = 0.356) (Fig. 4)7,35,39,40,43,44,47,48,49 . Hwang et al.27 (RR=1.07 for males, 95% CI: 1.03-1.12 and RR for females=1.02, 95% CI: 0.98-1.07) reported similar results in males. Likewise, Xiong et al.46reported an association (RR = 1.62, 95% CI: 1.12-2.33) for 5 µg/m3 increase of SO2 Concentration.

figure 4
figure 4

Forest plot showing the individual and pooled risk ratios and odds ratios for pulmonary tuberculosis occurrence for SO2 and oh3. The dashed line in the forest plot represents the pooled overall estimate. The gray squares and horizontal lines represent the odds ratios of each study and their 95% confidence intervals. The size of the gray square represents the weight contributed by each study in the meta-analysis. The diamond represents the pooled odds ratio and its 95% confidence intervals.

O3

There was no significant association between O3 Exposure and incidence of PTB, pooled adjusted RR = 1.01 (95% CI: 0.97-1.06), p = 0.560, N = 4, I2= 75.6% (Begg’s test, p = 0.734 and Egger’s test, p = 0.734) (Fig. 4)39,43,47,49. While Hwang et al.27had similar results (RR = 0.99 in males, 95% CI: 0.94-1.03 and RR in females = 1.01, 95% CI: 0.97-1.05), Lai et al.32found more of a protective effect (HR = 0.69, 95% CI: 0.49-0.98). Xion et al.46reported an association (RR = 0.96, 95% CI: 0.93-1.0) for 5 µg/m3increase in O3 Concentration.

Table 3 summarizes the percentage change in the PTB case numbers for the respective changes in air pollutant concentrations.

Tab. 3 Percentage change in the number of pulmonary tuberculosis cases with changes in air pollutant concentration.

Association between air pollutants and hospital admissions and mortality from pulmonary tuberculosis

Two studies reported a significant association between PM2.5 and PTB mortality; OR = 1.46 (95% CI: 1.15-1.85)33and percent change in cases of 0.08% (95% CI: 0.06-0.09)45. There was no significant association between CO, SO2and oh3 and PTB mortality47(Table 4). Likewise, there was no significant association between PM10CO, SO2O3 and hospitalization30.47. NO2 was associated with hospitalization for PTB, OR: 1.21 (95% CI: 1.10-1.33) (Table 4).

Table 4 Association between air pollutants and hospital admissions and mortality from pulmonary tuberculosis.

Subgroup analysis and meta-regression

Studies were categorized by duration (less than 5 years and 5 years or more), location (Asia and other), number of PTB cases (less than 5000 and 5000 or more), and study quality (good and fair/poor). None of these study characteristics could explain the observed between-study heterogeneity, with the exception of study site related to PM exposure2.5 air pollution. PM was at higher risk for PTB incidence2.5 Exposure in studies conducted outside Asia (Supplementary File 5).

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