Table 2.
Relevant meta-analyses that reported on the risk of pneumonia in patients treated with ICS for COPD.
| Meta-analysis | Number of studies | ICS (number of studies) | n | Heterogeneity (I2) | Follow up (months) | Pneumonia RR (95% CI)Ŧ | Mortality RR (95% CI)# | Dose–effect relationship |
|---|---|---|---|---|---|---|---|---|
| Drummond et al. [2008] ǂ | 11 | FP (6) TRI (1) BUD (4) |
14,426 | 72%¶ | 6–40 | 1.34 (1.03–1.75) | 0.86 (0.68–1.09) | Yes |
| Singh et al. [2009] ǂ | 18 | FP (16) BUD (2) |
16,996 | 16% | 6–36 | 1.60 (1.33–1.92) | 0.96 (0.86–1.08) | NR |
| Sin et al. [2009] | 7 | BUD | 7042 | NR | 6–11 | 1.05 (0.81–1.37) | NR | NA |
| Singh and Loke [2010] | 24 | FP (16) BUD (7) MOM (1) Total |
23,096 | 0% 23% NA 15% |
NR | 1.67 (1.47–1.89) 1.19 (0.92–1.53)ǁ 2.00 (0.83–4.81) 1.57 (1.41–1.75) |
NR | NR |
| Halpin et al. [2011] ¥ | 12 | BUD (4) versus
FP (8) |
5502 9586 |
23.3% 0% |
6–12 2–36 |
0.47 (0.28–0.80) | 0.18 (0.01–4.10)£ | NR |
| Kew and Seniukovich [2014] | 43 | FP (26) BUD (17) FP versus BUD¥ |
21,247 10,150 |
0% 0% NA |
3–36 3–36 |
1.78 (1.50–2.12)Þ 1.62 (1.00–2.62)Þ 1.86 (1.04–3.34) |
0.99 (0.87–1.13) 0.90 (0.65–1.24) 1.24 (0.74–2.07) |
No Yes˫ |
ICS, inhaled corticosteroids; COPD, chronic obstructive pulmonary disease; FP, fluticasone propionate; TRI, triamcinolone; BUD, budesonide; MOM, mometasone; RR, relative risk; CI, confidence interval; OR, odds ratio; NR, not reported; NA, not applicable.
‘Any pneumonia’ events (regardless of severity).
All-cause mortality unless otherwise specified.
No distinction was made between the different ICS for the pooled analysis.
A re-analysis of the data shows a consistently increased risk of pneumonia after removal of the substantial statistical heterogeneity [Loke and Singh, 2009].
The exclusion of one trial demonstrates a statistically significant increased risk of pneumonia with BUD (RR 1.34, 95% CI 1.01–1.79) and removes the statistical heterogeneity (I2 = 0%) in a sensitivity analysis.
Adjusted indirect comparison with placebo as a common comparator (Bucher method).
Pneumonia-related mortality. Data extracted from 3 studies (2 with FP, 1 with BUD). The authors concluded there were too few events to draw any firm conclusions on pneumonia-related mortality.
Nonfatal serious adverse pneumonia events (requiring hospital admission). Data for ‘any pneumonia’ events were not pooled because of heterogeneity.
The 640 µg dose increased nonfatal serious adverse pneumonia events (OR 2.02, 95% CI 1.15–3.57), and no significant difference was observed for the 320 µg dose (OR 0.68, 95% CI 0.27–1.71).