Table 3 Studies reporting pharmacological treatment efficacy in patients with mild COPD^a

 Kanner et al. 1999 [67]

COPD (FEV₁/FVC < 0.7 and FEV₁ 55–90% predicted)

Smoking cessation intervention with SAMA (ipratropium bromide) or placebo, versus usual care

Lower prevalence of symptoms (no additional effect of SAMA). Presence of symptoms associated with greater FEV₁ decline

 Gartlehner et al. 2006 [68]

COPD, including mild COPD

ICS (budesonide, fluticasone, triamcinolone) versus placebo

Reduced exacerbation rate. Sub-analysis of 3 RCTs on mild COPD found no effect (n = 191)

 Jones et al. 2003 [69]

COPD, stratified by severity

ICS (fluticasone propionate)

Reduced exacerbation rate in moderate/severe, but not mild COPD

 Hirai et al. 2017 [70]

Mild COPD (post-bronchodilator FEV₁/FVC < 5th percentile LLN and FEV₁ ≥ LLN)

Oral antioxidant (N-acetylcysteine) versus placebo

No effect on O₂ transport or exercise tolerance

 Gagnon et al. 2012 [71]

Mild COPD

SAMA/SABA (ipratropium bromide/salbutamol sulphate)

Improved FEV₁ and hyperinflation; no significant increase in walking time

 Zhou et al. 2017 [72]

Mild or moderate COPD

LAMA (tiotropium bromide) versus placebo

Improvement in pre- and post-dose FEV₁; bronchodilator, reduced annual decline in post-dose FEV₁

 Wise et al. 2003 [73]

Smokers with mild COPD (FEV₁/FVC < 0.7 and FEV₁ 50–90% predicted)

SAMA (ipratropium bromide) versus placebo, both with smoking cessation intervention (plus a usual care control group)

No effect on airway responsiveness compared with placebo or usual care

 Pauwels et al. 1999 [74]

COPD (pre-bronchodilator FEV₁/FVC < 0.7 and post-bronchodilator FEV₁ 50–100% predicted)

ICS (budesonide) versus placebo

Improvement in FEV₁ decline after 6 months, but similar rate to placebo from 9 months to end of study (36 months)