Table 1.

Post-hoc analyses of randomized controlled trials with ICS-LABA or ICS-LABA-LAMA treatments in COPD based on blood eosinophil count.

Sources	Study design	Study arms	Eosinophil count subgroup	ICS response
Pascoe et al. (2015) [71]	double-blind RCT	Fluticasone + vilanterol (all doses) vs. vilanterol	<2% and ≥2%; <150 cells/μL and ≥150 cells/μL	Mean exacerbation rate (per year): Fluticasone + Vilanterol vs. Vilanterol Alone < 2% eosinophil: 0.79 vs. 0.89 ≥ 2% eosinophil: 0.91 vs. 1.28
Barnes et al. (2016) [72]	Double-blind RCT	Fluticasone vs. placebo	<2% and ≥2%	Mean exacerbation rate (per year): Fluticasone vs. placebo < 2% eosinophil: 1.32 vs. 1.63 ≥ 2% eosinophil: 1.59 vs. 1.81
Watz et al. (2016) [73]	Double-blind RCT	Fluticasone + tiotropium + salmeterol vs. tiotropium + salmeterol	<2% and ≥2%; <150 cells/μL and ≥150 cells/μL; <300 cells/μL and ≥300 cells/μL	Mean exacerbation rate (per year): Fluticasone + tiotropium + salmeterol vs. tiotropium + salmeterol < 2% eosinophil: 0.18 vs. 0.19 ≥ 2% eosinophil: 0.18 vs. 0.22
Papi et al. (2017) [74]	Double-blind RCT	Fluticasone + formoterol vs. formoterol	<2% and ≥2%	Mean exacerbation rate (per year): Fluticasone + formoterol vs. formoterol < 2% eosinophil: 0.70 vs. 0.84 ≥ 2% eosinophil: 0.88 vs. 0.88
Vestbo et al. (2017) [75]	Double-blind RCT	Beclometasone + formoterol + glycopyrronium vs. tiotropium	<2% and ≥2%	Adjusted rate ratio of exacerbation for Beclometasone + formoterol + glycopyrronium vs. tiotropium < 2% eosinophil: 0.933 ≥ 2% eosinophil: 0.700
Roche et al. (2017) [76]	Double-blind RCT	Fluticasone + salmeterol vs. indacaterol + glycopyrronium	<2% and ≥2%; <300 cells/μL and ≥300 cells/μL	Mean exacerbation rate (per year): Fluticasone + salmeterol vs. indacaterol + glycopyrronium < 2% eosinophil: 1.24 vs. 0.99 ≥ 2% eosinophil: 1.15 vs. 0.98
Chapman et al. (2018) [77]	Double-blind RCT	indacaterol + glycopyrronium vs. Fluticasone + tiotropium + salmeterol	<2% and ≥2%; <300 cells/μL and ≥300 cells/μL	Rate ratio of exacerbation for indacaterol + glycopyrronium vs. Fluticasone + tiotropium + salmeterol <300 cells/μL : 0.97 ≥ 300 cells/μL: 1.86
Papi et al. (2018) [78]	Double-blind RCT	Beclometasone/formoterol/ glycopyrronium vs. indacaterol/ glycopyrronium	<2% and ≥2%	Adjusted rate ratio of exacerbation for Beclometasone/formoterol/ glycopyrronium vs. indacaterol/ glycopyrronium < 2% eosinophil: 0.943 ≥ 2% eosinophil: 0.806
Ferguson et al. (2018) [79]	Double-blind RCT	Budesonide/glycopyrolate/ formoterol vs. glycopyrolate/ formoterol	<150 cells/μL and ≥150 cells/μL	Rate ratio of exacerbation for Budesonide/glycopyrolate/ formoterol vs. glycopyrolate/ formoterol < 150 cells/μL: 0.61 ≥ 150 cells/µL: 0.39
Lipson et al. (2018) [53]	Double-blind RCT	Fluticasone furoate/ umeclidinium/ vilanterol vs. umeclidinium/vilanterol	< 150 cells/μL and ≥150 cells/μL	Mean exacerbation rate (per year): Fluticasone furoate/ umeclidinium/ vilanterol vs. umeclidinium/vilanterol < 150 cells/μL: 1.06 vs. 0.97 ≥ 150 cells/µL: 0.95 vs. 1.39

RCT: randomized controlled trial; ICS: inhaled corticosteroid.