Table 1.

Clinical trials of regular treatment with nebulizers versus inhalers and measures of lung function

First author, year	Study type	Sample and comparison	Study findings
Hansen, 1989 [32]	Crossover trial with measurements of outcome once each day, over two consecutive days, up to 60 min after exposure	22 with severe COPD 2 mg terbutaline via DPI vs. 5 mg terbutaline via nebulizer	No appreciable or statistically significant difference in FEV1 or FVC was observed according to inhalation device
Ikeda, 1999 [33]	Crossover trial with treatments over seven separate days with effects observed up to 4 h after inhalation	10 with stable COPD 200 mcg and 1000 mcg albuterol via DPI vs. pMDI with a large-volume spacer vs. the same doses via nebulizer	Greater increase in FEV1 with inhalers than nebulizers evident with the higher dose of albuterol
Ramlal, 2013 [34]	Crossover trial on 1 day with effects observed 45 min after inhalation	10 with COPD 400 mcg albuterol and 40 mcg ipratropium via pMDI with AeroChamber vs. the same doses via nebulizer	Increase in FEV1 was significantly greater via nebulizers than pMDIs with AeroChambers, although results for other parameters of lung function, such as inspiratory capacity and peak inspiratory flow, were statistically similar
Mahler, 2014 [35]	Crossover trial 1 day with effects observed up to 2 h after inhalation	20 with COPD 50 mcg salmeterol dry powder via DPI vs. arformoterol (15 mcg/2 ml) via nebulizer	Volume responses were greater with arformoterol via nebulizer than dry powder salmeterol
Mahler, 2019 [36]	28-day parallel-group clinical trial	206 patients with COPD, including 161 with predicted FEV1 < 50%) 175 mcg revefenacin via nebulizer vs. 18 mcg tiotropium dry powder via DPI	Nebulized revefenacin increased trough FEV1 in patients with FEV1 < 50% predicted and suboptimal peak flow (sPIRF) compared with tiotropium via inhaler