The crossover design of this study was chosen because of the anticipated diversity of the study population. Because of the crossover design, a separate analysis of the effect of treatment order was performed and did not identify any significant differences based on treatment order. A single instance where the baseline spirometry prior to HHN was different from baseline spirometry prior to MDI-spacer was noted for FVC in the subgroup with COPD. The FVC was lowest prior to HHN. These decreased FVC measurements prior to HHN were identified both in subjects who had HHN as their initial bronchodilator treatment and in subjects who already had MDI-spacer treatment. The subjects with COPD who received MDI-spacer as a first treatment (no carryover effect possible) had larger FVC than prior to their HHN. Therefore, even this difference in baseline FVC in the subjects with COPD is most likely not a carryover effect, but is related is the small sample size of this subgroup.
Even though the HHN resulted in more broncho-dilation in this study than the MDI-spacer, there are several theoretical reasons why the opposite should occur, that is the MDI-spacer combination should result in greater aerosol deposition in peripheral airways and produce greater bronchodilation.