The dose of albuterol that we chose for the nebulizer is the standard recommended dose, while that chosen for the MDI-spacer system was twice the usual dose. In the study of Jenkins et al, cumulative dose-response curves were generated to establish the doses of albuterol (salbutamol) by MDI and nebulizer which produced maximum bronchodilation in stable patients with chronic airflow obstruction. Nine of 19 patients had a maximal response at 2.5 mg via nebulizer, and 17 of 19 had a maximal response at 0.4 mg by MDI. Thus, it may be argued that we biased our results toward the MDI-spacer system by using a dose more likely to produce maximal bronchodilation. However, the study of Jenkins and co-workers was performed in patients in stable condition who presumably could use the MDIs in an optimal manner. Our population was quite different. We chose the 2.5-mg dose for the nebulizer because it is a standard one, and we chose the MDI-spacer dose because we believed that a dose higher than standard would be needed in the setting of an acute exacerbation. Indeed, even if six to eight puffs per MDI-spacer system were needed for equivalent effect, this would not detract from its potential usefulness. More info

In the study of Turner and co-workers, heart rate fell significantly following metaproterenol therapy in the MDI-spacer group but not the nebulizer group. They attributed this difference to cardiac stimulation from the large dose in the nebulizer. Our subjects had been treated for several hours before entry into the study, and this may explain a lack of fall in heart rate. Alternatively, the absence of significant changes in heart rate with either the MDI-spacer or nebulizer may have been due to the greater (J2_adrenergic selectivity of albuterol compared to metaproterenol.
The fact that active medication via the MDI-spacer system improved the FVC (percent change) much less when given in treatment block 2 (order-2 patients) requires comment. This group of patients had lower values for FVC overall. The FVC may be quite dependent on effort in severely obstructed patients, in the sense that a prolonged exhalation is needed. Perhaps because order-2 patients tended to have more obstruction, they were less able to produce optimal spirometry after extended testing. The fact that a larger improvement in the FEV1 than the FVC was noted in this group after treatment with active drug via MDI-spacer is evidence for this hypothesis. Another possibility is that these subjects used the MDI-spacer less well due to fatigue or more severe obstruction and therefore responded poorly. Some of our patients did have difficulty in using the MDI-spacer system. Thus, one cannot rule out the possibility that a subgroup of very severely obstructed patients may benefit more from nebulizer treatment.