What is the rationale/evidence to support doing 4 puffs of albuterol vs. 2 puffs for a reversibility study?

The rationale per ATS in 2005 is that 4 puffs of albuterol is higher on the dose-response curve and thus would potentially avoid getting a suboptimal (< 12%, < 200 mL) response from 2 puffs. Having said that, there was a study of this issue in 240 pediatric patients showing non-inferiority of 2 puff...

I agree with everything that Dr. @Dr. First Last says in his reply. As he points out, the noninferiority study was in children and it was open label. So even if 2 puffs is usually enough in smaller/younger children, I know of no specific downside to potentially "overdosing" with 4 puffs to be certai...

We do not tell our patients to take four (4) puffs of albuterol when they need to, so why are we using four (4) during the study? Also, a negative study does not keep us from prescribing these medications when clinically we have seen improvement in our patients.