Dr. Casaburi:   I think when they word it this way, you have to answer that there's no biologic rationale. I think that almost this is ethically; we sort of have a duty to use drugs on-label when there is an alternative. If there was no alternative, you might use an off-label drug, but there are alternatives, so I would suggest that people not use inhaled steroids off-label. I think this is a philosophy/art-of-medicine sort of question.

Dr. Mannino:   It's art-of-medicine. There's a little bit of data where some people have tried to suggest that the combination of a LABA and an ICS in the same fixed dose combination means that you're depositing both molecules in the same region at the same time, and therefore, whatever action one is doing, it's doing to the same, so it might have a greater effectiveness, if you gave two as monotherapies. The data on that is I guess, what I would say, in my mind is soft. It's certainly a theory that explores that, and so you would lose that impact if you were doing the ICS separate from it. If that was the only reason, I don't think that would be a reason not to. Again, it's something you can do, and quite honestly, in most of our clinical practice, formulary says you've got to follow the pathway that is approved.

Dr. Mannino:   For years in the VA-

Dr. Ferguson:   They ignored it.

Dr. Mannino:   Yeah, ICSs were being used off-label by the federal government. I actually had mentioned azithromycin, which of course is an off-label use, although commonly used.