Dr. Ferguson:   There's great data showing that bronchodilators improve hyper-inflation. Pretty much every study that I know of has been able to successfully show that with a long-acting bronchodilator, but Rich is the guru there, so am I wrong with that?

Dr. Casaburi:   No, I think you're not. I think the reduction in hyper-inflation is a classic effect of bronchodilator. If you improve FEV1 you're going to reduce hyper-inflation. I'm not really aware of good data that one does more than the other. There may have been a subtle thing put in our mind, because the first good studies that were done to show reduction to hyper-inflation were done with LAMAS, very well done studies that we participated in, and perhaps that's why it's in our mind. I'm not aware of good data that shows that one does it differentially better than the other, given the amount of FEV1.

Dr. Mannino:   Does oxygen improve hyper-inflation?

Dr. Casaburi:   Oxygen does a great job of improving hyper-inflation. So does pulmonary rehabilitation.

Dr. Ferguson:   Does it treat the airway muscles?

Dr. Casaburi:   No, it treats the limb muscles.

Dr. Ferguson:   We're trying to figure out A versus B, but A plus B versus B as well, and I would encourage you to go tomorrow to the abstracts, because there's two abstracts being presented that have looked at these registry trials and looked at them graded based on severity of symptoms, either by CAT score, or by mMRC score. In these different company studies with different criteria for symptoms, they all show that as your symptoms get worse, you have a better response not only in terms of FEV1 but in terms of patient-reported outcomes with the two versus one. In my own personal mind, as I'm trying to sort out placement of LABA/LAMAs versus say, LAMA as a starter therapy in my own mind, if they have either a CAT of 15 to 20 or higher, or at least symptoms that would go along with that, and they're very symptomatic patient, unless they have a contra indication, I probably would think about the combination LABA/LAMA as a starter for my patients now if they are less symptomatic, but I feel they need to be on a maintenance so they're a B, but they're a B with kind of a CAT of 11 or 12, and nothing else much going on. I probably, personally, would start with just a monotherapy, and that's just where I'm at at this moment in time with the data we have.

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