Adam, what you'll gain in oxygen saturation might be offset by the damn summer humidity. Trust me - a 125-degree heat index at 5000' will suck the strength from you as badly as 13,000' in the Sierra. AMS won't be a concern but heat stroke will. You trade one monkey on your back for another, at least in summer - thin air for thick air.
If/when it happens, look up John (catpappy) and myself. We're in Atlanta, just 3 hours hours south of Asheville, and try to get up into the Appalachians and Blue Ridge fairly regularly. This hike is coming up for us in the next couple of weeks, and is representative of the upper-end elevation gains you'll find here:
http://www.hikinginthesmokys.com/sterling_baxter_creek.htmOther than the elevation, I think you'll find the biggest difference in the trails out here versus the west is the steepness. Trail designers out here apparently didn't get the switchback memo till a couple dozen years ago. Gains of 1000 feet-per-mile are common, and stretches of 1300 fpm not that unusual. Each year 25% or more of Appalachian Trail through-hikers quit before they're out of Georgia (the first 75 miles of the AT), mostly because of underestimating the steepness and ruggedness of the trail. And the AT is the one of the easier mountain trails in GA and NC.
Yes, technical climbing is limited in these parts - severely, compared to the Sierra. But it
is there. The good news is that NC has more technical climbing opportunities than anywhere else for hundreds and hundreds of miles.
Laura's even made some noise recently about adding a Mount Mitchell notch to her belt. If you guys don't hook up for a climb before you leave, maybe that'll give her the motivation to finally head east with her gear. I'd pay good money to see that go down . . .
