The alert means it can be dangerous for certain people to be outside for extended periods of time. The group at risk includes people with heart or lung disease, as well as children and older adults.
According to the EPA, the biggest health threat is the fine particles from smoke that can get into your lungs and cause issues like runny nose, burning eyes and even heart or lung disease.
The North Carolina Division of Air Quality suggests everyone limit their outdoor physical activity. The group said pollution exposure depends on the length of time and level of exertion while exposed. So, you don't have to stay inside all day, but you should take it easy while outside.
Researchers at Duke University are studying the effects of the environment on our health every day, not only when we're experiencing a sharp spike in poor air quality.
"The Code Orange really signifies a dramatic decrease in air quality, but certainly we have to monitor our air quality on an ongoing basis," said Dr. Herbert Kim Lyerly.
The George Barth Gellar Professor at Duke University and Dir. of Duke's Environmental Health Scholars Program, co-authored a study recently published in PLOS One, showing the devastating effects of poor air quality on long-term health.
"The findings that we found were quite startling," said Lyerly. "If the air quality did not meet the World Health Organization's standards, the death rate for diseases such as Alzheimer's disease went up by as much as a third."
WATCH: Smoke and air quality forecast
FORECAST: Code Orange air quality alert from wildfire smoke
Smoke across America
Smoke and ash from massive wildfires in the American West clouded the sky and led to air quality alerts Wednesday on parts of the East Coast as the effects of the blazes were felt 2,500 miles (4,023 kilometers) away.
Strong winds blew smoke east from California, Oregon, Montana and other states all the way to other side of the continent. Haze hung over New York City, New Jersey and Pennsylvania.
The nation's largest wildfire, Oregon's Bootleg Fire, grew to 618 square miles (1,601 square kilometers) - just over half the size of Rhode Island. Fires also burned on both sides of California's Sierra Nevada and in Washington state and other areas of the West.
The smoke blowing to the East Coast was reminiscent of last fall, when large blazes burning in Oregon's worst wildfire season in recent memory choked the local sky with pea-soup smoke but also affected air quality several thousand miles away. So far this year, Seattle and Portland have largely been spared the foul air.
People in parts of New Jersey, Pennsylvania and elsewhere with heart disease, asthma and other health issues were told to avoid the outdoors. Air quality alerts for parts of the region were in place through Thursday.
"One of the things about this event that makes it so remarkable is that the smoke is affecting such a large swath of the U.S," said Jesse Berman, an assistant professor at the University of Minnesota School of Public Health and an expert on air quality. "You're not just seeing localized and perhaps upstate New York being affected, but rather you're seeing numerous states all along the East Coast that are being impacted."
David Lawrence, a meteorologist with the National Weather Service, said wildfire smoke usually thins out by the time it reaches the East Coast, but this summer it's "still pretty thick."
In California, a wildfire burning completely uncontained south of Lake Tahoe crossed the state line into Nevada. New voluntary evacuation orders were issued for portions of Douglas County, Nevada.
The Tamarack Fire, started by lightning in Alpine County, California, has now burned more than 68 square miles (176 square kilometers). Authorities say more than 1,200 firefighters are battling the blaze, which has destroyed at least 10 structures.
Meanwhile, Oregon on Wednesday banned all campfires on state-managed lands and in state campgrounds east of Interstate 5, the major highway that is commonly considered the dividing line between the wet western part of the state and the dry eastern half.
The regulation includes the designated fire rings at campsites, as well as candles and tiki torches. Propane grills are still allowed, but the state still urged campers to pack food that doesn't require heating or cooking.
The lightning-caused Oregon fire has ravaged the sparsely populated southern part of the state and has been expanding by up to 4 miles (6 kilometers) a day, pushed by gusting winds and critically dry weather that's turned trees and undergrowth into a tinderbox.
Fire crews have had to retreat from the flames for 10 consecutive days as fireballs jump from treetop to treetop, trees explode, embers fly ahead of the fire to start new blazes and, in some cases, the inferno's heat creates its own weather of shifting winds and dry lightning. Monstrous clouds of smoke and ash have risen up to 6 miles (10 kilometers) into the sky and are visible for more than 100 air miles (161 kilometers).
Authorities in Oregon said lower winds and temperatures allowed crews to improve fire lines, and they hoped to make more progress Wednesday. The fire was approaching an old burn area on its active southeastern flank, raising hopes it would not spread as much.
The blaze, which is being fought by more than 2,200 people, is about one-third contained. It was within a few hundred acres of becoming Oregon's third-largest wildfire in modern history.
At least 2,000 homes have been evacuated at some point during the fire and an additional 5,000 threatened. At least 70 homes and more than 100 outbuildings have burned, but no one is known to have died.
Extremely dry conditions and recent heat waves tied to climate change have made wildfires harder to fight. Climate change has made the West much warmer and drier in the past 30 years and will continue to make weather more extreme and wildfires more frequent and destructive.
While Berman is hopeful that the smoke will last only a couple of days, he said we may see more of it due to climate change.
"We fully expect that you're going to see more situations where smoke, from fires occurring farther away, is going to travel long distances and affect people in other parts of the country," Berman said. "I would not be surprised at all if these events did become more frequent in the future."