washington, d.c. — A new “good neighbor” rule issued by the Environmental Protection Agency will restrict smokestack emissions from power plants and other industrial sources that burden downwind areas with smog-causing pollution they can’t control. Nearly two dozen states will have to cut harmful industrial emissions of nitrogen oxide and other pollutants to improve air quality for millions of people living in downwind communities.

The final rule, issued Wednesday, will save thousands of lives, keep tens of thousands of people out of the hospital, prevent millions of asthma attacks and reduce sick days, according to the agency.

“Every community deserves fresh air to breathe. We know air pollution doesn’t stop at the state line,’’ said EPA Administrator Michael Regan.

The rule will take effect in May for power plants and “lock in significant pollution reductions to ensure cleaner air and deliver public health protections for those who’ve suffered far too long from air-quality related impacts and illness,” Regan said. The limits on industrial sites take effect in 2026.

States that contribute to ground-level ozone, or smog, are required to submit plans ensuring that coal-fired power plants and other industrial sites don’t add significantly to air pollution in other states. In cases where a state has not submitted a “good neighbor” plan — or where EPA disapproves a state plan — the federal plan would take effect to ensure downwind states are protected.

A 2015 rule set by EPA blocks states from adding to ozone pollution in other localities. The rule applies mostly to states in the South and Midwest that contribute to air pollution along the East Coast. Some states, such as Texas, California, Pennsylvania, Illinois and Wisconsin, both contribute to downwind pollution and receive it from other states.

Environmental and public health advocates hailed the final rule as a life-saving measure that will significantly cut air pollution that crosses state lines, harming people who live hundreds of miles away from power plants, cement factories, steel mills and other industrial polluters.

“Too many communities breathe unhealthy air because pollution from power plants and industrial sources blows across state lines,’’ said Harold Wimmer, president and CEO of the American Lung Association.

“This rule will curb emissions that contribute to unhealthy levels of ozone in downwind communities and help achieve cleaner air for people who live near polluting sources.’’

The National Mining Association slammed the rule as part of an ongoing, cumulative effort by the EPA under President Joe Biden to force the closure of coal-fired power plants across the country.

“With each rule that targets well-operating coal plants – the very same plants that are called on to keep the lights on when renewables or natural gas are unavailable and consumer demand soars – our electricity grid becomes increasingly vulnerable to crippling supply shortfalls,’’ said Conor Bernstein, vice president of the mining group.

The cross-state pollution rule, combined with rules on wastewater pollutionmercury and air toxics, and rules expected on greenhouse gas emissions, “make it impossible for utilities to make decisions based on the merits of what keeps the lights on, forcing those utilities to make decisions solely based on the EPA’s agenda,’’ Bernstein said.

He faulted EPA for failing to consider what he called “America’s energy reality.’’ As a result, “Americans and American businesses will continue to pay increasingly more for electricity that is less and less reliable,’’ Bernstein said. “Even worse, the EPA is unilaterally making these decisions for the states.’’

Regan disputed that, saying EPA considered thousands of comments on the rule, including from the power industry.

“We have worked with a lot of our grid operators and our regional planning organizations that focus on managing electricity. and we have really prioritized reliability,’’ he told reporters in a conference call Wednesday.

Regan dismissed complaints by West Virginia Sens. Joe Manchin and Shelley Moore Capito that the rule could threaten electricity affordability and reliability in their state and others.

The rule gives power plants flexibility for how to comply, including longstanding emissions trading programs and scrubbers used by many power plants, EPA said.

“This rule has some built-in features that we believe allows for us to achieve our public health goals, but also doesn’t jeopardize reliability,’’ Regan said.

Electricity produced from coal has dropped dramatically in the U.S. over the past decade and-a-half, thanks to competition from cheap and abundant natural gas, declining prices for renewable energy and environmental regulations. Many plants have been shuttered, and a further 23% of the country’s operating coal-powered fleet is scheduled to retire by 2029, according to the Energy Information Administration.

Ground-level ozone, which forms when industrial pollutants chemically react in the presence of sunlight, can cause respiratory problems, including asthma and chronic bronchitis. People with compromised immune systems, the elderly and children playing outdoors are particularly vulnerable.

A 2021 report by the lung association found that more than 123 million Americans lived in counties that experienced repeated instances of unhealthy ozone levels. Climate change will likely exacerbate the problem by causing more hot sunny days conducive to high ozone levels.

Hayden Hashimoto, a lawyer for the Boston-based Clean Air Task Force, said the new rule will protect residents of downwind states — including many in the East Coast — from smog caused by inadequate pollution controls in upwind states in the Midwest.

“Downwind states that have already reduced their emissions have been left in the untenable position of trying to solve air quality problems that have been largely caused by upwind sources” from nearby states, he said.

America’s Power, a group that advocates for the coal fleet and its suppliers, said EPA was imposing an “anti-coal bias” on states and the nation’s electricity supply. The final rule will result in more coal plant retirements and increase risks to grid reliability, said Michelle Bloodworth, the group’s president.