A third runway at Heathrow risks the health of thousands of Londoners, a Greater London Authority report states.
Its expansion would increase nitrogen dioxide emissions which already breach EU limits, said the draft report commissioned by mayor Boris Johnson.
At least 700 properties would have to be demolished, including 100 listed buildings, the report added.
The government is due to rule on the plans this week. If approved, the mayor said he would challenge the decision.
The airport industry, business and union leaders say the airport's expansion is vital for the British economy's long-term competiveness.
But opponents - including residents living near the airport, environmental groups, Conservative and Lib Dem MPs - continue to fight the plan to increase the number of flights from 480,000 to 720,000 by 2030.
"In spite of other efforts to improve air quality, the proposed expansion will continue to place Londoners' health at risk"
The mayor's Aviation and Airport Policy Review says the area around Heathrow has "some of the poorest air quality in London".
The government is unlikely to meet EU air quality targets by 2010, the report states.
"It will need to justify to the EU the need to increase emissions from the planned expansion of Heathrow Airport at a time when it will already be in breach of its duty," it adds.
But the report says: "In spite of other efforts to improve air quality, the proposed expansion will continue to place Londoners' health at risk, a situation that has not been adequately considered."
Road pollution around the airport would also rise due to increased passenger traffic, the report states.
A school and community centre would be among buildings demolished for the expansion, plus about 255 hectares of greenbelt land, it adds.
British Airways chief executive Willie Walsh said the new runway would probably not be completed until around 2020, by which time new aircraft would emit 55% less carbon dioxide than planes did in the year 2000.
The Unite and GMB unions also supported Heathrow's expansion, with Unite saying work on the runway could create up to 50,000 jobs with another 15,000 positions once the project was complete.
Society of British Aerospace Companies said the expansion of Heathrow was "the right decision to take for the benefit of the country".
But Mr Johnson said: "Everybody knows that if you increase Heathrow by 50% and you increase the number of flights coming over... you will reduce the quality of life for hundreds of thousands, if not millions, of Londoners."
There would be "any number of bases" on which to challenge a government decision to expand the airport, he added.
The mayor previously put forward the idea of a new 24-hour airport on an artificial island in the Thames Estuary, which could possibly replace Heathrow altogether.
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