Scientists say a substance which acts naturally to open airways could be used to protect against asthma.
Millions of people in the UK are treated for asthma
Duke University Medical Center researchers found mice with asthma had too little of the chemical, which relaxes airways so people can breathe.
Asthma research has previously tended to focus on what might cause airways to become constricted.
The researchers, writing in Science, said their findings could lead to new ways of treating the condition.
It is estimated that 5.2 million people in the UK are currently receiving treatment for asthma, including 1.1 million children.
The US researchers identified the natural compound, called nitrosoglutathione (GSNO), a molecule in the nitric oxide (NO) family, which keeps airways open.
Tests have shown people with asthma have too little GSNO.
So drugs which increase levels of the compound could offer a way of treating the obstructed airways, the researchers say.
They have been looking at what leads to low GSNO levels in the body.
The team had already discovered that a family of molecules called S-nitrosothiols (SNOs) played a role in carrying nitrous oxides such as GSNO around the body.
The Duke team have now looked at mice which lacked an enzyme called GSNO reductase, which breaks down SNOs and therefore governs GSNO levels in many tissues, including the lung.
If there is too much GSNO reductase, too much of the SNOs are broken down and there is too little GSNO to keep airways open.
They found mice prone to asthma were found to have increased GSNO reductase levels, and therefore lower concentrations of lung GSNO after being exposed to allergens.
The researchers suggest that it could be that exposure to allergens which triggers elevated GSNO reductase levels.
Jonathan Stamler, who led the research, said: "Scientists have generally focused on processes that actively constrict airways or lead to inflammation, making it difficult to get air in or out.
"Our findings suggest the disease may stem from a deficit in the natural bronchodilator that normally relaxes airways."
He added: "Our findings indicate that GSNO reductase is critical for regulation of airway tone under normal conditions and in response to allergic challenge, and that an imbalance of GSNO, and perhaps of other S-nitrosothiols, may contribute fundamentally to asthma.
"Our results further suggest that the GSNO deficit seen in patients with asthma may result from increased GSNO reductase activity.
"The enzyme may therefore offer a novel target for therapies designed to alleviate airway obstruction."
Professor Martyn Partridge, chief medical adviser at Asthma UK, said: "These are interesting results showing changes which add to existing understanding about what controls airway size in asthma.
"Whether the observations lead to possible new therapeutic approaches remains to be seen."