Asthma: study may explain why some patients do not respond to treatment

By Honor Whiteman
For some people with asthma, current treatments fail to work. Now, researchers may have shed light on why this is, after uncovering an alternative cause for the respiratory condition that is not targeted with current medications.Study co-author Reynold A. Panettieri – inaugural director of the Clinical and Translational Science Institute at Rutgers University in New Jersey – and colleagues say their results may open the door to new treatments for asthma patients.

They publish their findings in the Journal of Clinical Investigation.

According to the Centers for Disease Control and Prevention (CDC), around 25 million – or 1 in 12 – people in the US have asthma, and this number continues to rise.

The majority of asthma patients are able to manage their condition and prevent asthma attacks by avoiding triggers for the disease – such as exposure to pollen – and using medication, such as inhaled corticosteroids.

However, some asthma medications may prove ineffective for some patients, though exactly why this is has been unclear.

Panettieri and colleagues believe their new study may offer a much-needed explanation.

Higher NPY concentrations in mice with airway hyper-responsiveness
To reach their findings, the researchers inactivated a number of genes in mice, finding that the inactivation of specific genes led to the development of an asthma-like condition known as airway hyper-responsiveness (AHR).

AHR is a key characteristic of asthma, where the airways demonstrate increased sensitivity in response to inhaled stimuli. This can lead to airway inflammation and breathing problems.

The researchers then analyzed the gene activity within the airway epithelial cells of the rodents, comparing it with the gene activity of control mice that did not have AHR.

They found that the mice with AHR had more concentrated levels of neuropeptide Y (NPY) than the control mice. A signaling molecule and neurotransmitter, NPY is most commonly found in the central nervous system.

“NPY’s biological actions include stimulating the constriction of blood vessels,” says Panettieri. “Previous research has linked variants of its gene to increased asthma risk, but NPY hasn’t been known previously to have a direct role in asthma.”

Blocking NPR could be an effective asthma treatment
Next, the researchers set out to determine whether NPY may play a role in human asthma.

When exposing normal human lung airways to the NPY, the team found that the molecule triggered an AHR-like reaction, and it also activated pathways in smooth muscle that induce the narrowing of airway passages.

Based on their results, the researchers suggest that blocking NPY activity in asthma patients could be a viable treatment option for the disease, offering hope to patients who fail to respond to current asthma medications.

Panettieri notes that NPY-inhibiting drugs have already been developed for other conditions, including high blood pressure and obesity. He adds:

“Testing whether these NPY inhibitors would help human asthma patients is an exciting next step in developing a new drug therapy for asthma patients.”

In February, Medical News Today reported on a study suggesting that exposure to acetaminophen before birth may be linked to asthma development.

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