A study led by the University of Leicester that aimed to improve the health of severe asthma patients reveals that the presence of increased amounts of a protein called PP5 in the lungs of severe asthma patients blocks the effects of the best medicines to treat the condition.
According to Science Daily, the researchers have described their discovery as a ‘paradigm shift’ in understanding the life threatening condition and provides researchers with a target in order to try and help improve the symptoms of the condition in sufferers.
The lead author of the study Dr Yassine Amrani of the University of Leicester says, “The goal of this study was to provide mechanistic insight into the reasons why our best anti-asthma drugs called ‘corticosteroids’ provide little clinical benefit in patients with a severe form of the disease. This is an unmet clinical need.”
The researchers performed test tube experiments using cells from healthy and severe asthma patients isolated using bronchoscopy to identify the proteins that interfere with the beneficial action of corticosteroids in the lungs. This type of laboratory experiment enables the team to make conclusions about cause and effect at the cell level. The study also validated the test tube findings by observing the presence of PP5 in people. The researchers examined whether these inhibitory proteins were abnormally expressed in the lungs of severe patients.
The Science Daily report notes that the team is interested in lung cells because they are the first to encounter the anti-asthma drugs when given as inhalers.
“The study demonstrated for the first time that a protein called PP5 was significantly upregulated in the lungs of severe asthmatic patients compared to healthy controls. The test tube study allowed us to show that this protein was playing a key role in suppressing the anti-inflammatory action of corticosteroid, thus identifying this protein as a potential new player in reducing patients’ response to corticosteroid therapy,” says Amrani.
Amrani says previous studies by experts in the field have provided some potential mechanisms but were done mostly in non-lung cells. The originality of this work is demonstrated in that the blunted response to therapy in severe asthma may derive from a reduced sensitivity of key lung structural cells such as the airway muscle tissue, which is responsible for the acute asthma attacks via their ability to narrow the airways.
Amrani concludes, “We provide evidence that the airway muscle tissue behaves like an inflammatory cell that is capable of producing different asthmatic factors known to be involved in severe asthma.” The research team says the study shows that some severe asthma patients may fail to properly benefit from their corticosteroid therapy because of the presence of heightened inhibitory signals driven by this protein called PP5 which blunts patients’ response to their best medicine, reports Science Daily.
“We are extremely excited by this paradigm shift observation as a recent study from a different group provided additional evidence for a role of PP5 in blunting corticosteroid response in asthma,” says Amrani. “Whether assessing the expression levels of PP5 could serve as a biomarker to determine patients’ response to therapy needs to be further explored.”
Source: Science Daily
