People with asthma who are obese have harder-to-treat symptoms than lean or overweight patients. A large, bouquet-shaped molecule called surfactant protein A, or SP-A, may be why.
Researchers compared SP-A levels in lean and overweight asthmatics against SP-A levels in obese asthmatics (those with a body mass index, or BMI, over 30). The obese individuals had significantly less of the protein.
SP-A is a powerhouse of a protein that helps curb the lungs’ responses to environmental insults such as air pollution. It also regulates the numbers and locations of disease-fighting white blood cells called eosinophils. Without enough SP-A to rein them in, you end up with too much of a good thing. The eosinophils collect in the lungs and wreak havoc.
Researchers began the current research in 2010. WSP-A levels in asthmatic patients had been relatively well studied but little understood. The literature was shaky. Some research showed that asthmatic patients have more SP-A than healthy individuals, others found they have less, and still others found they had the same amount. Using about 50 samples from the patients of medical doctors also got mixed results.
“I saw a really wide discrepancy in levels,” says Julie Ledford, assistant professor of medicine at the University of Arizona. “My results matched everything that had been published, so Monica (Monica Kraft, professor of medicine) and I looked at patient demographics to see if anything stood out.”
There in the data it was plain as day: People with especially low levels of SP-A had especially high BMIs. It was the first time anyone had made the connection.
The study in the Journal of Allergy and Clinical Immunology shows the same connection made years ago—and also provides insights on what is driving that stark difference in SP-A levels between obese individuals and others.
It starts with something called cytokines, little proteins made by cells in the immune system, giving other cells a signal to take some kind of action. By moving out of a cell, one cytokine called tumor necrosis alpha, or TNF-a, tells other cells to activate the immune system. Obese individuals often have increased amounts of TNF-a.
If you have enough of it, TNF-a can actually suppress SP-A. And in obese asthmatics, it does just that, Ledford says.
“These results are eye-opening in that we’re finding out potentially why obese asthma patients don’t respond as well to treatments as other asthmatic patients. It could be due to the lack of this important immunoregulatory protein. I hope this study will lead to better patient care for this group of people.
“SP-A is well known to fight pathogens, so with pretty much any lung infection, someone with less SP-A would be at a higher risk for complications,” she says, adding that across all demographics of asthmatic patients, SP-A doesn’t work as well as it should to begin with.
The researchers are working to translate the findings into a new therapy.
“The active piece of surfactant protein A is, we think, 10 to 20 amino acids. We’re putting that piece of it into an inhaler as a delivery,” Ledford says.
They are now working to further understand what factors, beyond TNF-a, might lead to decreased levels of SP-A and would also like to study SP-A levels in bariatric patients before and after their weight-loss surgeries.
“I’m getting to see where and how my work in the lab can affect patient outcomes,” Ledford says, “and, as a scientist, that’s the best reward one can get.”
Ledford and Kraft are working with Tech Launch Arizona, the university office that commercializes inventions stemming from research, to develop and license the treatment for those with asthma and other respiratory diseases.
Source: University of Arizona