New asthma research effort aims for better understanding, treatments

Asthma is often referred to as one disease, but for researchers and physicians in the field, it isn’t one thing but a landscape of types and variations, with a mix of causes and factors.

New grant funding awarded to a research collaboration from the Brigham and Women’s Hospital and the Boston-based Wyss Institute will push forward research to determine how best to identify what those subtypes are with the goal of better treating the condition.

“Patients with asthma are often all lumped together as one disease, but truly, there are many different triggers for asthma, many causes of asthma, many types of asthma, and many immune dysregulations that lead to something at the end we refer to collaboratively, like or collectively as asthma,” said Dr. Tanya Laidlaw, one of the project leads.

The research looks at proteins from patients’ nasal fluid to try to identify what causes an individual’s asthma. In any person, proteins in the immune system can cause inflammation. If the levels of those inflammatory proteins are too high, they can cause the difficulty breathing that is typical in asthmatics.

Similarly, other proteins in the immune system can reduce inflammation. If those proteins are reduced, it can cause similar symptoms.

PHOTO: djeyewater

“You want, normally to walk around with a sort of balanced level of having some good anti-inflammatory proteins in there as well,” said Laidlaw, who is the director of translational research in allergy at Brigham and Women’s Hospital. “If your body somehow is missing that protective protein level, you’re more likely to develop asthma.”

The researchers are looking to see if they can use samples of nasal fluid to identify what proteins cause different subtypes of asthma.

The new work under the grant, which was awarded by the pharmaceutical company Sanofi, will build on existing collaboration between the groups.

So far, the teams have used samples from patients at Brigham and Women’s through which protein testing from the Wyss Institute was able to identify proteins with levels that distinctly varied between patients with asthma and those without.

“That’s the most blanket way we can do it, like, ‘Asthma? Yes, no.’ ‘Are there any differences? Yes, no,’” Laidlaw said. “That was encouraging to see that.”

With the new grant funding, the team hopes to expand in a handful of directions, including, prominently, working with 125 different patients with five types of asthma to try to detect differences in proteins.

Those subgroups will include asthmatics whose inflammation is caused by allergies — particularly dust mite allergies, since they impact patients year-round; those with aspirin-exacerbated respiratory disease — a type of asthma that is not caused by allergies and can be worsened by taking aspirin and other anti-inflammatory drugs; patients who also have type 2 diabetes, which is sometimes linked with asthma; and a fourth subgroup of patients who appear to have asthma but have no allergies or other conditions to point to as the cause. The fifth group will be a control group of patients with dust mite allergies but no asthma to act as a comparison and to understand what inflamed nasal fluid looks like without asthma.

Through the work, Laidlaw said the team is hoping to be able to identify proteins that are notably present or absent in each of the subgroups that could point to a cause for that variation of asthma.

“There are many other kinds of asthma that aren’t directly related to clear allergic triggers,” Laidlaw said. “The truth is, we don’t really know what causes them, and therefore can’t diagnose them properly, and can’t come up with an appropriate target to treat.”

At the crux of the work is a push from Laidlaw and the other researchers to see if there’s a better way to collect samples to identify protein counts in patients. Typically, the type of protein examination they’re pursuing is done through blood samples, something Laidlaw said she thinks has limited the search for the biomarker proteins.

“The blood is not necessarily a direct reflection of what’s going on in the respiratory tissue and in the lungs, so we would want to get something closer to the organ itself in order to really understand what’s wrong with it to immune system level,” she said.

Fluid or tissue from the lungs would be more ideal but is harder to get to, so the research team is looking to see if nasal fluid can work as a happier medium — closer to the lungs but still easily accessible.

Through grant funding, the researchers will also compare a selection of about 60 proteins in both blood and nasal fluid to work towards a better understanding of how the two compare in trying to identify the causes of asthma.

And if it works, Laidlaw said she thinks it could also make collecting samples easier across the range of patients with asthma. Though the team is not doing any of its testing in children, being able to take a sample of nasal fluid rather than drawing blood could be a simpler and more effective way of collecting from younger patients who might struggle with the needles required to draw blood.

The research from the teams is in early stages, but if successful, the goal — or, as Laidlaw described it, the “pie-in-the-sky dream” — would be to be able to insert a small slip of paper, about an inch and a half long and three millimeters wide, up the nose of a patient that would collect a nasal fluid sample which would help identify the type and cause of the asthma to allow the doctor to better treat it.

That kind of precision medicine would be new to asthma, but not to medical treatments generally, said Laidlaw, who pointed to care for other diseases like cancer as a model for how, with more research, better understanding of asthma could allow for more personalized care.

“If you have lung cancer, we don’t treat you with a breast cancer drug just because you have cancer. The same I think should be true for asthma, right?” she said. “Just because you have asthma, not all drugs will work for all patients with asthma.”