Eosinophilia Remodels, Thickens Airway Nerves in Asthma Patients

Dr. Drake and a colleague reviewing images from the confocal microscope.

A new 3D modeling method has, for the first time, shown how eosinophilia affects the structure of airway nerves in patients with asthma. Such alteration leads to increased sensitivity and airway constriction in many patients with the condition.

Eosinophils have long been implicated in altering nerve function in patients with asthma. However, a team of scientists from Oregon Health and Science University wanted to see what, if any, impact eosinophils had on the tree-like structure of these patients’ airway nerves.

“In previous studies, techniques only allowed researchers to visualize small sections of the branches, which meant you could never see the whole tree or how multiple trees fit together,” explained Matthew G. Drake, MD, an assistant professor in the Department of Pulmonary and Critical Care Medicine at OHSU.

The problem was that the typical way of measuring air nerves was 2D, despite the fact that nerves form multilayer 3D structures.

Drake and colleagues used a state-of-the-art confocal microscope to see if it could render 3D images that would lend a better understanding of any structural changes in the airways of patients with asthma. The result was a picture showing that in asthma patients with airway eosinophilia, the “trees” of airway nerves look more like a thick forest.

“This technique allowed us to determine that nerves in asthma form more branches and those branches are longer,” Drake told MD Magazine®.

Specifically, the study showed that patients with moderate persistent asthma had thicker nerve structures than patients with mild asthma or healthy controls. The findings suggest airway remodeling is a major factor in the increased severity of symptoms in certain patients with asthma.

The investigators also studied airways of mice. They found interleukin-5-overexpressing mice with airway eosinophilia had increased airway innervation and airway hyperresponsiveness. When they crossed those mice with mice born with a lack of eosinophils, the next generation of mice were born without eosinophils, but with high levels of airway Il5. Those mice showed neither excessive airway nerves nor hypersensitivity. As a result, Drake and colleagues concluded that it was the eosinophils that had made the difference.

Roughly 50% to 60% of patients with asthma also have eosinophilia.

The finding could be the first step down new avenues of therapy for patients with asthma.

“Our findings suggest that asthmatics with more nerves may respond to treatments differently than other patients,” he said, adding that treatment responses would need to be confirmed in additional studies.

In addition to treating asthma, it is also possible that a therapy could one day prevent the airway remodeling from occurring in the first place, though again, that strategy would need to be proved out in further research.

Drake added that the confocal microscopy technique might also be used in the future to categorize patients and devise treatment plans.

“This method is a potential technique to identify a unique subgroup of asthmatics who may benefit from different treatment regimens,” he said.

The study, “Eosinophils increase airway sensory nerve density in mice and in human asthma,” was in Science Translational Medicine.