White blood cells called neutrophils point the way to a clear diagnosis

Reaching for an inhaler to relieve the coughing and wheezing associated with chronic asthma is easy, but knowing whether it’s being used to treat the right condition has not been as simple. Now, researchers from the University of Wisconsin have found a biomarker that determines whether someone is suffering from asthma or an allergy. Their study was published today in Proceedings of the National Academy of Sciences (PNAS).

To find the asthma-related biomarker, researchers looked to the immune system and white blood cells known as neutrophils, which moved more slowly across a chemotactic gradient in asthmatic patients than they did in nonasthmatic patients. Chemotaxis is the movement of cells caused by a chemical stimulant.

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The researchers were somewhat surprised that neutrophil activity was so different, even in mildly asthmatic patients. “Neutrophilic inflammation has primarily [been] linked to patients with severe asthma, so it was interesting to observe this difference in neutrophil chemotaxis velocity for patients with mild asthma,” said study co-author Eric Sackmann, a researcher at the University of Wisconsin.

Asthma is an inflammatory disease of the lungs that can lead to airway constriction and difficulty breathing. Traditionally, asthma has been diagnosed by determining the amount of airway constriction a patient has. Instead of looking at the extent of airway constriction, a neutophil chemotaxis test looks at the behavior of immune cells to differentiate between patients who have asthma and those who are suffering from an allergy such as rhinitis, which is an irritation of mucus membranes in the nose.

“Rather than measuring at the endpoint of this process, we go upstream and measure one of the main inflammatory cells directly to determine whether the cells’ function has been altered,” Sackmann said. “This is a fundamentally different approach compared to traditional assessment.”

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While neutrophil chemotaxis may sound complicated, the test is relatively simply: A handheld device separates neutrophils from a blood sample within five minutes. Then the device generates a chemoattractant (chemical) gradient across which the neutrophils move. Slowly migrating neutrophils indicate that a patient has asthma. The traditional blood draw and processing used in previous techniques takes about an hour.

“Researchers have often only counted the number of neutrophils or eosinophils in the blood…but have not typically measured functional readouts such as chemotaxis,” said Sackmann. “The chemotaxis assay is easier to perform and provides, we would argue, more interesting readouts as we monitor the cells over time. With our technology we really tried to greatly simplify the entire process so the tests can be performed with limited user operation time, and relatively robustly.”

So instead of waiting for an asthma attack, or even a prolonged cough, determining asthma risk may be possible with this simple test on a single drop of blood.

Neutrophils may be handy not just as an asthma biomarker, but potentially as a biomarker for other conditions. Although neutrophil chemotaxis has not been thoroughly explored for other diseases, another study demonstrated that neutrophil chemotaxis was different in severe burn patients, Sackmann said.

“[Burns are] clearly not a disease, but rather a clinical condition; however, this and other studies in the literature indicate that a cell’s function can reveal underlying conditions for patients,” he said.