For patients with mild to moderate asthma, the effect of interruption of inhaled corticosteroid (ICS) treatment is not related to the classic inflammatory activation of eosinophils and neutrophils, according to results published in Chest. The results indicated that the process may point to another pathway that underpins the onset of loss of disease control and asthma exacerbations.

The study included participants with mild to moderate asthma from a standardized prospective ICS study (n=23). The researchers assessed various immune, inflammatory, and oxidative stress parameters in addition to markers of eosinophil and neutrophil activity in exhaled breath condensate, plasma, and sputum. These were assessed at 3 phases: at baseline, during loss of control, and after recovery.

Of the 23 participants, 22 lost control. The results indicated that loss of asthma control was characterized by increased sputum eosinophils.

The researchers did not find any differences in most of the inflammatory and oxidative stress parameters between the 3 phases. They also did not detect differences in markers of activated eosinophils (eosinophil cationic protein and bromotyrosine) or neutrophils (myeloperoxidase and chlorotyrosine).

During loss of asthma control, the researchers noted that free eosinophilic granules and citrullinated histone H3 were enhanced, which may suggest eosinophil cytolysis and eosinophil extracellular trap formation.

The results indicated that there was a correlation between baseline blood eosinophils and changes in asymmetric dimethylarginine in plasma, with a decrease in forced expiratory volume in 1 second percentage predicted on ICS withdrawal (both rs=0.46; P =.03).

The study included several limitations. The researchers noted that the study design did not use the spontaneous loss of control or exacerbations trigged by respiratory viruses.

“Eosinophil recruitment may therefore reflect eosinophil cytolysis and possibly extracellular DNA trap formation that may underlie the onset of loss of asthma control and asthma exacerbations,” the researchers wrote.

Disclosure: This clinical trial was supported by Chiesi Pharmaceuticals. Please see the original reference for a full list of authors’ disclosures.

Reference

de Groot LES, van de Pol MA, Fens N, et al. Corticosteroid withdrawal induced loss of control in mild to moderate asthma is independent of classic granulocyte activation [published online October 14, 2019]. Chest. doi:10.1016/j.chest.2019.09.027