Extracellular DNA traps in sputum from severe asthma patients

We have shown that activation of granulocytes in airways from asthma patients is not limited to respiratory burst activation. The baseline presence and increase of citrullinated histone H3 (CitH3) and cell-free eosinophilic granules in sputum from moderate asthma patients upon a corticosteroid-withdrawal induced exacerbation is suggestive of extracellular DNA traps, which may cause airway obstruction. Are these traps also present in sputum from severe asthma patients without an exacerbation? In this pilot study, from 20 severe asthma patients 16 sputum samples were analyzed. All patients used inhaled corticosteroids and 9 of whom also used oral corticosteroids. Lung function parameters are mean FEV1 (81.74%) with minimal reversibility (+1.6%), with airflow obstruction median MMEF25-75% (56%) and symptoms (ACQ>0.75). FeNO is positively correlated to % eosinophils (r 0.71; p=0.001) and its free intact granules (r 0.69; p=0.001) and negatively correlated to % neutrophils (r -0.61; p=0.007). The presence of high amounts of CitH3 (87.06 ± 24.13) together with cell-free eosinophilic granules suggests that DNA traps are present in severe asthma patients. In line herewith, trend wise (r 0.44; p=0.05) more DNase had to be added to liquefy sputum containing high eosinophils rather than neutrophils. Cell-free granules correlated positively to blood/ sputum eosinophils but not to sputum neutrophils. Also, CitH3 correlated (r 0.56; p=0.06) trend wise to the amount of DNase needed to liquefy sputum. Together this suggests the presence of extracellular DNA traps derived from eosinophils that obstruct airways in severe asthma patients. Therefore, it would be of interest to study the effect of DNase treatment in severe asthma.