Neutrophil-like low-density granulocytes are elevated in patients with moderate to severe persistent asthma

Abstract

BackgroundElevations in neutrophil-like low-density granulocytes (LDGs) are observed in association with disease severity in some autoimmune and other disorders. This study evaluated whether a similar association with disease severity is observed in asthma. ObjectiveTo determine LDG levels in peripheral blood mononuclear cells of subjects with intermittent or mild persistent asthma, subjects with moderate persistent or severe persistent (SP) asthma, and control subjects without a history or allergy or asthma. MethodsA brief medical history and physical examination, spirometry, and measurement of fraction of exhaled nitric oxide were performed. The LDGs were quantified by polychromatic flow cytometry. ResultsThe LDGs displaying the same phenotype as those described previously for LDGs in other diseases were significantly elevated in peripheral blood mononuclear cells of subjects with moderate persistent or SP asthma. The LDGs comprised up to 39% of peripheral blood mononuclear cells, with elevated LDG levels most prevalent in subjects with SP asthma. The highest LDG levels were observed in 4 subjects with SP asthma. Fraction of exhaled nitric oxide levels and body mass were significantly increased in subjects with low LDG levels compared with control subjects, whereas fraction of exhaled nitric oxide levels and body mass were not elevated in subjects with moderate persistent or SP asthma and high LDG levels compared with control subjects. ConclusionThese findings identify a previously unrecognized association between LDG levels and asthma severity. Identification of the factor(s) responsible for the increased LDG levels in moderate persistent or SP asthma may provide a serum biomarker to aid in the identification of neutrophil-associated phenotypes of severe asthma.