Sputum Extracellular DNA as a Marker for Lung Function Impairment in Asthma

Patients with severe asthma had higher sputum extracellular DNA concentrations than patients with mild to moderate asthma or those without asthma, according to the results of a recent study published in Respiratory Research.

Researchers conducted a multicenter, prospective, longitudinal cohort study (ALLIANCE adult arm; ClinicalTrials.gov Identifier: NCT02419274) by measuring extracellular DNA concentrations in induced sputum from patients with asthma and healthy control individuals. Lung function was evaluated using spirometry, body plethysmography, impulse oscillometry and inert gas multiple breath washout. The researchers examined the correlations of extracellular DNA concentrations with sputum neutrophils, eosinophils and macrophages, and fractional exhaled nitric oxide (FeNO).

Among the 162 study participants, 134 had asthma and 28 were healthy control individuals. When extracellular DNA concentrations were examined, patients with severe asthma had higher concentrations than both patients with mild to moderate asthma or healthy individuals. Furthermore, extracellular DNA concentrations correlated directly with sputum neutrophils (R=0.49; P <.0001), negatively with sputum macrophages to nonsquamous cells (R=-0.36; P <.0001), but had no correlation with sputum eosinophils or FeNO. Additionally, higher extracellular DNA concentrations were associated with impaired lung function.

 “[W]e have established that the increased production of extracellular DNA in the airways characterizes a subset of neutrophilic asthma patients who have broad lung function impairments, poor symptom control with an exacerbation-susceptible phenotype,” the study authors wrote. “Mechanistically, we propose that both corticosteroid treatment and the impaired macrophage phagocytic capacity are potential mechanisms that might contribute to the presence of persistent neutrophilic airway inflammation and [extracellular DNA/neutrophil extracellular traps enriched microenvironment in asthma.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Abdo M, Uddin M, Goldmann T, et al; on behalf of the ALLIANCE study group. Raised sputum extracellular DNA confers lung function impairment and poor symptom control in an exacerbation-susceptible phenotype of neutrophilic asthma. Respir Res. 2021;22(1):167. doi:10.1186/s12931-021-01759-z