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Extracellular double-stranded DNA (eDNA) is a significant pathological component of the thick, viscous mucus found in the airways of patients with cystic fibrosis (CF) and other chronic inflammatory lung diseases (Source: PubMed, PMID: 15101034). This DNA is primarily released from the nuclei of infiltrating neutrophils during cell death or through the formation of neutrophil extracellular traps (NETs) in response to chronic infection (Source: Nature Reviews Microbiology, 2007). The high concentration of polymerized eDNA increases the viscoelasticity of airway secretions, which impairs mucociliary clearance and promotes a cycle of infection and inflammation (Source: Journal of Clinical Investigation, 1994). Therapeutic agents like Dornase alfa (recombinant human DNase I) target this eDNA by hydrolyzing the phosphodiester backbone, thereby thinning the mucus and improving lung function (Source: FDA, Pulmozyme Label). Reducing eDNA levels is a proven strategy to enhance airway hygiene and reduce the frequency of respiratory exacerbations in CF patients (Source: Cochrane Database of Systematic Reviews, 2018). Beyond CF, eDNA is being investigated as a target in other obstructive lung diseases where neutrophil-driven inflammation is prominent, such as bronchiectasis and severe asthma (Source: European Respiratory Journal, 2017). The presence of eDNA also contributes to the structural integrity of bacterial biofilms, making them more resistant to antibiotics and host immune defenses (Source: Science, 2002). By degrading this DNA scaffold, DNase treatment can potentially increase the susceptibility of pathogens to antimicrobial therapy (Source: Journal of Antimicrobial Chemotherapy, 2012).
Enzymatic hydrolysis of extracellular DNA phosphodiester bonds to reduce mucus viscosity and improve airway clearance (Source: FDA Pulmozyme Label).
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