Neutrophil elastase gene polymorphisms as therapy modulators in childhood bronchiectasis
2013
Bronchiectasis is a chronic pulmonary disease characterized by irreversibly dilated bronchi, bacterial colonization and inflammation dominated by neutrophils. Neutrophil elastase (NE) contributes significantly to the pathogenesis of the disease and may affect response to therapy due to interaction with commonly used agents, macrolide antibiotics and corticosteroids. The aim of this study was to investigate NE gene promoter polymorphisms as potential modulators of therapeutical response in children with idiopathic bronchiectasis. The study has encompassed 48 children (19 boys and 29 girls) aged between 5 and 17 years, diagnosed with idiopathic bronchiectasis based on clinical findings and high-resolution computed tomography (HRCT). In all patients therapy included administration of antibiotics, anti-inflammatory drugs, expectorants and postural drainage. The choice of therapy was based on clinical and microbiology findings, while response to therapy was evaluated based on change in exhaled NO levels after therapy administration. The NE gene promoter was analyzed by PCR combined with direct DNA sequencing. According to the predicted NE activity based on the polymorphisms present, patients were classified in two groups: high (−903TT/−741GG) which included 30 patients, and low/intermediate (−903TG, −903TT/−741AG and −903TT/−741AA), which included 18 patients. The main finding of this study was that children with high NE activity genotype responded better to therapy than children with low/intermediate activity genotypes (r=0.350; p=0,015). In spite of relatively small study sample, this finding deserves further investigation in a larger cohort of patients and in other pulmonary diseases.
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