Neutrophil Elastase Gene Polymorphisms: Modulators of Response to Therapy in Childhood Bronchiectasis?

• Published in: Lung Vol. 192; no. 4; pp. 595 - 599
• Main Authors: Nikolic, Aleksandra, Milosevic, Katarina, Boskovic, Srdjan, Nestorovic, Branimir
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2014; Springer; Springer Nature B.V
• Subjects: Adolescent; Age Factors; Anti-Bacterial Agents - therapeutic use; Anti-Inflammatory Agents - therapeutic use; Breath Tests; Bronchiectasis; Bronchiectasis - diagnostic imaging; Bronchiectasis - enzymology; Bronchiectasis - genetics; Bronchiectasis - physiopathology; Bronchiectasis - therapy; Care and treatment; Child; Child, Preschool; Children & youth; Development and progression; Diagnosis; Drainage - methods; Elastases; Expectorants - therapeutic use; Female; Genes; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Humans; Leukocyte Elastase - genetics; Lung - physiopathology; Lung diseases; Male; Medicine; Medicine & Public Health; Neutrophils; Phenotype; Physiological aspects; Pneumology/Respiratory System; Polymorphism; Polymorphism, Genetic; Predictive Value of Tests; Promoter Regions, Genetic; Respiratory Function Tests; Tomography, X-Ray Computed; Treatment Outcome; Serbia; United States; Gene polymorphism; Neutrophil elastase; Bronchiectasis
• ISSN: 0341-2040; 1432-1750
• DOI: 10.1007/s00408-014-9596-3

Background
The aim of this study was to investigate polymorphisms in the promoter region of the neutrophil elastase (ELANE) gene as potential modulators of the therapeutic response in children with idiopathic bronchiectasis.
Methods
The study included 48 children between 5 and 17 years old who were diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of the thorax. In all patients therapy included administration of antibiotics, anti-inflammatory drugs, expectorants, and postural drainage. Response to therapy was evaluated by the change in FeNO levels before and after administration of therapy. The ELANE promoter region polymorphisms were analyzed by PCR-direct DNA sequencing.
Results
According to the predicted activity of ELANE genotypes, subjects were divided into two groups: low/intermediate activity (
n
 = 18) and high activity (
n
 = 30). Subjects in the group with high-activity genotype had higher initial FeNO levels and this difference was statistically significant (
t
 = 2.906;
p
 = 0.006). The difference between FeNO levels before and after therapy was also statistically significantly higher in children with high-activity genotype (
t
 = 3.329;
p
 = 0.002). Statistically significant correlation was observed between the change in FeNO levels and ELANE genotypes (
r
 = 0.350;
p
 = 0.015).
Conclusion
Children with high-activity genotype had higher initial FeNO levels and showed better response to therapy than children with low/intermediate-activity genotypes.