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Therapeutic implication of genetic variants of IL 13 and STAT 4 in airway remodelling with bronchial asthma
Author(s) -
Nakamura Y.,
Suzuki R.,
Mizuno T.,
Abe K.,
Chiba S.,
Horii Y.,
Tsuboi J.,
Ito S.,
Obara W.,
Tanita T.,
Kanno H.,
Yamauchi K.
Publication year - 2016
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12710
Subject(s) - medicine , asthma , pulmonary function testing , airway , interleukin 13 , immunology , gastroenterology , interleukin , cytokine , anesthesia
Summary Background Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched. Objective We determined the effects of high‐dose inhaled corticosteroids ( ICS s) on decreased pulmonary function in asthmatic Japanese patients with variants of IL 13 and STAT 4 during long‐term treatments with low to mild doses of ICS . Methods In this study, 411 patients with bronchial asthma who were receiving ICS s and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high‐dose ICS s administered to asthmatic patients who were homozygous for IL 13 AA of rs20541 or STAT 4 TT of rs925847 and who progressed to airway remodelling were investigated. Results High‐dose ICS treatment increased the pulmonary function of patients homozygous for IL 13 AA of rs20541 but not of patients homozygous for STAT 4 TT of rs925847. The increased concentrations of the mediators IL 23, IL 11, GMCSF , hyaluronic acid, IL 24, and CCL 8 in bronchial lavage fluid ( BLF ) were diminished after high‐dose ICS treatment in patients homozygous for IL 13 AA of rs20541. Conclusion and Clinical Relevance IL 13 AA of rs20541 and STAT 4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high‐dose ICS s to asthmatic patients with genetic variants of IL 13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT 4 TT did not respond to high‐dose ICS s. Therefore, using medications other than ICS s must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype‐specific therapies for bronchial asthma.