Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy.

WHAT IS KNOWN AND OBJECTIVE: Inhaled combination therapy composing of long-acting ß2-agonist and corticosteroid has been widely applied in the management of asthma, but observed treatment responses vary. The aim of this study was to evaluate the pharmacogenetic effect of the adenylyl cyclase type 9 (ADCY9) gene polymorphism on combination therapy. MATERIALS AND METHODS: Eighty-six mild to moderate Korean asthmatics were enrolled in this clinical trial. After the 2-week 'run-in' period, patients received budesonide (an inhaled corticosteroid) and formoterol (long-acting ß2-agonist) during the following 12-week active treatment period. Forced expiratory volume in 1 s (FEV(1) ) and maximum mid-expiratory flow (MMEF) levels were measured at all visits as primary outcome. ADCY9 (Ile772Met, 150127 C/T, 150130 C/T, 150397 C/T, 150479 C/T, TTTA (5/4) ) and ß2-adrenergic receptor (ADRB2, Arg16Gly) gene polymorphisms were genotyped. RESULTS: Significant associations were observed between the ADCY9 single nucleotide polymorphisms and percent changes in FEV(1) (Ile772Met T/C, P = 0·030) and MMEF (150397 C/T, P = 0·016) after 8 weeks of combination therapy. Haplotype associations were also observed with respect to percent changes in FEV(1) after 8 weeks of therapy (Ht3[TTCC], P = 0·017). Additive therapeutic effect was observed in those with the ADCY9 Ile772Met and ADRB2 Arg16Gly gene polymorphisms in terms of percent change in FEV(1) after 8 and 12 weeks of therapy (P = 0·002 and P = 0·027 respectively). WHAT IS NEW AND CONCLUSION: Our results suggest that ADCY9 gene polymorphisms may alone, and in combination with ADRB2 gene polymorphisms, contribute to individual response to combination therapy in mild to moderate asthmatics.

Impact of gender on clinical presentation of chronic rhinosinusitis with and without polyposis.

STUDY OBJECTIVE: To determine the impact of a patient's gender on the clinical presentation of chronic rhinosinusitis with and without nasal polyposis. STUDY DESIGN AND METHODS: Prospective study of 514 adult patients who presented with chronic rhinosinusitis with and without nasal polyposis. The patients were divided into two groups based on gender: female (n = 273) and male (n = 241). The following data were collected: presenting symptoms, co-morbidities, nasal endoscopy and sinus computed tomography findings, diagnosis, and outcome of surgery. Statistical analysis was performed using the chi-square test, with statistical significance set at p < 0.05. RESULTS: Facial pain and headache were more prevalent among women, while nasal obstruction was more prevalent among men (p < 0.05). There was no statistically significant difference in the prevalence of environmental allergy, asthma, psychiatric illness or anatomical variants obstructing the osteomeatal unit, comparing the genders. Chronic rhinosinusitis without polyposis was the more common diagnosis among women, while chronic rhinosinusitis with polyposis was the more common diagnosis among men (p < 0.05). Following surgery, a higher percentage of male patients reported improvement in nasal obstruction (p < 0.05), but there was no statistically significant difference in the improvement of the other presenting symptoms, comparing the genders. CONCLUSION: Women who suffer from chronic rhinosinusitis are more likely to complain of facial pain or headache on presentation and to be diagnosed with chronic rhinosinusitis without polyposis. On the other hand, men are more likely to complain of nasal obstruction, to be diagnosed with chronic rhinosinusitis with polyposis, and to report improvement in nasal obstruction following surgery.