title: P2X7-regulated protection from exacerbations and loss of control is independent of asthma maintenance therapy.
abstract: BACKGROUND
  The function of the P2X(7) nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied.
  
  
  OBJECTIVE
  To evaluate the association between P2X(7), asthma exacerbations, and incomplete symptom control in a more diverse population.
  
  
  METHODS
  A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Network trial participants enrolled before July 2006, and P2X(7) pore activity was determined in whole blood samples as an ancillary study to two trials completed subsequently.
  
  
  RESULTS
  A total of 187 exacerbations were studied in 742 subjects, and the change in asthma symptom burden was studied in an additional 110 subjects during a trial of inhaled corticosteroids (ICS) dose optimization. African American carriers of the minor G allele of the rs2230911 loss-of-function single nucleotide polymorphism were more likely to have a history of prednisone use in the previous 12 months, with adjustment for ICS and long-acting β(2)-agonists use (odds ratio, 2.7; 95% confidence interval, 1.2-6.2; P = 0.018). Despite medium-dose ICS, attenuated pore function predicted earlier exacerbations in incompletely controlled patients with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1-9.3; P = 0.033). After establishing control with low-dose ICS in patients with mild asthma, those with attenuated pore function had more asthma symptoms, rescue albuterol use, and FEV(1) reversal (P < 0.001, 0.03, and 0.03, respectively) during the ICS adjustment phase.
  
  
  CONCLUSIONS
  P2X(7) pore function protects against exacerbations of asthma and loss of control, independent of baseline severity and the maintenance therapy.
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. lcd@medicine.wisc.edu
authors.forename: Loren C
authors.initials: LC
authors.lastname: Denlinger
authors.forename: David M
authors.initials: DM
authors.lastname: Manthei
authors.forename: Max A
authors.initials: MA
authors.lastname: Seibold
authors.forename: Kwangmi
authors.initials: K
authors.lastname: Ahn
authors.forename: Eugene
authors.initials: E
authors.lastname: Bleecker
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchili
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: Greg A
authors.initials: GA
authors.lastname: Hawkins
authors.forename: Nicolina
authors.initials: N
authors.lastname: Icitovic
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: Tonya
authors.initials: T
authors.lastname: King
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Erik
authors.initials: E
authors.lastname: Lehman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Dagna
authors.initials: D
authors.lastname: Sheerar
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: E Rand
authors.initials: ER
authors.lastname: Sutherland
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000420:Albuterol / Q000008:administration & dosage; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D022022:Nuclear Pore / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D000305:Adrenal Cortex Hormones; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; D000420:Albuterol; D011241:Prednisone