title: Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease.
abstract: BACKGROUND
  Aspirin-exacerbated respiratory disease (AERD) is diagnosed through graded aspirin challenges that induce hypersensitivity reactions and eicosanoid level changes. It is not known whether diagnostically useful changes also occur after low-dose aspirin challenges that do not induce hypersensitivity reactions.
  
  
  OBJECTIVE
  To investigate the utility of low-dose oral aspirin challenges for diagnosing AERD by measuring different clinical parameters and eicosanoid changes.
  
  
  METHODS
  Sixteen patients with AERD and 13 patients with aspirin-tolerant asthma underwent oral challenges with low-dose (20 or 40 mg) aspirin and diagnostic oral graded aspirin challenges (up to 325 mg of aspirin). Forced expiratory volume in 1 second, nasal peak flow, the fraction of exhaled nitric oxide (FeNO), and eicosanoid levels in plasma and urine were analyzed.
  
  
  RESULTS
  In patients with AERD but not in those with aspirin-tolerant asthma, 40-mg aspirin challenges induced a significant mean (SEM) decrease from baseline in FeNO (19% [5.1%]; P = .001) without causing any hypersensitivity reaction. The FeNO decrease also occurred after higher-dose aspirin challenges (27.8% [4.9%]; P < .001). The sensitivity and specificity of 40-mg aspirin-induced FeNO changes for identifying AERD were 90% and 100% with an area under the curve of 0.98 (95% CI, 0.92-1.00). The low-dose challenge also induced a significant leukotriene E4 urine increase in patients with AERD (from 6.32 [0.08] to 6.91 [0.15] log-pg/mg creatinine; P < .001), but the sensitivity and specificity of these changes were less than for the FeNO changes.
  
  
  CONCLUSIONS
  The low-dose aspirin-induced decrease in FeNO in patients with AERD may be useful for the diagnosis of aspirin allergy without inducing a hypersensitivity reaction.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01320072.
authors.affiliation: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York. Electronic address: Elina.Jerschow@einstein.yu.edu.
authors.forename: Elina
authors.initials: E
authors.lastname: Jerschow
authors.affiliation: Jacobi Medical Center, Bronx, New York.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.
authors.forename: Golda
authors.initials: G
authors.lastname: Hudes
authors.affiliation: Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.affiliation: Ferkauf Graduate School of Psychology at Yeshiva University, Bronx, New York.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Morales
authors.affiliation: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.
authors.forename: Victor
authors.initials: V
authors.lastname: Schuster
authors.affiliation: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Spivack
authors.affiliation: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.
authors.forename: David
authors.initials: D
authors.lastname: Rosenstreich
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D055963:Asthma, Aspirin-Induced / Q000175:diagnosis*; D004342:Drug Hypersensitivity / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D000485:Allergens; D009569:Nitric Oxide; D017999:Leukotriene E4; D001241:Aspirin
references.citation: J Allergy Clin Immunol. 2014 Jun;133(6):1692-701.e3
references.pmid: 24486071
references.citation: Am Rev Respir Dis. 1992 Jul;146(1):96-103
references.pmid: 1320824
references.citation: J Allergy Clin Immunol. 1992 Oct;90(4 Pt 1):636-45
references.pmid: 1328344
references.citation: Eur Respir J. 1993 Mar;6(3):391-9
references.pmid: 8386106
references.citation: Eur Respir J Suppl. 1993 Mar;16:5-40
references.pmid: 8499054
references.citation: N Engl J Med. 1993 Dec 30;329(27):2002-12
references.pmid: 7504210
references.citation: J Allergy Clin Immunol. 1995 Aug;96(2):148-56
references.pmid: 7636051
references.citation: Am J Respir Crit Care Med. 1996 Feb;153(2):572-5
references.pmid: 8564100
references.citation: J Allergy Clin Immunol. 1996 Aug;98(2):421-32
references.pmid: 8757220
references.citation: J Allergy Clin Immunol Pract. 2015 Nov-Dec;3(6):926-31.e1
references.pmid: 26282158
references.citation: Respir Med. 2014 Jun;108(6):830-41
references.pmid: 24636813
references.citation: J Immunol. 2014 Jul 1;193(1):41-7
references.pmid: 24890720
references.citation: Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):391-8
references.pmid: 10673176
references.citation: J Allergy Clin Immunol. 2003 Jan;111(1):180-6
references.pmid: 12532116
references.citation: J Allergy Clin Immunol. 2003 Apr;111(4):743-9
references.pmid: 12704352
references.citation: J Allergy Clin Immunol. 2004 Feb;113(2):277-83
references.pmid: 14767442
references.citation: Kidney Int. 1998 Mar;53(3):645-53
references.pmid: 9507210
references.citation: J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):559-64
references.pmid: 10482828
references.citation: J Allergy Clin Immunol. 2005 Nov;116(5):970-5
references.pmid: 16275362
references.citation: Ann Allergy Asthma Immunol. 2005 Oct;95(4):330-5
references.pmid: 16279562
references.citation: Ann Allergy Asthma Immunol. 2006 Nov;97(5):688-93
references.pmid: 17165280
references.citation: Ann Allergy Asthma Immunol. 2007 Feb;98(2):172-4
references.pmid: 17304886
references.citation: Thorax. 2008 Jan;63(1):27-34
references.pmid: 17584993
references.citation: Allergol Int. 2008 Dec;57(4):429-36
references.pmid: 18797183
references.citation: J Allergy Clin Immunol. 2009 Feb;123(2):406-10
references.pmid: 19056109
references.citation: J Allergy Clin Immunol. 2010 May;125(5):1084-1091.e6
references.pmid: 20304469
references.citation: J Allergy Clin Immunol. 2010 Oct;126(4):738-44
references.pmid: 20728206
references.citation: J Allergy Clin Immunol. 2011 Jul;128(1):66-72.e1
references.pmid: 21397936
references.citation: Am J Respir Crit Care Med. 2011 Sep 1;184(5):602-15
references.pmid: 21885636
references.citation: J Allergy Clin Immunol. 2012 Feb;129(2):557-9, 559.e1-2
references.pmid: 22018904
references.citation: Am J Rhinol Allergy. 2012 Nov-Dec;26(6):428-32
references.pmid: 23050514
references.citation: Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):16987-92
references.pmid: 24085850
references.citation: PLoS One. 2014;9(2):e90018
references.pmid: 24587191
references.citation: J Allergy Clin Immunol. 2014 Sep;134(3):554-9
references.pmid: 24522091
references.citation: J Allergy Clin Immunol. 2014 Oct;134(4):883-90
references.pmid: 24767875
references.citation: Am J Physiol Lung Cell Mol Physiol. 2014 Dec 15;307(12):L987-97
references.pmid: 25326583
references.citation: J Allergy Clin Immunol. 2015 Jan;135(1):245-52
references.pmid: 25218285
references.citation: Eur Ann Allergy Clin Immunol. 2014 May;46(3):109-13
references.pmid: 24853569
references.citation: Allergy. 2004 Aug;59(8):827-32
references.pmid: 15230814
references.citation: N Engl J Med. 1984 Nov 8;311(19):1206-11
references.pmid: 6436696