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Previous Volume 347:1493-1499 November 7, 2002 Number 19 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Arm, J. P. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Patients with asthma who have aspirin sensitivity have greater cysteinyl leukotriene production and greater airway hyperresponsiveness to the effects of inhaled cysteinyl leukotrienes than their aspirin-tolerant counterparts. We hypothesized that the latter effect reflects elevated expression of the cysteinyl leukotriene receptor CysLT₁ on inflammatory cells in the target organ and that its expression is down-regulated by aspirin desensitization.

Methods We obtained nasal-biopsy specimens from 22 aspirin-sensitive and 12 non–aspirin-sensitive patients with chronic rhinosinusitis and nasal polyps. Additional specimens were then obtained from subgroups of the aspirin-sensitive patients after intranasal application of lysine aspirin or placebo for two weeks (five and four patients, respectively) or for six months (five and four patients, respectively). The numbers of leukocytes expressing the CysLT₁ and leukotriene B₄ (LTB₄) receptors per unit area of sections of the nasal submucosa were determined by immunohistochemistry.

Results The absolute number of cells expressing the CysLT₁ receptor was significantly higher in the aspirin-sensitive patients than in the non–aspirin-sensitive patients (median, 542 cells per square millimeter [range, 148 to 1390] vs. 116 cells per square millimeter [range, 40 to 259]; P<0.001). The percentage of CD45+ leukocytes expressing the CysLT₁ receptor was also higher in the aspirin-sensitive subjects (25 percent of CD45+ leukocytes [range, 4 to 50] vs. 5 percent of CD45+ leukocytes [range, 2 to 11]; P<0.001); the percentage of CD45+ leukocytes expressing the LTB₄ receptor did not differ significantly between these two groups. Desensitization was associated with a decrease in the numbers of inflammatory cells expressing CysLT₁.

Conclusions The elevated numbers of nasal inflammatory leukocytes expressing the CysLT₁ receptor in aspirin-sensitive patients with chronic rhinosinusitis as compared with their non–aspirin-sensitive counterparts and the down-regulation of receptor expression after desensitization to aspirin are probably fundamental in the pathogenesis of aspirin sensitivity and in the mechanism of aspirin desensitization.

Source Information

From Guy's, King's and St. Thomas' School of Medicine (A.R.S., C.J.C., T.H.L.) and the Royal National Throat, Nose and Ear Hospital (A.P., G.S.) — both in London.

Address reprint requests to Dr. Lee at the Department of Asthma, Allergy and Respiratory Science, Guy's Hospital, London SE1 9RT, United Kingdom, or at tak.lee{at}kcl.ac.uk.

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