Effects of leukotriene D4 and histamine nasal challenge on airway responsiveness and inflammation in persistent allergic rhinitis patients

Abstract

Background: Both histamine and leukotrienes are implicated in the pathogenesis of allergic rhinitis (AR), although the pattern and severity of the nasal response to these two potent inflammatory mediators may differ, which has not been adequately studied in patients with persistent AR.

Objective: We sought to compare the differential effects of nasal challenge with leukotriene D₄ (LTD₄ ) and histamine on the airway response and inflammation in patients with AR.

Methods: An open-label, crossover study was performed in 25 persistent AR patients (AR group) and 16 healthy subjects (control group). Participants randomly underwent histamine and LTD₄ nasal provocation within a two-week interval. Nasal symptoms according to a visual analogue scale (VAS), fractional exhaled nitric oxide (FENO), nasal lavage, induced sputum, and spirometry were evaluated before and after nasal challenge.

Results: Nasal airway resistance (NAR) increased significantly after both LTD₄ and histamine nasal challenge in AR patients (P < .05). The potency of LTD₄ was 142-fold higher than that of histamine in increasing NAR (P < .001). The nasal symptom score induced by histamine challenge was significantly higher than that triggered by LTD₄ (3.42 ± 0.83 vs. 1.16 ± 0.94, P < .05) in the AR group. LTD₄ and histamine nasal challenge led to a significant increase in neutrophils in the nasal lavage and induced sputum (P < .05) in AR patients. There were no significant differences in the changes of eosinophils before and after LTD4 and histamine nasal challenges in nasal lavage and induced sputum. No significant changes in NAR, the induced symptom score, or inflammatory cells in the nasal lavage and sputum were found in the control group.

Conclusions: LTD₄ and histamine nasal challenge caused different patterns and severities of nasal symptoms, which correlated with symptoms (TSS) that affect patient's daily life. LTD4 was far more potent than histamine at increasing the NAR, while histamine nasal challenge induced more sneezing and nasal discharge. These results may guide the prescription of anti-histamine or anti-leukotriene agents for treating different AR phenotypes.

Keywords: allergic rhinitis; histamine; leukotriene D4; nasal hyperreactivity; provocation test.