Effects of leukotriene D 4 and histamine nasal challenge on airway responsiveness and inflammation in persistent allergic rhinitis patients

Clin Respir J. 2018 Feb;12(2):587-594. doi: 10.1111/crj.12566. Epub 2016 Nov 1.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Airway Resistance / drug effects
  • Airway Resistance / immunology*
  • Case-Control Studies
  • Chronic Disease
  • Cross-Over Studies
  • Female
  • Histamine / immunology
  • Histamine / pharmacology*
  • Humans
  • Leukotriene D4 / immunology
  • Leukotriene D4 / pharmacology*
  • Male
  • Middle Aged
  • Nasal Provocation Tests / methods*
  • Reference Values
  • Rhinitis, Allergic / diagnosis*
  • Rhinitis, Allergic / immunology*
  • Severity of Illness Index
  • Young Adult


  • Leukotriene D4
  • Histamine