Leukotriene D4 Nasal Provocation Test in Allergic Rhinitis

Study Overview
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Brief Summary
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Leukotrienes play critical roles in the inflammatory process in allergic rhinitis and bronchial asthma, therefore, anti-leukotriene therapy is part of treatment for asthma. However, not all allergic rhinitis accompanied with or without asthma treated with anti-leukotriene were effective. So it is critical to develop a method to identify the response subgroup. In this study, it is assumed that nasal physiological responsiveness to leukotriene nasal provocation test (NPT) is able to gain evidence on the effect of leukotriene on the development of allergic rhinitis and asthma, and is helpful to the use of anti-leukotriene agent. The purpose of the study is to establish the methodology and diagnostic value of leukotriene D4 (LTD4) nasal provocation.

Detailed Description
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Nasal provocation test induced by LTD4 will be conducted by measuring nasal airway resistance and airway symptoms in a stepwise concentration of LTD4 by nasal spray. Inflammation biomarkers, such as eosinophilic granulocyte in sputum and nasal lavage, fractional exhaled nitric oxide(FeNO), and lung function before and after nasal provocation will be studied to explore the impact of LTD4 nasal provocation test on airway inflammation.

Official Title
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Leukotriene D4 Nasal Provocation Test: Rationale, Methodology, Diagnostic Value and Its Impact on Airway Inflammation in Allergic Rhinitis With or Without Asthma

Conditions
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Allergic Rhinitis, Asthma

Intervention / Treatment
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* Drug: leukotriene D4
* Drug: histamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with allergic rhinitis accompanied with or without asthma positive skin prick test (SPT) had no acute upper or lower airway infection 2 weeks prior to study no oral or nasal anti-histamines no leukotriene receptor antagonists for 1 week no oral or nasal and inhaled corticosteroids for 2 weeks Exclusion Criteria: smokers a past confirmed history of chronic respiratory disease other than asthma other severe systemic diseases (myocardial infarction, malignant tumor, etc.) under immunotherapy unable to complete the test or had limited understanding pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: leukotriene D4<br>Nasal provocation test was induced by leukotriene D4 with a stepwisely concentration method (4 mcg/ml, 8 mcg/ml, 16 mcg/ml). | Drug: histamine<br>* Nasal challenge using 0.9% saline, was undertaken for exclusion of subjects hypersensitive to saline. The histamine nasal challenge could be initiated provided that NAR increase was <30%. Ranges of 0.4 to 3.2 mg.mL-1 histamine diluents were applied for a double-fold increment approach at intervals of 3 minutes.<br>* Other names: Guangzhou chemical company (serial number: 1703 );|
| Experimental: histamine<br>Nasal provocation test was induced by histamine with a stepwisely concentration method (0.4 mg/ml, 0.8 mg/ml, 1.6 mg/ml, 3.2mg/ml). | Drug: leukotriene D4<br>* Nasal challenge using 16% ethanol diluent, the concentration of which corresponded to the highest concentration of LTD4, was undertaken for exclusion of subjects hypersensitive to ethanol or saline. The LTD4 challenge could be initiated provided that NAR increase was <30%. Ranges of 4 to 16 mcg.mL-1 LTD4 diluents were applied for a double-fold increment approach at intervals of 6 minutes.<br>* Other names: Cayman chemical company (1-800-364-9897 Cat 20310).;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants positive response to leukotriene D4 or histamine nasal provocation test | Nasal airway resistance measured by positive anterior rhinomanometry. Concentration induced 60% increase of nasal airway resistance (PC60-NAR) will be measured and reported; Composite symptoms score defined by reichmann H and his colleagues showed as follows:3-5 sneezes = 1 point (pt), >5 sneezes = 2 points (pts); rhinorrhoea < 1 milliliter (mL) = 1 pt, rhinorrhoea > 1 milliliter = 2 pts; pruritus of the palate or ear or eye= 1 pt, conjunctivitis or cough or urticaria or difficult breathing= 2 pts. Total score ranges from 0 to 6 pts. Positive response to LTD4 nasal provocation test was defined as PC60-NAR less than 16mcg/mL or the symptom score higher than 3. | Until 1 hour after the nasal provocation test | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of eosinophils in sputum and nasal lavage and fractional exhaled nitric oxide (FeNO) | Biomarkers in upper and lower airways such as eosinophils in sputum and nasal lavage and fractional exhaled nitric oxide (FeNO) will be studied. | 4 and 24 hours after the nasal provocation test | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukotriene D4, allergic rhinitis, nasal airway resistance, nasal provocation test, nasal hyperreactivity, airway inflammation, asthma