Asthma, Allergic Rhinitis
Conditions
Brief summary
Background: Nasal allergen challenge (NAC) is useful to study the pathophysiology of rhinitis, and multiple challenges may more adequately approximate natural exposure. Objective: To determine the effect of 4 consecutive daily NAC, on clinical and inflammatory parameters in rhinitics with or without asthma.
Detailed description
The study will be performed outside the pollen season. On a baseline visit, 2 to 7 days prior to control challenge, allergy skin prick tests and methacholine inhalation test will be done. Prior to first allergen challenge, skin titration will be done using tenfold dilutions of the allergen chosen for nasal challenges. Subsequent to baseline visit, a control challenge will be done, followed, a week later, by repeated NACs. NACs will be done over 4 consecutive days, in the morning. Nasal peak inspiratory flows (NPIF), oral peak expiratory flows (PEF), and symptoms will be recorded at baseline and at regular intervals over 7 hours post-challenge on each challenge day. Induced sputum and nasal lavage specimen will be obtained 7 hours following the control challenge and the first and last NAC.
Interventions
PROCEDURENasal allergen challenge
Allergen sprayed into nostrils. Allergen used will be house dust mite or cat allergen. Allergens will be given in increasing ten-fold dilutions until a positive response occurs.
Sponsors
AllerGen NCE Inc.
Laval University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* To have a positive reaction to one or more allergen on prick tests. * Non smokers * No respiratory track infection for at least one month prior to the study. * Positive reaction to cat hair and/or house dust mite (Dermatophagoides pteronyssinus) aeroallergens on allergy skin prick tests and report rhinitis symptoms when exposed to an environment containing this allergen. * Asthmatic subjects using only inhaled beta-2 agonists on an as needed basis for their asthma treatment. * Asthmatic subjects with a history of asthma of at least 6 months. * Asthmatic subjects with PC20 methacholine lower or equal to 8 mg/ml. * Allergic rhinitic subjects never experienced any asthma symptoms or took any asthma medication in the past. * Allergic rhinitic subjects with a provocative concentration of methacholine (PC20 higher than 16 mg/ml.
Exclusion criteria
* Smokers or ex smokers less than 6 months or more than 10 pack-years. * Asthmatic subjects using or used in the past 3 months inhaled or oral corticosteroids.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sputum Eosinophils Following Allergen Challenge | At 7 hours post first and last challenge compared to baseline | Eosinophil is an inflammatory cell found in the lungs. Sputum is obtained from hypertonic inhalation. patients expectorate in a sterile dish and mucus plugs are selected and treated to obtain cells. cells are transferred on a slide and a differential count is obtained where eosinophils are counted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nasal Lavage Eosinophils After Allergen Challenge | At 7 hours post first and last challenge compared to baseline | Change in nasal lavage eosinophil percentages in allergic asthmatic and allergic non asthmatic at baseline and at 7h post first and last challenge |
Countries
Canada
Participant flow
Recruitment details
Subjects were recruited from advertisement between November 2005 and october 2008
Pre-assignment details
After enrollment, there was a one to 7 days run-in period. Subjects that could not produce a quality sputum sample were excluded from the trial.
Participants by arm
| Arm | Count |
|---|---|
| Allergic Asthmatic Subjects with allergic asthma will undergo nasal allergen provocations with either house dust mite or cat pelt. | 27 |
| Allergic Rhinitic Without Asthma Subjects with allergic rhinitis without asthma will undergo nasal allergen provocations with either house dust mite or cat pelt. | 18 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Could not comply with study requirements | 4 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Allergic Rhinitic Without Asthma | Allergic Asthmatic | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 27 Participants | 45 Participants |
| Age, Continuous | 24 years STANDARD_DEVIATION 7 | 24 years STANDARD_DEVIATION 4 | 24 years STANDARD_DEVIATION 5 |
| Region of Enrollment Canada | 18 participants | 27 participants | 45 participants |
| Sex: Female, Male Female | 8 Participants | 20 Participants | 28 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 0 / 13 |
| serious Total, serious adverse events | 0 / 19 | 0 / 13 |
Outcome results
Primary
Change in Sputum Eosinophils Following Allergen Challenge
Eosinophil is an inflammatory cell found in the lungs. Sputum is obtained from hypertonic inhalation. patients expectorate in a sterile dish and mucus plugs are selected and treated to obtain cells. cells are transferred on a slide and a differential count is obtained where eosinophils are counted.
Time frame: At 7 hours post first and last challenge compared to baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Allergic Asthmatic | Change in Sputum Eosinophils Following Allergen Challenge | Baseline percentage eosinophils | 5.6 percentage of sputum eosinophils | Standard Error 1.8 |
| Allergic Asthmatic | Change in Sputum Eosinophils Following Allergen Challenge | 7h post first challenge percentage eosinophils | 6.0 percentage of sputum eosinophils | Standard Error 1.7 |
| Allergic Asthmatic | Change in Sputum Eosinophils Following Allergen Challenge | 7h post last challenge percentage eosinophils | 4.1 percentage of sputum eosinophils | Standard Error 1.4 |
| Allergic Rhinitic Without Asthma | Change in Sputum Eosinophils Following Allergen Challenge | Baseline percentage eosinophils | 2.0 percentage of sputum eosinophils | Standard Error 1.3 |
| Allergic Rhinitic Without Asthma | Change in Sputum Eosinophils Following Allergen Challenge | 7h post first challenge percentage eosinophils | 1.3 percentage of sputum eosinophils | Standard Error 1.5 |
| Allergic Rhinitic Without Asthma | Change in Sputum Eosinophils Following Allergen Challenge | 7h post last challenge percentage eosinophils | 1.6 percentage of sputum eosinophils | Standard Error 1 |
Secondary
Change in Nasal Lavage Eosinophils After Allergen Challenge
Change in nasal lavage eosinophil percentages in allergic asthmatic and allergic non asthmatic at baseline and at 7h post first and last challenge
Time frame: At 7 hours post first and last challenge compared to baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Allergic Asthmatic | Change in Nasal Lavage Eosinophils After Allergen Challenge | Baseline percentage eosinophils | 2.1 percentage of nasal lavage eosinophils | Standard Error 0.6 |
| Allergic Asthmatic | Change in Nasal Lavage Eosinophils After Allergen Challenge | 7h post first challenge percentage eosinophils | 7.5 percentage of nasal lavage eosinophils | Standard Error 4.3 |
| Allergic Asthmatic | Change in Nasal Lavage Eosinophils After Allergen Challenge | 7h post last challenge percentage eosinophils | 15.7 percentage of nasal lavage eosinophils | Standard Error 5.4 |
| Allergic Rhinitic Without Asthma | Change in Nasal Lavage Eosinophils After Allergen Challenge | Baseline percentage eosinophils | 1.3 percentage of nasal lavage eosinophils | Standard Error 0.9 |
| Allergic Rhinitic Without Asthma | Change in Nasal Lavage Eosinophils After Allergen Challenge | 7h post first challenge percentage eosinophils | 3.0 percentage of nasal lavage eosinophils | Standard Error 1.3 |
| Allergic Rhinitic Without Asthma | Change in Nasal Lavage Eosinophils After Allergen Challenge | 7h post last challenge percentage eosinophils | 15.5 percentage of nasal lavage eosinophils | Standard Error 9.6 |