Asthma
Conditions
Keywords
asthma, atopy, allergen challenge, sputum myeloid and plasmacytoid dendritic cells
Brief summary
Summary: A picture is emerging of dendritic cells migrating through the blood to the airways following allergen inhalation in atopic asthmatics. Although the Koh and McCarthy articles present novel findings, both do not provide a comprehensive view of sputum DCs following allergen challenge. Therefore, the proposed study will examine the kinetics of mDCs and pDCs in the induced sputum of atopic asthmatics following inhalation of allergen. Hypothesis: Following allergen challenge, sputum myeloid and plasmacytoid DCs will migrate into the airway lumen in atopic asthmatics during the timeframe of the late asthmatic response. Objective: The objective of this study is to examine the kinetics of dendritic cells in induced sputum following allergen challenge in atopic asthmatic subjects.
Detailed description
Subjects will be put through two study periods. Each study period will consist of four visits and will be separated by 2-4 weeks. On the first visit, subjects will undergo screening procedures, including complete history and physical examination. In addition, methacholine inhalation challenge and skin-prick testing will be preformed to assess airway hyper-responsiveness and determine atopic status respectively. Lastly, sputum will be induced before challenge (0 hrs) and peripheral blood will be collected. On the second visit, subjects will inhale diluent or allergen and sputum will be collected 7 hours following inhalation challenge. Next, on the third visit, subjects will return 24 hours following inhalation challenge and sputum will be induced. On the final visit, subjects will return 72 hours following inhalation challenge and sputum will be collected, along with peripheral blood. Before the next study period begins, there will be a washout period of 2-4 weeks. On the first visit of the second study period, a methacholine challenge will be performed to ensure the return of PC20 to within one doubling dose of baseline values. Also, sputum will be induced before challenge (0hrs) and peripheral blood will be collected. On the second visit, subjects will inhale diluent or allergen and sputum will be collected 7hrs following inhalation challenge. Next, on the third visit, subjects will return 24 hours following inhalation challenge and sputum will be induced. On the final visit, subjects will return 72 hours following inhalation challenge and sputum will be collected, along with peripheral blood.
Interventions
DRUGAeroallergen
Sponsors
Hamilton Health Sciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Mild atopic asthmatics, presently well controlled on ß2-agonists. * Non-smokers. * Baseline FEV1 more than 70% of predicted normal.
Exclusion criteria
* Airway infection during the last 4 weeks. * Exacerbation during the last 4 weeks. * Inhaled or oral steroids during the last 4 weeks. * Antihistamines during the last 48 hours. * Asthma medication other than inhaled and/or oral ß2-agonists during the last 4 weeks. * Pregnant women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure for This Study is the Number of Sputum Myeloid Dendritic Cells | 24 hrs | Flow-cytometric acquisitions were used to determine the percentage of each type of mononuclear cell. These percentages were multiplied by the number of sputum mononuclear cells calculated by using total and differential cell counts of the sputum sample. |
| The Primary Outcome Measure for This Study is the Number of Sputum Plasmacytoid Dendritic Cells | 24 hrs | Flow-cytometric acquisitions were used to determine the percentage of each type of mononuclear cell. These percentages were multiplied by the number of sputum mononuclear cells calculated by using total and differential cell counts of the sputum sample. |
Secondary
| Measure | Time frame |
|---|---|
| The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant. | Before inhalation (0hrs) |
| The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant | 7 hrs |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mild Asthmatics Mild asthmatics who require only short-acting beta agonist bronchodilator treatment as required. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Mild Asthmatics |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 28.6 years STANDARD_DEVIATION 3.2 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
The Primary Outcome Measure for This Study is the Number of Sputum Myeloid Dendritic Cells
Flow-cytometric acquisitions were used to determine the percentage of each type of mononuclear cell. These percentages were multiplied by the number of sputum mononuclear cells calculated by using total and differential cell counts of the sputum sample.
Time frame: 24 hrs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diluent | The Primary Outcome Measure for This Study is the Number of Sputum Myeloid Dendritic Cells | 32800 number of cells/g of sputum | Standard Deviation 13100 |
| Allergen | The Primary Outcome Measure for This Study is the Number of Sputum Myeloid Dendritic Cells | 89100 number of cells/g of sputum | Standard Deviation 27000 |
Primary
The Primary Outcome Measure for This Study is the Number of Sputum Plasmacytoid Dendritic Cells
Flow-cytometric acquisitions were used to determine the percentage of each type of mononuclear cell. These percentages were multiplied by the number of sputum mononuclear cells calculated by using total and differential cell counts of the sputum sample.
Time frame: 24 hrs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diluent | The Primary Outcome Measure for This Study is the Number of Sputum Plasmacytoid Dendritic Cells | 16000 number of cells/g of sputum | Standard Deviation 8700 |
| Allergen | The Primary Outcome Measure for This Study is the Number of Sputum Plasmacytoid Dendritic Cells | 39900 number of cells/g of sputum | Standard Deviation 12200 |
Secondary
The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant
Time frame: 7 hrs
Secondary
The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant
Time frame: 24 hrs
Secondary
The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant
Time frame: 72 hrs
Secondary
The Secondary Outcome Measure is the Level of Specific Chemokines Released in the Sputum Supernatant.
Time frame: Before inhalation (0hrs)