Airway Microbiome in Asthma: Relationships to Asthma Phenotype and Inhaled Corticosteroid Treatment

Study Overview
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Brief Summary
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There are new, very sensitive methods for detecting bacteria. These methods show that hundreds of millions of microbes (organisms that can only be seen with microscopes), especially bacteria, live in healthy people. The collection of different microbes found in a site is called a microbiome. The investigators know that microbiomes of the skin, sinuses, mouth, gastro-intestinal tract, etc. differ from each other. The make-up of the microbiome - which bacteria are found in a site - may be necessary for good health. For example, the microbiome of the mouth is different in people with inflammation of the gums (periodontitis), and the microbiome of the bowel is different in people with inflammation of the intestinal tract (inflammatory bowel disease). The purpose of this research study is to find out if the microbiome in the lungs is different in healthy people without asthma compared to people with asthma. This study will also find out if the microbiome of the lungs changes when people with asthma take a daily controller medication called an inhaled corticosteroid.

Detailed Description
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Two broad specific aims of this study are: 1)To evaluate whether the microbiota of the bronchial airways in atopic asthmatics and atopic healthy controls differ in microbial diversity, richness, evenness, or composition of specific bacterial taxa. 2) To determine whether inhaled corticosteroid treatment alters bronchial microbial community composition in asthmatics.

Official Title
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Airway Microbiome in Asthma: Relationships to Asthma Phenotype and Inhaled Corticosteroid Treatment

Conditions
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Atopy, Asthma

Intervention / Treatment
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* Drug: fluticasone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asthmatic: History of physician-diagnosed asthma. Methacholine PC20 < 8mg/ml and/or FEV1 improvement ≥ 12% in response to 180 mcg albuterol. FEV1 ≥ 70% of predicted after 180 mcg albuterol. Stable asthma for ≥ 3 months prior to enrollment (no urgent care visits, no systemic corticosteroid treatment). Asthma Control Questionnaire 6 Score < 1.5. Able to provide informed consent. Able to perform spirometry as per ATS criteria. Evidence by allergen skin test of sensitivity to an aeroallergen. Willingness, if female and able to conceive, to utilize one medically-acceptable form of contraception. Healthy Control: Evidence by allergen skin test of sensitivity to an aeroallergen. Able to provide informed consent. Able to perform spirometry as per ATS criteria. Exclusion Criteria: Asthmatic: Presence of lung disease other than asthma. Use of > 10 doses of nasal corticosteroids in the previous 3 months. Presence of significant medical illness or other chronic diseases whose treatment could affect the clinical features measured, responses to the therapies to be given in this study, or risks of participating in the study. History of atrial or ventricular tachyarrhythmia. Changes suggestive of cardiac ischemia on ECG at baseline. History of upper respiratory infection, sinusitis, bronchitis, or antibiotic use in the previous 3 months. History of chronic sinus disease. Smoking > 5 pack-years, or within the past year History of long-term controller medication use for asthma (inhaled or oral corticosteroid, leukotriene pathway antagonist, cromolyn, or theophylline within the preceding 6 months. History of bleeding disorder. Reduced creatinine clearance. Inability, in the opinion of the Study Investigator, to coordinate use of inhaler or otherwise comply with medication regimens. Contraindication to bronchoscopy on history or examination. Healthy Control: History of chronic respiratory disease including asthma. Presence of significant medical illness or other chronic diseases whose treatment could affect the clinical features measured, responses to the therapies to be given in this study, or risks of participating in the study. History of atrial or ventricular tachyarrhythmia. Changes suggestive of cardiac ischemia on ECG at baseline. History of upper respiratory infection, sinusitis, bronchitis, or antibiotic use in the previous 3 months. Methacholine PC20 < 16 mg/ml or FEV1 improvement ≥ 12% in response to albuterol. History of chronic sinus disease Smoking > 5 pack-years, or within the past year Use of > 10 doses of a nasal corticosteroid preparation in the previous 3 months FEV1 or FVC < 80% predicted. History of bleeding disorder. Reduced creatinine clearance. Contraindication to bronchoscopy on history or examination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled corticosteroid<br>Fluticasone (250 mcg/puff, one puff, twice a day) | Drug: fluticasone<br>* Dry Powder Inhaler: 250 mcg/puff, one puff, twice a day<br>* Other names: Flovent 250;|
| Placebo Comparator: Placebo<br>Placebo fluticasone (one puff, twice a day) | Drug: Placebo<br>* Dry Powder Inhaler: Placebo<br>|
| No Intervention: Healthy Control<br> | |
| No Intervention: Atopic Non-asthmatics<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbial Community Richness | Richness is the total number of different bacterial taxa detected in the sample. | baseline and after 6 weeks of treatment | 
| Microbial Community Diversity | The Shannon diversity index is a type of entropy measure and is a function of the distribution of the total number of organisms across all of the species. If S is the total number of species in the sample and p_i is the number of organisms in the i-th species divided by the total number of organisms, then Diversity = -Σ p_i log(p_i). | baseline and after 6 weeks of treatment | 
| Microbial Community Evenness | Pielou's evenness index is a scaled measure of biodiversity and is equal to the observed Shannon diversity index divided by the maximum possible Shannon diversity index, which would occur if all of the species in the sample were equally abundant. Evenness = D/log(S), where D is the Shannon Diversity index and log(S) is the maximum diversity of the sample. | baseline and after 6 weeks of treatment |