Clinical trial NCT01537133: Airway Microbiome in Asthma: Relationships to Asthma Phenotype and Inhaled Corticosteroid Treatment
Official title: Airway Microbiome in Asthma: Relationships to Asthma Phenotype and Inhaled Corticosteroid Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Atopy
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-02-23
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Microbial Community Richness
timeFrame: baseline and after 6 weeks of treatment
measure: Microbial Community Diversity
timeFrame: baseline and after 6 weeks of treatment
measure: Microbial Community Evenness
timeFrame: baseline and after 6 weeks of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco, Adult
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Adult
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Brigham and Women's Hospital
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern Memorial Hospital
name: Lewis Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: Richard Martin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Mario Castro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Monica Kraft, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Stephen Peters, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Homer Boushey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Medical Center
name: Sally Wenzel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Christine Sorkness, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Durack J, Christian LS, Nariya S, Gonzalez J, Bhakta NR, Ansel KM, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Peters SP, Rosenberg SR, Sorkness CA, Wechsler ME, Wenzel SE, White SR, Lynch SV, Boushey HA, Huang YJ; National Heart, Lung, and Blood Institute's "AsthmaNet". Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma. J Allergy Clin Immunol. 2020 Nov;146(5):1016-1026. doi: 10.1016/j.jaci.2020.03.028. Epub 2020 Apr 13.