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

NCT ID: NCT01537133

Last Updated: 2016-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-07-31

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.

Conditions

Asthma; Atopy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

Inhaled corticosteroid

Fluticasone (250 mcg/puff, one puff, twice a day)

Group Type: EXPERIMENTAL

fluticasone

Intervention Type: DRUG

Dry Powder Inhaler: 250 mcg/puff, one puff, twice a day

Placebo

Placebo fluticasone (one puff, twice a day)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Dry Powder Inhaler: Placebo

Healthy Control

Group Type: NO_INTERVENTION

No interventions assigned to this group

Atopic Non-asthmatics

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

fluticasone

Dry Powder Inhaler: 250 mcg/puff, one puff, twice a day

Intervention Type: DRUG

Placebo

Dry Powder Inhaler: Placebo

Intervention Type: DRUG

Other Intervention Names

Flovent 250

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

dave mauger

Professor of Public Health Sciences

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elliot Israel, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Lewis Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern Memorial Hospital

Richard Martin, MD

Role: PRINCIPAL_INVESTIGATOR

National Jewish Health

Mario Castro, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Monica Kraft, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Stephen Peters, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Homer Boushey, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Sally Wenzel, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medical Center

Christine Sorkness, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of California, San Francisco, Adult

San Francisco, California, United States

National Jewish Health

Denver, Colorado, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Duke University School of Medicine

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

University of Pittsburgh, Adult

Pittsburgh, Pennsylvania, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32298699 (View on PubMed)

Other Identifiers

U10HL098115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AsthmaNet 003

Identifier Type: -

Identifier Source: org_study_id