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

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Atopy
• Intervention / Treatment: Drug: fluticasone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143-0130
      • University of California, San Francisco, Adult
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • North Carolina
    • Durham, North Carolina, United States, 27110
      • Duke University School of Medicine
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh, Adult
  • Wisconsin
    • Madison, Wisconsin, United States, 53972
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Lewis Smith, MD, Northwestern Memorial Hospital; Principal Investigator: Richard Martin, MD, National Jewish Health; Principal Investigator: Christine Sorkness, MD, University of Wisconsin, Madison; Principal Investigator: Sally Wenzel, MD, University of Pittsburgh Medical Center; Principal Investigator: Stephen Peters, MD, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: February 9, 2012
• First Submitted That Met QC Criteria: February 16, 2012
• First Posted (Estimate): February 23, 2012

Study Record Updates

• Last Update Posted (Estimate): November 30, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone
• Other Study ID Numbers: AsthmaNet 003; U10HL098115 (U.S. NIH Grant/Contract)