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

Name

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

Accession Number

HLB02232020a

Acronym

AsthmaNet-Microbiome

Related studies

BSI Study IDs

AN5

Is public use dataset

False

Keywords

16S ribosomal RNA; Asthma; T(H)2 inflammation; atopy; bacteria; corticosteroids; metabolic pathways; microbiome; short-chain fatty acids; three-gene mean

Has Study Datasets

True

Has Specimens

True

Specimen ID Type

Coded

Study Website

The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

False

Study type

Clinical Trial

Collection Type

Open BioLINCC Study

Cohort type

Adult

Interventions

Drug: fluticasone

Drug: Placebo

Study Open Date (Data)

2020-04-15

Study Open Date (Specimens)

2022-01-21

Date materials available

2020-04-15

Last updated

2022-01-21

Study period

Oct 2012 – July 2014

Study Contacts
NHLBI Division

DLD

Classification

Lung

HIV study classification

non-HIV

COVID study classification

non-COVID

Pre-Website # of Specimens Shipped

None

# of Returned Specimens

None

Conditions

Asthma
Atopy

Objectives

The MICROBIOME study aimed to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, with atopy but no asthma, and non-atopic healthy subjects; and to determine whether inhaled corticosteroid treatment alters bronchial microbial community composition in adults with asthma.

Background

Recent studies have shown that the composition of lower respiratory tract bacteria (microbiota) differs between healthy adults and adults with asthma. Additionally, phenotypic features of asthma, such as measures of airway hyper-responsiveness, asthma control, and transcriptional response to steroids, correlate with patterns of bronchial microbiota composition. In most of the previous studies, subjects with asthma were treated with inhaled corticosteroids (ICS), casting some uncertainty on whether the findings reflect the effects of ICS treatment or of asthma itself. Similarly, many patients with asthma are atopic, raising the question as to whether asthma-associated differences in respiratory microbiota are related to underlying atopy. The MICROBIOME study sought to elucidate differences in bronchial microbiota associated with asthma versus atopy, and with important phenotypic features of this disease, such as responsiveness to ICS treatment.

Subjects

The MIROBIOME study was conducted in adults at nine AsthmaNet sites. 84 subjects were enrolled: 42 atopic asthmatics (AA), 21 atopic non-asthmatics (ANA) and 21 non-atopic healthy control subjects (HC). Atopy was defined by serologic evidence (>0.35 kU/l) of sensitivity to more than 1 of 12 aeroallergens. Asthma was confirmed by airway hyperresponsiveness (methacholine PC20 ≤8 mg/mL or FEV1 improvement >12% post albuterol). At enrollment, subjects with asthma had been clinically stable for three months, and had an Asthma Control Questionnaire score of less than 1.5 without the use of a controller medication. Exclusion criteria included a history of smoking, respiratory infection within six weeks or antibiotic use within three months of enrollment.

Design

The MICROBIOME study was a multicenter clinical trial. Samples processed for microbiota analysis included oral wash, a saline flush (10 mL) of the bronchoscope suction channel (“scope-flush”) and protected bronchial brushings (BB). Potential oral contamination of BB was evaluated by comparing a random subset of 30 BB-paired scope-flushes. Nucleic acids were extracted using a modified bead-beating protocol. Bacterial communities from the subjects were profiled by 16S rRNA gene sequencing. 16S rRNA gene copy number was assessed by quantitative PCR using universal primers. A 97% sequence homology cut-off was used to define bacterial taxa (also referred to as operational taxonomic units; OTUs). Sequence-based bacterial community analysis could be performed in the same proportion (67%) of samples collected from AA, ANA, and HC subjects.


AA were randomized in a 2:1 ratio to treatment with inhaled fluticasone propionate (250 mcg) or placebo twice daily for six weeks and re-assessed post-treatment.


Expression levels of three bronchial epithelial genes (CLCA1, SERPINB2 and POSTN) previously shown to be induced by IL-13, were measured using RNA extracted in parallel with DNA to calculate the “three-gene mean” (TGM) score for each participant. Type 2-high asthma was defined by TGM scores greater than 1.117 (two standard deviations above the average TGM-score in HC), confirmed by unsupervised cluster and principal component analysis.


The primary outcome was a comparison of the microbial community richness, diversity, and evenness between AA, ANA, and HC subjects.

Conclusions

The bronchial bacterial microbiota of both atopic asthmatics and atopic non-asthmatics differ from that of healthy controls and also differ from each other. There were no significant changes in bacterial burden or diversity between measurements at baseline and after six weeks of treatment with ICS in adults with asthma.


Durack J, Lynch SV, Nariya S, et al. Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment. J Allergy Clin Immunol. 2017;140(1):63–75. doi:10.1016/j.jaci.2016.08.055

Disease classification

Publications

Mat types

DNA
Plasma

The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.

  • Subjects

    84 randomized: 42 atopic asthmatics (28 ICS and 14 placebo) and 42 healthy controls
    96 failed screening


    Last Modified: Jan. 31, 2022, 12:41 p.m.
  • Age
      Healthy Control ICS Placebo All
    <20 1 3 . 4
    20-29 23 12 4 39
    30-39 5 6 4 15
    40-49 8 7 4 19
    50+ 5 . 2 7
     

    Last Modified: Jan. 31, 2022, 12:41 p.m.
  • Sex
      Healthy Control ICS Placebo All
    Male 19 12 7 38
    Female 23 16 7 46
     

    Last Modified: Jan. 31, 2022, 12:41 p.m.
  • Race
      Healthy Control ICS Placebo All
    Black 9 7 3 19
    White 26 16 9 51
    Hispanic/Latino 2 3 . 5
    Other 5 2 2 9
     

    Last Modified: Jan. 31, 2022, 12:41 p.m.

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process

  • Material Types

    Plasma
    DNA


    Last Modified: Jan. 31, 2022, 12:41 p.m.
  • General Freeze/Thaw Status

    All plasma samples have 0 thaws
    86% of DNA samples have 0 thaws. The remaining 14% have 1 thaw


    Last Modified: Jan. 31, 2022, 12:41 p.m.
  • Visits (Vials)
      Plasma DNA Total
    Visit 1 430 355 785
    Visit 2 28 28 56
    Visit 5 7 7 14
     

    Last Modified: Jan. 31, 2022, 12:41 p.m.
  • Visits (Subjects)
      Plasma
    Total number of subjects Average volume (ml) per subject
    Visit 1 59 11.41
    Visit 2 4 10.76
    Visit 5 1 11.20

      DNA
    Total number of subjects Average mass (µg) per subject Average vials per subject
    Visit 1 48 79.59 7.40
    Visit 2 4 76.48 7.00
    Visit 5 1 76.14 7.00
     

    Last Modified: Feb. 1, 2022, 11:36 a.m.