Genomics and Metagenomics of Asthma Severity (GEMAS)

The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics, the microbiome, and the interaction between them in the development of asthma exacerbations in European patients with asthma.

Study Overview

• Status: Recruiting
• Conditions: Asthma; Asthma Attack

Detailed Description

Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow obstruction and a bronchial hyperreactivity in response to a variety of stimuli. In most patients, the onset of asthma symptoms may be controlled. However, many of them may manifest asthma attacks or crises of breathing called exacerbations, which occur with breathing problems, wheezing, coughing or tightness of chest, and may threaten their life. Such exacerbations are caused by a combination of environmental and genetic factors. However, since studies so far have been limited, a reduced number of genes associated with the predisposition to these complications have been identified. In addition, some studies have used next-generation DNA sequencing techniques to characterize the microbiome (i.e., microbial community) of the airways, finding changes related to asthma. The main hypothesis of the Genomics and Metagenomics of Asthma Severity (GEMAS) study is that exacerbations of asthma are caused by a combination of the intrinsic genetic factors of the individual, changes in the respiratory microbiome and the interaction between both factors. The objectives of this project are: 1) to identify genetic variants that are associated with asthma exacerbations; 2) to examine the changes occurring in the microbial communities of the oral cavity and respiratory tract in individuals with exacerbations; 3) to analyze the association of the host genetic variants and the microbiome changes related to exacerbations.

A total of 300 Spanish subjects with asthma with and without a history of asthma exacerbations in the past 12 months will be recruited. Saliva, nasal and pharyngeal samples will be collected to study the oral cavity and the upper respiratory tract microbiome through next-generation sequencing technologies. Sequencing of the 16S ribosomal RNA (16S rRNA) gene will allow to characterize the bacterial diversity and abundance, as well as to infer the functionality of the microbiome in each sample. These parameters will be used to establish correlations between the microbiome and the presence of asthma exacerbations. Finally, the association between the genetic variation associated with exacerbations in genomic studies and the measurements of abundance, diversity and functions related to exacerbations will be jointly examined.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Maria Pino-Yanes, Ph.D.; Phone Number: 6343 +34 922 316 502; Email: mdelpino@ull.edu.es
• Study Contact Backup: Name: Fabian Lorenzo-Diaz, Ph.D.; Phone Number: 8350 +34 922 316 502; Email: florenzo@ull.edu.es

Study Locations

• Spain
  • Arrecife, Spain
    • Recruiting
    • Hospital Doctor José Molina Orosa
    • Contact: Berta Roman-Bernal, MD
  • Breña Alta, Spain
    • Recruiting
    • Hospital General de La Palma
    • Contact: Jose M Hernandez-Perez, MD, Ph.D.
  • San Cristobal de la Laguna, Spain
    • Recruiting
    • Hospital Universitario de Canarias
    • Contact: Ruperto Gonzalez-Perez, MD, Ph.D.
  • San Sebastián, Spain
    • Recruiting
    • Hospital Universitario Donostia
    • Contact: Olaia Sardon, MD, Ph.D.
  • Santa Cruz De Tenerife, Spain
    • Recruiting
    • Hospital Universitario Nuestra Señora de Candelaria
    • Contact: Jose M Hernandez-Perez, MD, Ph.D.
  • Santa Cruz De Tenerife
    • San Cristobal de la Laguna, Santa Cruz De Tenerife, Spain, 38200
      • Active, not recruiting
      • University of La Laguna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 85 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients are recruited from the allergy and/or pulmonary medicine units from hospitals located in the Canary Islands, Spain (Hospital Universitario de Canarias, Hospital Universitario Nuestra Señora de Candelaria, Hospital General de La Palma, and Hospital Doctor Jose Molina Orosa), and in the division of pediatric respiratory medicine of Hospital Universitario Donostia in the Basque Country, Spain.

Description

Inclusion Criteria:

• Male or female aged older or equal than 8 years and younger or equal than 85 years
• Physician diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines
• Treated on GINA step 1-5

Exclusion Criteria:

• One or more grandparents of non-European origin
• Pregnancy
• Coexistence of other chronic pulmonary disorders including cystic fibrosis, chronic obstructive pulmonary disease (emphysema or chronic bronchitis), or congenital disorders of the lungs or airways
• Known family relatedness (first or second degree) with another participant already included in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Controls; Asthma patients who did not report asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.
Cases; Asthma patients that reported asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe asthma exacerbations	Defined by one of the following events because of asthma during the past year, the past 6 months, and the past week: oral corticosteroids use, emergency room visit, and/or hospitalizations	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthma control	Asthma control questionnaire (ACQ) score	1 week
Asthma severity	Category of severity defined by treatment step according to GINA 2020 at recruitment	1 year
Lung function measurement: forced expiratory volume in the first second (FEV1)	Baseline and post-bronchodilator measurements of the forced expiratory volume in the first second (FEV1) measured in liters	3 months
Lung function measurement: forced vital capacity (FVC)	Baseline and post-bronchodilator measurements of the forced vital capacity (FVC) measured in liters	3 months
Lung function measurement: FEV1/FVC ratio	The ratio of FEV1/FVC measurements	3 months
Atopy testing	Atopy status evaluated by skin prick tests and/or specific immunoglobulin E (IgE) levels assessing the most common aeroallergens of each recruiting center	1 year

Collaborators and Investigators

• Sponsor: Maria Pino-Yanes
• Collaborators: Hospital Universitario de Canarias; University of La Laguna; University Hospital of the Nuestra Señora de Candelaria; Spanish Ministry of Science, Innovation, and Universities; Consorcio Centro de Investigación Biomédica en Red, M.P.; Hospital General de La Palma; Hospital Universitario Donostia; Hospital Doctor Jose Molina Orosa

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Asthma; Transcriptomics; Genome-Wide Association Study; Microbiome, Human; Epigenomics
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: PI-29/17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No