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Genomics and Metagenomics of Asthma Severity

Conditions
Asthma
Asthma Attack
Registration Number
NCT04501926
Lead Sponsor
Maria Pino-Yanes
Brief Summary

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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
300
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Severe asthma exacerbations1 year

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

Secondary Outcome Measures
NameTimeMethod
Asthma control1 week

Asthma control questionnaire (ACQ) score

Lung function measurement: forced expiratory volume in the first second (FEV1)3 months

Baseline and post-bronchodilator measurements of the forced expiratory volume in the first second (FEV1) measured in liters

Lung function measurement: forced vital capacity (FVC)3 months

Baseline and post-bronchodilator measurements of the forced vital capacity (FVC) measured in liters

Lung function measurement: FEV1/FVC ratio3 months

The ratio of FEV1/FVC measurements

Asthma severity1 year

Category of severity defined by treatment step according to GINA 2020 at recruitment

Atopy testing1 year

Atopy status evaluated by skin prick tests and/or specific immunoglobulin E (IgE) levels assessing the most common aeroallergens of each recruiting center

Trial Locations

Locations (6)

University of La Laguna

🇪🇸

San Cristobal de la Laguna, Santa Cruz De Tenerife, Spain

Hospital Doctor Jose Molina Orosa

🇪🇸

Arrecife, Spain

Hospital General de La Palma

🇪🇸

Breña Alta, Spain

Hospital Universitario de Canarias

🇪🇸

San Cristobal de la Laguna, Spain

Hospital Universitario Donostia

🇪🇸

San Sebastián, Spain

Hospital Universitario Nuestra Señora de Candelaria

🇪🇸

Santa Cruz De Tenerife, Spain

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