Genomics and Metagenomics of Asthma Severity
Genomics and Metagenomics of Asthma Severity
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.
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.
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