Clinical trial NCT04501926: Genomics and Metagenomics of Asthma Severity
Official title: Genomics and Metagenomics of Asthma Severity
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthma
Asthma Attack
Keywords: Genome-Wide Association Study
Microbiome, Human
Asthma
Epigenomics
Transcriptomics
Lead sponsor: University of La Laguna
Sponsor class: OTHER
Collaborators: name: University of La Laguna
name: Ministry of Science and Innovation, Spain
name: Consorcio Centro de Investigación Biomédica en Red (CIBER)
name: University Hospital of the Nuestra Señora de Candelaria
name: Hospital Universitario de Canarias
name: Hospital General de La Palma
name: Hospital Donostia
name: Hospital Doctor Jose Molina Orosa
First posted: 2020-08-06
Enrollment: 300
Sex: ALL
Minimum age (years): 8
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Severe asthma exacerbations
timeFrame: 1 year
Secondary outcomes:
measure: Asthma control
timeFrame: 1 week
measure: Asthma severity
timeFrame: 1 year
measure: Lung function measurement: forced expiratory volume in the first second (FEV1)
timeFrame: 3 months
measure: Lung function measurement: forced vital capacity (FVC)
timeFrame: 3 months
measure: Lung function measurement: FEV1/FVC ratio
timeFrame: 3 months
measure: Atopy testing
timeFrame: 1 year
Other outcomes:
Locations:
city: San Cristobal de la Laguna
country: Spain
facility: University of La Laguna
state: Santa Cruz De Tenerife
city: Arrecife
country: Spain
facility: Hospital Doctor Jose Molina Orosa
city: Breña Alta
country: Spain
facility: Hospital General de La Palma
city: San Cristobal de la Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Santa Cruz De Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de Candelaria
Study officials:
References: