Microbiome and Exacerbations in Neutrophilic Asthma

Study Overview
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Brief Summary
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Neutrophilic asthma (NA) is the least known severe asthma phenotype. It is associated with more exacerbations, worse control and impaired lung function. One of its possible etiologies is bronchial infections. The study of bronchial microbiology and its relationship with exacerbations is a new line of research. Objectives: 1) To analyze bronchial microbiome in patients with AN and non-neutrophilic (ANN), with frequent exacerbations and without exacerbations. 2) To relate the presence of bronchial infections with differences in the microbiome. 3) Correlate the characteristics of the microbiome with other evidence used in exacerbations. Methods: Prospective study involving 40 non-smoking asthmatics without bronchiectasis (20 with AN and 20 with ANN). Of these, 10 in each group will have frequent exacerbations (>2 rounds of systemic steroids in the last year, of >3 days each) and 10 non- frequent exacerbations. AN will be defined as >65% neutrophils in stable phase sputum. All patients will have two stable visits in which clinical variables, asthma control, lung function and induced sputum samples will be collected (for analysis of bronchial inflammatory cell count and for the study of the microbiome by 16 subunit rRNA). Specific Immunoglobulin A (IgA) for Chlamydia Pneumoniae will be determined. In exacerbations, sputum samples will be collected for culture and nasopharyngeal smears for the study of major respiratory viruses and bacteria by multiple polymerase chain reaction.

Detailed Description
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See above

Official Title
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Exacerbations in Neutrophilic Asthma: Influence of Bronchial Microbiome

Conditions
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Asthma, Microbiome, Exacerbation

Intervention / Treatment
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* Diagnostic Test: Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab
* Diagnostic Test: Induced sputum microbiome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 -80 Confirmed diagnose of asthma Severe persistent asthma Exclusion Criteria: Respiratory infection during the previous month Other significant lung disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Neutrophilic asthma<br>Patients with asthma diagnosed according to guidelines, with eosinophils <300/mm3 in blood and <3% in induced sputum | Diagnostic Test: Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab<br>* PCR for viruses and bacteria in nasal swab<br>Diagnostic Test: Induced sputum microbiome<br>* Microbiome in induced sputum<br>|
| Eosinophilic asthma<br>Patients with asthma diagnosed according to guidelines, with eosinophils >300/mm3 in blood and/or >3% in induced sputum | Diagnostic Test: Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab<br>* PCR for viruses and bacteria in nasal swab<br>Diagnostic Test: Induced sputum microbiome<br>* Microbiome in induced sputum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences between neutrophilic and non-neutrophilic asthma, with and without frequent exacerbations in bronchial microbiome using 16S rDNA sequencing | Qualitative and quantitative analysis of bronchial microbiome in patients including bacterial communities and major bacterial phyla in neutrophilic and non-neutrophilic asthma, with frequent exacerbations and without exacerbations. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in absolute and relative abundance using 16S rDNA sequencing of bronchial microbiota due to asthma exacerbations, in patients with neutrophilic and eosinophilic asthma | Influence of bronchial infections in qualitative and quantitative characteristics of lung microbiome. (Bacterial communities and major bacterial phyla) | 1 year | 
| Changes in absolute and relative abundance of bronchial microbiota over a year using 16S rDNA sequencing | Qualitative and quantitative changes of lung microbiome (Bacterial communities and major bacterial phyla) | 1 year | 
| Relationship between lung microbiome andlevels of specific immunoglobulin A of C. pneumoniae, PCR, and immunoglobulin G of aspergillus | Relationship between qualitative and quantitative characteristics of lung microbiome with levels of specific IgA C. pneumoniae, PCR, IgG aspergillus | 6 months |