Non-Eosinophilic Neutrophilic Asthma

Study Overview
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Brief Summary
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Define and characterize the neutrophilic phenotype of severe asthma.

Detailed Description
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Neutrophilic asthma (NA) is the asthma phenotype less known, causes a severe disease and does not have a specific treatment. Research on the neutrophilia mechanisms, new neutrophil (NEU) types and bronchial microbiome, can provide an opportunity to better understand the NA pathogenesis. OBJECTIVES: 1. To describe the clinical characteristics of NA and its sub-phenotypes (SUBSTUDY 1); 2. To determine the NEU types associated with the NA and its sub-phenotypes (SUBSTUDY 2); and 3. To identify the bronchial microbiological flora of the NA, specifically related to lung microbiome and the immune response against Chlamydia Pneumoniae (SUBSTUDY 3). METHODS: Multicenter prospective study including 100 patients with severe asthma (GINA/GEMA criteria): 50 with non-neutrophilic asthma (<65% NEU in induced sputum [IS]); and 50 with NA (> 64% NEU in IS). SUBSTUDY 1: clinical variables (years of evolution, exacerbations, asthma control test, mini asthma quality of life questionnary), comorbidities (GERD, nasal polyposis, obesity, ASS), pulmonary function (FEV1, exhaled fraction of nitric oxide, total lung capacity, Aspergillus), prick-test and CT scan chest; SUBSTUDY 2 (in IS and plasma): apoptotic index by means NE culture and flux cytometer (Annexin-V-FITC), NEU phenotype by surface markers (CD16, CD66b, CD62L, HLADR, CD177, CD11b, CD63, CXCR2, CXCR4) with density gradient study and determination of cytokines (IL-6, IL-8, IL-17, IL-1, IL-22) by ELISA; SUBSTUDY 3 (in IS): bronchial microbiome for 16 subunit rRNA by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and anti-Chlamydia Pneumoniae Immunoglobuling A by ELISA.

Official Title
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Non-Eosinophilic Neutrophilic Asthma

Conditions
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Neutrophilic Asthma

Intervention / Treatment
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* Diagnostic Test: Induced sputum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 80 years old Confirmed diagnosis of asthma (according to spanish guideline GEMA) Severe persistent asthma (step 5-6 GEMA) Eosinophils<300/mm3 in peripheral blood Exclusion Criteria: Respiratory infection during the previous month Significant lung pathology not attributable to asthma (bronchiectasis with Reiff score>3)

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 18 to 80 years old diagnosed of severe asthma, requiring treatment at least with long acting beta agonists (LABA) + high doses inhaled corticosteroids (ICS) with eosinophil count in blood<300/mm3. They must be ex-smokers with less than 10 packs-year and no other relevant pulmonary disease. | Diagnostic Test: Induced sputum<br>* Characterization with flow cytometry of the phenotype of the neutrophils isolated in the sputum, microbiome<br>|
| Non neutrophilic asthma<br>Patients 18 to 80 years old diagnosed of severe asthma, requiring treatment at least with LABA+ high doses ICS, with eosinophil count in blood<300/mm3. They must be ex-smokers with less than 10 packs-year and no other relevant pulmonary disease. | Diagnostic Test: Induced sputum<br>* Characterization with flow cytometry of the phenotype of the neutrophils isolated in the sputum, microbiome<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenotype of neutrophils | To determine the types of neutrophils (in induced sputum and blood) associated with neutrophilic asthma and its subphenotypes according to flow cytometry | 24 hours | 
| Microbiome analysis | To analyse the bronchial microbiological flora of neutrophilic asthma | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical demographic characteristics | To describe the clinical characteristics and natural history of the neutrophilic asthma and its subphenotypes | 1 year | 
| Demographic characteristics | To describe demographic characteristics | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe asthma, induced sputum, asthma phenotypes, neutrophilic inflammation, microbiome