Clinical trial NCT03479138: Non-Eosinophilic Neutrophilic Asthma
Official title: Non-Eosinophilic Neutrophilic Asthma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neutrophilic Asthma
Keywords: severe asthma
induced sputum
asthma phenotypes
neutrophilic inflammation
microbiome
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
Collaborators: name: Spanish Clinical Research Network - SCReN
First posted: 2018-03-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients bewteen 18-80 years with severe asthma.

Brief summary: Define and characterize the neutrophilic phenotype of severe asthma.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Phenotype of neutrophils
timeFrame: 24 hours
measure: Microbiome analysis
timeFrame: 6 months
Secondary outcomes:
measure: Clinical demographic characteristics
timeFrame: 1 year
measure: Demographic characteristics
timeFrame: 1 year
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90.
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
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