Neutrophilic AsthmaANNENCT03479138
Non-Eosinophilic Neutrophilic Asthma
An observational study of Neutrophilic Asthma, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 2 sites in Spain.
Trial summary
Define and characterize the neutrophilic phenotype of severe asthma. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neutrophilic Asthma
- What is being tested?
- Induced sputum
- How many people
- 10 participants
- Where
- 2 sitesSpain
- Study dates
- 21 Feb 2018to 30 Jul 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients bewteen 18-80 years with severe asthma.
Who may be able to join
- 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
Who cannot join
- Respiratory infection during the previous month
- Significant lung pathology not attributable to asthma (bronchiectasis with Reiff score>3)
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90.
Barcelona, 08041
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
About this study
Define and characterize the neutrophilic phenotype of severe asthma.
Read the 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.
- Conditions
- Neutrophilic Asthma
- Being tested
- Induced sputum
- Keywords
- severe asthma, induced sputum, asthma phenotypes, neutrophilic inflammation, microbiome
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induced sputumDiagnostic test
Characterization with flow cytometry of the phenotype of the neutrophils isolated in the sputum, microbiome
| Study group | Role | What they receive |
|---|---|---|
| Neutrophilic asthma | 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. Receives: Diagnostic Test: Induced sputum | |
| Non neutrophilic asthma | 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. Receives: Diagnostic Test: Induced sputum |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 hours
Microbiome analysis
To analyse the bronchial microbiological flora of neutrophilic asthma
Measured: 6 months
Secondary outcomes (2)
Clinical demographic characteristics
To describe the clinical characteristics and natural history of the neutrophilic asthma and its subphenotypes
Measured: 1 year
Demographic characteristics
To describe demographic characteristics
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start21 Feb 2018
- Primary completion30 Jun 2023
- Study completion30 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Neutrophilic AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
- Sponsor type
- University, hospital or other
- Collaborators
- Spanish Clinical Research Network - SCReN
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03479138
- Sponsor's protocol ID
- IIBSP-ANN-2017-77
- Acronym
- ANNE
- Status last verified
- Oct 2022
- First submitted
- 14 Mar 2018
- Last updated
- 11 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Nair P, Aziz-Ur-Rehman A, Radford K. Therapeutic implications of 'neutrophilic asthma'. Curr Opin Pulm Med. 2015 Jan;21(1):33-8. doi: 10.1097/MCP.0000000000000120.
PubMed 25415406Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):737-43. doi: 10.1164/ajrccm.156.3.9610046.
PubMed 9309987Simpson JL, Baines KJ, Ryan N, Gibson PG. Neutrophilic asthma is characterised by increased rhinosinusitis with sleep disturbance and GERD. Asian Pac J Allergy Immunol. 2014 Mar;32(1):66-74. doi: 10.12932/AP0322.32.1.2014.
PubMed 24641293Shaw DE, Berry MA, Hargadon B, McKenna S, Shelley MJ, Green RH, Brightling CE, Wardlaw AJ, Pavord ID. Association between neutrophilic airway inflammation and airflow limitation in adults with asthma. Chest. 2007 Dec;132(6):1871-5. doi: 10.1378/chest.07-1047. Epub 2007 Oct 9.
PubMed 17925424Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012 May 4;18(5):716-25. doi: 10.1038/nm.2678.
PubMed 22561835Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med. 2008 Jan 15;177(2):148-55. doi: 10.1164/rccm.200707-1134OC. Epub 2007 Oct 18.
PubMed 17947611Polosa R, Thomson NC. Smoking and asthma: dangerous liaisons. Eur Respir J. 2013 Mar;41(3):716-26. doi: 10.1183/09031936.00073312. Epub 2012 Aug 16.
PubMed 22903959Sutherland ER, Martin RJ. Asthma and atypical bacterial infection. Chest. 2007 Dec;132(6):1962-6. doi: 10.1378/chest.06-2415.
PubMed 18079229Uddin M, Nong G, Ward J, Seumois G, Prince LR, Wilson SJ, Cornelius V, Dent G, Djukanovic R. Prosurvival activity for airway neutrophils in severe asthma. Thorax. 2010 Aug;65(8):684-9. doi: 10.1136/thx.2009.120741.
PubMed 20685741Newcomb DC, Peebles RS Jr. Th17-mediated inflammation in asthma. Curr Opin Immunol. 2013 Dec;25(6):755-60. doi: 10.1016/j.coi.2013.08.002. Epub 2013 Sep 11.
PubMed 24035139Chesne J, Braza F, Mahay G, Brouard S, Aronica M, Magnan A. IL-17 in severe asthma. Where do we stand? Am J Respir Crit Care Med. 2014 Nov 15;190(10):1094-101. doi: 10.1164/rccm.201405-0859PP.
PubMed 25162311Bruijnzeel PL, Uddin M, Koenderman L. Targeting neutrophilic inflammation in severe neutrophilic asthma: can we target the disease-relevant neutrophil phenotype? J Leukoc Biol. 2015 Oct;98(4):549-56. doi: 10.1189/jlb.3VMR1214-600RR. Epub 2015 May 14.
PubMed 25977288Pillay J, Ramakers BP, Kamp VM, Loi AL, Lam SW, Hietbrink F, Leenen LP, Tool AT, Pickkers P, Koenderman L. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010 Jul;88(1):211-20. doi: 10.1189/jlb.1209793. Epub 2010 Apr 16.
PubMed 20400675Beyrau M, Bodkin JV, Nourshargh S. Neutrophil heterogeneity in health and disease: a revitalized avenue in inflammation and immunity. Open Biol. 2012 Nov;2(11):120134. doi: 10.1098/rsob.120134.
PubMed 23226600Green BJ, Wiriyachaiporn S, Grainge C, Rogers GB, Kehagia V, Lau L, Carroll MP, Bruce KD, Howarth PH. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS One. 2014 Jun 23;9(6):e100645. doi: 10.1371/journal.pone.0100645. eCollection 2014.
PubMed 24955983
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Eosinophilic Neutrophilic Asthma
- ClinicalTrials.gov ID
- NCT03479138
- Acronym / sponsor ID
- ANNE / IIBSP-ANN-2017-77
- Conditions
- Neutrophilic Asthma
- Keywords
- severe asthma, induced sputum, asthma phenotypes, neutrophilic inflammation, microbiome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Collaborators
- Spanish Clinical Research Network - SCReN
- Study start
- 21 Feb 2018 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Jul 2023 (actual)
- First posted
- 27 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neutrophilic asthma | – | Diagnostic Test: Induced sputumPatients 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. |
| Non neutrophilic asthma | – | Diagnostic Test: Induced sputumPatients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients bewteen 18-80 years with severe asthma.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- Respiratory infection during the previous month
- Significant lung pathology not attributable to asthma (bronchiectasis with Reiff score>3)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Induced sputumCharacterization with flow cytometry of the phenotype of the neutrophils isolated in the sputum, microbiome | Diagnostic test | Neutrophilic asthma, Non neutrophilic asthma |
Primary outcome
Phenotype of neutrophils
Time frame: 24 hours
To determine the types of neutrophils (in induced sputum and blood) associated with neutrophilic asthma and its subphenotypes according to flow cytometry
Microbiome analysis
Time frame: 6 months
To analyse the bronchial microbiological flora of neutrophilic asthma
2 secondary outcomes
Clinical demographic characteristics
Time frame: 1 year
Demographic characteristics
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2024.
- Background: PubMed 25415406Nair P, Aziz-Ur-Rehman A, Radford K. Therapeutic implications of 'neutrophilic asthma'. Curr Opin Pulm Med. 2015 Jan;21(1):33-8. doi: 10.1097/MCP.0000000000000120.
- Background: PubMed 9309987Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):737-43. doi: 10.1164/ajrccm.156.3.9610046.
- Background: PubMed 24641293Simpson JL, Baines KJ, Ryan N, Gibson PG. Neutrophilic asthma is characterised by increased rhinosinusitis with sleep disturbance and GERD. Asian Pac J Allergy Immunol. 2014 Mar;32(1):66-74. doi: 10.12932/AP0322.32.1.2014.
- Background: PubMed 17925424Shaw DE, Berry MA, Hargadon B, McKenna S, Shelley MJ, Green RH, Brightling CE, Wardlaw AJ, Pavord ID. Association between neutrophilic airway inflammation and airflow limitation in adults with asthma. Chest. 2007 Dec;132(6):1871-5. doi: 10.1378/chest.07-1047. Epub 2007 Oct 9.
- Background: PubMed 22561835Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012 May 4;18(5):716-25. doi: 10.1038/nm.2678.
- Background: PubMed 17947611Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med. 2008 Jan 15;177(2):148-55. doi: 10.1164/rccm.200707-1134OC. Epub 2007 Oct 18.
- Background: PubMed 22903959Polosa R, Thomson NC. Smoking and asthma: dangerous liaisons. Eur Respir J. 2013 Mar;41(3):716-26. doi: 10.1183/09031936.00073312. Epub 2012 Aug 16.
- Background: PubMed 18079229Sutherland ER, Martin RJ. Asthma and atypical bacterial infection. Chest. 2007 Dec;132(6):1962-6. doi: 10.1378/chest.06-2415.
- Background: PubMed 20685741Uddin M, Nong G, Ward J, Seumois G, Prince LR, Wilson SJ, Cornelius V, Dent G, Djukanovic R. Prosurvival activity for airway neutrophils in severe asthma. Thorax. 2010 Aug;65(8):684-9. doi: 10.1136/thx.2009.120741.
- Background: PubMed 24035139Newcomb DC, Peebles RS Jr. Th17-mediated inflammation in asthma. Curr Opin Immunol. 2013 Dec;25(6):755-60. doi: 10.1016/j.coi.2013.08.002. Epub 2013 Sep 11.
- Background: PubMed 25162311Chesne J, Braza F, Mahay G, Brouard S, Aronica M, Magnan A. IL-17 in severe asthma. Where do we stand? Am J Respir Crit Care Med. 2014 Nov 15;190(10):1094-101. doi: 10.1164/rccm.201405-0859PP.
- Background: PubMed 25977288Bruijnzeel PL, Uddin M, Koenderman L. Targeting neutrophilic inflammation in severe neutrophilic asthma: can we target the disease-relevant neutrophil phenotype? J Leukoc Biol. 2015 Oct;98(4):549-56. doi: 10.1189/jlb.3VMR1214-600RR. Epub 2015 May 14.
- Website of the spanish guideline of asthmaLink provided by the sponsor.
- Website of the european guideline of asthmaLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neutrophilic Asthma, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 2 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phenotype of neutrophils (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03479138, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2024.