AsthmaAsmaExNCT04260282
Microbiome and Exacerbations in Neutrophilic Asthma
An observational study of Asthma and Microbiome, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Asthma, Microbiome, Exacerbation
- What is being tested?
- Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab and Induced sputum microbiome
- How many people
- 40 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2021to 1 Jan 2025
- 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: Severe asthma according to guidelines, 18-80 years
Who may be able to join
- Age between 18 -80
- Confirmed diagnose of asthma
- Severe persistent asthma
Who cannot join
- Respiratory infection during the previous month
- Other significant lung disease
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90.
Barcelona, 08041
Astrid Crespo, MD, +34-935565972, acrespo@santpau.cat
About this study
Official title: Exacerbations in Neutrophilic Asthma: Influence of Bronchial Microbiome
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.
Read the detailed description
See above
- Conditions
- Asthma, Microbiome, Exacerbation
- Being tested
- Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab, Induced sputum microbiome
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swabDiagnostic test
PCR for viruses and bacteria in nasal swab
Induced sputum microbiomeDiagnostic test
Microbiome in induced sputum
| Study group | Role | What they receive |
|---|---|---|
| Neutrophilic asthma | Patients with asthma diagnosed according to guidelines, with eosinophils <300/mm3 in blood and <3% in induced sputum Receives: Diagnostic Test: Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab; Diagnostic Test: Induced sputum microbiome | |
| Eosinophilic asthma | Patients with asthma diagnosed according to guidelines, with eosinophils >300/mm3 in blood and/or >3% in induced sputum Receives: Diagnostic Test: Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab; Diagnostic Test: Induced sputum microbiome |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (3)
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)
Measured: 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)
Measured: 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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start1 Jan 2021
- Primary completion1 Jan 2024 (estimated)
- Study completion1 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe sponsor's other registered studies.
- 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
- 40 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Sociedad Española de Neumología y Cirugía Torácica, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Astrid Crespo, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04260282
- Sponsor's protocol ID
- IIBSP-ANE-2020-04
- Acronym
- AsmaEx
- Status last verified
- Jan 2023
- First submitted
- 23 Jan 2020
- Last updated
- 30 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Reddel HK, FitzGerald JM, Bateman ED, Bacharier LB, Becker A, Brusselle G, Buhl R, Cruz AA, Fleming L, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Pedersen SE, Sheikh A, Yorgancioglu A, Boulet LP. GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J. 2019 Jun 27;53(6):1901046. doi: 10.1183/13993003.01046-2019. Print 2019 Jun. No abstract available.
PubMed 31249014Plaza Moral V; Comite Ejecutivo de GEMA. [GEMA(4.0). Guidelines for Asthma Management]. Arch Bronconeumol. 2015 Jan;51 Suppl 1:2-54. doi: 10.1016/S0300-2896(15)32812-X. Epub 2015 Nov 30. No abstract available. Spanish.
PubMed 26707419Nair 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 9309987Shaw 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 17925424Brusselle GG, Vanderstichele C, Jordens P, Deman R, Slabbynck H, Ringoet V, Verleden G, Demedts IK, Verhamme K, Delporte A, Demeyere B, Claeys G, Boelens J, Padalko E, Verschakelen J, Van Maele G, Deschepper E, Joos GF. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax. 2013 Apr;68(4):322-9. doi: 10.1136/thoraxjnl-2012-202698. Epub 2013 Jan 3.
PubMed 23291349Polosa 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 20685741Simpson 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 24641293Green 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 24955983Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, Boushey H. The airway microbiome in patients with severe asthma: Associations with disease features and severity. J Allergy Clin Immunol. 2015 Oct;136(4):874-84. doi: 10.1016/j.jaci.2015.05.044. Epub 2015 Jul 26.
PubMed 26220531Blasi F. Atypical pathogens and respiratory tract infections. Eur Respir J. 2004 Jul;24(1):171-81. doi: 10.1183/09031936.04.00135703.
PubMed 15293621Frehn L, Jansen A, Bennek E, Mandic AD, Temizel I, Tischendorf S, Verdier J, Tacke F, Streetz K, Trautwein C, Sellge G. Distinct patterns of IgG and IgA against food and microbial antigens in serum and feces of patients with inflammatory bowel diseases. PLoS One. 2014 Sep 12;9(9):e106750. doi: 10.1371/journal.pone.0106750. eCollection 2014.
PubMed 25215528Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G, Bruce KD. characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16s ribosomal DNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol. 2004 Nov;42(11):5176-83. doi: 10.1128/JCM.42.11.5176-5183.2004.
PubMed 15528712
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exacerbations in Neutrophilic Asthma: Influence of Bronchial Microbiome
- ClinicalTrials.gov ID
- NCT04260282
- Acronym / sponsor ID
- AsmaEx / IIBSP-ANE-2020-04
- Conditions
- Asthma, Microbiome, Exacerbation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Collaborators
- Sociedad Española de Neumología y Cirugía Torácica, GlaxoSmithKline
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 1 Jan 2024 (estimated)
- Study completion
- 1 Jan 2025 (estimated)
- First posted
- 7 Feb 2020 (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.
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
See above
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neutrophilic asthma | – | Diagnostic Test: Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab, Diagnostic Test: Induced sputum microbiomePatients with asthma diagnosed according to guidelines, with eosinophils <300/mm3 in blood and <3% in induced sputum |
| Eosinophilic asthma | – | Diagnostic Test: Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swab, Diagnostic Test: Induced sputum microbiomePatients with asthma diagnosed according to guidelines, with eosinophils >300/mm3 in blood and/or >3% in induced sputum |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Severe asthma according to guidelines, 18-80 years
Key inclusion criteria (3 listed)
- Age between 18 -80
- Confirmed diagnose of asthma
- Severe persistent asthma
Key exclusion criteria (2 listed)
- Respiratory infection during the previous month
- Other significant lung disease
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 |
|---|---|---|
| Polymerase Chain Reaction (PCR) for viruses and bacteria in nasal swabPCR for viruses and bacteria in nasal swab | Diagnostic test | Eosinophilic asthma, Neutrophilic asthma |
| Induced sputum microbiomeMicrobiome in induced sputum | Diagnostic test | Eosinophilic asthma, Neutrophilic asthma |
Primary outcome
Differences between neutrophilic and non-neutrophilic asthma, with and without frequent exacerbations in bronchial microbiome using 16S rDNA sequencing
Time frame: 6 months
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.
3 secondary outcomes
Changes in absolute and relative abundance using 16S rDNA sequencing of bronchial microbiota due to asthma exacerbations, in patients with neutrophilic and eosinophilic asthma
Time frame: 1 year
Changes in absolute and relative abundance of bronchial microbiota over a year using 16S rDNA sequencing
Time frame: 1 year
Relationship between lung microbiome andlevels of specific immunoglobulin A of C. pneumoniae, PCR, and immunoglobulin G of aspergillus
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
- Background: PubMed 31249014Reddel HK, FitzGerald JM, Bateman ED, Bacharier LB, Becker A, Brusselle G, Buhl R, Cruz AA, Fleming L, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Pedersen SE, Sheikh A, Yorgancioglu A, Boulet LP. GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J. 2019 Jun 27;53(6):1901046. doi: 10.1183/13993003.01046-2019. Print 2019 Jun. No abstract available.
- Background: PubMed 26707419Plaza Moral V; Comite Ejecutivo de GEMA. [GEMA(4.0). Guidelines for Asthma Management]. Arch Bronconeumol. 2015 Jan;51 Suppl 1:2-54. doi: 10.1016/S0300-2896(15)32812-X. Epub 2015 Nov 30. No abstract available. Spanish.
- 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 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 23291349Brusselle GG, Vanderstichele C, Jordens P, Deman R, Slabbynck H, Ringoet V, Verleden G, Demedts IK, Verhamme K, Delporte A, Demeyere B, Claeys G, Boelens J, Padalko E, Verschakelen J, Van Maele G, Deschepper E, Joos GF. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax. 2013 Apr;68(4):322-9. doi: 10.1136/thoraxjnl-2012-202698. Epub 2013 Jan 3.
- 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 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 24955983Green 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.
- Background: PubMed 26220531Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, Boushey H. The airway microbiome in patients with severe asthma: Associations with disease features and severity. J Allergy Clin Immunol. 2015 Oct;136(4):874-84. doi: 10.1016/j.jaci.2015.05.044. Epub 2015 Jul 26.
- Individual participant dataSharing planned: No
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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.
Astrid Crespo principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma and Microbiome, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site 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 3 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: status not confirmed, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Astrid Crespo, PhD (932919000 ext. 7684, acrespo@santpau.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences between neutrophilic and non-neutrophilic asthma, with and without frequent exacerbations in bronchial microbiome using 16S rDNA sequencing (time frame: 6 months). 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 NCT04260282, which also lists 15 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 30 Jan 2023.