Severe AsthmaCLASSENCT03784781
Type 2 Innate Lymphoid Cells in Severe Pediatric Asthma
An observational study of Severe Asthma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The main objectives of this study are to show that the number of type 2 innate lymphoid cells (ILC2) of the bronchial mucosa and in bronchoalveolar lavages (BAL) are higher in asthmatic children than in non-asthmatics, that the number of ILC2 of the bronchial mucosa and in BAL correlate with the number of bronchial… Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Severe Asthma
- What is being tested?
- Biopsy, Blood collection and Bronchoalveolar lavage
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 9 Jun 2016to Apr 2020
- 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 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Minors hospitalized in the department of pediatric pulmonology and allergy of Necker Hospital
Who may be able to join
- Controls :
- Minors aged 6 to 18 matched in age with severe asthmatic children
- Non-asthmatic children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
- To undergo bronchial endoscopy with bronchoalveolar lavage, biopsy and blood collection
- Severe asthmatic children :
- Minors aged 6 to 18
Show all 9Show fewer
- Children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
- To undergo bronchial endoscopy with bronchoalveolar lavage, biopsy and blood collection
- Severe uncontrolled asthma is defined by the need to maintain a treatment with high doses of inhaled corticosteroids and a long-acting bronchodilator (B2LDA) and/or an anti-leukotriene
Who cannot join
- Children with an immune deficiency, will be excluded
Trial locations and contacts
1 site in 1 country.
About this study
The main objectives of this study are to show that the number of type 2 innate lymphoid cells (ILC2) of the bronchial mucosa and in bronchoalveolar lavages (BAL) are higher in asthmatic children than in non-asthmatics, that the number of ILC2 of the bronchial mucosa and in BAL correlate with the number of bronchial and BAL eosinophils, and to determine whether there is a correlation between plasma and bronchial and BAL ILC2.
Read the detailed description
Severe asthma of the child is characterized by chronic eosinophilic infiltration of the bronchial mucosa associated with bronchial remodeling.
The mechanisms responsible for these phenomena are still misunderstood. Animal models suggest that type 2 innate lymphoid cells (ILC2) may be responsible for inflammation and bronchial remodeling in asthma. In mice, ILC2 stimulated by the pulmonary epithelium by viral aggression or allergenic exposure release cytokines of the TH2 type such as IL-5 and IL-13 and amphiregulin, involved in the recruitment and differentiation of eosinophils, bronchoconstriction, mucus secretion and the restoration of epithelial integrity.
In humans, ILC2 would be more abundant in the bronchoalveolar lavage (BAL) and peripheral blood of asthmatic patients compared to control subjects. However, the presence of ILC2 in the bronchial mucosa of asthmatic patients has never been identified.
The hypothesis tested is that ILC2 are more abundant in bronchial mucosa, BAL, and blood in children with severe asthma than in non-asthmatics. The results of this study would improve the knowledge of the mechanisms responsible for bronchial inflammation in asthma, consider therapies to prevent its development and modify the natural history of the disease.
The main objectives of this study are to show that the number of ILC2 in bronchial mucosa and BAL is higher in asthmatic children than in non-asthmatics, that the number of ILC2 in the bronchial mucosa and BAL is correlated with the number of eosinophils in bronchial mucosa and BAL, to determine whether the number of ILC2 in lungs correlate with asthma symptoms, and to determine whether there is a correlation between plasma and bronchial ILC2.
Bronchoscopy with BAL and bronchial mucosal biopsies will be performed in 20 children with severe asthma and 20 control subjects in the department of pediatric pulmonology and allergy of Necker Hospital.
ILC2 will be identified in the BAL, in the bronchial mucosa and peripheral blood by flow cytometry. The median values of the number of ILC2 will be compared between asthmatic and non-asthmatic patients by the Mann-Whitney non-parametric test. The correlations will be established by the Spearman rank test. A value of p < 0.05 will be considered significant.
- Conditions
- Severe Asthma
- Being tested
- Biopsy, Blood collection, Bronchoalveolar lavage
- Keywords
- Severe asthma in children, Type 2 innate lymphoid cells (ILC2), bronchial mucosa, bronchoalveolar lavages
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyBiological
Mucosal biopsies under general anesthesia of the segmental bronchi of the right or left lower lobe
Blood collectionBiological
Blood collection (+15mL/ current care)
Bronchoalveolar lavageBiological
Bronchoalveolar lavage fluid (3mL/Kg)
| Study group | Role | What they receive |
|---|---|---|
| Asthmatic children | Severe uncontrolled asthma is defined by the need to maintain a treatment with high doses of inhaled corticosteroids and a long-acting bronchodilator (B2LDA) and/or an anti-leukotriene Receives: Biological: Biopsy; Biological: Blood collection; Biological: Bronchoalveolar lavage | |
| Controls | Non-asthmatic children, paired in age, requiring bronchial endoscopy with BAL and bronchial mucosa biopsy. Receives: Biological: Biopsy; Biological: Blood collection; Biological: Bronchoalveolar lavage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of type 2 innate lymphoid cells
Type 2 innate lymphoid cells
Measured: Day 0
Secondary outcomes (11)
Number of Eosinophils
Eosinophils
Measured: Day 0
Airway remodeling: reticular basement membrane thickness
Reticular basement membrane thickness will be expressed in µm.
Measured: Day 0
Airway remodeling: airway smooth muscle area
The percentage of the submucosa occupied by airway smooth muscle will be determined on hematoxylin-eosin-stained and anti-airway smooth muscle antibody treated sections, respectively. The bundles of airway smooth muscle will be enclosed by a line and the area they occupied will be calculated by image analysis. The airway smooth muscle area will be expressed as the percentage of surface of the submucosa occupied by airway smooth muscle.
Measured: Day 0
Airway remodeling: epithelial integrity
Epithelial integrity will be defined as the percentage of the total length of epithelium that will be intact.
Measured: Day 0
Airway remodeling: vessel number
The number of vessels stained with anti-CD31 mAb will be determined from at least one grid (0.1 mm2) per biopsy, and reported as the median number of positive sections per 0.1 mm2.
Measured: Day 0
Airway remodeling: mucus gland area
The percentage of the submucosa occupied by mucus gland will be determined on hematoxylin-eosin-stained and anti-airway smooth muscle antibody treated sections, respectively. The mucus glands will be enclosed by a line and the area occupied will be calculated by image analysis. The mucus gland area will be expressed as the percentage of surface of the submucosa occupied by mucus gland.
Measured: Day 0
Airway inflammation: bronchoalveolar lavage (BAL)
BAL fluid will be assed for inflammation
- The number of eosinophils will be assessed and expressed percentage of total cells in BAL
- The number of neutrophils will be assessed and expressed percentage of total cells in BAL
- The number of macrophages will be assessed and expressed percentage of total cells in BAL
- The number of basophils will be assessed and expressed percentage of total cells in BAL
- The number of mast cells will be assessed and expressed percentage of total cells in BAL
- The number of innate lymphoid cells will be assessed and expressed percentage of total cells in BAL
- The number of mucosal associated invariant T (MAIT) cells will be assessed and expressed percentage of total cells in BAL
- The number of invariant natural killer T cells will be assessed and expressed percentage of total cells in BAL
- The number of gammadelta T cells will be assessed and expressed percentage of total cells in BAL
Measured: Day 0
Airway inflammation: bronchial mucosa
Bronchial sections will be stained with May-Grunwald-Giemsa.The number of inflammatory cells will be assessed in the submucosa and expressed as the number of cells per square millimeters of submucosal area.
- The number of eosinophils will be assessed and expressed per square millimeters of submucosal area
- The number of neutrophils in the submucosa will be assessed and expressed per square millimeters of submucosal area
- The number of mast cells (c-kit positive cells) in the submucosa will be assessed and expressed per square millimeters of submucosal area
- The number of IgE stained with anti-IgE Ab in the submucosa and the epithelium will be assessed and expressed per square millimeters of submucosal area
- The expression of cytokines in the mucosa will be assessed by multiplex
Measured: Day 0
Inflammation in blood
- The number of eosinophils will be assessed and expressed percentage of total cells in blood
- The number of neutrophils will be assessed and expressed percentage of total cells in blood
- The number of basophils will be assessed and expressed percentage of total cells in blood
- The number of lymphocytes will be assessed and expressed percentage of total cells in blood
- The number of innate lymphoid cells will be assessed and expressed percentage of total cells in blood
- The number of mucosal associated invariant T (MAIT) cells will be assessed and expressed percentage of total cells and T cells in blood
- The number of invariant natural killer T cells will be assessed and expressed percentage of total cells and T cells in blood
- The number of gammadelta T cells will be assessed and expressed percentage of total cells and T cells in blood
- The expression of cytokine will be assessed using multiplex analysis
Measured: Day 0
Metabolomic signature
Non-targeted metabolomics analysis will be performed on plasma. Metabolic profiles will be obtained using two complementary LC-MS methods, to identify metabolites discriminating different patients.
Measured: Day 0
Microbiota analysis
Microbiota analysis will be performed on BAL using PCR ARN 16S.
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2018
- Study start9 Jun 2016
- Primary completionApr 2020 (estimated)
- Study completionApr 2020 (estimated)
Why it stopped: The study never started
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe AsthmaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Guillaume Lezmi, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03784781
- Sponsor's protocol ID
- APHP180357
- Acronym
- CLASSE
- Status last verified
- Nov 2022
- First submitted
- 2 Nov 2018
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Type 2 Innate Lymphoid Cells in Severe Pediatric Asthma
- ClinicalTrials.gov ID
- NCT03784781
- Acronym / sponsor ID
- CLASSE / APHP180357
- Conditions
- Severe Asthma
- Keywords
- Severe asthma in children, Type 2 innate lymphoid cells (ILC2), bronchial mucosa, bronchoalveolar lavages
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: The study never started
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 9 Jun 2016 (actual)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Apr 2020 (estimated)
- First posted
- 24 Dec 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.
The main objectives of this study are to show that the number of type 2 innate lymphoid cells (ILC2) of the bronchial mucosa and in bronchoalveolar lavages (BAL) are higher in asthmatic children than in non-asthmatics, that the number of ILC2 of the bronchial mucosa and in BAL correlate with the number of bronchial and BAL eosinophils, and to determine whether there is a correlation between plasma and bronchial and BAL ILC2.
Detailed description
Severe asthma of the child is characterized by chronic eosinophilic infiltration of the bronchial mucosa associated with bronchial remodeling.
The mechanisms responsible for these phenomena are still misunderstood. Animal models suggest that type 2 innate lymphoid cells (ILC2) may be responsible for inflammation and bronchial remodeling in asthma. In mice, ILC2 stimulated by the pulmonary epithelium by viral aggression or allergenic exposure release cytokines of the TH2 type such as IL-5 and IL-13 and amphiregulin, involved in the recruitment and differentiation of eosinophils, bronchoconstriction, mucus secretion and the restoration of epithelial integrity.
In humans, ILC2 would be more abundant in the bronchoalveolar lavage (BAL) and peripheral blood of asthmatic patients compared to control subjects. However, the presence of ILC2 in the bronchial mucosa of asthmatic patients has never been identified.
The hypothesis tested is that ILC2 are more abundant in bronchial mucosa, BAL, and blood in children with severe asthma than in non-asthmatics. The results of this study would improve the knowledge of the mechanisms responsible for bronchial inflammation in asthma, consider therapies to prevent its development and modify the natural history of the disease.
The main objectives of this study are to show that the number of ILC2 in bronchial mucosa and BAL is higher in asthmatic children than in non-asthmatics, that the number of ILC2 in the bronchial mucosa and BAL is correlated with the number of eosinophils in bronchial mucosa and BAL, to determine whether the number of ILC2 in lungs correlate with asthma symptoms, and to determine whether there is a correlation between plasma and bronchial ILC2.
Bronchoscopy with BAL and bronchial mucosal biopsies will be performed in 20 children with severe asthma and 20 control subjects in the department of pediatric pulmonology and allergy of Necker Hospital.
ILC2 will be identified in the BAL, in the bronchial mucosa and peripheral blood by flow cytometry. The median values of the number of ILC2 will be compared between asthmatic and non-asthmatic patients by the Mann-Whitney non-parametric test. The correlations will be established by the Spearman rank test. A value of p < 0.05 will be considered significant.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Asthmatic children | – | Biological: Biopsy, Biological: Blood collection, Biological: Bronchoalveolar lavageSevere uncontrolled asthma is defined by the need to maintain a treatment with high doses of inhaled corticosteroids and a long-acting bronchodilator (B2LDA) and/or an anti-leukotriene |
| Controls | – | Biological: Biopsy, Biological: Blood collection, Biological: Bronchoalveolar lavageNon-asthmatic children, paired in age, requiring bronchial endoscopy with BAL and bronchial mucosa biopsy. |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Minors hospitalized in the department of pediatric pulmonology and allergy of Necker Hospital
Key inclusion criteria (9 listed)
- Minors aged 6 to 18 matched in age with severe asthmatic children
- Non-asthmatic children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
- To undergo bronchial endoscopy with bronchoalveolar lavage, biopsy and blood collection
- Minors aged 6 to 18
- Children hospitalized in the department of pediatric pulmonology and allergy in Necker Hospital
Key exclusion criteria (1 listed)
- Children with an immune deficiency, will be excluded
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 |
|---|---|---|
| BiopsyMucosal biopsies under general anesthesia of the segmental bronchi of the right or left lower lobe | Biological | Asthmatic children, Controls |
| Blood collectionBlood collection (+15mL/ current care) | Biological | Asthmatic children, Controls |
| Bronchoalveolar lavageBronchoalveolar lavage fluid (3mL/Kg) | Biological | Asthmatic children, Controls |
Primary outcome
Number of type 2 innate lymphoid cells
Time frame: Day 0
Type 2 innate lymphoid cells
11 secondary outcomes
Number of Eosinophils
Time frame: Day 0
Airway remodeling: reticular basement membrane thickness
Time frame: Day 0
Airway remodeling: airway smooth muscle area
Time frame: Day 0
Airway remodeling: epithelial integrity
Time frame: Day 0
Airway remodeling: vessel number
Time frame: Day 0
Airway remodeling: mucus gland area
Time frame: Day 0
Airway inflammation: bronchoalveolar lavage (BAL)
Time frame: Day 0
Airway inflammation: bronchial mucosa
Time frame: Day 0
Inflammation in blood
Time frame: Day 0
Metabolomic signature
Time frame: Day 0
Microbiota analysis
Time frame: Day 0
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- 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.
Guillaume Lezmi, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Severe Asthma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 9 inclusion and 1 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: withdrawn, as of the sponsor's last update on 25 Sep 2025. 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 France. 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 was withdrawn before enrolling participants, so there are no results.
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?
Number of type 2 innate lymphoid cells (time frame: Day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2025.