Asthma, AllergicNCT03455959
Lung-Resident Memory Th2 Cells in Asthma
A study testing Bronchoscopy/BAL and Airway Brushing in people with Asthma, Allergic, run by Andrew D. Luster, M.D.,Ph.D. at 1 site in United States.
Trial summary
Determining how memory T helper type 2 (Th2) initiate recall responses to aeroallergens has the potential to change the therapeutic approach to allergic asthma, the most common asthma subtype. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma, Allergic
- What is being tested?
- Bronchoscopy/BAL and Airway Brushing
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 23 May 2019to 8 Sep 2026
- Phase
- Interventional
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All subjects will have a baseline FEV1 no less than 75% of the predicted value.
- All subjects will have a clinical history of allergic symptoms to an indoor allergen present in their home environment, either cat, dog or dust mite allergen, and confirmed skin reactivity (a positive allergen prick test) to the same allergen. The investigators will recruit both:
- subjects with mild intermittent or mild persistent asthma (consistent with NAEP Step 1 or Step 2 treatment options) who are not taking regular daily inhaled corticosteroids (ICS), and
- subjects with moderate persistent asthma (consistent with NAEP Step 3 treatment options) who are taking regular daily inhaled corticosteroids (ICS). In this subgroup, the maximum allowable daily ICS dose will be 220 MCG twice daily of fluticasone or equivalent ICS at screening.
- Life-long absence of cigarette smoking (lifetime total of < 5 pack-years and none in 5 years).
- Willing and able to give informed consent.
Show all 9Show fewer
- Expressed the desire to participate in an interview with the principal investigator.
- Age between 18 and 55 years.
- All subjects will have a positive methacholine challenge with a PC20 < 16 mg/ml.
Who cannot join
- Women of childbearing potential who are pregnant (based on urine beta-HCG testing), are sexually active and not using contraception, are seeking to become pregnant or who are nursing.
- The presence of spontaneous asthmatic exacerbation or clinical evidence of upper respiratory tract infection within the previous 6 weeks and not requiring a change in daily inhaled corticosteroids (ICS) in the past 4 weeks.
- Participation in a research study involving a drug or biologic agent during the 30 days prior to the study.
- Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.
- Antihistamines within 7 days of the screening visit.
- Presence of diabetes mellitus, congestive heart failure, ventricular arrhythmias, history of a cerebrovascular accident, renal failure, history of anaphylaxis or cirrhosis.
Show all 20Show fewer
- Use of systemic steroids, increased use of inhaled steroids, beta blockers and MAO inhibitors or a visit for an asthma exacerbation within 1 month of the screening visit.
- Antibiotic use for respiratory disease within 1 month of the characterization visit or a respiratory tract infection within 6 weeks of the bronchoscopy visits.
- A history of asthma-related respiratory failure requiring intubation.
- Taking beta-adrenergic blocking agents or monoamine oxidase inhibitors.
- Subjects with a high possibility of poor compliance with the study.
- No history of cigarette smoking within the past 5 years or > 5 pack years total.
- No indoor animal or second-hand cigarette smoke exposure. (It is also preferred but not required that dust mite allergic subjects have dust mite-proof encasings on their mattress and pillows.)
- Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection.
- Use of Xolair (omalizumab - anti-IgE monoclonal antibody) within 6 months.
- Immunotherapy with cat, dog, or dust mite extract now or in the past 10 years
- Use of other biologics for treatment of asthma or other medical condition, such as Nucala (mepolizumab, anti-IL-5 monoclonal antibody), Cinqair (reslizumab, anti-IL-5 monoclonal antibody), Fasenra (benralizumab, anti-IL-5 receptor monoclonal antibody), Dupixent (dupilumab, anti-IL-4 receptor-alpha monoclonal antibody), or other immunomodulatory biologics within 6 months.
- Healthy Control (HC) Subjects HC subjects will be individuals who are in good overall health, age and sex matched to the asthmatic group, age 18 - 55 and nonallergic, i.e. entirely negative on a panel of prick skin tests that includes trees, grasses, weeds, cat, dog, dust mites, cockroach and molds, with no history of allergic rhinitis or asthma, no history of allergic symptoms caused by cats, dogs, or dust mite allergen exposure, life-long nonsmokers of cigarettes (defined as a lifetime total of < 5 packyears and none in 5 years), normal spirometry (i.e. FEV1 and FVC of at least 90% of predicted) and with a negative methacholine challenge test (PC20 of > 25 mg/ml).
- A history of allergy, asthma, nasal or sinus disease.
- Exclusion criteria #1, 3-8 and 10-17 as indicated above for mild to moderate allergic asthma.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02116
About this study
Determining how memory T helper type 2 (Th2) initiate recall responses to aeroallergens has the potential to change the therapeutic approach to allergic asthma, the most common asthma subtype. ~5-10% of effector Th2 cells recruited into the lung give rise to long-lived tissue resident memory cells that are poised to respond upon allergen re-exposure.Consequently, targeting memory Th2 cell activation is an attractive therapeutic strategy. However, it is not well understood how allergen inhalation initiates a memory Th2 cell response in the lung. The focus of this new study on the role of lung-resident memory Th2 cells in orchestrating the recall response to allergen in the lung, including the recruitment and activation of circulating Th2 cells, is a natural, timely and exciting extension of the investigators' ongoing Allergen Challenge Protocol.
Read the detailed description
The objective of this study is to define the mechanisms whereby Th2-Trm persisting in the lung orchestrates a recall response to inhaled allergens. The investigators' central hypothesis is that Th2-Trm ignite allergic airway inflammation via a rapid and enhanced response to cognate antigen in the airway and the ability to recruit circulating Th2 cells (Th2-Tcr) to the sites of antigen presentation in the lung. Mechanistically, the investigators hypothesize that Th2-Trm co-localize with DCs expressing the Th2 cell-attracting chemokine CCL17 and after allergen re-challenge rapidly produce type 2 cytokines that initiate allergic inflammation and markedly enhance DC expression of CCL17. This increased CCL17 expression recruits Th2-Tcr cells from the blood to sites of antigen presentation where Th2-Tcr receive a "second touch" from cognate antigen loaded and activated DCs and become fully competent to amplify allergic inflammation. The investigators propose to use innovative experimental systems to define the function of Th2-Trm, including single cell RNA-seq analysis of human airway mucosal CD4+ T cells obtained via bronchial brushing. Specifically, the investigators propose to define the transcriptional phenotype of human lung Th2-Trm and Th2-Tcr. Defining the mechanisms regulating Th2-Trm function in the asthmatic airway has the potential to yield new therapeutic approaches for allergic asthma. Memory CD4+ T helper type 2 (Th2) cells are critical in promoting allergic asthma, the most common asthma endotype. The investigators propose to define the function of newly described lung-resident memory Th2 cells in driving recurrent allergic airway inflammation. The successful completion of the proposed study has the potential to focus new asthma therapies on specifically targeting the biology of lung-resident memory Th2 cells.
- Conditions
- Asthma, Allergic
- Being tested
- Bronchoscopy/BAL, Airway Brushing
- Keywords
- Asthma, Allergic, Inflammation, Airway
- Medical subject headings
- Asthma, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchoscopy/BALProcedure or surgery
Participants may receive 3 inhalations (90 ug ea) of albuterol to minimize bronchoconstriction. Medication includes midazolam by intravenous injection, and fentanyl by intravenous injection as judged necessary. 2% lidocaine is delivered via atomizer spray to the oral pharynx for local anesthesia. 1% lidocaine is delivered through the bronchoscope to the vocal cords and lung segments for local anesthesia. The bronchoscope is then passed through the vocal cords into the trachea. Throughout the procedure, all participants will have continuous blood pressure, heart rate, and oxygen saturation monitoring. Participants will be instructed to relate any discomfort or problems through a series of standardized hand signals. Once in the lung, aliquots of sterile saline are instilled into two subsegments of the right middle lobe (preferred and if not possible then the right upper lobe) and withdrawn into a trap by gentle suction.
Airway BrushingProcedure or surgery
After completion of the BALs, endobronchial brushing of the airways will be performed using the airway brushings with a Conmed Harrell™ 4 mm unsheathed cytology brush. Upon completing the brushing the investigators remove the bronchoscope with the brush in place to avoid shearing off isolated cells. The brush will be gently glided back and forth on the airway epithelium 10 times in 2 different locations within the same airway. The brush is then placed in media and flicked to remove the cells. A second brush will then be introduced into an adjacent airway of the same lobe and gently glided back and forth on the airway epithelium 10 times in 2 different locations as was done with the first brush. The second brush will also be placed in media and flicked to remove the cells. There is some airway bleeding caused by the procedure, and participants are made aware that they may cough up small amounts of blood for 24-48 hours following the procedure.
| Study group | Role | What they receive |
|---|---|---|
| Allergic Asthmatic or Healthy Control Adults | Experimental | Allergic Asthmatic or Healthy Control Adults will undergo Bronchoscopy/BAL and airway brushing Receives: Procedure: Bronchoscopy/BAL; Procedure: Airway Brushing |
What is being measured
The primary outcome is the main question the study is designed to answer.
The phenotype of Th2-Trm recovered from the airway mucosa
The investigators will determine the phenotype of Th2-Trm recovered from the airway mucosa of humans with asthma via flow cytometry to define the phenotype of human Th2-Trm. The T cells will be recovered from airway bronchial brushing samples of patients with allergic asthma and allergy to an indoor allergen, and the investigators will obtain comparative samples from nonallergic healthy control subjects.
Measured: This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
The transcriptional profile of Th2-Trm recovered from the airway mucosa
The investigators will determine the transcriptional profile of Th2-Trm recovered from the airway mucosa of humans with asthma via single-cell RNA-seq analysis to define the phenotype of human Th2-Trm. The T cells will be recovered from airway bronchial brushing samples of patients with allergic asthma and allergy to an indoor allergen, and the investigators will obtain comparative samples from nonallergic healthy control subjects.
Measured: This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study start23 May 2019
- Primary completion15 Nov 2024
- Study completion8 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Asthma, AllergicStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A single time point study with all information obtained at the time of bronchoscopy
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrew D. Luster, M.D.,Ph.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andrew D. Luster, M.D.,Ph.D., Massachusetts General Hospital
- Investigators
- Andrew D Luster, Principal investigator, MGH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03455959
- Sponsor's protocol ID
- 2018P000117
- Other IDs
- 2R01AI040618-21
- Status last verified
- Sep 2026
- First submitted
- 28 Feb 2018
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rahimi RA, Smith NP, Selle A, Best R, Martin S, Tuttle E, Said W, Samanta N, Ling MF, Medoff BD, Villani AC, Luster AD. Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma. Mucosal Immunol. 2026 Apr;19(2):1799-1807. doi: 10.1016/j.mucimm.2026.01.001. Epub 2026 Jan 8.
PubMed 41519381
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung-Resident Memory Th2 Cells in Asthma
- ClinicalTrials.gov ID
- NCT03455959
- Acronym / sponsor ID
- 2018P000117
- Conditions
- Asthma, Allergic
- Keywords
- Asthma, Allergic, Inflammation, Airway
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Andrew D. Luster, M.D.,Ph.D.University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 23 May 2019 (actual)
- Primary completion
- 15 Nov 2024 (actual)
- Study completion
- 8 Sep 2026 (actual)
- First posted
- 7 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.
Determining how memory T helper type 2 (Th2) initiate recall responses to aeroallergens has the potential to change the therapeutic approach to allergic asthma, the most common asthma subtype. ~5-10% of effector Th2 cells recruited into the lung give rise to long-lived tissue resident memory cells that are poised to respond upon allergen re-exposure.Consequently, targeting memory Th2 cell activation is an attractive therapeutic strategy. However, it is not well understood how allergen inhalation initiates a memory Th2 cell response in the lung. The focus of this new study on the role of lung-resident memory Th2 cells in orchestrating the recall response to allergen in the lung, including the recruitment and activation of circulating Th2 cells, is a natural, timely and exciting extension of the investigators' ongoing Allergen Challenge Protocol.
Detailed description
The objective of this study is to define the mechanisms whereby Th2-Trm persisting in the lung orchestrates a recall response to inhaled allergens. The investigators' central hypothesis is that Th2-Trm ignite allergic airway inflammation via a rapid and enhanced response to cognate antigen in the airway and the ability to recruit circulating Th2 cells (Th2-Tcr) to the sites of antigen presentation in the lung. Mechanistically, the investigators hypothesize that Th2-Trm co-localize with DCs expressing the Th2 cell-attracting chemokine CCL17 and after allergen re-challenge rapidly produce type 2 cytokines that initiate allergic inflammation and markedly enhance DC expression of CCL17. This increased CCL17 expression recruits Th2-Tcr cells from the blood to sites of antigen presentation where Th2-Tcr receive a "second touch" from cognate antigen loaded and activated DCs and become fully competent to amplify allergic inflammation. The investigators propose to use innovative experimental systems to define the function of Th2-Trm, including single cell RNA-seq analysis of human airway mucosal CD4+ T cells obtained via bronchial brushing. Specifically, the investigators propose to define the transcriptional phenotype of human lung Th2-Trm and Th2-Tcr. Defining the mechanisms regulating Th2-Trm function in the asthmatic airway has the potential to yield new therapeutic approaches for allergic asthma. Memory CD4+ T helper type 2 (Th2) cells are critical in promoting allergic asthma, the most common asthma endotype. The investigators propose to define the function of newly described lung-resident memory Th2 cells in driving recurrent allergic airway inflammation. The successful completion of the proposed study has the potential to focus new asthma therapies on specifically targeting the biology of lung-resident memory Th2 cells.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A single time point study with all information obtained at the time of bronchoscopy
| Arm | Type | Receives |
|---|---|---|
| Allergic Asthmatic or Healthy Control Adults | Experimental | Procedure: Bronchoscopy/BAL, Procedure: Airway BrushingAllergic Asthmatic or Healthy Control Adults will undergo Bronchoscopy/BAL and airway brushing |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- All subjects will have a baseline FEV1 no less than 75% of the predicted value.
- All subjects will have a clinical history of allergic symptoms to an indoor allergen present in their home environment, either cat, dog or dust mite allergen, and confirmed skin reactivity (a positive allergen prick test) to the same allergen. The investigators will recruit both:
- Life-long absence of cigarette smoking (lifetime total of < 5 pack-years and none in 5 years).
- Willing and able to give informed consent.
- Expressed the desire to participate in an interview with the principal investigator.
Key exclusion criteria (20 listed)
- Women of childbearing potential who are pregnant (based on urine beta-HCG testing), are sexually active and not using contraception, are seeking to become pregnant or who are nursing.
- The presence of spontaneous asthmatic exacerbation or clinical evidence of upper respiratory tract infection within the previous 6 weeks and not requiring a change in daily inhaled corticosteroids (ICS) in the past 4 weeks.
- Participation in a research study involving a drug or biologic agent during the 30 days prior to the study.
- Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.
- Antihistamines within 7 days of the screening visit.
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 |
|---|---|---|
| Bronchoscopy/BALParticipants may receive 3 inhalations (90 ug ea) of albuterol to minimize bronchoconstriction. Medication includes midazolam by intravenous injection, and fentanyl by intravenous injection as judged necessary. 2% lidocaine is delivered via atomizer spray to the oral pharynx for local anesthesia. 1% lidocaine is delivered through the bronchoscope to the vocal cords and lung segments for local anesthesia. The bronchoscope is then passed through the vocal cords into the trachea. Throughout the procedure, all participants will have continuous blood pressure, heart rate, and oxygen saturation monitoring. Participants will be instructed to relate any discomfort or problems through a series of standardized hand signals. Once in the lung, aliquots of sterile saline are instilled into two subsegments of the right middle lobe (preferred and if not possible then the right upper lobe) and withdrawn into a trap by gentle suction. | Procedure or surgery | Allergic Asthmatic or Healthy Control Adults |
| Airway BrushingAfter completion of the BALs, endobronchial brushing of the airways will be performed using the airway brushings with a Conmed Harrell™ 4 mm unsheathed cytology brush. Upon completing the brushing the investigators remove the bronchoscope with the brush in place to avoid shearing off isolated cells. The brush will be gently glided back and forth on the airway epithelium 10 times in 2 different locations within the same airway. The brush is then placed in media and flicked to remove the cells. A second brush will then be introduced into an adjacent airway of the same lobe and gently glided back and forth on the airway epithelium 10 times in 2 different locations as was done with the first brush. The second brush will also be placed in media and flicked to remove the cells. There is some airway bleeding caused by the procedure, and participants are made aware that they may cough up small amounts of blood for 24-48 hours following the procedure. | Procedure or surgery | Allergic Asthmatic or Healthy Control Adults |
Primary outcome
The phenotype of Th2-Trm recovered from the airway mucosa
Time frame: This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
The investigators will determine the phenotype of Th2-Trm recovered from the airway mucosa of humans with asthma via flow cytometry to define the phenotype of human Th2-Trm. The T cells will be recovered from airway bronchial brushing samples of patients with allergic asthma and allergy to an indoor allergen, and the investigators will obtain comparative samples from nonallergic healthy control subjects.
The transcriptional profile of Th2-Trm recovered from the airway mucosa
Time frame: This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.
The investigators will determine the transcriptional profile of Th2-Trm recovered from the airway mucosa of humans with asthma via single-cell RNA-seq analysis to define the phenotype of human Th2-Trm. The T cells will be recovered from airway bronchial brushing samples of patients with allergic asthma and allergy to an indoor allergen, and the investigators will obtain comparative samples from nonallergic healthy control subjects.
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 30 Sep 2026.
- Results publication: PubMed 41519381Rahimi RA, Smith NP, Selle A, Best R, Martin S, Tuttle E, Said W, Samanta N, Ling MF, Medoff BD, Villani AC, Luster AD. Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma. Mucosal Immunol. 2026 Apr;19(2):1799-1807. doi: 10.1016/j.mucimm.2026.01.001. Epub 2026 Jan 8.
- 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.
Andrew D Luster principal investigator
MGH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bronchoscopy/BAL and Airway Brushing in people with Asthma, Allergic, run by Andrew D. Luster, M.D.,Ph.D. at 1 site in United States.
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 20 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 30 Sep 2026. 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 United States. 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?
The phenotype of Th2-Trm recovered from the airway mucosa (time frame: This is a single time point study with all information obtained at the time of bronchoscopy defined as Day 0.). 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 NCT03455959, which also lists 1 linked publication.
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 Sep 2026.