Understanding Immune Cell Response in Asthma

Overseen By Rod A Rahimi, MD PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Andrew D. Luster, M.D.,Ph.D.

Must be taking: Inhaled corticosteroids

Must not be taking: Antihistamines, Systemic steroids, Beta blockers, MAO inhibitors

Disqualifiers: Pregnancy, Diabetes, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

37 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain medications like systemic steroids, beta blockers, or specific biologics within certain time frames before the study. If you are on daily inhaled corticosteroids, you may continue them if they are within the allowed dose.

What data supports the effectiveness of the treatment Airway Brushing, Bronchoscopy/BAL in asthma?

Research shows that bronchoalveolar lavage (BAL) is a valuable tool in asthma research, helping to understand airway inflammation without causing additional inflammation in stable asthmatics. This suggests that BAL can be safely used to study asthma and potentially guide personalized treatment. ^{1 2 3 4 5}

Is the procedure of bronchoscopy with bronchoalveolar lavage (BAL) and bronchial brushing safe for people with asthma?

Bronchoscopy with bronchoalveolar lavage (BAL) and bronchial brushing is generally safe for people with asthma, though some may experience mild side effects like chest pain, shortness of breath, or flu-like symptoms. Most complications occur when both BAL and endobronchial biopsy are performed together, and the procedure is well-tolerated with minimal risks when guidelines are followed. ^{6 7 8 9 10}

How does the treatment Airway Brushing, Bronchoscopy/BAL differ from other treatments for asthma?

Airway Brushing, Bronchoscopy/BAL is unique because it involves directly examining and collecting samples from the airways using a bronchoscope, which helps researchers understand the immune cell response in asthma. Unlike typical asthma treatments that focus on relieving symptoms, this method is used for research to study the underlying inflammation and cellular changes in the airways. ^{1 4 11 12 13}

Research Team

Andrew D Luster

Principal Investigator

MGH

Eligibility Criteria

This trial is for adults aged 18-55 with allergic asthma, who've never smoked much (less than 5 pack-years and none in the past 5 years), have a certain level of lung function, react to indoor allergens like pet dander or dust mites, and are not pregnant or nursing. People can't join if they're on certain medications, have other lung diseases, severe allergies to specific drugs used in the study, recent infections or steroid use.

Inclusion Criteria

Willing and able to give informed consent.

I am willing to talk with the lead researcher.

You will need to have a positive test for methacholine challenge with a PC20 less than 16 mg/ml.

Exclusion Criteria

I have been intubated due to severe asthma in the past.

I haven't used steroids, beta blockers, or MAO inhibitors for asthma in the last month.

Subjects with a high possibility of poor compliance with the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bronchoscopy and Airway Brushing

Participants undergo bronchoscopy and airway brushing to collect samples for analysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedure

4 weeks

Treatment Details

Interventions

• Airway Brushing
• Bronchoscopy/BAL

Trial Overview The study investigates how memory Th2 cells in the lungs respond to common airborne allergens by performing bronchoscopy/BAL and airway brushing on participants. It aims to understand these cells' role in allergic reactions which could lead to new treatments for allergic asthma.

Participant Groups

Group I: Allergic Asthmatic or Healthy Control Adults Experimental Treatment 2 Interventions

Allergic Asthmatic or Healthy Control Adults will undergo Bronchoscopy/BAL and airway brushing

Who Is Running the Clinical Trial?

Andrew D. Luster, M.D.,Ph.D.

Lead Sponsor

Trials

3

Recruited

250+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Findings from Research

Phenotyping refractory asthma through direct bronchoscopic observation and analysis of bronchoalveolar lavage (BAL) and biopsies allows for personalized therapy, improving treatment outcomes.

Using fiberoptic bronchoscopy, specific asthma phenotypes can be identified, such as laryngopharyngeal reflux and tissue eosinophilia, which helps tailor effective treatments for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of fiberoptic bronchoscopy in identifying asthma phenotypes to direct personalized therapy. Lommatzsch, SE., Martin, RJ., Good, JT.[2015]

In a study involving 159 asthmatic patients who underwent 273 bronchoscopies, the procedures were found to be generally safe, with adverse events occurring in only 34 instances, none of which followed allergen challenges.

Most complications were associated with the combination of endobronchial biopsy and bronchoalveolar lavage, indicating that bronchoalveolar lavage may be responsible for the majority of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of research bronchoscopy, biopsy and bronchoalveolar lavage in asthma. Elston, WJ., Whittaker, AJ., Khan, LN., et al.[2013]

Bronchial brushing is a safe and well-tolerated method for collecting bronchial epithelial cells (BECs) in patients with asthma and chronic bronchitis, with no complications observed during the procedure in a study involving 70 participants.

While the procedure effectively recovers BECs, the viability of these cells is significantly lower in asthmatic and chronic bronchitis patients compared to healthy controls, indicating potential differences in cell health related to these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and cellular assessment of bronchial brushing in airway diseases. Romagnoli, M., Vachier, I., Vignola, AM., et al.[2019]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Bronchoalveolar lavage in asthma research. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Bronchoalveolar lavage in stable asthmatics does not cause pulmonary inflammation. [2007]

3. United States pubmed.ncbi.nlm.nih.gov

Importance of fiberoptic bronchoscopy in identifying asthma phenotypes to direct personalized therapy. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Inhaled albuterol does not inhibit cellular influx or lung injury produced by segmental antigen challenge in humans. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Benefits and risks of bronchoalveolar lavage in severe asthma in children. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in asthmatics. [2008]

7. England pubmed.ncbi.nlm.nih.gov

Safety of research bronchoscopy, biopsy and bronchoalveolar lavage in asthma. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Safety and cellular assessment of bronchial brushing in airway diseases. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

National Institutes of Health workshop summary. Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in individuals with asthma. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Bronchoalveolar lavage (BAL) for research; obtaining adequate sample yield. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation. [2010]

12. England pubmed.ncbi.nlm.nih.gov

Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Mucosal inflammation in asthma. [2004]