Lung-Resident Memory Th2 Cells in Asthma

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. \~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.

Conditions

• Asthma, Allergic

Interventions

PROCEDURE

Bronchoscopy/BAL

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instilled into two subsegments of the right middle lobe (preferred and if not possible then the right upper lobe) and withdrawn into a trap by gentle suction.

PROCEDURE

Airway Brushing

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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• Andrew D. Luster, M.D.,Ph.D.

  lead OTHER

Principal Investigators

• Andrew D Luster · MGH

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-05-23

Primary Completion

2024-11-15

Completion

2027-12-15

Countries

• United States

Study Locations