Aspirin-exacerbated Respiratory Disease, Nasal Polyps
Conditions
Brief summary
The overarching hypothesis of this proposal is that IL-5 acts on multiple sinus tissue cell types, including plasma cells and epithelial cells, to promote immune dysregulation, and that inhibition of IL-5 affects several relevant effector pathways that lead to clinical benefit.
Detailed description
Further characterization of the role of IL-5Rα expression and function on human plasma cells will determine whether inhibiting IL-5 signaling on these cells offers therapeutic promise in other diseases related to plasma cell proliferation. Further characterization of human upper airway epithelial cell IL-5Rα expression and function will determine whether or not inhibiting IL-5 signaling on these cells offers therapeutic promise in other diseases related to epithelial dysfunction. IL-5Rα expression has been identified on several relevant sinus tissue effector cells, including on nasal polyp plasma cells and epithelial cells, and the aim of this study is to further the field by determining the consequences of IL-5 signaling on those cells.
Interventions
OTHERNon-Interventional
No intervention.
Sponsors
Brigham and Women's Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* AERD, CRSwNP, healthy controls
Exclusion criteria
* Not on any systemic steroids or respiratory biologics at time of surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Nasal Polyp Plasma Cell Transcriptome | At baseline | We will determine the number of participants from whom a transcriptional profile of nasal polyp plasma cells is analyzable from bulk RNA sequencing of sorted nasal polyp plasma cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Functional Readouts of IL-5Ra on Nasal Polyp Plasma Cells. | At baseline | We will determine the number of participants from whom a readout of IL-5Ra is analyzable from the plasma cells in their nasal tissue |
| Number of Patients for Whom IL-5Ra Signaling on Nasal Epithelial Cells Can be Analyzed | At baseline | We will determine the number of participants from whom IL-5-elicited signaling on their nasal epithelial tissue can be analyzed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aspirin-exacerbated Respiratory Disease (AERD) Aspirin-exacerbated respiratory disease (AERD)
Non-Interventional: No intervention. | 10 |
| Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) Aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP)
Non-Interventional: No intervention. | 10 |
| Healthy Controls Individuals who do not have AERD or CRSwNP
Non-Interventional: No intervention. | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Aspirin-exacerbated Respiratory Disease (AERD) | Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) | Healthy Controls | Total |
|---|---|---|---|---|
| Age, Continuous | 54 years | 52 years | 49 years | 52 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Number of Participants With Nasal Polyp Plasma Cell Transcriptome
We will determine the number of participants from whom a transcriptional profile of nasal polyp plasma cells is analyzable from bulk RNA sequencing of sorted nasal polyp plasma cells.
Time frame: At baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin-exacerbated Respiratory Disease (AERD) | Number of Participants With Nasal Polyp Plasma Cell Transcriptome | 10 Participants |
| Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) | Number of Participants With Nasal Polyp Plasma Cell Transcriptome | 10 Participants |
| Healthy Controls | Number of Participants With Nasal Polyp Plasma Cell Transcriptome | 10 Participants |
Secondary
Number of Participants With Functional Readouts of IL-5Ra on Nasal Polyp Plasma Cells.
We will determine the number of participants from whom a readout of IL-5Ra is analyzable from the plasma cells in their nasal tissue
Time frame: At baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin-exacerbated Respiratory Disease (AERD) | Number of Participants With Functional Readouts of IL-5Ra on Nasal Polyp Plasma Cells. | 10 Participants |
| Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) | Number of Participants With Functional Readouts of IL-5Ra on Nasal Polyp Plasma Cells. | 10 Participants |
| Healthy Controls | Number of Participants With Functional Readouts of IL-5Ra on Nasal Polyp Plasma Cells. | 10 Participants |
Secondary
Number of Patients for Whom IL-5Ra Signaling on Nasal Epithelial Cells Can be Analyzed
We will determine the number of participants from whom IL-5-elicited signaling on their nasal epithelial tissue can be analyzed.
Time frame: At baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin-exacerbated Respiratory Disease (AERD) | Number of Patients for Whom IL-5Ra Signaling on Nasal Epithelial Cells Can be Analyzed | 10 Participants |
| Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) | Number of Patients for Whom IL-5Ra Signaling on Nasal Epithelial Cells Can be Analyzed | 10 Participants |
| Healthy Controls | Number of Patients for Whom IL-5Ra Signaling on Nasal Epithelial Cells Can be Analyzed | 10 Participants |