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Non-Type 2 and Mixed Inflammation in Chronic Rhinosinusitis and Lower Airway Disease
Austin Heffernan1, Amir Shafiee1, Teffran Chan1
1Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, Canada.
Objective:
The aim was to discuss the role of non-type 2 inflammation in patients diagnosed with chronic rhinosinusitis (CRS) and comorbid lower airway disease.
Data Sources:
Medline, Embase, National Institute for Health and Care Excellence, TRIP Database, ProQuest, Clinicaltrials.gov, Cochrane Central Registry of Controlled Trials, Web of Science, government and health organizations, and graduate-level theses.
Review Methods:
This scoping review followed PRISMA-ScR guidelines. Search strategy was peer-reviewed by medical librarians. Studies were included if they utilized airway sampling, non-type 2 cytokines, and patients with CRS and lower airway disease.
Results:
Twenty-seven from 7060 articles were included. In patients with CRS and comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and chronic obstructive pulmonary disease (COPD)/bronchiectasis, 60% (n = 12), 33% (n = 2), and 100% (n = 1), respectively, demonstrated mixed or non-type 2 endotypes. Comorbid CRS and asthma produced type 1 (n = 1.5), type 2 (n = 8), type 3 (n = 1), mixed type 1/2 (n = 1), and mixed type 1/2/3 (n = 8.5) endotype shifts. AERD demonstrated type 2 (n = 4), mixed type 2/3 (n = 1), and mixed type 1/2/3 (n = 1) endotype shifts. CRS with COPD or bronchiectasis demonstrated a mixed 1/2 (n = 1) endotype shift.
Conclusion:
Type 2 disease has been extensively reviewed due to advent biologics targeting type 2 inflammation, but outcomes may be suboptimal due to the presence of non-type 2 inflammation. A proportion of patients with CRS and comorbid lower airway disease demonstrated mixed and non-type 2 endotype shifts. This emphasizes that patients with unified airway disease may have forms of inflammation beyond classical type 2 disease which could inform biologic development. Laryngoscope, 134:1005-1013, 2024.
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