Morphopathogenic Endotypes of Primary and Recurrent Nasal Polyps: Pirmreizēju un atkārtotu deguna polipu morfopatoģenēzes endotipi

Chronic rhinosinusitis (CRS) is a condition that is characterised by nasal discharge, congestion, facial pressure/fullness and loss of smell for longer than 3 months. CRS is further divided into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Nasal polyps are soft benign growths that are diagnosed during objective examination by an otolaryngologist or radiological imaging like computed tomography (CT) scan. Approximately third of the patients with CRS develop nasal polyps which are associated with more significant morbidity, decrease in quality of life and more difficult conservative and surgical management. Surgical treatment of CRSwNP still remains difficult because as much as 40 % of patients experience recurrence. Aetiology of CRS is still unclear and in the past few decades modern approach to understanding CRS has been more and more associated with classifying inflammatory endotypes. Research has focused on analysing cytokines and other biomarkers obtained from nasal tissue and classifying separate clusters or so called endotypes by using hierarchical cluster analysis. Classifying distinctive endotypes has been considered an important step towards tailored, patient specific treatment. The aim of this research was investigating the relative appearance and distribution of inflammatory, regulatory, anti-inflammatory cytokines, antimicrobial peptides and proliferation marker in the human nasal mucosa affected by CRSwNP to classify the morphopathogenetic endotypes in the formation of primary and recurrent nasal polyps. The study group included 48 samples taken from patients with CRSwNP during surgery. The control group comprised 17 samples of normal healthy nasal mucosa. Tissues were stained for interleukin 1 alpha (IL-1α), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 7 (IL-7), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 12 (IL-12), proliferation marker Ki-67 (Ki-67), human beta defensin 2 (HBD-2), human beta defensin 3 (HBD-3), and cathelicidin LL 37 (LL 37) using IHC. A semi-quantitative counting method as well as a hierarchical cluster analysis was used. Most of the factors showed an elevated presence in the connective tissue but a decreased presence in the nasal polyp epithelium compared to the controls. Unique correlation patterns emerged. Five specific endotypes of CRSwNP, each characterised by distinct biomarker patterns, were identified. They are characterised with: less aggressive clinical presentation and strong presence of IL-12 in the first endotype, aggressive inflammation, increased IL-1α, intermediate IL-12 and increased IL-6 in the second endotype, increased IL-8, IL-10 and antimicrobial peptides LL 37 and HBD-3 in the third endotype, increased IL-8 but reduced presence of antimicrobial peptides and IL-7 in the fourth endotype and increased IL-8, HBD-3, 4 LL 37 as well as intermediate IL-12 presence and the strongest increase of IL-4 among other clusters in the fifth endotype. In Latvia the third endotype with neutrophilic inflammation, increased presence of LL 37 and HBD-3 and IL-12 was the most common