# The Importance of Gram-Negative Rods in Chronic Rhinosinusitis  
[PERSON]  
1 Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; [EMAIL_ADDRESS]  
[PERSON]  
2 Municipal Hospital F. Raszei, Mickiewicza 2, 60-834 Poznan, Poland; [EMAIL_ADDRESS]  
[PERSON]  
1 Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; [EMAIL_ADDRESS]  
[PERSON]  
3 Department of Oduaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Przybyszewskego 49, 60-355 Poznan, Poland; [EMAIL_ADDRESS]  
[PERSON]  
1 Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland; [EMAIL_ADDRESS]  
Footnote 1: [[https://www.dol.org/10/1](https://www.dol.org/10/1)]([https://www.dol.org/10/1](https://www.dol.org/10/1))  
However, these phenotypic classifications fail to fully reflect the diverse spectrum of CRS variants. The EPOS 2020 offers a more detailed classification, dividing CRS into primary and secondary types, with further subcategories based on anatomic distribution, as illustrated in Figure 1[1]. EPOS 2020 classifies primary CRS subtypes based on anatomic distribution, distinguishing between localized (unilateral) and diffuse (bilateral) inflammation and/or polyps. The disease is further categorized by endotype dominance, differentiating between type 2 and non-type 2 inflammatory patterns. However, the non-type 2 classification does not fully capture the heterogeneity of CRS. While CRSwNP was traditionally associated with type 2 inflammation, recent studies suggest that inflammatory profiles may vary based on geographical distribution. Localized CRS is additionally classified by clinical phenotype, including allergic fungal rhinosiusitis (AFRS) and isolated sinusitis. Diffuse CRS, on the other hand, is primarily subdivided into eosinophilic CRS (eCRS) and non-eCRS, with eosinophil defined as an eosinophil count of 10/hpf or higher [1]. CRS is a complex inflammatory disease whose etiology and exact pathophysiological mechanisms are not fully known. In recent years, many studies suggest that CRS is a group of disorders with multifactorial etiology involving sinonasal epithelium and immune components influenced by a host (e.g., allergy, asthma, upper respiratory tract infections, immunodeficiency) and environmental (smoking, air pollution) factors that result in inflammation of the sinonasal mucosa. In addition, the role of the sinonasal microbiome, the occurrence of bacterial biofilms on the surface of mucous membranes, and the role of staphylococcal superantigens in CRS pathogenesis have also been highlighted [8; 9; 10; 11; 12]. Numerous studies in the last decades revealed that the sinuses in the healthy state are not sterile, and the presence of bacteria in paranasal sinuses is well documented [13; 14; 15; 16; 17]. Differences in the microbiome and its impact on the frequency of upper respiratory tract infections have already been observed in children. Colonization in the early months of life has been shown to have a long-term effect on respiratory diseases. The presence of bacteria from the genera _Streptococcus_, _Monxella_, and _Haemophilus_, among others, increases the risk of respiratory diseases, and the dominance of _Streptococcus_ in the microbiota indicates an increased risk of asthma [18; 19]. A \"healthy\" microbiota plays an important role in maintaining microbial balance and modulating the immune response of a healthy host. It also prevents the excessive  
Figure 1: EPOS Division of Primary CRS Subtypes based on Fokkens, 2020 [1]. AFRS-allergic fungal rhinosinusitis; CCAD-central compartment allergic disease; CRSwNP-chronic rhinosinusitis with nasal polyps; eCRS-eosinophilic CRS. multiplication of potentially pathogenic microorganisms.