Pediatric rhinosinusitis are common encountered disorders caused by different pathogenic factors or predisposing conditions with a proportion of them progressing to chronicity with a meaningful impact on quality of life and related adverse effects. A deep understanding of pathophysiology, disease course and prognosis are the fundamental building block to an appropriate management of rhinosinusitis in order to avoid risks related to complications. This review gives concise answers to clinicians who want to know "when do we need imaging?" "what do we aspect from imaging?" and "what are the appropriate imaging modalities in different settings?” in pediatric patients in order to increase the appropriateness of imaging examinations.

Chronic rhinosinusitis (CRS) can have a significant impact on quality of life. With persistent symptoms and the failure of initial medical treatments, surgical management is indicated. Despite the excellent results of endoscopic sinus surgery for persistent CRS, it is quite a challenging procedure for frontal sinusitis given the complex anatomy and location of the frontal sinus. Frontal sinus cells significantly contribute to the complexity of the frontal sinus, and numerous studies have sought to establish their association with sinusitis. This review offers a comprehensive understanding of the frontal sinus cells, their different classifications, their prevalence among different populations, and their relationship to sinusitis. After an extensive review of the current literature, the International Frontal Sinus Anatomy Classification (IFAC) is the most recent classification method and a preferred practical preoperative assessment tool. Although the Agger Nasi Cell is the most prevalent cell among all reported populations, ethnic variations are still influencing the other cells' distribution. Studies are inconsistent in reporting a relationship between frontal sinus cells and sinusitis, and that is mainly because of the difference in the classification method used. More research using a standardized classification method is needed to understand the association between frontal sinus cells and sinusitis.

Chronic rhinosinusitis (CRS) is a significant health problem. It affects 5%–12% of the general population. The causes that underlie the onset of CRS are not yet well known. However, many factors may contribute to its onset, such as environmental factors and the host’s condition. Medical treatment mainly uses local corticosteroids, nasal irrigation, and antibiotics. In recent years, a new therapeutic approach that employs the use of probiotics emerged. Probiotics have been extensively studied as a therapy for dysbiosis and inflammatory pathologies of various parts of the body . We aimed to examine the studies in the existing literature to update probiotics’ role in rhinosinusitis chronic medical treatment.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic necrotizing vasculitis, affecting small-to-medium sized vessels. EGPA’s clinical manifestations are heterogeneous affecting different organs and systems and the upper respiratory tract can be affected with Ear, Nose and Throat (ENT) involvement. The aim of our study was to assess type manifestations at time of diagnosis in a cohort of EGPA patients and correlate findings with baseline variables (sex, age, antineutrophil cytoplasmic antibodies –ANCA- status) and literature reports. Main ENT manifestations in our patients at time of diagnosis were: nasal polyposis (CRSwNP) (52%), turbinate hypertrophy (48%), nasal swelling (40%), rhinorrhoea (40%), chronic rhinosinusitis without nasal polyposis (CRSsNP) (32%), nasal bone deformities (32%), nasal crusts (20%), nasal mucosal ulcers (12%), corditis (12%), hoarseness/dysphonia (12%), hearing loss (12%), mucoceles(4%) eosinophilic rhinitis (4%). No correlations were found between sex, age, ANCA status and ENT clinical manifestations. A polymorphic ENT involvement is often observed at early stages of EGPA. The presence of nasal, sinus, ear and/or laryngeal manifestations in patients with asthma and hypereosinophilia, independently of sex, age or ANCA status, should raise allert for further investigation and differential diagnosis for EGPA. ENT specialists should be aware of their leading position in this diagnostic race.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nasal nitric oxide measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF) based on the latest literature. CONCLUSION: nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis, acute and chronic rhinosinusitis.

ABSTRACT: Objectives: Oncostatin M (OSM), a member of the interleukin (IL)-6 family of cytokines, is known to elicit pathogenic effects involving disruption of the epithelial barrier function as a part of immunological response networks. It is not yet known how these integrated cytokine signals influence inflammation and other physiological processes in the pathology of chronic rhinosinusitis (CRS). We investigated the expression and distribution of OSM and OSM receptor (OSMR) in sinonasal specimens of CRS patients, and we compared the results with a panel of inflammatory cytokine levels and clinical features. Materials and Methods: We classified CRS patients as eosinophilic (ECRS, n=36) or non-eosinophilic (non-ECRS, n=35) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, and we compared their cases with those of 68 non-CRS subjects. We also examined stimulatory effects of OSM on the expression levels of cytokine receptors by using the human bronchial epithelium cell line BEAS-2B. Results: An RT-PCR showed that the OSM mRNA levels were significantly increased in the ethmoid sinus mucosa of the CRS patients. The OSM mRNA levels were positively correlated with those of TNF-α, IL-1β, IL-13, and OSMR-β. In BEAS-2B cells, OSM treatment induced significant increases in the OSMR-β, IL-1R1, and IL-13Ra mRNA levels. Conclusions: Our findings indicate that OSM is involved in the pathogenesis of CRS in both type 1 and type 2 inflammation, suggesting the OSM signaling pathway as a potential therapeutic target for modulating epithelial stromal interactions.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-5 cytokine and infiltration of eosinophils. Humanized monoclonal antibodies targeting IL-5 or its receptor, represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in CRS patients is associated to the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their typical phenotype acquiring a mesenchymal phenotype. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered in EMT during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these altered signaling pathways are able to interfere with EMT; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells which can be easily isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to delineating inflammatory process underlying the development of nasal polyps.

Malassezia are lipid-dependent basidiomycetous yeast of the normal skin microbiome, although Malassezia DNA has been recently detected in other body sites and has been associated with cer-tain chronic human diseases. This new perspective raises many questions. Are these yeasts truly present in the investigated body site or were they contaminated by other body sites, adjacent or not? Does this DNA contamination come from living or dead yeast? If these yeasts are alive, do they belong to the resident mycobiota or are they transient colonizers which are not permanently established within these niches? And, finally, are these yeasts associated with certain chronic diseases or not? In an attempt to shed light on this knowledge gap, we critically re-viewed the 31 published studies focusing on the association of Malassezia spp. with chronic human diseases, including psoriasis, atopic dermatitis (AD), chronic rhinosinusitis (CRS), asthma, cystic fibrosis (CF), HIV infection, inflammatory bowel disease (IBD), colorectal cancer (CRC), and neurodegenerative diseases.

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator, triggering various inflammatory conditions, including eosinophil activation and recruitment. Despite the unclear mechanism underlying the formation and maintenance of nasal polyp in chronic rhinosinusitis with nasal polyps (CRSwNP), there is strongly indication of its association with type 2 inflammation. This study aimed to quantify PAF-associated gene expression, examining enzymes involved in PAF synthesis (lysophosphatidylcholine acyltransferase 1 (LPCAT1), LPCAT2, LPCAT3, and LPCAT4), and PAF degradation (PAF acetylhydrolases 1 B2 (PAFAH1B2), PAFAH1B3, and PAF acetylhydrolases 2 (PAFAH2)), and PAF receptor (PTAFR). Transcriptomic analysis encompassed CRSwNP, including eosinophilic CRS (ECRS) (n=9), nonECRS (n=8), and a subgroup of ECRS with aspirin exacerbated respiratory disease (Asp) (n=3) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria. Gene expression profiles from nasal polyps in CRSwNP patients and the uncinate process in normal subjects (controls) (n=6) were analyzed using bulk RNA barcoding and sequencing (BRB-seq). Hierarchal analysis, utilizing the average linkage method with iDEP1.1, clarified the relationship between Differentially Expressed Genes (DEG) expressions and cluster formation. Two clusters (cluster 1 (n=11) and cluster 2 (n=9)) of CRSwNP divided by hierarchal analysis showed distinct gene expression profiles in the specific pathway of “cytokine-cytokine receptor interaction” in KEGG pathway and upregulated type 2 inflammatory gene expression in cluster 2. In CRSwNP subclassification of ECRS, nonECRS, and Ctrl, PTAFR was only upregulated in ECRS and nonECRS. In cluster analysis, cluster 1 showed significant downregulation of LPCAT2 and upregulation of PTAFR expression, while cluster 2 showed significant upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. These findings suggest that cluster 2, characterized by severe type 2 inflammatory gene expression, manifest a prominent PAF-associated pathophysiology. Understanding this high PAF-associated pathophysiology in cluster 2 could provide valuable insights into the treatment and management of CRSwNP.