Materiały źródłowe

• #1 The Etiology and Pathogenesis of Chronic Rhinosinusitis: a Review of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4874491/

  Chronic rhinosinusitis (CRS) is a broad clinical syndrome that is characterized by prolonged mucosal inflammation of the nose and paranasal sinuses, and is typically divided into two subtypes based on the presence or absence of nasal polyps. The etiology and pathogenesis of both forms remain areas of active research. […] Over the last 15 years, a number of hypotheses have been proposed to explain all or part of the clinical CRS spectrum. These hypotheses reflect the concept that CRS results from a dysfunctional interplay between individual host characteristics and factors exogenous to the host. […] Six broad theories on CRS etiology and pathogenesis are discussed as follows: (1) the fungal hypothesis, (2) the superantigen hypothesis, (3) the biofilm hypothesis, and (4) the microbiome hypothesis, all of which emphasize key environmental factors, and (5) the eicosanoid hypothesis and (6) the immune barrier hypothesis, which describe specific host factors.

• #2 Frontiers | Pathogenesis and treatment of chronic rhinosinusitis from the perspective of sinonasal epithelial dysfunction

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1139240/full

  Chronic rhinosinusitis (CRS) is a clinical syndrome primarily characterized by long-term mucosal inflammation of the nasal cavity and sinuses. The pathogenesis of CRS is still unclear due to its high heterogeneity. […] Undoubtedly, epithelial dysfunction plays a vital role in the onset and development of CRS. […] Impaired mucociliary clearance (MCC) and an abnormal sinonasal epithelial barrier are usually considered to be the main causative factors in CRS. Epithelial-derived bioactive substances, such as cytokines, exosomes, and complements, play a vital role in the regulation of innate and adaptive immunity and contribute to the pathophysiological alterations of CRS. […] The presence of a normal epithelium is fundamental for maintaining homeostasis in the nasal and paranasal sinuses.

• #3 Chronic Rhinosinusitis | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/1015/p500.html

  Chronic rhinosinusitis is an inflammatory disease of the paranasal sinuses that occurs in 1% to 5% of the U.S. population. […] There is increasing evidence that chronic rhinosinusitis is an inflammatory disease and not an infectious process. […] Consistent with its underlying inflammatory etiologies, chronic rhinosinusitis is associated with other inflammatory diseases such as allergic rhinitis and asthma. […] Moreover, specific inflammatory and immunodeficiency conditions may rarely cause chronic rhinosinusitis, although symptoms that are not typical of chronic rhinosinusitis may also be present. […] The goals of treatment in patients with chronic rhinosinusitis are to manage symptoms and improve or maintain quality of life. […] Treatment is directed at enhancing mucociliary clearance, improving sinus drainage/outflow, eradicating local infection and inflammation, and improving access for topical medications.

• #4 Advances in Understanding the Pathogenesis of Chronic Rhinosinusitis | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/6123/advances-in-understanding-the-pathogenesis-of-chronic-rhinosinusitis/articles

  Chronic rhinosinusitis (CRS) is a common and morbid condition that affects about 5% of the population in western societies. […] Our understanding of the role of changes in the microbial biota in this condition were until recently based on cultivation studies, and these failed to find a consistent link between bacterial species and chronic rhinosinusitis. A subgroup of CRS patients are colonized by fungi to which they mount a local immune reaction (allergic fungal sinusitis). […] Modern molecular techniques have enabled the whole sinonasal microbiome to be determined, leading to a fundamental change in the way that we now perceive the microbiology of the sinus mucosa. We now understand that bacteria can adopt different phenotypes depending on the physical conditions, and that intramucosal or intracellular growth of bacteria may be part of the reason for their recalcitrance.

• #5 The Etiology and Pathogenesis of Chronic Rhinosinusitis: a Review of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4874491/

  The overwhelming majority of CRS cases are idiopathic however, with classification systems commonly dividing the disorder into two phenotypes based on nasal endoscopy: chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP). […] Research over the last 20 to 30 years has indicated that the etiology and pathogenesis for both forms are far more complex and overlapping. […] The development of a detailed classification system for CRS based on molecular pathways or endotypes is a goal, but this awaits a much more detailed understanding of the inflammatory disease processes and the correlation of proposed endotypes with clinical course and response to therapy. […] At present for CRS, several broad hypotheses have been proposed that emphasize one or more host or environmental factors that have been associated with CRS etiology.

• #6 Immunological Aspects of Chronic Rhinosinusitis

  https://www.mdpi.com/2075-4418/12/10/2361

  Chronic rhinosinusitis (CRS) is related to persistent inflammation with a dysfunctional relationship between environmental agents and the host immune system. […] The major processes involved in the pathogenesis of CRS include airway epithelial dysfunctions that are influenced by external and host-derived factors which activate multiple immunological mechanisms. […] The pathogenesis is mainly influenced by the activation of multiple immunological mechanisms, leading to persistent chronic inflammation (PCI). […] The different types of CRS reflect the variety of immunological response pathways and advancements in the understanding of the immunology and endotyping of CRS that are essential for improving the treatment regimen. […] CRS can be divided into CRS with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) depending on the endoscopically observed presence of nasal polyps in the middle nasal meatus.

• #7 Chronic Rhinosinusitis – Eye & Ear Foundation of Pittsburgh

  https://eyeandear.org/2023/12/chronic-rhinosinusitis/

  The truth is the majority of people in both conditions, whether its chronic rhinitis and sinusitis or allergic rhinitis, get better with just these two straightforward nasal medications, Dr. Wang said. […] One of the biggest concepts that has advanced since the 80s is that CRS is not an infection that does not go away; it really is an inflammatory imbalance more akin to asthma than a chronic infectious problem. This is a bit of a huge paradigm shift in our field, Dr. Wang said. […] What is really occurring is a dysregulation of the balance system of necessary inflammation in the sinuses. When that balance gets thrown off, chronic inflammation occurs. In one of its end stages, the pockets of lining or mucosa pooch out and become polyps.

• #8 Chronic Rhinosinusitis Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4680986/

  There are a variety of medical conditions associated with chronic sinonasal inflammation including chronic rhinosinusitis (CRS) and cystic fibrosis. […] Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier and tissue remodeling all contribute to the chronic inflammatory and tissue deforming processes characteristic of CRS. […] Additionally, the host innate and adaptive immune responses are also significantly activated and may be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review with special focus placed on the roles of epithelial cells and the host immune response in cystic fibrosis, CRSsNP and CRSwNP.

• #9 The Etiology and Pathogenesis of Chronic Rhinosinusitis: a Review of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4874491/

  Overall, this leads to the concept that CRS is most inclusively described as a dysfunctional interaction that occurs at the site of interface between the host and the environment—the sinonasal mucosa. […] Environmental factors implicated in CRS include allergens, toxins, and microbial agents, while host factors center on defects of the immune system. […] Overall, six broad hypotheses on CRS etiology and pathogenesis have thus far been proposed, each describing a central role for one or more aspects of these factors: (1) the fungal hypothesis, (2) the superantigen hypothesis, (3) the biofilm hypothesis, and (4) the microbiome hypothesis, all of which emphasize key environmental factors, and (5) the eicosanoid hypothesis and (6) the immune barrier hypothesis, which focus on host factors.

• #10

  https://link.springer.com/article/10.1007/s11882-006-0026-3

  Chronic rhinosinusitis (CRS) is a heterogenous disorder and represents a major public health problem. […] Although insights into the pathophysiology of CRS have largely expanded over the last two decades, the exact etiology and mechanism of persistence is still unrevealed. CRS is a multifactorial disease, and, with variable evidence, impaired ostial patency, mucociliary impairment, allergy, bacterial or fungal infection (or triggering), immunocompromised state, and environmental and genetic factors have been suggested to be associated or risk factors. Pathomechanisms in CRS are better understood currently, allowing us to characterize and differentiate the heterogeneous pathology of chronic sinonasal inflammation based on histopathology, inflammatory pattern, cytokine profile, and remodeling processes.

• #11 Chronic Sinusitis: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/232791-overview

  Chronic sinusitis is an inflammatory process involving the paranasal sinus and persisting for at least 12 weeks. […] Chronic rhinosinusitis is one of the more common chronic diseases in the United States, and it affects those of all ages. […] CRS may be noninfectious and associated with allergy, cystic fibrosis, gastroesophageal reflux, or exposure to environmental pollutants. Known risk factors include allergic rhinitis, nonallergic rhinitis, anatomic obstruction in the ostiomeatal complex, and immunologic disorders. […] Although most cases of CRS result from unresolved acute sinusitis, the two conditions have different manifestations. […] Stasis of secretions inside the sinuses can be triggered by (1) mechanical obstruction at the ostiomeatal complex due to anatomic factors or (2) mucosal edema caused by various etiologies (eg, acute viral or allergic rhinitis).

• #12 Chronic rhinosinusitis and premorbid autoimmune diseases: a population-based case–control study | Scientific Reports

  https://www.nature.com/articles/s41598-020-75815-x

  Evidence shows that chronic rhinosinusitis (CRS) is associated with prior presence of autoimmune diseases; however, large-scale population-based studies in the literature are limited. […] In conclusion, a significant association between CRS and premorbid autoimmune diseases has been identified. These underlying mechanisms need further investigation. […] The possible mechanism of premorbid autoimmune diseases on the development of CRS is largely unknown. Genetic factors, immunity, and inflammatory processes may play essential roles in the association between premorbid autoimmune diseases and CRS. Alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier, tissue remodeling, and innate and adaptive immune responses have been known to contribute to CRS pathogenesis. […] Underlying autoimmune diseases might influence CRS pathogenesis by altering these signaling pathways, inflammatory cytokines, and remodeling patterns.

• #13 Frontiers | Pathogenesis and treatment of chronic rhinosinusitis from the perspective of sinonasal epithelial dysfunction

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1139240/full

  Here, we describe various aspects of the sinonasal epithelium and highlight the contributions of epithelial dysfunction to CRS pathogenesis. […] As CRS is a highly heterogeneous disease, its pathogenesis has not yet been well-elucidated. A number of factors have been found to be associated with the onset and development of CRS, including geographical and racial factors, environmental exposures, sinus microbiota dysbiosis, mucociliary clearance (MCC) dysfunction, epithelial barrier impairment, and disrupted immune response. […] Essentially, the sinonasal epithelium plays a key role in both innate and adaptive immunity. However, abnormal capability of the epithelium can have a significant impact on the onset and development of CRS. […] Epithelial-to-mesenchymal transition (EMT), mucosal remodeling, and autophagy have been commonly observed in CRS, presenting new insight into sinonasal epithelium malfunction; these phenomena might have some connection with the pathogenesis of this disease.

• #14 Rhinosinusitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Rhinosinusitis_pathophysiology

  The pathophysiology for both acute and chronic rhinosinusitis involves blockage of the nasal sinuses and inflammation of the nasal sinuses. However, biofilms play a role in the pathogenesis of chronic rhinosinusitis. […] There are several proposed mechanisms for the pathophysiology of chronic rhinosinusitis: […] Fungus: Proteins of the fungus trigger T cell response, causing cytokine storm which in turn leads to recruitment of the eosinophils to mucus. Degranulated eosinophils target the fungi causing collateral tissue damage. […] Bacteria, mostly contribute to the pathogenesis of chronic rhinosinusitis without nasal polyps and are composed of three hypotheses: […] Super antigen: Staphylococcus aureus superantigenic exotoxins bind T cells outside their antigen binding site, bypassing the antigen recognition pathway, thus provoking polyclonal T cell response which in turn leads to cytokine storm.

• #15 Biofilm in Chronic Sinusitis with Nasal Polyps: Pilot study | Brazilian Journal of Otorhinolaryngology

  https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-biofilm-in-chronic-sinusitis-with-S1808869415305383

  Chronic rhinosinusitis’ pathogenesis is not completely established and there are some explanations for this disease, such as osteitis, superantigens, fungal-mediated hypersensitivity and, more recently, biofilms. […] Several theories have been raised to explain the pathophysiology of chronic rhinosinusitis. It is currently thought that chronic rhinosinusitis is an immunological inflammatory disease caused simultaneously or singly by several factors, such as: immune conditions, intrinsic upper airway factors, Staphylococcus aureus superantigens, fungal colonization that induces and maintains eosinophilic inflammation, metabolic disorders such as aspirin hypersensitivity, and persistent insult by biofilms and/or osteitis. […] Biofilm consists of gathered microorganism cells anchored irreversibly to a live or inert surface, encased in a self-produced extracellular polymer matrix consisting mostly of polysaccharides, which comprises over 90% of the biofilm mass.

• #16

  https://link.springer.com/article/10.1007/s11882-006-0026-3

  In nasal polyposis (NP), but not CRS without NP, an abundant eosinophilic inflammation and local immunoglobulin E production could be demonstrated, and Staphylococcus-derived superantigens may at least modulate disease severity and expression. These findings question the current assumption that NP is a subgroup of CRS, but suggest that CRS and NP should probably be considered as distinct disease entities.

• #17 Rhinosinusitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Rhinosinusitis_pathophysiology

  Biofilm: Biofilms are composed of bacteria embedded in an extracellular matrix, protecting them from antibiotics. […] Microbiome: It is suggested that external factors could change the normal microbiome of the nasal and sinus mucosa facilitating the growth of pathogens that were normally suppressed by the commensals. […] Host related factors: […] Immune barrier: […] Mechanical barrier: Defect in mucociliary clearance, increased susceptibility to exogenous protease and decreased tight junction proteins of the epithelium causing the formation of a porous barrier contribute to the increased access and transmit time of the foreign materials. […] Innate immune response: Abnormal secretion of the antimicrobials of the mucosa (i.e. defensins, lysozyme, cathelicidins, collectins, lactoferrin, S100s and PLUNC) in response to pathogen recognition receptors (PRR), results in abnormal microbiome, increased exposure to foreign materials and increased compensatory response of the innate and adaptive immune system.

• #18 Biofilm in Chronic Sinusitis with Nasal Polyps: Pilot study | Brazilian Journal of Otorhinolaryngology

  https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition–497-articulo-biofilm-in-chronic-sinusitis-with-S1808869415305383

  Biofilms may explain why antibiotics are unable to eliminate this chronically established bacterial population. […] The importance given to human diseases is recent also in our specialty. […] Recent studies have correlated the presence of biofilms with a worse prognosis in patients with chronic rhinosinusitis. […] Other factors are also relevant in chronic rhinosinusitis with nasal polyps, since polyps were not seen in nearly half of such patients in this study. The bacterial superantigen, osteitis, and fungus-mediated hypersensitivity also contribute significantly to the pathogenesis of chronic rhinosinusitis; these factors were not investigated in this pilot study, although they modify the progression of chronic rhinosinusitis with polyps. […] This study evidences the presence of biofilms in chronic rhinosinusitis patients with nasal polyps, showing their 3-dimensional structure, spherical structures surrounded by an amorphous matrix and its water channels.

• #19 Rhinosinusitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Rhinosinusitis_pathophysiology

  Anatomic variations: Variations that affect the ostio-meatal complex (i.e. anomalies in the middle turbinate, concha, cells of the infraorbital ethmoid and nasoseptal deviation) or the drainage of the frontal sinus contribute to chronic rhinosinusitis with polyps. […] There are limited evidence proposing some other mechanisms involved in the pathogenesis of chronic rhinosinusitis: […] Eicosanoids: Eicosanoids are the product of Arachidonic acid metabolism which function as signaling molecules. Defects in the Eicosanoid pathway causes an increased pro-inflammatory leukotriene and decreased anti-inflammatory prostaglandin resulting in the mucosal inflammation. […] Vitamin D deficiency: Vitamin D has anti-microbial and anti-inflammatory effects. Thus, its deficiency results in increased Th2 and eosinophilic response resulting mostly in chronic rhinosinusitis without polyps.

• #20 The Etiology and Pathogenesis of Chronic Rhinosinusitis: a Review of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4874491/

  The immune barrier hypothesis proposes that defects in the physical barrier and the innate immune response predispose to the development of CRS when challenged by relatively common microbial agents. […] The immune barrier hypothesis proposes that mechanical and innate immune barrier defects are broadly present in CRS, including CRSwNP and CRSsNP, resulting in an abnormal microbiome, increased exposure to foreign material, and excessive compensatory innate cellular and adaptive immune responses. […] The immune barrier hypothesis specifically emphasizes the likely role of genetics and epigenetics in the development of functional deficits at the level of the sinonasal epithelium. […] In summary, while there is strong evidence supporting an important role for both host and environmental factors in CRS pathophysiology, we have a very incomplete understanding of the molecular pathways that lead to the tissue manifestations and clinical symptomatology that define CRS.

• #21 Immunological Aspects of Chronic Rhinosinusitis

  https://www.mdpi.com/2075-4418/12/10/2361

  The sinus mucosa (SM) is an anatomical site that is exposed to EFs and where precisely regulated cooperation between innate and adaptive immunity is crucial for homeostatic balance. […] In CRS, mucosa activity is compromised by PCI, leading to tissue remodeling, which might result from AE cells dysfunction and enhanced barrier permeability. […] The first line of defense in SM constitutes the mechanical barrier of AE and mucociliary clearance. […] The next line of local defense provides the innate and complement immune system (IIS and CIS, respectively). […] Their activities lead to the identification and elimination of external pathogenic agents and also antigen presentation to activate cells of the adaptive immune response (AIR). […] The AIR appears later, but is highly specialized in action and employs multiple subpopulations of T and B cells.

• #22 Recurrent Acute Rhinosinusitis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/35995

  In rhinosinusitis, altered sinus secretions exacerbate the susceptibility to persistent infection and subsequent inflammation. Normally, the mucous blanket in the respiratory tract consists of 2 distinct layers: the periciliary liquid phase, a thin, low-viscosity layer surrounding the cilia shaft allowing free ciliary movement, and the gel phase, a more viscous layer atop the periciliary liquid. In the presence of inflammation, derangements in the mucous layer separation can impair ciliary movement by disrupting the usual low-viscosity environment. […] Additionally, bacterial biofilms contribute to sinusitis pathogenesis, although they are more prevalent in chronic cases rather than in RARS. Biofilms hinder antibiotic penetration because bacteria within this layer are not only attached firmly to one another as well as their substrate but they are also surrounded by a protective proteinaceous or polysaccharide matrix. S aureus, notably, is adept at producing biofilms, which often require chemical and possibly mechanical disruption for definitive infection clearance.

• #23 Frontiers | Pathogenesis and treatment of chronic rhinosinusitis from the perspective of sinonasal epithelial dysfunction

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1139240/full

  When the integrity of the epithelium is destroyed, epithelial permeability can effectively increase. Invading exogenous irritants can thus activate the immune cells and thereby initiate an immune response. […] Mucociliary dysfunction can weaken protection of the nasal mucosa and has been found to be conducive to bacterial colonization, biofilm formation, and mucositis, which is a non-negligible factor in CRS pathogenesis. […] Epithelial disorder is pivotal in the etiology or pathogenesis of CRS; epithelial barrier disruption and MCC dysfunction constitute the fundamental pathogenesis of CRS. […] EMT, mucosal remodeling, and autophagy can affect the sinonasal epithelium and thus can also participate in the genesis of CRS. […] Overall, considering the importance of sinonasal epithelium-mediated immunity disorders for CRS pathogenesis, vigorous efforts should be applied to the development of novel biological agents that can antagonize the actions of inflammatory bioactive components produced by the epithelium, maintain the immune balance of the nasal mucosa, alleviate local inflammation, and reduce nasal polyp formation.

• #24 Chronic Sinusitis: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/232791-overview

  Mucous stagnation in the sinus forms a rich medium for the growth of various pathogens. […] Most cases of chronic sinusitis are due to acute sinusitis that either is untreated or does not respond to treatment. […] Current thinking supports the concept that chronic rhinosinusitis (CRS) is predominantly a multifactorial inflammatory disease. […] All of these factors can play a role in disruption of the intrinsic mucociliary transport system. […] These changes create a favorable environment for bacterial growth that, in turn, further contributes to increased mucosal inflammation.

• #25 Recurrent Acute Rhinosinusitis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/35995

  The pathogenesis of rhinosinusitis likely involves a combination of viscous sinus secretions and dysfunction of the sinus ostia and ciliary apparatus. Viral upper respiratory infections and allergens cause mucosal edema, narrowing the sinus ostia and causing direct mechanical obstruction. Obstruction of the sinus may lead to the accumulation of secretions, providing an environment conducive to bacterial and fungal growth. Outflow blockage may also cause pressure changes within the sinus as oxygen is resorbed by the mucosa, resulting in a partial vacuum. This negative pressure can be painful and result in the transudation of more fluid into the sinus. The excess fluid, combined with inflammation and the influx of neutrophils and lymphocytes, can ultimately create excessive positive pressure, causing discomfort for patients.

• #26

  https://www.abacademies.org/abstract/role-of-anatomical-obstruction-in-the-pathogenesis-of-chronic-sinusitis-3989.html

  Sinusitis is a commonly diagnosed condition in the general population. This article is a study to asses the role of anatomical obstruction in the pathogenesis of chronic sinusitis, based on symptomatology and radiological findings of the patients. The frequency of major anatomical variants like deviated nasal septum, concha bullosa, and paradoxical middle turbinate leading to chronic sinusitis has been analyzed. […] In majority of cases the obstruction at osteomeatal complex is found to be caused by more than one factor.

• #27 Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02309-9

  Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by an alteration in airway epithelial cell functions including barrier function, wound repair mechanisms, mucociliary clearance. […] The mechanisms leading to epithelial cell dysfunction in nasal polyps (NPs) remain poorly understood. […] Our hypothesis was that among the inflammatory cytokines involved in NPs, IL-6 could alter epithelial repair mechanisms and mucociliary clearance. […] The up-regulated epithelial cell proliferation observed in polyps could be induced by IL-6 in the case of prior epithelial damage. IL-6 could be a major cytokine in NP physiopathology. […] In CRSwNP pathogenesis, the initial mechanism in the formation of polyps could be a rupture of both the epithelial continuity and the basement membrane. A defective epithelial barrier has already been found in patients with CRSwNP with decreased tissue resistance and decreased expression of tight junction proteins.

• #28 Frontiers | Pathogenesis and treatment of chronic rhinosinusitis from the perspective of sinonasal epithelial dysfunction

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1139240/full

  The optimal treatment of CRS has undoubtedly been found to be complicated due to its multifactorial pathogenesis. […] However, this option does not provide effective prevention of relapse of the disease. […] In this article, we provide an elegant summary of the contributions of altered epithelial functions to the pathogenesis of CRS and discuss the possible influence of the current treatment regime on the sinonasal epithelium. […] The physical-mechanical barrier consists of tight junctions (TJs), adherens junctions, gap junctions, desmosomes, and hemidesmosomes; these components facilitate strong cell–cell contact, form a tight barrier, establish cell polarity, and can effectively regulate the mobility of different ions and molecules. […] Interestingly, some studies have observed significantly decreased expression of ZO-1, occludin, claudin-1, JAM-1, DSG1, and DSG2 in the primary epithelial cells of CRS patients as compared with those of healthy controls.

• #29 Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02309-9

  However, restoring the integrity of the epithelial barrier after injury is also a key element in the defence capabilities of the respiratory epithelium. Dysfunction of repair of the epithelial barrier has been implicated in the pathogenesis of NPs. […] Our hypothesis was that among the inflammatory cytokines involved in NPs, IL-6 could alter epithelial repair mechanisms. […] Among the cytokines involved in the pathophysiology of CRSwNP such as IL-5, IL-9 and IL-6 or the regulatory cytokine, IL-10 only IL-6 was found to have an effect on wound healing by significantly accelerating the wound closure rate. […] This study also showed quantitative up-regulation of cell proliferation with IL-6 in the case of prior epithelial damage compared with other IL-stimulated conditions. […] While some authors suggest that IL-6 plays an important role in chronic inflammation in CRSwNP, its mechanism of action remains poorly understood.

• #30 Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02309-9

  However, we found that IL-6 could also be involved in other roles such as up-regulation of epithelial cell proliferation and partial ciliary beating control. […] The IL-6 effect observed in our study could be explained by the up-regulation of metalloproteases. […] In conclusion, IL-6 trans-signaling could induce chronic proliferation of epithelial cells after wound healing of the epithelial barrier and growth of NPs. […] Overall, the epithelial barrier dysfunction could be involved in physiopathology of nasal polyps.

• #31 A mini-update on chronic rhinosinusitis

  https://www.explorationpub.com/Journals/eaa/Article/100959

  In another study, CRS pathophysiology was mainly defined based on T cells, where three types of immune responses were proposed in accordance with the immune polarization induced by T cell cytokine production. […] Many studies have suggested endotypic correlations with histopathologic and clinical findings in CRS patients. […] CRS patients are categorized according to distinct endotype subsets, presenting with T1 endotype [interferon- (IFN-) expression], T2 endotype (eosinophil cationic protein and charcot-leyden crystal galectin), and T3 endotype (IL-17A expression), or a mix of two. […] The importance of these 3 types of immune responses lies in the definition of certain endotypes, which may greatly affect the clinical manifestations. […] CRSwNP is considered a diffuse inflammatory process with downregulation of Tregs, while CRSsNP occurs due to up-regulation of Tregs and the resultant sinus outflow tract obstruction, leading to secondary inflammation and infection.

• #32 Sinusitis – Wikipedia

  https://en.wikipedia.org/wiki/Sinusitis

  Chronic rhinosinusitis is a multifactorial process hypothesized to be caused by inflammatory processes driven by dysfunction between local host and environmental interactions. […] It is divided into two phenotypes that depend on the presence or absence of nasal polyps. Chronic rhinosinusitis with nasal polyps and chronic rhinosinusitis without nasal polyps are thought to have two different inflammatory pathways, with the latter form driven by a Th1 response and the former driven by a Th2 response. […] Both pathways result in an increase in inflammatory molecules (cytokines). The Th1 response is characterized by secretion of interferon gamma. The Th2 response is characterized by secretion of interleukin-4 receptor, interleukin 5, and interleukin 13. […] Both forms of chronic rhinosinusitis are considered to be highly heterogenous, each with the ability to demonstrate three inflammatory endotypes, the third being a Th17 response.

• #33 A mini-update on chronic rhinosinusitis

  https://www.explorationpub.com/Journals/eaa/Article/100959

  When it comes to CRSwNP, insufficient or exaggerated immune response to external stimuli may progress to persistent mucosal inflammation with morphological alterations in respiratory epithelium of nasal polyps. […] Other studies demonstrate that about 80% of patients with CRSwNP in the western developed countries predominantly show a T2 response, including expression of IL-4, IL-5, and IL-13 with elevated levels of IgE. […] High-levels of IFN- and IL-17A expressions have been reported in NP of patients with cystic fibrosis, indicating T3 immune response. […] This subset of inflammation is clinically associated with purulent nasal discharge. […] Considering CRS to be an inflammatory sinonasal disease, it is generally classified into eosinophilic inflammation versus non-eosinophilic inflammation with three distinct patterns, namely allergic, eosinophilic, and non-eosinophilic CRS.

• #34 Resources at Biohippo

  https://www.ebiohippo.com/en/research-reveals-a-new-mechanism-for-causing-chronic-sinusitis.html?srsltid=AfmBOopfwPCbHBR6-FW_5l608owbfVVCY3FvyK6GjXOq7j9ELxEBsBw5

  Chronic sinusitis is different from seasonal allergies. It causes inflammation and swelling of the sinuses for months to years, which causes breathing difficulties and other symptoms that can cause pain to the patient. […] A global cell map. Analysis of these data suggests a new mechanism that may explain what maintains chronic sinusitis. […] The findings also explain why some patients with sinusitis produce nasal polyps caused by airway epithelial cells. […] This analysis revealed significant differences in gene expression in basal epithelial cells (a tissue stem cell) from patients with chronic sinusitis with and without nasal polyps. […] Scientists have observed this type of tissue abnormality for decades through histological experiments, but this new study reveals that basal cells from patients with chronic sinusitis that produce nasal polyps have initiated a specific gene expression program, which explains Their slow differentiation trajectories.

• #35 Resources at Biohippo

  https://www.ebiohippo.com/en/research-reveals-a-new-mechanism-for-causing-chronic-sinusitis.html?srsltid=AfmBOopfwPCbHBR6-FW_5l608owbfVVCY3FvyK6GjXOq7j9ELxEBsBw5

  This procedure appears to be directly maintained by IL-4 and IL-13, which are known to be over-produced at the pathological level of immune response cytokines that promote allergic inflammation. […] Given that as a stem cell, basal cells produce other cells found in the airway epithelium, this memory may affect their subsequent gene expression patterns and their ability to produce mature specialized epithelial cells. […] These findings suggest that efforts to block the effects of IL-4 and IL-13 may be a good way to try to treat chronic sinusitis. […] This suggests that blocking IL-4 and IL-13 helps restore basal and secretory cells to a healthier state, but there is still some residual genetic trait. […] These researchers are now planning further detailed analysis of how the basal cells store the molecular mechanisms of inflammatory memory, which may help them discover other drug targets.

• #36 Rhinosinusitis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Rhinosinusitis_pathophysiology

  Osteitis and neo-osteogenesis: Histopathological changes of the bone including inflammation, fibrosis and new bone formation were observed in harvested ethmoid bones of patients with chronic rhinosinusitis. […] Reflux: Laryngopharyngeal reflux exposes the nasal cavity and sinuses to gastric acid and possible H. Pylori infection causing inflammatory response and defective mucociliary clearance. Also, the reflux triggers the esophagus resulting in stimulation of vagus nerve.

• #37 Bacterial flora in chronic sinusitis in children • New Medicine 4/2018 • Czytelnia Medyczna BORGIS

  https://www.czytelniamedyczna.pl/6639,bacterial-flora-in-chronic-sinusitis-in-children.html

  Chronic rhinosinusitis is one of the main causes of morbidity in the paediatric population. The aetiology of chronic sinusitis (CS) is still investigated. Most cases of chronic sinusitis develop from unresolved acute sinusitis. Acute sinusitis is usually associated with one species of bacteria (most often aerobic), whereas chronic sinusitis is dominated by a mixed bacterial flora including 2-3 bacterial strains. The most common pathogens in chronic sinusitis are S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, coagulase-negative staphylococci, as well as Gram-negative bacteria, such as Pseudomonas aeruginosa, Proteus spp., Klebsiella spp., Enterobacter spp., Escherichia coli and anaerobic bacteria. Staphylococci predominated in the study group of patients: 36 strains of S. aureus and 31 strains of S. epidermidis were isolated. Typical respiratory pathogens were practically absent, and constituted only a small percentage of all isolated microorganisms. Chronic sinusitis has a multifactorial aetiology and may be associated with mucociliary dysfunction, immune disorders, allergy, environmental or social factors, gastro-oesophageal disorders, reflux disease, and chronic bacterial infection. Furthermore, chronic sinusitis may be caused by nasal polyps, nasal septum deviation, facial injury, respiratory infections, cystic fibrosis, HIV, and exposure to environmental pollutants. The presence of normal flora may protect against pathogens, while changes in commensal bacterial flora seem to be associated with the pathogenesis of CS. Chronic sinusitis involves formation of biofilm, which plays a crucial role in the pathogenesis and persistence of infection. Biofilms are bacterial aggregates characterised by increased antibiotic resistance. The ability of bacteria to form biofilms also contributes to therapeutic failures in children with CS.

• #38

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/rhino-sinusitis/

  A distinct entity, allergic fungal sinusitis (AFS), occurs in immunocompetent patients and results from an immunologic reaction to fungi that colonize the sinuses. […] Because of the extent of sinus blockage and the strong association with polyps, surgery is usually indicated to remove the inspissated allergic mucin and polyps, followed by systemic corticosteroids to decrease the inflammatory response.

• #39 Fungal sinusitis – Wikipedia

  https://en.wikipedia.org/wiki/Fungal_sinusitis

  The mechanism of fungal sinusitis depends on which form, such as: […] Chronic invasive fungal hyphae invades tissue leaving necrosis with minimal inflammation […] Eosinophil related Allergic fungal sinusitis though not completely understood, a possible mechanism sees the protein component of fungus elicits IgE mediated allergic mucosal inflammation.

• #40 Sinusitis – Wikipedia

  https://en.wikipedia.org/wiki/Sinusitis

  Exposure to fine particulate matter (PM2.5), which consists of particles less than 2.5 micrometers in diameter, has been associated with an increased risk of developing rhinosinusitis. […] The fine particles cause oxidative stress and inflammation, contributing to the pathogenesis of rhinosinusitis. […] Chronic rhinosinusitis represents a multifactorial inflammatory disorder, rather than simply a persistent bacterial infection.

• #41 How PM2.5 Pollution Can Cause Chronic Sinusitis

  https://www.vejthani.com/2024/05/how-pm2-5-pollution-can-cause-chronic-sinusitis/

  Chronic sinusitis is a chronic inflammation of the sinus cavities, resulting in symptoms like stuffy nose, runny nose, facial pain, and a decreased sense of smell. […] Numerous clinical studies have linked PM2.5 exposure to chronic sinusitis. The primary mechanism is the irritation of the nasal mucosa and sinuses by PM2.5 dust particles. This irritation leads to swelling, nasal congestion, and runny nose.

• #42 Sinusitis – Whole Health Library

  https://www.va.gov/WHOLEHEALTHLIBRARY/tools/sinusitis.asp

  Sinusitis can be classified into the following categories: […] Chronic: Symptoms lasting eight weeks or longer and of varying severity. Symptoms are typically similar to acute sinusitis, but often, more fatigue is present. […] While fungal and bacterial infections are likely to play a part, it seems that host response and chronic inflammation also play a significant role in pathophysiology. […] Fine particulate air pollution seems to increase population prevalence of chronic sinusitis. […] Chronic, untreated allergic rhinitis also increases the risk of sinusitis. […] Because inappropriate inflammation has a role in the pathophysiology of sinus disease, paying attention to the impact of nutrition on the inflammatory response is likely to be helpful. […] The balance between omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) in our diets is of particular importance.

• #43

  https://newsroom.uw.edu/news-releases/chronic-sinus-inflammation-appears-alter-brain-activity

  Chronic rhinosinusitis affects about 11% of U.S. adults, according to the Centers for Disease Control and Prevention. […] New research links sinus inflammation with alterations in brain activity, specifically with the neural networks that modulate cognition, introspection and response to external stimuli. […] The magnitude of brain-activity differences seen in the study group paralleled the severity of sinus inflammation among the subjects, Jafari said. […] The subjective feelings of attention decline, difficulties to focus or sleep disturbances that a person with sinus inflammation experiences might be associated with subtle changes in how brain regions controlling these functions communicate with one another, said Simonyan. […] It is plausible, she added, that these changes may cause more clinically meaningful symptoms if chronic sinusitis is left untreated. […] Jafari sees the study findings as a launch pad to explore new therapies for the disease.

• #44 Chronic sinus inflammation appears to alter brain activity | ScienceDaily

  https://www.sciencedaily.com/releases/2021/04/210408153646.htm

  Chronic sinus inflammation appears to alter brain activity. […] New research links sinus inflammation with alterations in brain activity, specifically with the neural networks that modulate cognition, introspection and response to external stimuli. […] „This is the first study that links chronic sinus inflammation with a neurobiological change,” said lead author Dr. Aria Jafari. […] „Now we have a prospective mechanism for what we observe clinically.” […] The magnitude of brain-activity differences seen in the study group paralleled the severity of sinus inflammation among the subjects, Jafari said. […] „The subjective feelings of attention decline, difficulties to focus or sleep disturbances that a person with sinus inflammation experiences might be associated with subtle changes in how brain regions controlling these functions communicate with one another,” said Simonyan. […] „It is also possible that we might have detected the early markers of a cognitive decline where sinus inflammation acts as a predisposing trigger or predictive factor,” Simonyan said.

• #45 Chronic Rhinosinusitis | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/1015/p500.html

  Chronic rhinosinusitis is an inflammatory disease of the paranasal sinuses that occurs in 1% to 5% of the U.S. population. […] There is increasing evidence that chronic rhinosinusitis is an inflammatory disease and not an infectious process. […] Consistent with its underlying inflammatory etiologies, chronic rhinosinusitis is associated with other inflammatory diseases such as allergic rhinitis and asthma. […] Moreover, specific inflammatory and immunodeficiency conditions may rarely cause chronic rhinosinusitis, although symptoms that are not typical of chronic rhinosinusitis may also be present. […] The goals of treatment in patients with chronic rhinosinusitis are to manage symptoms and improve or maintain quality of life. […] Treatment is directed at enhancing mucociliary clearance, improving sinus drainage/outflow, eradicating local infection and inflammation, and improving access for topical medications.

• #46 A mini-update on chronic rhinosinusitis

  https://www.explorationpub.com/Journals/eaa/Article/100959

  Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses and the nasal cavity lasting longer than 12 weeks. […] Pediatric chronic sinusitis is distinct from adult chronic sinusitis and is currently considered an infectious process, characterized by persistent inflammation representing an exaggerated immune response to an external stimulus. […] The recent application of biological, monoclonal therapies which target specific mediators has the potential to change the course of the disease, yet the patients exact CRS endotype must be first determined appropriately so that the biological, monoclonal treatments could be applied accordingly. […] In one study, CRS was described as an interaction at the site of the interface between the host immune system and the environmental factors such as microbial agents, toxins, and allergens.

• #47 A mini-update on chronic rhinosinusitis

  https://www.explorationpub.com/Journals/eaa/Article/100959

  Most of the patients with eosinophilic inflammation are immunocompetent adults from 30 years to 50 years of age with CRSwNP and increased concentrations of T2 cytokines. […] The cornerstone of the treatment of CRS patients, whether with or without NP, is medical management. […] The primary goal of the therapy should be the improvement of the quality of life by individualizing the treatments for each patient. […] The next step in therapy is deciding between consultation with an otolaryngologist for functional endoscopic sinus surgery (FESS) and available biologic therapies. […] Disease-endotyping may help the better understanding of the natural history, pathophysiology, and therefore treatment of CRS.

• #48 Chronic Rhinosinusitis — The Oto Approach

  https://theotoapproach.com/the-oto-approach-episodes/chronic-rhinosinusitis

  CRS is inflammation of the nose and the paranasal sinuses. The pathogenesis of this inflammation is still being studied, but contributing factors appear to be multifactorial. It is hypothesized that impaired mucociliary clearance, sinonasal epithelial barrier abnormalities, tissue remodeling, and host immune responses all play a role. […] It is important to note that CRS is typically not an acute infection that was unsuccessfully treated. […] Biologic therapy and research for use in CRS patients have been a developing field in recent years. It is being increasingly recognized that type 2 immune responses may contribute to the pathophysiology of CRS. These immune responses have shown the ability to respond to biologics in other disease states. […] The unified airway theory or one airway, one disease, suggests that the respiratory tract is not separated into partitions, but is rather one functional unit. As such, it is thought that the pathophysiology behind inflammatory diseases of the respiratory tract, such as asthma and CRS are not individual and separate, but rather are linked through the unified airway.

• #49 Chronic Rhinosinusitis | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/1015/p500.html

  Endoscopic sinus surgery is an effective treatment of chronic rhinosinusitis when appropriate medical therapy is ineffective. […] The goals of endoscopic sinus surgery in the treatment of chronic rhinosinusitis are to provide ventilation and drainage of the paranasal sinuses and to enlarge the paranasal sinuses to create greater access for topical medications.

Zobacz więcej