Biologics for Chronic Rhinosinusitis—A Modern Option for Therapy

Life, Год журнала: 2023, Номер 13(11), С. 2165 - 2165

Опубликована: Ноя. 5, 2023

Chronic rhinosinusitis (CRS) is an important ENT pathology which affects about 5–12% of the general population. The treatment CRS can be pharmacological (nasal sprays, douches, systemic antibiotics and steroids), surgical (endoscopic sinus surgery) or immunological according to established algorithms. was divided for many years into with nasal polyps (CRSwNP) without (CRSsNP). New ways classifying by endotypes (presence neutrophilia, eosinophilia, fibrosis, glandular hypertrophy epithelial dysmorphisms) appeared after most recent understandings pathophysiology disease. Other classifications divide primary secondary forms, localized/diffuse types anatomical presentation. A new type has been administered in last years, biologics. For moment, biologics are indicated just cases patients who have undergone ESS contraindications surgery bilateral meet a minimum three following criteria: necessity therapies oral parenteral corticosteroids steroids, significant loss smell impaired QoL score, comorbid asthma 2 inflammation. This article aims present relevant studies used (anti-IgE, anti-IL5 anti-IL4/IL3) wishes increase awareness this that some cases.

Язык: Английский

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The Impact of Tonsillectomy on Chronic Rhinosinusitis in Adults: A Retrospective Cohort Study

Опубликована: Янв. 1, 2025

Язык: Английский

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The correlation between periostin and eosinophillic cationic protein demonstrate its potential biomarker of mucosal remodeling in chronic rhinosinusitis with nasal polyps

Acta Oto-Laryngologica, Год журнала: 2025, Номер unknown, С. 1 - 7

Опубликована: Апрель 21, 2025

Chronic rhinosinusitis (CRS) is classified into CRS with nasal polyps (CRSwNP), a type 2 inflammation elevated CLC and ECP levels, without (CRSsNP), non-type inflammation. Periostin plays crucial role in mucosal remodeling, but its involvement CRSwNP remains unclear. To investigate correlation between endotype periostin levels. This cross-sectional study measured biomarkers (ECP, CLC, IFN-γ, IL-17A) levels uncinate process using ELISA to assess their correlation. 99.6% of 36.67% polyp tissue samples displayed mixed pattern, while were untype-able. significantly higher compared (p = .0116) control. Only the showed significant (r 0.326, p .038). polyps, highlighting CRSwNP. Its suggests inflammation, warranting further research as therapeutic target. confirms periostin's CRSwNP, it potentially occurs or depending on pathways.

Язык: Английский

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Impaired Coordination of the Ciliary Movement in Patients with Chronic Rhinosinusitis with Nasal Polyps: The Role of Decreased Planar Cell Polarity Protein Expression

Опубликована: Июль 24, 2024

The planar cell polarity (PCP) of epithelial ciliated cells is essential for effective mucociliary clearance (MCC) in the sinonasal mucosa. We hypothesize that MCC coordination impaired nasal polyp (NP) mucosae due to suppressed expression a series CPLANE (ciliogenesis and effector) complex proteins chronic rhinosinusitis (CRS) patients. To inves-tigate this hypothesis, we subjected mucosal samples live video recording measure transport velocity (MCTV) scanning electron microscopy evaluate surface morphology. distribution panel PCP proteins, e.g. WDPCP FUZ, were investigated relation inflammatory cytokine levels clinical features. mean MCTV NP was significantly lower than inferior turbinate mucosae. CRS group with NPs (CRSwNP group) (n=28) showed increased IL-13 CCL26 mRNA compared patients without (n=25) controls (n=30). FUZ decreased ethmoid sinus CRSwNP protein reduced cytoplasmic region conclude suppression responsible polyps type-2 inflammation. This mechanism might explain potential worsening symptoms CRSwNP.

Язык: Английский

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The Impact of NO₂ on Epithelial Barrier Integrity of a Primary Cell‐Based Air–Liquid Interface Model of the Nasal Respiratory Epithelium

Journal of Applied Toxicology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

ABSTRACT Nitrogen dioxide (NO 2 ) is a pervasive gaseous air pollutant with well‐documented hazardous effects on health, necessitating precise toxicological characterization. While prior research has primarily focused lower airway structures, the upper airways, serving as first line of defense against airborne substances, remain understudied. This study aimed to investigate functional NO exposure alone or in combination hypoxia secondary stimulus nasal epithelium and elucidate its molecular mechanisms because considered pathophysiological factor onset persistence chronic rhinosinusitis, disease airways. Air–liquid interface cell cultures derived from primary mucosa cells were utilized an vitro model, offering high vitro–in vivo correlation. Our findings demonstrate that induces malfunction epithelial barrier, evidenced by decreased transepithelial electrical resistance increased fluorescein isothiocyanate (FITC)‐dextran permeability. mRNA expression analysis revealed significant increase IL‐6 IL‐8 expressions following . Reduced tight junction component occludin was identified structural correlate damaged barrier. Notably, hypoxic conditions did not alter barrier integrity. These provide information harmful human epithelium, including compromised integrity induction inflammatory responses. Overall, this contributes our understanding underlying also respiratory diseases associated pollution emphasizes importance mitigating emissions safeguard health.

Язык: Английский

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Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Май 24, 2024

Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics localized diseases with non-invasive treatment modalities may capitalize on benefits plant proteins while avoiding inherent Dupilumab, which effective against variety autoimmune but has systemic responses injection-related side effects, be more beneficial if delivered locally using small biological form. In this study, we engineered single-chain variable fragment (scFv) dupilumab, termed Dup-scFv produced Nicotiana benthamiana, evaluated its tissue permeability anti-inflammatory efficacy in air-liquid interface cultured human nasal epithelial cells. Despite showing 3.67- 17-fold lower binding affinity IL-4Ra surface plasmon resonance assays cell assays, respectively, retained most was originally high, dissociation constant (KD) 4.76 pM. cells at interface, administered air inhibited inflammatory marker CCL26 hard-to-reach basal effectively than dupilumab. addition, had an overall 0.8% across layers compared undetectable levels These findings suggest that plant-produced can non-invasively alleviate signaling, providing practical approach utilize topical therapeutic applications.

Язык: Английский

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Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 24, 2024

Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics localized diseases with non-invasive treatment modalities may capitalize on benefits plant proteins while avoiding inherent Dupilumab, which effective against variety autoimmune but has systemic responses injection-related side effects, be more beneficial if delivered locally using small biological form. In this study, we engineered single-chain variable fragment (scFv) dupilumab, termed Dup-scFv produced Nicotiana benthamiana, evaluated its tissue permeability anti-inflammatory efficacy in air-liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- 17-fold lower binding affinity IL-4Ra surface plasmon resonance assays cell assays, respectively, retained most was originally high, dissociation constant (KD) 4.76 pM. HNECs at interface, administered air inhibited inflammatory marker CCL26 hard-to-reach basal effectively than dupilumab. addition, had an overall 0.8% across layers compared undetectable levels These findings suggest that plant-produced can non-invasively HNESc alleviate signaling, providing practical approach utilize topical therapeutic applications.

Язык: Английский

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Impaired Coordination of the Ciliary Movement in Patients with Chronic Rhinosinusitis with Nasal Polyps: The Role of Decreased Planar Cell Polarity Protein Expression

Immuno, Год журнала: 2024, Номер 4(3), С. 247 - 265

Опубликована: Авг. 21, 2024

The planar cell polarity (PCP) of epithelial ciliated cells is essential for effective mucociliary clearance (MCC) in the sinonasal mucosa. We hypothesize that MCC coordination impaired nasal polyp (NP) mucosae due to suppressed expression a series CPLANE (ciliogenesis and effector) complex proteins chronic rhinosinusitis (CRS) patients. To investigate this hypothesis, we subjected mucosal samples live video recording measure transport velocity (MCTV) scanning electron microscopy evaluate surface morphology. distribution panel PCP proteins, e.g., WDPCP FUZ, were investigated relation inflammatory cytokine levels clinical features. mean MCTV NP was significantly lower than inferior turbinate mucosae. CRS group with NPs (CRSwNP group) (n = 28) showed increased IL-13 CCL26 mRNA compared patients without 25) controls 30). FUZ decreased ethmoid sinus CRSwNP protein reduced cytoplasmic region conclude suppression responsible polyps type-2 inflammation. This mechanism might explain potential worsening symptoms CRSwNP.

Язык: Английский

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Synergistic Cytotoxicity of Permethrin and N,N-Diethyl-Meta-Toluamide on Sinonasal Epithelial Cells

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

ABSTRACT Background N,N-Diethyl-Meta-Toluamide (DEET) and permethrin are pesticides commonly used in combination due to their synergistic insecticidal repellent properties. This study investigates whether simultaneous exposure these compounds elicits cytotoxicity sinonasal epithelial cells (SNECs). Material Methods Ethmoid sinus mucosal specimens were procured from eight patients during endoscopic surgery. SNECs expanded on culture plates exposed various concentrations of DEET (0-5μm), individually concurrently, for up 156 hours. Experiments replicated triplicates cell viability was recorded every 2 hours using IncuCyte real-time imaging system. Synergy score calculated the basis Loewe additivity synergy finder model. Results exhibited across all tissues, albeit with variations onset magnitude. Peak observed at 144h tissue 1 ( S 4.2, 95% CI 1.8-7.3; [permethrin concentration, concentration] [2.5μ M , 1.25μ ]), 48h (19.9, 16.5-23.6; [1.25, 0.625]), 3 (15.2, 3.9-30.4; [0.625, 1.25]), 4 (6.4, −3.6 18.0; 5 (10.1, 8.9-12.5; 96h 6 (24.7, 12.2-36.3; 7 (47.7, 29.6-62.2; 8 (47.4, 26.8-67.0; 0.625]). Conclusion The concurrent can lead epithelia. Further research is warranted preclinical animal models explore this accelerates pathogenesis chronic rhinosinusitis.

Язык: Английский

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Quercetin Alleviates the Progression of Chronic Rhinosinusitis Without Nasal Polyps by Inhibiting Nasal Mucosal Inflammation and Epithelial Apoptosis

Molecular Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 6, 2024

Язык: Английский

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