RESUMEN
OBJECTIVE: This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis. METHOD: Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not. RESULTS: Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01). CONCLUSION: These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.
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Endoscopía/métodos , Senos Paranasales/cirugía , Rinitis/cirugía , Sinusitis/cirugía , Esteroides/administración & dosificación , Implantes Absorbibles/efectos adversos , Administración Tópica , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad Crónica , Eosinofilia/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Olfato/epidemiología , Senos Paranasales/efectos de los fármacos , Periodo Posoperatorio , Recurrencia , Estudios Retrospectivos , Rinitis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Sinusitis/tratamiento farmacológico , Esteroides/uso terapéutico , Tomografía Computarizada por Rayos X/estadística & datos numéricosRESUMEN
PURPOSE: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. METHODS: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-ß and IL-1. RESULTS: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-ß significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. CONCLUSION: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.
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Antagonistas de Dopamina/administración & dosificación , Emulsiones , Antagonistas de los Receptores Histamínicos H1 no Sedantes/administración & dosificación , Loratadina/administración & dosificación , Mucosa Nasal/efectos de los fármacos , Rinitis Alérgica/metabolismo , Sulpirida/administración & dosificación , Tensoactivos , Administración Intranasal , Animales , Rastreo Diferencial de Calorimetría , Modelos Animales de Enfermedad , Antagonistas de Dopamina/farmacología , Combinación de Medicamentos , Liberación de Fármacos , Glicerol , Antagonistas de los Receptores Histamínicos H1 no Sedantes/farmacología , Técnicas In Vitro , Interleucina-1/metabolismo , Lecitinas , Loratadina/farmacología , Nanoestructuras , Mucosa Nasal/metabolismo , Aceite de Oliva , Ovalbúmina , Senos Paranasales/efectos de los fármacos , Senos Paranasales/metabolismo , Polisorbatos , Conejos , Rinitis Alérgica/inducido químicamente , Colato de Sodio , Glycine max , Espectroscopía Infrarroja por Transformada de Fourier , Sulpirida/farmacología , Factor de Crecimiento Transformador beta/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.
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Administración por Inhalación , Administración Intranasal/métodos , Betacoronavirus , Infecciones por Coronavirus/prevención & control , Sistemas de Liberación de Medicamentos/métodos , Rociadores Nasales , Pandemias/prevención & control , Neumonía Viral/prevención & control , COVID-19 , Simulación por Computador , Infecciones por Coronavirus/virología , Humanos , Hidrodinámica , Cavidad Nasal/anatomía & histología , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/virología , Nebulizadores y Vaporizadores , Senos Paranasales/efectos de los fármacos , Senos Paranasales/virología , Neumonía Viral/virología , SARS-CoV-2 , Vacunas Virales/administración & dosificaciónRESUMEN
BACKGROUND: Eosinophilic chronic rhinosinusitis (eCRS) is an inflammatory endotype of CRS. Contemporary treatment includes creation of a "neo-sinus" cavity and postoperative corticosteroid irrigations. Not all patients gain control with local therapy. This study aims to determine, in patients with polyp recurrence, the most common sinuses involved. METHODS: A prospective case-series was conducted on consecutive adult (≥18 years) post-FESS eCRS patients followed for a minimum of 12 months. All patients had a neo-sinus cavity created surgically and used corticosteroid irrigations daily for 3-6 months, then tapered to disease control. Sinus cavities were assessed by endoscopy on last follow-up. Polyp recurrence was defined as a score of 5 or 6 in the MLMES in ≥3 sinus cavities. Patient-reported outcomes based on SNOT22 and NSS, frequency of corticosteroid irrigations, and courses of systemic antibiotics and corticosteroid were collected. The pattern of sinus involvement was analyzed. RESULT: A total of 342 sinus cavities were assessed (mean ± standard deviation, 54.9 ± 13.4 years, 43.2% female). Polyp recurrence occurred in 4.3% (6.4% of patients, n = 7 unilateral) of sinus cavities. Frontal and ethmoid sinus cavities were most affected in those with polyp recurrence, compared to the maxilla and sphenoid (100% vs 100% vs 53% vs 53%, p < 0.01). Although those patients with polyp recurrence utilized more systemic corticosteroids courses per year (0.4 ± 0.4 vs 0.1 ± 0.3, p < 0.01), the use of corticosteroid irrigations was similar (% >4/week; 66.7% vs 48.9%, p = 0.13). Prior surgery was more common in patients with polyp recurrence (86.7% vs 53.5%, p = 0.01). CONCLUSION: The frontal and ethmoid sinuses were most affected in those patients with polyp recurrence. Whether the disease is more active in this location or topical therapy has limited access requires further evaluation.
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Eosinofilia/patología , Pólipos Nasales/patología , Rinitis/patología , Sinusitis/patología , Adulto , Anciano , Enfermedad Crónica , Eosinofilia/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/terapia , Senos Paranasales/efectos de los fármacos , Senos Paranasales/patología , Senos Paranasales/cirugía , Estudios Prospectivos , Recurrencia , Rinitis/terapia , Sinusitis/terapiaAsunto(s)
Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Pólipos Nasales/tratamiento farmacológico , Senos Paranasales/efectos de los fármacos , Eosinofilia Pulmonar/tratamiento farmacológico , Método Doble Ciego , Humanos , FenotipoRESUMEN
BACKGROUND: Based on endoscopic examination, chronic rhinosinusitis (CRS) is divided into chronic inflammation with (CRSwNP) or without nasal polyps (CRSsNP). On the basis of the pathomechanism of inflammation, CRS is divided into endotypes. Eosinophilic CRSwNP with coexisting bronchial asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is a real therapeutic challenge. AIM: Comparative analysis of the results of treatment of patients with CRSwNP, bronchial asthma, or hypersensitivity to NSAIDs (NSAID-exacerbated respiratory disease, NERD), using antileukotrienes (leukotriene receptor antagonists, LTRAs) or intranasal glucocorticoids or both drugs together after endoscopic sinus surgery (ESS). MATERIAL AND METHODS: 33 patients (11 male, 33%) with NERD divided into three groups treated with LTRAs or intranasal glucocorticoids or both drugs together were assessed in terms of general well-being, state of pathological changes, and olfactory disorders using the following tools: Sino-Nasal Outcome Test, Visual Analogue Scale, Brief Identification Smell Test, and Lund-Kennedy score before and at 12 months after surgery. CT assessments were made prior to surgery using the Lund-MacKay scale. RESULTS: Comparable efficacy of treatment with nasal steroids and antileukotrienes was found after 12 months of observation of patients. CONCLUSIONS: The results suggest comparable efficacy of treatment with nasal steroids and antileukotrienes in patients with NERD after ESS. Treatment with montelukast and mometasone has not been shown to be superior to both drugs administered separately.
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Asma Inducida por Aspirina/tratamiento farmacológico , Antagonistas de Leucotrieno/uso terapéutico , Pólipos Nasales/tratamiento farmacológico , Senos Paranasales/efectos de los fármacos , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Adulto , Anciano , Asma Inducida por Aspirina/complicaciones , Asma Inducida por Aspirina/cirugía , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/cirugía , Senos Paranasales/cirugía , Periodo Posoperatorio , Rinitis/cirugía , Sinusitis/cirugía , Esteroides/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Topical antibiotic therapies have been investigated for their use in chronic rhinosinusitis (CRS). However, society guidelines and evidence-based medicine reviews have recommended against the use of topical antibiotic therapy based on randomized controlled trials (RCTs). The purpose of this article is to review recent clinical research published since the aforementioned guidelines were published. METHODS: A structured literature review was performed on clinical studies published in the last 5 years investigating the use of topical antibiotic therapies. RESULTS: One double-blinded, randomized controlled trial (DB-RCT) supported the use of tobramycin using a vibrating aerosolizer; 1 non-blinded non-randomized controlled prospective trial lent support to use of topical ofloxacin for its anti-biofilm properties; and 1 meta-analysis found mupirocin irrigations to be beneficial in the short term. One Cochrane Review was unable to make a recommendation as no trial met the inclusion criteria. An additional systematic review found limited evidence to support the use of topical antibiotics with the exception of mupirocin irrigations that may be considered in Staphylococcus aureus infections. Two retrospective studies found that topical antibiotics change bacterial cultures of the sinuses. CONCLUSION: There is additional evidence to support continuing investigation of topical antibiotic therapies. Further, larger RCTs are required to establish the efficacy of topical antibiotic therapies.
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Antibacterianos/uso terapéutico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Administración Intranasal , Antibacterianos/administración & dosificación , Enfermedad Crónica , Humanos , Senos Paranasales/efectos de los fármacos , Guías de Práctica Clínica como Asunto , Infecciones Estafilocócicas/tratamiento farmacológico , Resultado del TratamientoAsunto(s)
Procedimientos Quirúrgicos Ambulatorios , Antiinflamatorios/administración & dosificación , Furoato de Mometasona/administración & dosificación , Pólipos Nasales/terapia , Senos Paranasales/cirugía , Implantación de Prótesis , Implantes Absorbibles , Adulto , Antiinflamatorios/efectos adversos , Enfermedad Crónica , Stents Liberadores de Fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Furoato de Mometasona/efectos adversos , Rociadores Nasales , Senos Paranasales/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Rinitis/terapia , Sinusitis/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: A corticosteroid-eluting sinus implant was recently approved by the FDA as a drug to treat adult patients with nasal polyps who have undergone previous endoscopic sinus surgery (ESS) of the ethmoid sinuses. ESS is performed in an operating room under general anesthesia, whereby diseased tissue and bone are removed to provide improved drainage. ESS typically involves dissection of 1 or more of the 4 paired sinus cavities (maxillary, ethmoid, sphenoid, or frontal). The implant, containing 1,350 mcg of mometasone furoate, is inserted by a physician in an office setting and offers controlled localized release of corticosteroid to the polypoid sinus tissue. The implant has demonstrated significant improvements in clinical testing; however, little research has been conducted on its economic impact. OBJECTIVE: To evaluate and quantify the budget impact to a commercial payer of using this implant instead of ESS in patients with nasal polyps after a previous ESS. Since essentially all patients with recurrent nasal polyps after ESS are patients with chronic sinusitis (CS) diagnosis, this study also identified patients with CS with nasal polyposis (CSwNP) for consistency with the patient population studied in clinical trials evaluating the implant. METHODS: A budget impact analysis was conducted from a U.S. commercial payer perspective over a 1-year time horizon with patients who received the implant or revision ESS. Primary outcomes of interest were annual total and per-member per-month (PMPM) direct health care costs. Costs were estimated using a decision analysis model, assuming 50% implant utilization as an alternative to revision ESS in eligible patients, with other levels (25%, 75%) also considered. The model utilized the results of a recently published analysis of 86,052 patients in the Blue Health Intelligence database, results from published clinical trials evaluating the implant, a literature review, and published Medicare national payment amounts. RESULTS: A commercial health plan with 1 million members could anticipate 1,000 CSwNP patients as candidates for receiving the implant or revision ESS. Estimated direct treatment costs for refractory CSwNP using only revision ESS are $11.03 million ($0.92 PMPM). If the implant replaced surgery in 50% of cases and if 63% those patients received a second treatment with the implant during the year, the estimated total cost savings would be $2.56 million ($0.21 PMPM). Cost savings associated with using the implant changed to $0.11 PMPM and $0.32 PMPM with implant adoption of 25% and 75%, respectively. CONCLUSIONS: In a large commercially insured U.S. population, annual revision ESS costs are substantial. Using the implant instead of revision ESS could result in considerable cost savings for payers at various levels of adoption. DISCLOSURES: This study was sponsored by Intersect ENT, which was involved in study design and manuscript review. Ernst and Imhoff are employed by CTI Clinical Trial and Consulting Services, which contracted with Intersect ENT to conduct this study. Ernst and Imhoff also report other financial support from Intersect ENT during the conduct of the study. DeConde reports personal fees from Intersect ENT during the conduct of the study, as well as personal fees from Optinose, Stryker Endoscopy, and Olympus, outside the submitted work. Manes reports grants from Intersect ENT during the conduct of the study, as well as grants from Optinose and Sanofi outside the submitted work.
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Enfermedad Crónica/economía , Pólipos Nasales/economía , Prótesis e Implantes/economía , Sinusitis/economía , Esteroides/economía , Adolescente , Presupuestos , Enfermedad Crónica/tratamiento farmacológico , Endoscopía/métodos , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Medicare/economía , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/cirugía , Senos Paranasales/efectos de los fármacos , Senos Paranasales/cirugía , Sinusitis/tratamiento farmacológico , Sinusitis/cirugía , Esteroides/uso terapéutico , Resultado del Tratamiento , Estados UnidosRESUMEN
PURPOSE: Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS. METHODS: Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund-Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale. RESULTS: Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different. CONCLUSIONS: Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.
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Budesonida/administración & dosificación , Endoscopía , Lavado Nasal (Proceso)/métodos , Obstrucción Nasal , Senos Paranasales , Rinitis , Sinusitis , Adulto , Antiinflamatorios/administración & dosificación , Enfermedad Crónica , Endoscopía/efectos adversos , Endoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obstrucción Nasal/diagnóstico , Obstrucción Nasal/etiología , Obstrucción Nasal/prevención & control , Senos Paranasales/diagnóstico por imagen , Senos Paranasales/efectos de los fármacos , Senos Paranasales/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control , Pronóstico , Rinitis/diagnóstico , Rinitis/cirugía , Sinusitis/diagnóstico , Sinusitis/cirugía , Resultado del TratamientoRESUMEN
Introduction: Chronic rhinosinusitis (CRS) is a broad heterogeneous inflammatory disorder of the nose and paranasal sinuses, resulting from the dysfunctional interplay between host immunity, defective epithelial barrier, and environmental factors. CRS with nasal polyps (CRSwNP) is considered a more severe clinical phenotype with greater burden of symptoms and higher relapse rate, especially with comorbid asthma or aspirin sensitivity. Available treatment options after endoscopic sinus surgery (ESS) - systemic corticosteroids or revision surgery - have significant risks and limitations. Areas covered: Bioabsorbable, steroid-eluting implants have been studied extensively for the ability to dilate and re-establish sinus patency by the localized, controlled delivery of topical corticosteroids to diseased sinonasal lining and nasal polyps. This review provides a comprehensive, up to date analysis of the literature regarding a novel, office-based, mometasone furoate (MF) sinus implant that may treat patients with recurrent CRSwNP after ESS. Expert commentary: Clinical evidence has demonstrated the safety and efficacy of steroid-eluting implant in the reduction of polyp size, symptom burden, and the need for revision sinus surgery. MF sinus implants may play an important role in the management of patients with recurrent polyposis after sinus surgery.
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Furoato de Mometasona/administración & dosificación , Pólipos Nasales/tratamiento farmacológico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Enfermedad Crónica , Implantes de Medicamentos , Endoscopía/métodos , Humanos , Furoato de Mometasona/farmacología , Pólipos Nasales/cirugía , Senos Paranasales/efectos de los fármacos , Senos Paranasales/patología , Recurrencia , Rinitis/patología , Sinusitis/patologíaRESUMEN
BACKGROUND: Postoperative care is an important factor affecting the outcome of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). The aim of this study was to test the effect of mometasone furoate (MF)-soaked biodegradable nasal dressings (BNDs) on endoscopic appearance in CRS patients with nasal polyps (CRSwNP) after ESS. METHODS: This study was a prospective, randomized, double-blinded, placebo-controlled study. A total of 64 CRSwNP patients with bilateral ESS were enrolled and randomly given 4 mL or 8 mL of MF-soaked BNDs (NasoPore) in 1 nasal cavity and the same amount of normal saline-soaked BNDs in the contralateral side. The BNDs were removed on the 7th or 14th postoperative day. Perioperative sinus endoscopy (POSE) and Lund-Kennedy scores were collected, on the 7th or 14th postoperative days and at 1, 2, and 3 postoperative months. RESULTS: The POSE and Lund-Kennedy scores showed that in the 4-mL, 1-week group, no significant differences between the sides treated with MF-soaked BNDs and the normal saline-soaked control were observed at any postoperative visits. In the 4-mL, 2-week group, significant differences were found at the 2-week and 1-month postoperative visits but not at the 2-month and 3-month visits. In the 8-mL, 1-week group, significant differences were found at the 1-week, 1-month, and 2-month postoperative visits but not at the 3-month visit. In the 8-mL, 2-week group, significant differences were found at all postoperative visits. CONCLUSION: This study reveals that MF-impregnated BNDs improve the endoscopic appearance in the healing process of CRSwNP after ESS.
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Antiinflamatorios/administración & dosificación , Vendajes , Furoato de Mometasona/administración & dosificación , Pólipos Nasales/tratamiento farmacológico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Administración Intranasal , Adulto , Anciano , Enfermedad Crónica , Método Doble Ciego , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/cirugía , Procedimientos Quírurgicos Nasales , Senos Paranasales/efectos de los fármacos , Senos Paranasales/cirugía , Rinitis/cirugía , Sinusitis/cirugía , Cicatrización de Heridas/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu. Current animal models fail to recapitulate many of the innate and adaptive immunologic hallmarks of the disease, thus hindering the development of effective therapeutics. In the present study, mice were exposed intranasally to the cysteine protease papain, which shares functional similarities with parasitic proteases and aeroallergens, to generate a rapidly inducible murine model of eosinophilic rhinosinusitis. METHODS: C57BL/6 mice were intranasally instilled with 20 µg papain or heat-inactivated papain (HP) on days 0-2 and days 7-10, and then euthanized on day 11. Nasal lavage fluid (NALF) was analyzed to quantify eosinophils and inflammatory cytokine secretion. Sinonasal tissue was sectioned and stained for goblet cells or homogenized to analyze cytokine levels. Serum samples were assayed for immunoglobulin E (IgE) by enzyme-linked immunoassay. Sinonasal mucosal tissue was dissociated and analyzed by flow cytometry. RESULTS: Compared with HP treatment, papain induced significant eosinophilia in NALF, goblet cell hyperplasia, innate and adaptive immune cell infiltration, type 2 cytokine production, and IgE responses. Flow cytometric analysis of sinonasal tissues revealed significant inflammatory cell infiltration and interleukin-13-producing cell populations. CONCLUSION: In this study, we demonstrated that the cysteine protease papain induces allergic sinonasal eosinophilic rhinosinusitis and resembles T-helper 2 cell inflammation and innate immune characteristics of ECRS. This model permits further study into the molecular mechanisms underlying ECRS pathology and provides a model system for the evaluation of potential pharmacologic interventions.
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Modelos Animales de Enfermedad , Eosinófilos/efectos de los fármacos , Papaína/toxicidad , Rinitis/inducido químicamente , Sinusitis/inducido químicamente , Animales , Enfermedad Crónica , Citocinas/metabolismo , Eosinófilos/metabolismo , Femenino , Células Caliciformes/patología , Masculino , Ratones Endogámicos C57BL , Líquido del Lavado Nasal/citología , Líquido del Lavado Nasal/inmunología , Senos Paranasales/efectos de los fármacos , Senos Paranasales/patología , Rinitis/sangre , Rinitis/inmunología , Rinitis/patología , Sinusitis/sangre , Sinusitis/inmunología , Sinusitis/patologíaRESUMEN
BACKGROUND: Topical intranasal corticosteroid sprays (INCSs) are standard treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient compliance and impaired access of drug to the sinus mucosa. A corticosteroid-eluting sinus implant was designed to address these limitations in patients with recurrent polyposis after sinus surgery by delivering 1350 µg of mometasone furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days. METHODS: A randomized, sham-controlled, double-blind trial was undertaken in 300 adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were candidates for repeat surgery. Eligible patients were randomized (2:1) and underwent in-office bilateral placement of 2 implants or a sham procedure. All patients used the MF INCS 200 µg once daily. Co-primary efficacy endpoints were the change from baseline in nasal obstruction/congestion score and bilateral polyp grade, as determined by an independent panel based on centralized, blinded videoendoscopy review. RESULTS: Patients treated with implants experienced significant reductions in both nasal obstruction/congestion score (p = 0.0074) and bilateral polyp grade (p = 0.0073) compared to controls. At day 90, implants were also associated with significant reductions in 4 of 5 prespecified secondary endpoints compared to control: proportion of patients still indicated for repeat sinus surgery (p = 0.0004), percent ethmoid sinus obstruction (p = 0.0007), nasal obstruction/congestion (p = 0.0248), and decreased sense of smell (p = 0.0470), but not facial pain/pressure (p = 0.9130). One patient experienced an implant-related serious adverse event (epistaxis). CONCLUSION: Significant improvements over a range of subjective and objective endpoints, including a reduction in the need for sinus surgery by 61%, suggest that MF sinus implants may play an important role in management of recurrent NP.
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Implantes de Medicamentos/uso terapéutico , Furoato de Mometasona/uso terapéutico , Mucosa Nasal/efectos de los fármacos , Pólipos Nasales/terapia , Senos Paranasales/cirugía , Sinusitis/terapia , Adulto , Enfermedad Crónica , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/fisiología , Mucosa Nasal/efectos de la radiación , Senos Paranasales/efectos de los fármacos , Senos Paranasales/patología , Placebos , RecurrenciaRESUMEN
In the upper respiratory epithelium, bitter and sweet taste receptors present in solitary chemosensory cells influence antimicrobial innate immune defense responses. Whereas activation of bitter taste receptors (T2Rs) stimulates surrounding epithelial cells to release antimicrobial peptides, activation of the sweet taste receptor (T1R) in the same cells inhibits this response. This mechanism is thought to control the magnitude of antimicrobial peptide release based on the sugar content of airway surface liquid. We hypothesized that d-amino acids, which are produced by various bacteria and activate T1R in taste receptor cells in the mouth, may also activate T1R in the airway. We showed that both the T1R2 and T1R3 subunits of the sweet taste receptor (T1R2/3) were present in the same chemosensory cells of primary human sinonasal epithelial cultures. Respiratory isolates of Staphylococcus species, but not Pseudomonas aeruginosa, produced at least two d-amino acids that activate the sweet taste receptor. In addition to inhibiting P. aeruginosa biofilm formation, d-amino acids derived from Staphylococcus inhibited T2R-mediated signaling and defensin secretion in sinonasal cells by activating T1R2/3. d-Amino acid-mediated activation of T1R2/3 also enhanced epithelial cell death during challenge with Staphylococcus aureus in the presence of the bitter receptor-activating compound denatonium benzoate. These data establish a potential mechanism for interkingdom signaling in the airway mediated by bacterial d-amino acids and the mammalian sweet taste receptor in airway chemosensory cells.
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Aminoácidos/metabolismo , Células Quimiorreceptoras/inmunología , Inmunidad Innata , Mucosa Nasal/inmunología , Senos Paranasales/inmunología , Gusto/fisiología , Aminoácidos/biosíntesis , Células Cultivadas , Células Quimiorreceptoras/efectos de los fármacos , Células Quimiorreceptoras/metabolismo , Humanos , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/metabolismo , Senos Paranasales/efectos de los fármacos , Senos Paranasales/metabolismo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/fisiologíaRESUMEN
BACKGROUND: Postoperative wound healing after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS) is an important factor in procedural success. Local steroids and separation of opposing mucosa are commonly implemented to optimize healing. A bioabsorbable, fluticasone propionate (FP)-eluting implant, SinuBand FP, was assessed for its safety and efficacy when used in patients with CRS and nasal polyps, who were indicated for ESS including bilateral anterior and posterior ethmoidectomy. METHODS: A first-in-human, randomized, partially double-blind, single-tertiary-referral-center, controlled trial enrolling 30 patients receiving 2 of 3 treatments (1 per sinus, intrapatient control): SinuBand FP, SinuBand (without FP), or standard nasal pack (Merocel®). Primary outcome measures were local safety, ocular safety (intraocular pressure [IOP], lens opacity), and 24-hour urine cortisol. Secondary measures (evaluated by independent review of postoperative video endoscopies) were ethmoid inflammation, polyp score, adhesion formation, and Lund-Kennedy score. Patient-reported outcomes of postoperative pain, nasal congestion, and nasal discharge were collected. RESULTS: Of 30 enrolled patients (used for safety analysis), 27 patients completed the trial. SinuBand FP showed local safety, ocular safety, and no significant change in 24-hour urine cortisol. SinuBand FP showed a trend to do better concerning inflammation. Concerning polyp score SinuBand FP did significantly better compared to Merocel (p = 0.03). No significance compared to SinuBand without corticosteroids (p = 0.97). Adhesions were comparable across treatments. Patient reported pain was nominally lower in the SinuBand group. CONCLUSION: SinuBand FP was well tolerated and showed evidence of efficacy. A larger study is needed to further evaluate and confirm the benefits of SinuBand FP.
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Implantes Absorbibles , Antiinflamatorios/administración & dosificación , Implantes de Medicamentos/administración & dosificación , Fluticasona/administración & dosificación , Procedimientos Quírurgicos Nasales , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Senos Paranasales/efectos de los fármacos , Senos Paranasales/cirugía , Periodo Posoperatorio , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Upper airway inflammation is one of the most commonly identified causes of chronic cough, although the underlying mechanism is not clear. This study compared normal saline solution nasal-pharyngeal irrigation (NSNPI) and fluticasone propionate nasal spray (FPNS) treatment for chronic cough associated with allergic rhinitis (AR). METHODS: Patients with suspected AR to house-dust mite were enrolled, and the symptom of cough was assessed by a cough symptom score and the Leicester Cough Questionnaire, and cough response to capsaicin was evaluated. AR was assessed by using the visual analog scale (VAS) and the Mini Juniper Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Mediators, including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein from nasal lavage fluid (NLF) were examined. The patients were treated with NSNPI (the NSNPI group) or FPNS (the FPNS group) for 30 days, after which they were reassessed. RESULTS: Forty-five of 50 patients completed this study. The scores of the cough symptom and the Leicester Cough Questionnaire, and the capsaicin cough threshold all improved statistically after NSNPI but did not change after FPNS. There were statistically significant changes in the evaluations of the MiniRQLQ and the mediators, including histamine and leukotriene C4, in the NLF in the NSNPI group. However, significant changes were found in the assessments of VAS, MiniRQLQ, and all above mediators including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein in the NLF of the FPNS group. Furthermore, the assessments of VAS and all the mediators were reduced more in the FPNS group compared with those in the NSNPI group. CONCLUSION: The patients with suspected AR to house-dust mite reported a better relief of the cough symptom after 30 days of treatment with NSNPI compared with that after nasal corticosteroid.
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Tonsila Faríngea/patología , Tos/prevención & control , Fluticasona/uso terapéutico , Senos Paranasales/patología , Rinitis Alérgica/terapia , Cloruro de Sodio/uso terapéutico , Irrigación Terapéutica , Tonsila Faríngea/efectos de los fármacos , Adolescente , Adulto , Anciano , Animales , Antígenos Dermatofagoides/inmunología , Enfermedad Crónica , Tos/etiología , Humanos , Persona de Mediana Edad , Rociadores Nasales , Senos Paranasales/efectos de los fármacos , Pyroglyphidae/inmunología , Rinitis Alérgica/complicaciones , Adulto JovenRESUMEN
Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8°C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature (≈34°C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses.
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Quitosano/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Derivados de la Hipromelosa/metabolismo , Mucosa Nasal/metabolismo , Poloxámero/metabolismo , Temperatura , Animales , Química Farmacéutica , Quitosano/administración & dosificación , Quitosano/química , Evaluación Preclínica de Medicamentos/métodos , Geles , Humanos , Derivados de la Hipromelosa/administración & dosificación , Derivados de la Hipromelosa/química , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/metabolismo , Mucosa Nasal/efectos de los fármacos , Técnicas de Cultivo de Órganos , Senos Paranasales/efectos de los fármacos , Senos Paranasales/metabolismo , Poloxámero/administración & dosificación , Poloxámero/química , Solubilidad , PorcinosRESUMEN
BACKGROUND: Saline irrigation of the nasal cavity is a classic and effective treatment for acute or chronic rhinosinusitis. Topical antibiotics such as mupirocin have been widely used for recalcitrant chronic rhinosinusitis. Therefore, the purpose of this study was to evaluate the effect of saline irrigation using mupirocin. METHODS: A systematic literature review and meta-analysis of mupirocin saline irrigation were performed using EMBASE, MEDLINE, and Cochrane library through December 2015. Data were analyzed with R 3.2.2 software. A random effects model was used because of the diversity of included studies. Sensitivity analysis of particular tested groups and single proportion tests were also performed. The main outcome measure was residual staphylococcal infection, as confirmed by culture or PCR. RESULTS: Two RCTs, two prospective studies and two retrospective studies were included. A random effects model meta-analysis of the pooled data identified a relative risk of residual infection of 0.13 (95% CI: 0.06-0.26, p<0.05) with low heterogeneity (I2 = 0%). The proportion of residual staphylococcal infections after 1 month was 0.08 (95% CI: 0.04-0.16). However, this proportion increased to 0.53 at 6 months (95% CI: 0.27-0.78). CONCLUSIONS: The short-term use of mupirocin has a strongly reductive effect on staphylococcal infection in chronic rhinosinusitis. Although there is currently a lack of clear evidence, future studies with well-designed inclusion criteria and randomized controlled trials are needed to examine mupirocin's long-term effect on chronic rhinosinusitis.
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Mupirocina/uso terapéutico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Administración Intranasal , Humanos , Cavidad Nasal/efectos de los fármacos , Cavidad Nasal/microbiología , Lavado Nasal (Proceso) , Senos Paranasales/efectos de los fármacos , Senos Paranasales/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Rinitis/microbiología , Sinusitis/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Irrigación TerapéuticaRESUMEN
Granulomatosis with polyangiitis (GPA), a disease capable of affecting any organ, most often acts upon the upper respiratory tract. Diagnostic imaging is primarily represented by computed tomography (CT) of paranasal sinuses. The aim of this study was to define the characteristic changes in paranasal CT in patients with GPA and to evaluate diagnostic usefulness of the Lund-Mackey scoring system (L-M System). The study encompassed 43 patients with GPA of the mean age of 47.7 ± 12.8 years who were treated topically with mupirocin. We found that inflammation occurred mainly in the maxillary sinuses (72%). The mean L-M score was 5.8 ± 6.1. The right maxillary sinus had the highest percentage (12.6%) of score hits of 1, i.e., partial opacification and the left ostiomeatal complex had the highest percentage (7.6%) of score of 2, i.e., complete opacification or obstruction. The following changes were the most characteristic for GPA: sinus mucosal thickening, widespread bone damage, and osteogenesis. We conclude that the long-term topical mupirocin treatment of GPA may inhibit nasal bone damage, but also may led to permanent rhinological changes of the rhinosinusitis type. The Lund-Mackey staging system is a useful diagnostic imaging option in GPA patients.