A real world study of anti-IgE monoclonal antibody in the treatment of allergic united airway disease / 中华预防医学杂志

Objective: To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody (omazumab) in the treatment of allergic united airway disease (UAD) in the real-wold. Methods: Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody (omalizumab) for more than 16 weeks from March 1, 2018 to June 30, 2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis (AA+AR) or allergic asthma combined with chronic sinusitis with nasal polyps (AA+CRSwNP) or allergic asthma combined with allergic rhinitis and nasal polyps (AA+AR+CRSwNP). The control of asthma was evaluated by asthma control test (ACT), lung function test and fractional exhaled nitric oxide (FeNO). The AR was assessed by total nasal symptom score (TNSS). The CRSwNP was evaluated by nasal visual analogue scale (n-VAS), sino-nasal outcome test-22 (SNOT-22), nasal polyps score (TPS) and Lund-Mackay sinus CT grading system. The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded. Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody (omazumab) before and after treatment, and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody (omazumab) response. Results: A total of 117 patients with UAD were enrolled, ranging in age from 19 to 77 years; The median age of patients was 48.7 years; Among them, 60 were male, ranging from 19 to 77 years old, with a median age of 49.9 years; There were 57 females, ranging from 19 to 68 years old, with a median age of 47.2 years. There were 32 cases in AA+AR subgroup, 59 cases in AA+CRSwNP subgroup, and 26 cases in AA+AR+CRSwNP subgroup. The total serum IgE level was 190.5 (103.8,391.3) IU/ml. The treatment course of anti IgE monoclonal antibody was 24 (16, 32) weeks. Compared with pre-treatment, omalizumab increased ACT from 20.0 (19.5,22.0) to 24.0 (23.0,25.0) (Z=-8.537, P<0.001), increased pre-bronchodilator FEV1 from 90.2 (74.8,103.0)% predicted value to 95.4 (83.2,106.0)% predicted value (Z=-5.315,P<0.001), increased FEV1/FVC from 80.20 (66.83,88.38)% to 82.72 (71.26,92.25)% (Z=-4.483,P<0.001), decreased FeNO from(49.1±24.8) ppb to (32.8±24.4) ppb (t=5.235, P<0.001), decreased TNSS from (6.5±2.6)to (2.4±1.9) (t=14.171, P<0.001), decreased n-VAS from (6.8±1.2) to (3.4±2.0)(t=14.448, P<0.001), decreased SNOT-22 from (40.0±7.9) to (21.3±10.2)(t=15.360, P<0.001), decreased TPS from (4.1±0.8) to (2.4±1.0)(t=14.718, P<0.001) and decreased Lund-Mackay CT score from (6.0±1.3) to (3.1±1.6)(t=17.012, P<0.001). The global response rate to omalizumab was 67.5%(79/117). The response rate in AA+AR (90.6%,29/32) was significantly higher than that in AA+CRSwNP (61.0%,36/59) and AA+AR+CRSwNP (53.8%,14/26) subgroups (χ2=11.144,P=0.004). Only 4 patients (3.4%,4/117) had mild side effects. Conclusion: The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD. To provide basis for preventing the progress and precise treatment of allergic UAD.

Interferon-α action in cytokine profile in eosinophilic nasal polyp cultures / Ação do interferon-α sobre o perfil de citocinas em culturas de pólipos nasais eosinofílicos

Abstract Introduction Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern. Objective To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant. Methods Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed. Results Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations. Conclusion We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.

Resumo Introdução A rinossinusite crônica, atualmente, é classificada em dois tipos: Rinossinusite Crônica sem Pólipos Nasais (RSCsPN) e Rinossinusite Crônica com Pólipos Nasais (RSCcPN). No Ocidente, cerca de 80% dos casos de RSCcPN caracterizam-se por um infiltrado celular predominantemente eosinofílico e um padrão de citocinas Th2. Objetivo Avaliar o efeito do Interferon-alpha nos níveis de citocinas do sobrenadante de culturas celulares de pólipos nasais eosinofílicos. Método Foram feitas culturas celulares a partir de amostras de tecido polipoide nasal coletadas de 13 pacientes com RSCcPN eosinofílica. Os pólipos eram considerados eosinofílicos segundo exame histopatológico. As culturas celulares foram estimuladas com 3000 UI de IFN-α. Antes e após tal estímulo, foram avaliadas, no sobrenadante das culturas celulares, as concentrações do Interferon-γ (IFN-γ), do Fator de Necrose Tumoral alfa (TNF-α) e das Interleucinas (IL) 2, 4, 6 e 10, usou-se o Cytometric Bead Array. Resultados Foram incluídas no estudo amostras celulares dos pólipos nasais eosinofílicos de 13 pacientes. Vinte e quatro horas após o estímulo com IFN-α, os sobrenadantes das culturas dos pólipos nasais eosinofílicos apresentaram, de forma significante, diminuição da concentração de IL-4 e aumento das concentrações de IFN-γ, IL-10 e IL-6, em relação ao controle. Não houve diferença significante nas concentrações de TNF-α e IL-2. Conclusão Demonstramos que o IFN-α, in vitro, altera o padrão de citocinas nas culturas celulares de pólipos nasais eosinofílicos. A análise do conjunto dessas alterações sugere que o IFN-α promove, nas culturas celulares, um rebalanceamento dos perfis inflamatórios, favorece a expressão de citocinas Th1 e regulatórias, em detrimento de citocinas do padrão Th2.

Prospective evaluation of clarithromycin in recurrent chronic rhinosinusitis with nasal polyps / Avaliação prospectiva da claritromicina na rinossinusite crônica com polipose nasossinusal recorrente

Abstract Introduction The antiinflammatory effects of macrolides, especially clarithromycin, have been described in patients with chronic rhinosinusitis without polyps and also other chronic inflammatory airway diseases. There is no consensus in the literature regarding the effectiveness of clarithromycin in patients with chronic rhinosinusitis with sinonasal polyposis and the national literature does not report any prospective studies on the efficacy of clarithromycin in chronic rhinosinusitis in our population. Objective To evaluate the effect of clarithromycin in the adjunctive treatment of recurrent chronic rhinosinusitis with sinonasal polyposis refractory to clinical and surgical treatment. Methods Open prospective study with 52 patients with chronic rhinosinusitis and recurrent sinonasal polyposis. All subjects received nasal lavage with 20 mL 0.9% SS and fluticasone nasal spray, 200 mcg / day, 12/12 h for 12 weeks; and clarithromycin 250 mg 8/8 h for 2 weeks and, thereafter, 12/12 h for 10 weeks. The patients were assessed by SNOT 20, NOSE and Lund-Kennedy scales before, immediately after treatment and 12 weeks after treatment. The patients were also evaluated before treatment with paranasal cavity computed tomography (Lund-Mackay) and serum IgG, IgM, IgA, IgE and eosinophil levels. The outcomes evaluated were: SNOT-20, NOSE and Lund-Kennedy. Results Most patients were women, aged 47 (15) years (median / interquartile range), and 61.5% (32/52) had asthma. All patients completed the follow-up after 12 weeks and 42.3% (22/52) after 24 weeks. Treatment resulted in a quantitative decrease in the SNOT-20 [2.3 (1.6) vs. 1.4 (1.6); Δ = −0.9 (1.1); p < 0.01]; NOSE [65 (64) vs. 20 (63); Δ = −28 (38), p < 0.01] and Lund-Kennedy [11 (05) vs. 07 (05); Δ = −2 (05); p < 0.01] scores. SNOT-20 showed a qualitative improvement (>0.8) in 54% (28/52, p < 0.04) of patients, a group that showed lower IgE level [108 (147) vs. 289 (355), p < 0.01]. The group of patients who completed follow-up 12 weeks after the end of treatment (n = 22) showed no worsening of outcomes. Conclusion Long-term adjuvant use of low-dose clarithromycin for chronic rhinosinusitis patients with recurrent sinonasal polyposis refractory to clinical and surgical treatment has resulted in improved quality of life and nasal endoscopy findings, especially in patients with normal IgE levels. This improvement persisted in the patient group evaluated 12 weeks after the end of the treatment.

Resumo Introdução Os efeitos anti-inflamatórios dos macrolídeos são reconhecidos, principalmente da claritromicina para os pacientes com rinossinusite crônica sem pólipos e outras doenças inflamatórias crônicas das vias aéreas em outras populações. Não existe consenso na literatura quanto a sua prescrição para os pacientes de rinossinusite crônica com polipose nasossinusal e a literatura nacional não dispõe de estudos prospectivos sobre a eficácia da claritromicina na rinossinusite crônica em nossa população. Objetivo Avaliar o efeito da claritromicina no tratamento adjuvante da rinossinusite crônica recorrente com polipose nasossinusal refratária ao tratamento clínico e cirúrgico. Método Estudo prospectivo aberto, com 52 pacientes, portadores de rinossinusite crônica com polipose nasossinusal recorrente. Todos os indivíduos receberam lavagem nasal com SF 0,9% 20 mL e fluticasona spray nasal, 200 mcg/dia, 12/12 horas por 12 semanas; e claritromicina 250 mg, de 8/8 horas, por 2 semanas e posteriormente 12/12 horas, por 10 semanas. Os pacientes foram avaliados através do SNOT 20, do NOSE e Lund-Kennedy antes, pós-tratamento imediato e 12 semanas após o tratamento. Os pacientes também foram avaliados antes do tratamento por tomografia computadorizada das cavidades paranasais (Lund-Mackay) e dosagem sérica de IgG, IgM, IgA, IgE e eosinófilos. Os desfechos avaliados foram: SNOT-20, NOSE e Lund-Kennedy. Resultados A maioria dos pacientes era mulher, idade de 47 (15) anos (mediana/intervalo interquartílico) e 61,5% (32/52) portadores de asma. Todos os pacientes completaram o seguimento após 12 semanas e 42,3% (22/52) após 24 semanas. O tratamento resultou em uma diminuição quantitativa do SNOT-20 [2,3 (1,6) vs. 1,4 (1,6); Δ = -0,9 (1,1); p< 0,01]; do NOSE [65 (64) vs. 20 (63); Δ = -28 (38), p< 0,01] e do Lund-Kennedy [11 (05) vs. 07 (05); Δ = -2 (05); p< 0,01]. O SNOT-20 mostrou uma melhoria qualitativa (> 0,8) em 54% (28/52, p< 0,04) dos pacientes, grupo que evidenciou menor nível de IgE [108 (147) vs. 289 (355), p< 0,01]. O grupo de pacientes que completou o seguimento 12 semanas após o término do tratamento (n = 22) não mostrou uma pioria dos desfechos. Conclusão O uso prolongado adjuvante da claritromicina em baixas doses para pacientes com rinossinusite crônica com polipose nasossinusal recorrente refratária ao tratamento clínico e cirúrgico resultou em melhoria na qualidade de vida e endoscopia nasal, principalmente em pacientes com níveis de IgE normal. Essa melhoria se sustentou no grupo de pacientes avaliado 12 semanas após o término do tratamento.

Short-term efficacy of anti-IgE monoclonal antibody in patients with recurrent chronic rhinosinusitis with nasal polyps combined with asthma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the short-term efficacy of anti-IgE monoclonal antibody (Omalizumab) in the treatment of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) complicated with asthma. Methods: Patients with recurrent CRSwNP and comorbid asthma in Beijing TongRen Hospital from May to December of 2020 were continuously recruited and received a 4-month therapy of stable background treatment plus Omalizumab. Results of visual analog scales (VAS) of nasal symptoms, sino-nasal outcome test-22 (SNOT 22) and nasal polyp scores were collected at baseline and post-treatment (1, 2, 3 and 4 months after treatment). Blood routine tests, total nasal resistances (TNR), minimum cross-sectional areas (MCA), total nasal cavity volumes (NCV), forced expiratory volumes in one second (FEV1)/forced vital capacity (FVC) and adverse events were collected at baseline and 4 months after treatment. All results were evaluated for short-term efficacy of Omalizumab. GraphPad Prism 8.2.1 was used for statistic analysis. Results: Ten patients were collected, including 3 males and 7 females, aged (41.13±12.64) years old (x¯±s). Compared to results at baseline, the VAS scores of nasal obstruction, rhinorrhea, hyposmia and headache after 4 months treatment were significantly decreased (1.80±1.48 vs 6.70±2.83, 2.40±1.27 vs 6.40±3.44, 2.70±2.91 vs 8.20±2.25, 0.60±1.08 vs 3.60±2.72, t value was 5.045, 4.243, 5.312, 3.402, respectively, all P<0.01). The scores of SNOT-22 (25.6±20 vs 61.3±33.32, t=4.127, P=0.002 6), nasal polyp scores (2.20±0.92 vs 4.60±0.84, t=9.000, P<0.01) and the count and percentage of eosinophils in peripheral blood were significantly decreased ((94.10±97.78)×109/L vs (360.00±210.80)×109/L, (32.90±27.06)% vs (64.40±20.73)%, t value was 3.678, 2.957, respectively, all P<0.05). NCV (0-5 cm and 0-7 cm) of patients were improved from baseline ((12.62±2.84) cm3 vs (10.40±2.09) cm3, (27.50±14.15) cm3 vs (16.81±6.40) cm3, t value was 2.371, 2.445, respectively, all P<0.05). Conclusions: The 4-month treatment of Omalizumab can significantly improve the nasal symptoms and quality of life of patients with recurrent CRSwNP complicated with asthma, shrink nasal polyps size and reduce the number of peripheral blood eosinophils. Omalizumab can be used as an alternative therapy for refractory CRSwNP patients in the future.

Enfrentamiento práctico a patologías otorrinolaringológicas frecuentes durante el embarazo, una revisión de la literatura / Treatment of frequent otorhinolaryngological pathologies during pregnancy, a review of the literature

RESUMEN Durante el embarazo ocurren una serie de cambios, como edema y disminución de la actividad ciliar en la mucosa respiratoria alta, que pueden favorecer la aparición de síntomas y patologías del área otorrinolaringológica. La eficacia de los tratamientos farmacológicos en la rinitis del embarazo es pobre. El tratamiento de primera línea de la rinitis alérgica son los corticoides intranasales. Existe evidencia sobre la seguridad en el embarazo para furoato de fluticasona, mometasona y budesonida intranasal. El tratamiento del resfrio común está enfocado en el manejo sintomático, los antinflamatorios no esteroidales están contraindicados. En rinosinusitis aguda bacteriana la amoxicilina es de primera línea. En rinosinusitis crónica el manejo quirúrgico está reservado sólo para las complicaciones. Tanto la otitis media aguda como la amigdalitis aguda deben ser tratadas con antibióticos sólo si se sospecha origen bacteriano, el esquema de primera linea es amoxicilina y en caso de alergias se debe usar cefpodoxime o azitromicina. En caso de otorrea no existe evidencia sobre la seguridad de las gotas de antibióticos ótico durante el embarazo. Múltiples medicamentos utilizados habitualmente en otorrinolaringologia no pueden ser usados durante el embarazo. Se debe privilegiar la seguridad materno fetal, utilizando aquellos medicamentos con seguridad demostrada.

ABSTRACT During pregnancy a series of changes occur, such as edema and decreased ciliary activity in the upper respiratory mucosa, which may favor the appearance of symptoms and pathologies of the otorhinolaryngological area. The efficacy of pharmacological treatments in rhinitis of pregnancy is poor. The first-line treatment of allergic rhinitis is intranasal corticosteroids. There is evidence on safety in pregnancy for fluticasone furoate, mometasone and intranasal budesonide. The treatment of the common cold is focused on symptomatic management, nonsteroidal anti-inflammatory drugs are contraindicated. In acute bacterial rhinosinusitis, amoxicillin is first-line. In chronic rhino-sinusitis in surgical management is reserved only for complications. Both acute otitis media and acute tonsillitis should be treated with antibiotics only if bacterial origin is suspected, the first-line treatment is amoxicillin, in the case of allergies, cefpodoxime or azithromycin should be used. In case of otorrhea there is no evidence on the safety of otic antibiotic drops during pregnancy. Conclusion: multiple medications commonly used in otorhinolaryngology cannot be used during pregnancy. Maternal and fetal safety should be privileged, using those medications with proven safety.

Postoperative Management of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps: Impact of High-Dose Corticosteroid Nasal Spray

Abstract Introduction Eosinophilic chronic rhinosinusitis (ECRS) is characterized by an eosinophilic inflammation driven by Th2-type cytokines. Glucocorticosteroids are the most common first-line treatment for ECRS with nasal polyps. Objective We have evaluated the long-term treatment with double-dose intranasal corticosteroids in refractory ECRS nasal polyps resistant to the conventional dose and assessed the risk of adverse systemic effects Methods Sixteen subjects were enrolled in this study. All subjects had ECRS after endoscopic sinus surgery that resulted in recurrentmild andmoderate nasal polyps and were undergoing a postoperative follow-up application of mometasone furoate at a dose of 2 sprays (100 μg) in each nostril once a day (200 μg). All the patients were prescribed mometasone furoate, administered at a dose of 2 sprays (100 μg) in each nostril twice a day (400 μg) for 6 months. Results The average scores of the symptoms during the regular dose of intranasal steroid treatment were 5.2 ± 2.2, but 6 months after the high-dose application, they had significantly decreased to 2.5 ± 1.4 (p < 0.05). The polyp size showed an average score of 1.38 during the regular dose which was significantly reduced to 0.43 (p < 0.01) by the double dose. Glycated hemoglobin (HbA1c) showed normal ranges in all the patients tested. The cortisol plasma concentration was also normal. Conclusion Doubling the dose of the nasal topical spray mometasone furoate might be recommended for the treatment of recurrent nasal polyps in the postoperative follow-up of intractable ECRS. (AU)

Síndrome de Churg Strauss como diagnóstico diferencial de poliposis nasosinusal, a propósito de un caso / Churg Strauss Syndrome as a differential diagnosis of nasosinusal poliposis, case report

RESUMEN El síndrome de Churg-Strauss (SCS) es una vasculitis necrotizante sistémica de etiología desconocida, que afecta vasos sanguíneos de pequeño y mediano tamaño. Característicamente se definen tres estadios: prodrómico, hipereosinofílico y una etapa de vasculitis sistémica. Dentro del prodrómico se encuentran manifestaciones del área otorrinolaringológica, que suelen preceder por años a las manifestaciones propias de las vasculitis. Entre ellas destacan la otitis media crónica, rinitis alérgica y rinosinusitis crónica poliposa. Reportamos el caso de un paciente de sexo masculino de 64 años con poliposis nasosinusal bilateral, con biopsia compatible con SCS, encontrándose en estado prodrómico de la enfermedad. Además, presentamos una revisión de la literatura sobre esta patología.

ABSTRACT Churg-Strauss syndrome (CSS) is a necrotizing systemic vasculitis of unknown etiology, which involves small and medium-sized vessels. It is characterized by three stages: prodromic, hypereosinophilic and systemic vasculitis. In the prodromal stage we can find otolaryngological manifestations (including chronic otitis media, allergic rhinitis, chronic rhinosinusitis with polyps) that usually precede the proper manifestations of the vasculitis by years. Here, we report a 64-year old male patient with sinonasal polyps and biopsy compatible with CSS, being in the prodromal stage of the illness. Also, we present a review of this disease.

Clinical differences between children with asthma and rhinitis in rural and urban areas / Diferencias clínicas entre niños con asma y rinitis de áreas rurales y urbanas

Abstract Background: Epidemiological studies have shown that children who grow up on traditional farms are protected from allergic diseases. However, less is known about if the environment influences the pharmacotherapy in these patients. Objective: To compare the treatment of asthmatic and rhinitis children from urban and rural areas in Medellín, Colombia. Methods: During one year, we follow up a group of children (6 to 14 years) with diagnostic of asthma or rhinitis living for more than five years in urban or rural area. A questionnaire with socio-demographic characteristics, pharmacotherapy treatments, was obtained each three months. Atopy evaluation, spirometry and clinical test for asthma and rhinitis severity were done at the beginning and one year later. Results: Eighty six point four percent patients completed the follow up (rural n: 134, urban n: 248). Patients in rural location required less salbutamol (p: 0.01), visit to emergency department (p <0.01) and have a less number of patients with FEV1 <80% (p: 0.05). For clinical control rural children require less pharmacotherapy than urban children (p: 0.01) and more patients with rhinitis (18% vs 8% p: 0.03) and asthma (23% vs 12% p: 0.01) in the rural group could suspended pharmacotherapy. Atopy (p: <0.07) and poli-sensitization (p: <0.08) was a little higher in urban than rural area. We observe that poverty/unhygienic indicators were risk factors for higher levels of specific IgE among patients from urban area. Conclusion: Patients with respiratory allergies located in urban area require more pharmacotherapy and have less clinical response than rural children.

Resumen Introducción: Los estudios epidemiológicos han demostrado que los niños que crecen en las granjas suelen tener menos frecuencia de enfermedades alérgicas. Sin embargo, se sabe menos si el tipo de ambiente (rural vs urbano) también puede influir en la respuesta clínica de a la farmacoterapia. Objetivo: Comparar un grupo de niños localizados en área rural y área urbana de Antioquia, Colombia, en cuanto al tratamiento farmacológico recibido para el asma y/o la rinitis. Métodos: Fueron incluidos niños con asma y/o rinitis que llevaran viviendo al menos 5 años en la misma zona rural o urbana con edades entre 6 a 14 años. A todos los pacientes se les realizó un seguimiento clínico cada 3 a 4 meses. La evaluación de la atopia, la espirometría y test para evaluar la gravedad del asma y la rinitis se realizaron al principio y al final del estudio. Resultados: De los pacientes candidatos, 382 (86.4%) completaron el seguimiento (rural n= 134 urbano n= 248). Los pacientes en área rural requirieron menos salbutamol (p: 0.01), visitas al departamento de emergencias (p <0.01) y tenían un menor número de pacientes con FEV1 <80% (p <0.05). Para el control clínico, los niños en zonas rurales requieren menos farmacoterapia que los niños en zona urbana (p: 0.01). Igualmente, para la rinitis (18% vs 8% p: 0.03) y el asma (23% vs 12% p= 0.01) un mayor número de los pacientes en zona rural pudieron suspender la farmacoterapia. La atopia (p <0.07) y la poli-sensibilización (p <0.08) fue mayor en las zonas urbanas que en las rurales. Se observó que los indicadores de pobreza y los servicios de aseo, eran factores de riesgo para mayores niveles de IgE entre los pacientes de área urbana. Conclusión: Los pacientes con asma o rinitis localizado en el área urbana tienen síntomas más severos y refractarios al tratamiento farmacológico, por lo que requieren más farmacoterapia que los niños rurales. Algunos factores ambientales intra y extra domiciliarios propios de la zona rural y urbana podrían influir en estos resultados.

How to avoid the inappropriate use of antibiotics in upper respiratory tract infections? A position statement from an expert panel / Como evitar o uso inadequado de antibióticos nas infecções de vias aéreas superiores? Posição de um painel de especialistas

Abstract Introduction: Bacterial resistance burden has increased in the past years, mainly due to inappropriate antibiotic use. Recently it has become an urgent public health concern due to its impact on the prolongation of hospitalization, an increase of total cost of treatment and mortality associated with infectious disease. Almost half of the antimicrobial prescriptions in outpatient care visits are prescribed for acute upper respiratory infections, especially rhinosinusitis, otitis media, and pharyngotonsillitis. In this context, otorhinolaryngologists play an important role in orienting patients and non-specialists in the utilization of antibiotics rationally and properly in these infections. Objectives: To review the most recent recommendations and guidelines for the use of antibiotics in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, adapted to our national reality. Methods: A literature review on PubMed database including the medical management in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, followed by a discussion with a panel of specialists. Results: Antibiotics must be judiciously prescribed in uncomplicated acute upper respiratory tract infections. The severity of clinical presentation and the potential risks for evolution to suppurative and non-suppurative complications must be taken into 'consideration'. Conclusions: Periodic revisions on guidelines and recommendations for treatment of the main acute infections are necessary to orient rationale and appropriate use of antibiotics. Continuous medical education and changes in physicians' and patients' behavior are required to modify the paradigm that all upper respiratory infection needs antibiotic therapy, minimizing the consequences of its inadequate and inappropriate use.

Resumo Introdução: A resistência bacteriana a antibióticos nos processos infecciosos é um fato crescente nos últimos anos, especialmente devido ao seu uso inapropriado. Ao longo dos anos vem se tornando um grave problema de saúde pública devido ao prolongamento do tempo de internação, elevação dos custos de tratamento e aumento da mortalidade relacionada às doenças infecciosas. Quase a metade das prescrições de antibióticos em unidades de pronto atendimento é destinada ao tratamento de alguma infecção de vias aéreas superiores, especialmente rinossinusites, otite média aguda supurada e faringotonsilites agudas, sendo que uma significativa parcela dessas prescrições é inapropriada. Nesse contexto, os otorrinolaringologistas têm um papel fundamental na orientação de pacientes e colegas não especialistas, para o uso adequado e racional de antibióticos frente a essas situações clínicas. Objetivos: Realizar uma revisão das atuais recomendações de utilização de antibióticos nas otites médias, rinossinusites e faringotonsilites agudas adaptadas à realidade nacional. Método: Revisão na base PubMed das principais recomendações internacionais de tratamentos das infecções de vias aéreas superiores, seguido de discussão com um painel de especialistas. Resultados: Os antibióticos devem ser utilizados de maneira criteriosa nas infecções agudas de vias aéreas superiores não complicadas, a depender da gravidade da apresentação clínica e dos potenciais riscos associados de complicações supurativas e não supurativas. Conclusões: Constantes revisões a respeito do tratamento das principais infecções agudas são necessárias para que sejam tomadas medidas coletivas no uso racional e apropriado de antibióticos. Somente com orientação e transformações no comportamento de médicos e pacientes é que haverá mudanças do paradigma de que toda infecção de vias aéreas superiores deva ser tratada com antibióticos, minimizando por consequência os efeitos de seu uso inadequado.

Terapia anti interleukina 5 para la rinosinusitis crónica con pólipos / Anti-interleukin 5 therapy for chronic rhinosinusitis with polyps

Resumen INTRODUCCIÓN: La rinosinusitis crónica es la inflamación de la mucosa nasosinusal de duración superior a 12 semanas. Se distinguen dos formas clínicas: rinosinusitis crónica con pólipos y sin pólipos. Los pacientes con rinosinusitis crónica con pólipos presentan niveles elevados de interleukina 5, la cual promueve la diferenciación y supervivencia de eosinófilos, por lo que se ha propuesto minimizar su circulación como una nueva estrategia de tratamiento. Sin embargo, no hay claridad respecto a su real efectividad. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas que en conjunto incluyeron tres estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que los inhibidores de interleukina 5 podrían disminuir el puntaje de pólipos nasales. Si bien podrían asociarse a efectos adversos, estos serían poco frecuentes y de baja severidad. Sin embargo, la certeza de la evidencia es baja.

Abstract INTRODUCTION: Chronic rhinosinusitis is the inflammation of sinonasal mucosa lasting longer than 12 weeks. Two clinical forms are distinguished: chronic rhinosinusitis with polyps and without polyps. Patients with chronic rhinosinusitis with polyps exhibit high levels of interleukin 5, which promotes differentiation and survival of eosinophils. So, minimizing their circulation has been proposed as a new treatment strategy. However, there is no clarity regarding its real effectiveness. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews included three primary studies overall, all corresponding to randomized trials. We concluded inhibitors of interleukin 5 might decrease nasal polyps score. Although they might be associated with adverse effects, these would be infrequent and of low severity. However, the certainty of the evidence is low.

Omalizumab para la rinosinusitis crónica / Omalizumab for chronic rhinosinusitis

Resumen INTRODUCCIÓN: La rinosinusitis crónica es una enfermedad inflamatoria crónica de alta prevalencia que compromete la mucosa de la cavidad nasal y senos paranasales. La inmunoglobulina E es un mediador inflamatorio que juega un rol etiopatogénico en esta condición, por lo que se ha planteado que omalizumab, un anticuerpo monoclonal anti-inmunoglobulina E, podría constituir una alternativa de tratamiento. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyeron cinco estudios primarios, de los cuales dos corresponden a ensayos controlados aleatorizados. Concluimos que en pacientes con rinosinusitis crónica, no está claro si omalizumab lleva a una mejoría en la escala de pólipos nasales, la calidad de vida, el bienestar general o los síntomas nasales porque la certeza de la evidencia es muy baja. Por otra parte, el uso de omalizumab probablemente se asocia a efectos adversos frecuentes.

Abstract INTRODUCTION: Chronic rhinosinusitis is a high prevalence chronic inflammatory disease that involves nasal mucosa and paranasal sinuses. Immunoglobulin E is an inflammatory mediator that plays an etiopathogenic role in this condition, so omalizumab, an anti-immunoglobulin E monoclonal antibody, might be a therapeutic alternative. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified five systematic reviews that included five primary studies overall, of which two correspond to randomized trials. We concluded it is not clear whether omalizumab leads to an improvement in the nasal polyps scale, quality of life, general well-being or nasal symptoms in patients with chronic rhinosinusitis, because the certainty of the evidence is very low. On the other hand, omalizumab is probably associated with frequent adverse effects.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis / O papel potencial da amlodipina na rinossinusite bacteriana induzida experimentalmente

Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

Resumo Introdução: Antibióticos são frequentemente usados para o tratamento de rinossinusite. Questões têm sido levantadas sobre os efeitos adversos dos antibióticos e a resistência crescente. A falta de desenvolvimento de novos compostos antibióticos aumentou a necessidade da exploração de compostos não antibióticos que têm atividade antibacteriana. A amlodipina é um composto não antibiótico com atividade anti-inflamatória. Objetivo: O objetivo desse estudo foi investigar o papel potencial da amlodipina no tratamento da rinossinusite, avaliando seus efeitos sobre o estado oxidativo do tecido, histologia da mucosa e inflamação. Método: Quinze cobaias albinas adultas foram inoculadas com Staphylococcus aureus e tratadas com solução salina, cefazolina ou amlodipina durante sete dias. O grupo controle incluiu cinco cobaias saudáveis. Os animais foram sacrificados após o tratamento. Alterações histopatológicas foram identificadas com a coloração de hematoxilina-eosina. A inflamação foi avaliada pela densidade de infiltração de leucócitos polimorfonucleares. Foram determinados os níveis teciduais de antioxidantes (superóxido dismutase, glutationa) e um produto de oxidação (malondialdeído). Resultados: Em animais com rinossinusite induzida, a amlodipina reduziu a perda dos cílios, edema da lâmina própria e deposição de colágeno em comparação com o grupo placebo (solução salina) e embora não seja superior à cefazolina, a amlodipina diminuiu a infiltração de leucócitos polimorfonucleares. Os níveis de atividade da superóxido dismutase e glutationa foram reduzidos, enquanto os níveis de malondialdeído aumentaram significativamente nos três grupos de tratamento em comparação ao grupo controle. O grupo tratado com amlodipina apresentou aumento significante dos níveis de superóxido dismutase e glutationa e diminuição dos níveis de malondialdeído em comparação com todos os grupos de tratamento. Conclusão: O composto não antibiótico amlodipina pode ter um papel no tratamento da rinossinusite aguda através de mecanismos protetores de tecido, antioxidantes e anti-inflamatórios.

Position statement of the Brazilian Academy of Rhinology on the use of antihistamines, antileukotrienes, and oral corticosteroids in the treatment of inflammatory sinonasal diseases / Posicionamento da Academia Brasileira de Rinologia sobre o uso de anti-histamínicos, antileucotrienos e corticosteroides orais no tratamento de doenças inflamatórias nasossinusais

Abstract Introduction: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. Objective: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. Methods: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors’ needs. Results: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. Conclusion: There is support in the literature for the use of these drugs; however, final considerations about the role of each of them have been made.

Resumo Introdução: As afecções inflamatórias do nariz e dos seios paranasais são muito prevalentes na população geral, causam acentuada perda de qualidade de vida dos pacientes afetados, geram perdas significativas das atividades de trabalho, lazer e sociais. Esses pacientes necessitam de tratamento específico e especializado e uma ampla gama de medicações orais está disponível. Objetivo: O presente documento tem por objetivo esclarecer àqueles que tratam das doenças nasossinusais inflamatórias, tanto especialistas quanto generalistas, sobre as terapêuticas orais nas afecções inflamatórias nasais não infecciosas. Método: A metodologia usada para elaboração deste artigo incluiu a busca das palavras chave: corticosteroides orais, anti-histamínicos, antileucotrienos, rinite, rinossinusite nos bancos de dados Medline e Embase nos últimos 5 anos. Como não foi achado artigo relevante para o texto sobre o assunto de interesse nos últimos 5 anos, a busca foi estendida por mais 5 anos, e assim por diante, de acordo com a necessidade dos autores. Resultados: Literatura relevante foi encontrada com relação ao uso dos anti-histamínicos, antileucotrienos e corticosteroides orais nessas afecções. A Academia Brasileira de Rinologia ressalta, após amplo debate do colegiado, pontos-chave no tratamento com esses medicamentos. Conclusão: Há respaldo na literatura para o uso desses medicamentos, entretanto considerações finais acerca do papel de cada deles foram feitas.

Topical therapy with high-volume budesonide nasal irrigations in difficult-to-treat chronic rhinosinusitis / Terapia tópica de irrigação nasal de alto volume com solução de budesonida em rinossinusite crônica de difícil tratamento

ABSTRACT INTRODUCTION: Chronic rhinosinusitis (CRS) is termed difficult-to-treat when patients do not reach acceptable level of control despite adequate surgery, intranasal corticosteroid treatment and up to 2 short courses of systemic antibiotics or corticosteroids in the preceding year. Recently, high-volume corticosteroid nasal irrigations have been recommended for CRS treatment. OBJECTIVE: To assess high-volume budesonide nasal irrigations for difficult-to-treat CRS. METHODS: Prospective uncontrolled intervention trial. Participants were assessed before- and 3 months after nasal irrigation with 1 mg of budesonide in 500 mL of saline solution daily for 2 days. Subjective (satisfactory clinical improvement) and objective (SNOT-22 questionnaire and Lund-Kennedy endoscopic scores) assessments were performed. RESULTS: Sixteen patients were included, and 13 (81.3%) described satisfactory clinical improvement. SNOT-22 mean scores (50.2-29.6; p = 0.006) and Lund-Kennedy mean scores (8.8-5.1; p = 0.01) improved significantly. Individually, 75% of patients improved SNOT-22 scores, and 75% improved Lund-Kennedy scores after high volume budesonide nasal irrigations. CONCLUSION: High-volume corticosteroid nasal irrigations are a good option in difficult-to-treat CRS control of disease, reaching 81.3% success control and significant improvement of SNOT-22 and Lund-Kennedy scores.

RESUMO INTRODUÇÃO: A rinossinusite crônica (RSC) de difícil tratamento é aquela inadequadamente controlada com cirurgia, corticosteroides tópicos em spray e até dois ciclos de medicação sistêmica em um ano. Atualmente, tem sido preconizado o uso de irrigações nasais de corticosteroides em alto volume para seu tratamento. OBJETIVO: Avaliar o uso da terapia tópica de irrigações nasais com budesonida em alto volume nos pacientes com RSC de difícil tratamento. MÉTODO: Estudo prospectivo de intervenção não controlado em RSC de difícil tratamento com 3 meses de terapia tópica de irrigação (1 mg de budesonida diluído em 500 mL de soro fisiológico para ser utilizado em dois dias). Realizada avaliação subjetiva (melhora clínica satisfatória) e objetiva (questionário SNOT-22 e classificação endoscópica de Lund-Kennedy). RESULTADOS: Foram incluídos 16 pacientes, sendo que 13 (81,3%) consideraram sua melhora clínica satisfatória. Houve melhora significante das médias de SNOT-22 (50,2 a 29,6; p = 0,006) e de Lund-Kennedy (8,8 a 5,1; p = 0,01). Individualmente, 75% dos pacientes apresentaram melhora do SNOT-22 e 75%, do Lund-Kennedy. CONCLUSÃO: A terapia tópica de irrigação de alto volume de corticosteroide é uma boa opção no controle clínico dos pacientes com rinossinusite crônica de difícil tratamento, com controle adequado de 81,3% destes pacientes e melhora significante do SNOT-22 e do Lund-Kennedy.

Efectividad y seguridad del corticosteroide nasal mometasona como tratamiento de rinosinusitis crónica sin pólipos / Effectiveness and safety of nasal corticosteroid mometasone as a treatment of chronic rhinosinusitis without polyps

Introducción: la rinosinusitis crónica (RSC) es definida como una inflamación de la mucosa nasal y senos paranasales durante al menos 12 semanas o superior, afecta a todas las edades, pero es más prevalente en la edad adulta. Debido a que la rinosinusitis crónica idiopática es una enfermedad inflamatoria crónica, el manejo médico debe estar dirigido a controlar la inflamación y el manejo de las exacerbaciones. El uso diario de corticosteroides tópicos nasales es la piedra angular en el tratamiento de la rinosinusitis crónica idiopática. Objetivo: examinar la efectividad y seguridad del corticosteroide tópico nasal Mometasona como tratamiento de síntomas relacionado con rinosinusitis crónica idiopática en pacientes niños y adultos. Metodología: se realizó una búsqueda sistemática y exhaustiva de literatura, de revisiones sitemáticas de literatura de alta calidad en los últimos 5 años. Todo el proceso se acogió a los estándares de calidad internacional utilizados por la Colaboración Cochrane. Resultados: de las búsquedas, se obtuvieron 531 referencias, de las que, luego de tamización de título y resumen, se obtuvieron 6 para evaluar en texto completo, y de las cuáles se excluyeron 4, para incluir dos en el análisis de este reporte. Conclusiones: los CEN son más efectivos que el placebo para controlar los síntomas nasales y, adicionalmente, se relacionan con mayor proporción de pacientes con cirugía de senos paranasales que responden al tratamiento. En el caso de pacientes sin cirugía de senos paranasales, no hubo diferencias entre los CEN y el placebo, ni tampoco se encontraron diferencias entre ellos en mejorar la calidad de vida, ni diferencias en la mejoría evaluada con cambios endoscópicos. No hay evidencia de diferencias entre ellos mismos (beclometasona, fluticasona y mometasona), en cuanto a efectividad. No hay evidencia para determinar que beclometasona, fluticasona, mometasona y ciclesonida, son diferentes en cuanto a eventos adversos.

Posicionamento da Academia Brasileira de Rinologia sobre terapias tópicas nasais / Brazilian Academy of Rhinology position paper on topical intranasal therapy

Opresente documento tem por objetivo esclarecer àqueles que tratam das doenças nasossinusais, tanto especialistas quanto generalistas, sobre as terapêuticas tópicas nasais. Por meio de uma revisão das evidências científicas, a Academia Brasileira de Rinologia vem proporcionar sua visão prática e atualizada sobre as medicações tópicas nasais mais utilizadas, excetuando-se as medicações que possuam antibióticos tópicos na sua formulação.

This documents aims at educating those who treat sinonasal diseases - both general practitioners and specialists - about topical nasal treatments. By means of scientific evidence reviews, the Brazilian Academy of Rhinology provides its practical and updated guidelines on the most utilized topical nasal medication, except for the drugs that have topical antibiotics in their formulas.

Recurrent central serous chorioretinopathy with dexamethasone eye drop used nasally for rhinitis

Central serous chorioretinopathy [CSC] is characterized by serous retinal detachment at the posterior pole. Several factors have been implicated in the pathogenesis, and endogenous or exogenous corticosteroids are thought to play a major role. Here we present a case of a 35-year-old male with complaints of a dark circle in front of his right eye. Fundus examination, optical coherence tomography and fundus fluorescein angiography were performed. The patient was diagnosed with CSC. CSC resolved completely within seven weeks. Four weeks later the CSC recurred and spontaneously resolved over eight weeks. Overall, the patient had three additional recurrences of CSC in the same eye over the next year. A detailed history taking revealed the patient was using 0.1% dexamethasone eye drops nasally for recurrent rhinitis for few days prior to each episode of CSC. This indicates the strong correlation between steroids given by any route and the pathogenesis of CSC