Non-antibiotic antimicrobial agents for chronic rhinosinusitis: a narrative review.

OBJECTIVE: This narrative review explores alternative non-antibiotic antimicrobial agents for CRS management in adults. METHODS: Alternative antimicrobial agents using EPOS 2020 guidelines as reference were selected, and articles dated from 2003 to 2022 in English, Portuguese, or Spanish using PubMed and EMBASE databases. The parameters analyzed included study design, evidence level, population characteristics, CRS characteristics, interventions, outcomes, sample size, randomization, blinding, and side effects. Reviews, unrelated contexts,in vitro experiments, and duplicates were excluded. RESULTS: 148 articles were screened; 19 articles were selected for analysis. Randomized controlled trials and cohort studies assessing non-antibiotic antimicrobial treatments for CRS were included. Xylitol demonstrated effectiveness in reducing CRS symptoms, particularly SNOT-22 scores, surpassing saline irrigation benefits. Manuka honey showed potential microbiological benefits in recalcitrant CRS, but symptomatic and endoscopic improvements remained inconclusive. Baby shampoo irrigation improved nasal mucociliary clearance and postoperative outcomes. Colloidal silver nasal irrigation showed limited efficacy in reducing CRS symptoms or endoscopic scores. Povidone-Iodine (PI) nasal irrigation yielded mixed results, with varying effects on culture negativity and SNOT-20 scores. Bacteriophage treatment exhibited promise in decreasing specific bacterial strains and cytokine levels. CONCLUSION: Non-antibiotic antimicrobial therapies, including xylitol, manuka honey, baby shampoo, colloidal silver, PI, bacteriophages, lactoferrin, and carrageenan offer potential alternatives for CRS in adult patients. Xylitol, baby shampoo, and PI presented benefits in improving symptoms and nasal endoscopic scores, however, the number of studies is limited for conclusive recommendations and safety assessments. CRS management should adopt a comprehensive approach, particularly for non-infectious or immune-related cases, moving beyond antibiotics. Antibiotics should be reserved for confirmed bacterial infections. Overall, this review shows the importance of exploring non-antibiotic therapies to enhance the management of CRS.

Enfrentamiento diagnóstico de la rinosinusitis aguda en pacientes adultos ambulatorios / Diagnostic Approach of acute rhinosinusitis in adults outpatients

Acute rhinosinusitis is a common condition, mainly of viral etiology and self-limiting course. There is coexistence of microbiological agents that favor bacterial superinfection. Therefore, it is necessary to know evidence that supports diagnostic approach in adults out- patients. Having reviewed the evidence, we mention the isolated symptoms and signs have such a low performance to guide the diagnostic approach, some with statistical evidence such as hemifacial pain, colored nasal discharge and radiographic alterations suggestive of rhinosinusitis. Also, it is possible to improve clinical performance by combining suggestive findings. The imaging study has little evidence that supports them, because non-specific and non-concordant findings. Finally, empirical management with antibiotics does not statistically or clinically modify the evolution of an acute non-complicated condition.

La rinosinusitis aguda es una condición frecuente, principalmente de etiología viral y de curso autolimitado. Existe coexistencia de agentes microbiológicos que favorece la sobreinfección bacteriana. Por ello, es necesario conocer la evidencia que dirige el enfrentamiento diagnóstico en pacientes adultos ambulatorios. Habiéndose revisado la evidencia, mencionamos que los síntomas y signos aislados poseen bajo rendimiento para guiar el proceso diagnóstico, destacando algunos con mejores atributos diagnósticos, pero de significancia estadística bastante discreta, como lo son el dolor hemifacial, la descarga nasal coloreada y alteraciones de la radiografía sugerentes de rinosinusitis. También, que se puede mejorar discretamente el rendimiento clínico combinando algunos de estos hallazgos sugerentes. El estudio imagenológico posee poca evidencia que lo respalde, dado la presencia de hallazgos inespecíficos o no concordantes, inclusive en pacientes asintomáticos. Finalmente, respecto de manejo empírico con antibióticos, destaca que su uso no modifica estadística ni clínicamente la evolución de un cuadro agudo no complicado.

Efficacy of the posterior nasal nerve resection combined with hormone transnasal nebulization on difficult-to-treat rhinosinusitis: a retrospective analysis.

OBJECTIVE: A retrospective analysis was performed to explore the clinical effect of the Posterior Nasal Nerve (PNN) resection combined with hormone transnasal nebulization on Difficult-to-Treat Rhinosinusitis (DTRS). METHODS: A total of 120 DTRS patients were selected and divided into a control group (n = 60) and a study group (n = 60) according to different treatments. The control group patients were treated via PNN resection, followed by normal saline transnasal nebulization; the study group patients were given PNN resection and then treated with budesonide suspension transnasal nebulization. Subsequently, the comparison was performed between the two groups in terms of (1) Clinical baseline characteristics; (2) Sino-nasal Outcome Test (SNOT)-22 scores before treatment and after 3-months, 6-months and 12-months of treatment; (3) Lund-MacKay scores before treatment and after 10, 30, 90, and 180 days of treatment; (4) Incidence of adverse reactions during treatment. RESULTS: There was no significant difference in SNOT-22 or Lund-Kennedy scores between the two groups before treatment (p > 0.05). After treatment, the SNOT-22 and Lund-Kennedy scores of the control and the study groups were decreased, and compared with the control group, the SNOT-22 and Lund-Kennedy scores in the study group improved more significantly (p < 0.05). In addition, the study group and the control group presented with 1 and 4 cases of nasal adhesion, 2 and 3 cases of epistaxis, 1 and 4 cases of sinus orifice obstruction, 1 and 3 cases of lacrimal duct injuries, respectively. The incidence of adverse reactions in the study group was significantly lower than that in the control group (8.3% vs. 23.3%) (p < 0.05). CONCLUSION: PNN resection combined with hormone transnasal nebulization treatment can improve the symptoms and quality of life of DTRS patients, with good clinical efficacy but few adverse reactions. Therefore, such combination treatment deserves a promotion and application clinically. LEVEL OF EVIDENCE: Level 3.

Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update.

INTRODUCTION: Biologics targeting type 2 inflammation have revolutionized the way we treat patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Particularly in severe and difficult-to-control cases, these drugs have provided a new reality for these patients, allowing for the effective and safe treatment of extensive diseases that were not completely managed with the typical strategy of surgery and topical medications. OBJECTIVES: The experience achieved with the approval of these medications by ANVISA for use in CRSwNP and the knowledge obtained regarding outcomes, adverse effects, and the ideal patient profile prompted the update of the previously published guideline, with a detailed review of the most recent scientific literature, the personal experiences of experts, and the adaptation to the reality of the Brazilian healthcare system, both public and private. RESULTS: We proposed a new eligibility criterion for biologics in patients with CRSwNP based on four pillars of indication: the impact of the disease on the patient's life, whether in the presence of specific symptoms or in overall quality of life; the extent of sinonasal disease; the presence of type 2 comorbidities, considering other associated diseases that may also benefit from anti-T2 biologics, and the presence of biomarkers to define type 2 inflammation, especially those associated with worse disease prognoses. CONCLUSIONS: This innovative and pioneering method has two major advantages. First, it ensures a comprehensive evaluation of patients; second, it is flexible, as advancements in our understanding of the disease and changes in cost-effectiveness can be addressed by simply adjusting the required score for indication, without the need to modify the entire evaluation scheme.

The influence of inhibitors of apoptosis proteins (IAPs) on chronic rhinosinusitis with nasal polyps.

BACKGROUND: Inhibitors of apoptosis proteins (IAPs) modulate the inflammatory process, and may facilitate the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to observe if IAPs were differently expressed between patients with CRSwNP and controls, and to correlate the expression of IAPs with some inflammatory markers, as with the response to nasal corticosteroids in patients with CRSwNP. METHODOLOGY: We obtained nasal biopsies from patients with CRSwNP (n=27) and controls (n=16). qRT-PCR measured the expression of IAPs and caspases, while Luminex assay measured the concentration of cytokines. Unpaired parametric tests and Principal Component Analysis (PCA) were used for statistical analysis. RESULTS: We observed lower expression of IAP genes (XIAP, BIRC2/IAP1, and BIRC3/IAP2) in CRSwNP patients compared to controls, and we identified that patients with bad response to corticosteroids presented lower levels of BIRC2/IAP1, XIAP, BCL2, CASP9, and IL-17, and higher levels of CASP7 and TGF-B. CONCLUSIONS: IAPs expression was downregulated in CRSwNP, and was associated with poorer response to nasal corticosteroids. The present findings suggest the importance of IAPs as a link between environment and the host inflammatory responses, and this pathway could be explored as a potential new target therapy for patients with CRSwNP.

Cost-utility analysis of dupilumab compared with endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyps. Evaluation in Colombia, a developing country.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) compromises respiratory function, sleep, concentration, work capacity, and quality of life, generating high costs for patients and health systems. The aim of the study was to analyze the cost utility of Dupilumab compared to endoscopic sinus surgery for patients with CRSwNP. RESEARCH DESIGN AND METHODS: We developed a model-based cost-utility analysis from the perspective of the Colombian health system to compare Dupilumab vs. endoscopic nasal surgery in patients with difficult-to-treat CRSwNP. Transition probabilities were extracted from the published literature about CRSwNP, and costing was based on local tariffs. We performed probabilistic sensitivity analysis for outcomes, probabilities, and costs (10.000 Monte Carlo simulations). RESULTS: The cost of dupilumab ($ 142.919) was 7.8 times higher than nasal endoscopic sinus surgery ($ 18.347). In terms of quality-adjusted life years (QALYs), surgery generates better results than Dupilumab: 11.78 vs. 9.05 QALYs. CONCLUSIONS: From the perspective of the health system, endoscopic sinus surgery for the management of CRSwNP is a dominant alternative in all the analyzed scenarios compared to the use of Dupilumab. From a cost-utility point of view, the use of dupilumab should be considered when the patient requires multiple surgeries or when there is a contraindication for surgery performance.

Real-world study: drug reduction in children with allergic rhinitis and asthma receiving immunotherapy.

Background: The reduction of pharmacological treatment after allergen immunotherapy (AIT) for house dust mites (HDMs) has been little studied in children. Objective: To evaluate the reduction of pharmacological treatment comparing children that receive HDM immunotherapy (AIT group) versus only pharmacotherapy. Methods: A historic cohort of children with rhinitis or asthma was assessed. The main outcome was the frequency of complete drug discontinuation. Results: 100% drug reduction was higher for rhinitis (4-year cumulative incidence: 30 vs 10.7%) and asthma (24.1 vs 10.5%) in the AIT group (n = 987) than in the pharmacotherapy group (n = 2012). Conclusion: Immunotherapy is associated with a significant reduction of pharmacotherapy in children. This is a marker of clinical control and could be associated with positive economic impact.

The benefits of allergen immunotherapy for house dust mites has been little studied in children. The usefulness of this treatment in asthma over the use of pharmacotherapy has also not been clearly evaluated. The use of immunotherapy allowed greater reductions in pharmacological treatment in children with rhinitis and asthma. Immunotherapy is a useful treatment for childhood rhinitis and asthma and reduces the risk of adverse effects from pharmacological treatments.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil.

INTRODUCTION: Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. OBJECTIVE: To review the current status of biologic treatment indications in chronic rhinosinusitis. METHODS: The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. RESULTS: Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. CONCLUSION: The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Nasal irrigation with corticosteroids in Brazil: the clinical response of 1% compounded budesonide drops and betamethasone cream.

INTRODUCTION: High-volume corticosteroid nasal irrigation is a treatment option in patients with chronic rhinosinusitis. In Brazil, alternatives are used to optimize its cost and popularize its use, such as 1% compounded budesonide drops or betamethasone cream, and it is necessary to study these treatment modalities. OBJECTIVE: To evaluate the clinical response of nasal irrigation with 1% compounded budesonide drops or betamethasone cream compared to nasal sprays utilized in patients with chronic rhinosinusitis. METHODS: This was a retrospective observational study with 257 patients. One hundred and eight patients using corticosteroid nasal irrigation (292 treatment cycles) and 149 using corticosteroid nasal spray (300 treatment cycles) were included. Evaluation of subjective improvement, adverse events, exacerbations, and objective assessments with SNOT-22 and Lund-Kennedy endoscopic score were performed, in addition to sub-analyses related to nasal polyps and previous surgery. RESULTS: Corticosteroid nasal irrigation and corticosteroid nasal spray improved the Lund-Kennedy endoscopic score, with more adverse events in the corticosteroid nasal irrigation group. Previous surgery increased corticosteroid nasal irrigation improvement, with greater subjective improvement and fewer exacerbations. 1% compounded budesonide drops were better than betamethasone cream in the Lund-Kennedy endoscopic score, with fewer adverse events. A 1,000 µg dose of 1% compounded budesonide drops was more effective than 500 µg. CONCLUSION: Corticosteroid nasal irrigation was effective in improving the Lund-Kennedy endoscopic score in chronic rhinosinusitis, especially in patients with nasal polyps and previous surgery, in addition to promoting a higher rate of subjective improvement and fewer exacerbations than corticosteroid nasal spray, but with more adverse events. 1% compounded budesonide drops improved the Lund-Kennedy endoscopic score with fewer adverse events than betamethasone cream, particularly at higher doses (1000 µg).

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.

Topical tretinoin in chronic rhinosinusitis with nasal polyps: a randomized clinical trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is usually treated with corticosteroids, given their anti-inflammatory effects. Unlike the nasal administration, the oral and ocular use of tretinoin, an immunoregulatory drug, is well established. Therefore, tretinoin was thought to act on nasal polyps, and possible adverse and/or therapeutic effects were investigated. METHODS: A first-in-human open-label trial was conducted enrolling patients with CRSwNP randomized into: a control group (CTR, n = 15), treated with budesonide for 24 weeks; and an intervention group (TRT, n = 15), who received budesonide and 0.1% tretinoin in the last 12 weeks. Primary endpoint included histopathological analysis and tissue immunoassay (Multiplex) for tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-4, IL-5, IL-13, and matrix metalloproteinase 9 (MMP-9) at 12 and 24 weeks. Secondary endpoints were: adverse events report, endoscopy (modified Lund-Kennedy scoring system [LKS]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), and olfactory test (Connecticut Chemosensory Clinical Research Center) at baseline, at 12 weeks, and at 24 weeks, in addition to serum biochemistry and tomographic findings (Lund-Mackay computed tomography [CT] staging system [LMS]) at baseline and 24 weeks. RESULTS: TRT showed less microscopic edema (2/13 [15.4%] vs 8/13 [61.5%]; p = 0.044) as well as no increase in cytokines levels. All adverse events were categorized as "grade 1" (asymptomatic; mild). The most interesting part of this study was the improvement in smell between baseline (T0) and week 24 (T2) in TRT only (p = 0.041). CONCLUSION: Transnasal tretinoin associated with budesonide was safe and well tolerated, and it should be investigated as a treatment option for some CRSwNP endotypes. ©2021 ARSAAOA, LLC.

Interferon-α action in cytokine profile in eosinophilic nasal polyp cultures.

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.

Prospective evaluation of clarithromycin in recurrent chronic rhinosinusitis with nasal polyps.

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.

Azithromycin for chronic eosinophilic rhinosinusitis with nasal polyp: a placebo-controlled trial.

BACKGROUND: Chronic eosinophilic rhinosinusitis with nasal polyps (CRSwNP eosinophilic) is characterised by the formation of benign and bilateral nasal polyps. We aimed to compare the effectiveness of azithromycin as an immunomodulator with the use of a placebo in patients presenting with CRSwNP concomitant with asthma and aspirin intolerance after 3 months of treatment and at a 1-year follow-up. METHODOLOGY: We performed a randomised, double-blind, placebo-controlled trial. Patients received 500 mg azithromycin orally three times/week for 12 weeks. Improvement was evaluated by staging, the Sino-Nasal Outcome Test (SNOT-22), and nasal polyp biopsy. Data collected at pretreatment and 3 months posttreatment were compared. Quality of life was evaluated at the 1-year follow-up. RESULTS: Twenty-seven and 21 patients were treated with azithromycin and a placebo, respectively. The medication was well tolerated overall. Twenty patients (74%) in the azithromycin group and three patients (14%) in the placebo group were not refer- red for surgery at the end of the 3-month treatment. Regarding subjective improvement, there was a median decrease only in the azithromycin group, and the between-group difference was significant. SNOT-22 improvement was maintained in the azithromy- cin group at the 1-year follow-up. CONCLUSIONS: Azithromycin could be considered a therapeutic option for patients presenting with CRSwNP concomitant with asthma and aspirin intolerance.

Rhino-orbital mucormycosis due to Apophysomyces ossiformis in a patient with diabetes mellitus: a case report.

BACKGROUND: The most common aetiological agents of mucormycosis are Rhizopus, Mucor, Apophysomyces and Lichtheimia. Apophysomyces is comparatively rare, as it has been reported in less than 3% of mucormycosis cases. The genus Apophysomyces includes six species, and only A. elegans, A. mexicanus, A. variabilis and A. ossiformis have been reported to cause infections in both immunocompetent and immunocompromised patients. CASE PRESENTATION: We present a case of a 46-year-old male patient with bilateral blepharoedema, corneal opacity in the left eye and poorly controlled diabetes mellitus. The patient was subjected to total maxillectomy, exenteration of the left orbit and treatment with liposomal amphotericin B. Direct mycological analysis with KOH 10% revealed hyaline, coenocytic, long and wide hyphae. Apophysomyces ossiformis was identified from maxillary biopsy using 18S-ITS1-5.8S-ITS2-28S rRNA gene amplification and sequencing. The patient requested to be transferred to another hospital to continue treatment, where he died on the ninth day after admittance. CONCLUSION: To the best of our knowledge, this is the first case of rhino-orbital mucormycosis due to A. ossiformis with a fatal outcome. This case reveals the need to identify the fungus causing mucormycosis with molecular methods to identify adequate treatment therapies for patients with this infection.

Prescription and indications for the use of fluoroquinolones in a group of outpatients in Colombia / [Prescripción e indicaciones de uso de fluoroquinolonas en un grupo de pacientes ambulatorios de Colombia].

Introduction: There is evidence of the indiscriminate use of antibiotics for different pathologies. Objective: To determine the prescription patterns and indications for the use of fluoroquinolones in a group of outpatients in Colombia. Materials and methods: We conducted a descriptive pharmaco-epidemiological study on prescription-indication using a population database where patients with outpatient fluoroquinolone prescriptions were included from May to October, 2018. We obtained the information on sociodemographic, pharmacological, and clinical variables, as well as on the diagnosis according to the International Classification of Diseases, version 10, and we established if the use was approved by the regulatory agencies or if it was off-label. Results: A total of 23,373 patients were identified who were using fluoroquinolones; their mean age was 47.9 ± 18.1 years and women predominated (n=15,767, 67.5%). Ciprofloxacin was the medication most commonly prescribed (n=19,328, 82.7%), followed by norfloxacin (n=3076, 13.2%), levofloxacin (n=573, 2.5%), and moxifloxacin (n=394; 1.7%). The main indications were urinary tract infection in unspecified site (n=10,777, 46.1%), diarrhea and gastroenteritis of presumed infectious origin (n=3077, 13.2%), and acute cystitis (n=956; 4.2%). The prescriptions followed approved indications in 76% (n=17,759) of cases while the rest were used off-label or without indication for nasopharyngitis or soft-tissue infections, for example. Being male (OR=1.26, 95%CI:1.18-1.34) and under 35 years of age (OR=1.92, 95%CI:1.48-1.50) were associated with a greater probability of using fluoroquinolones in unapproved indications. Conclusions: Fluoroquinolones, particularly ciprofloxacin, are being prescribed especially to women with urinary tract infections, but up to a quarter of the patients received them for unapproved indications by regulatory agencies.

Introducción. Existen evidencias sobre el uso indiscriminado de antibióticos en el tratamiento de diversas enfermedades. Objetivo. Determinar los patrones de prescripción y de indicaciones de uso de las fluoroquinolonas en un grupo de pacientes ambulatorios en Colombia. Materiales y métodos. Se llevó a cabo un estudio descriptivo farmacoepidemiológico del tipo de prescripción e indicaciones de uso a partir de una base de datos poblacionales que incluía pacientes con prescripciones ambulatorias de fluoroquinolonas entre mayo y octubre de 2018. Se recabó la información sobre las variables sociodemográficas, farmacológicas y clínicas (diagnóstico según la Clasificación Internacional de Enfermedades, versión 10) y se estableció la proporción del uso de fluoroquinolonas en indicaciones aprobadas y no aprobadas por las agencias reguladoras. Resultados. Se identificaron 23.373 pacientes que habían recibido fluoroquinolonas; su edad media era de 47,9 ± 18,1 años y 15.767 eran mujeres (67,5 %). La ciprofloxacina fue el medicamento más prescrito (n=19.328; 82,7 %), seguida de la norfloxacina (n=3.076; 13,2 %), la levofloxacina (n=573; 2,5 %) y la moxifloxacina (n=394; 1,7 %). Las principales indicaciones fueron la infección de las vías urinarias en sitio no especificado (n=10.777; 46,1 %), la diarrea y la gastroenteritis de presunto origen infeccioso (n=3.077, 13,2 %) y la cistitis aguda (n=956; 4,2 %). El 76 % (n=17.759) de las prescripciones correspondía a indicaciones aprobadas y el resto a usos no aprobados, como la rinofaringits o las infecciones de tejidos blandos. El ser hombre (odds ratio, OR=1,26; IC95%: 1,18-1,34) y tener menos de 35 años (OR=1,92; IC95%:1,48-1,50) se asociaron con una mayor probabilidad de uso de fluoroquinolonas en indicaciones no aprobadas. Conclusión. Las fluoroquinolonas, en particular la ciprofloxacina, se están prescribiendo especialmente a mujeres con infecciones de las vías urinarias, pero hasta la cuarta parte de los pacientes las recibieron para usos no aprobados por las agencias reguladoras.

10-year experience in patients operated for acute invasive fungal rhinosinusitis. / Experiencia de 10 años en pacientes operados por rinosinusitis fúngica invasiva aguda.

INTRODUCTION: Acute invasive fungal rhinosinusitis (AIFRS) is rare but has high mortality. It is more frequent in immunocompromised patients with multiple comorbidities, which make their management more difficult. The aim of this study is to describe a cohort of patients operated due to AIFRS, their clinical characteristics, mortality, aetiological agent and efficacy of diagnostic tests. MATERIAL AND METHOD: Non-concurrent prospective study of patients with AIFRS who were operated between 2005 and 2015 in our centre. RESULTS: Thirty-two patients were included, 62.5% (20/32) men, with an average age of 39.4 years (16-65 years). Overall mortality was 71.9%; acute mortality 46.9% and late mortality 25%. Haematological malignancies were the most common underlying disease, present in 84.4% (27/32) of cases, followed by diabetes mellitus in 9.4% (3/32). On diagnosis, 62.5% (20/32) of patients were neutropenic, 80% (16/20) of them with febrile neutropenia. Fever was the most frequent symptom, present in 65.6% (21/32) of patients, followed by facial pain or headache in 53.1% (17/32). Aspergillus was identified in 37.5% (12/32) of cases and Rhizopus in 31.3% (10/32). There was no association between the analysed variables and increased risk of mortality. CONCLUSIONS: AIFRS is an aggressive disease with a high mortality rate, therefore a timely diagnosis is fundamental. It is necessary to optimise suspicion criteria for an early diagnosis in order to improve the prognosis.