Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on diagnosis and treatment / Rinossinusite crônica e polipose nasossinusal na fibrose cística: atualização sobre diagnóstico e tratamento

Although cystic fibrosis (CF) is an irreversible genetic disease, advances in treatment have increased the life expectancy of CF patients. Upper airway involvement, which is mainly due to pathological changes in the paranasal sinuses, is prevalent in CF patients, although many are only mildly symptomatic (with few symptoms). The objective of this literature review was to discuss the pathophysiology and current therapeutic management of chronic rhinosinusitis (CRS) in CF patients. The review was based on current evidence, which was classified in accordance with the Oxford Centre for Evidence-Based Medicine criteria. When symptomatic, CRS with nasal polyps can affect quality of life and can lead to pulmonary exacerbations, given that the paranasal sinuses can be colonized with pathogenic bacteria, especially Pseudomonas aeruginosa. Infection with P. aeruginosa plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Although clinical treatment of the upper airways is recommended as initial management, this recommendation is often extrapolated from studies of CRS in the general population. When sinonasal disease is refractory to noninvasive therapy, surgery is indicated. Further studies are needed in order to gain a better understanding of upper airway involvement and improve the management of CRS in CF patients, with the objective of preserving lung function and avoiding unnecessary invasive procedures.

A fibrose cística (FC) é uma doença genética irreversível, mas os avanços no tratamento têm aumentado a expectativa de vida dos pacientes. O acometimento das vias aéreas superiores, principalmente por alterações patológicas dos seios paranasais, é prevalente nesses pacientes, embora muitos apresentem poucos sintomas. O objetivo desta revisão é discutir a fisiopatologia e o manejo terapêutico atual da rinossinusite crônica (RSC) na FC. A revisão fundamentou-se nas evidências mais recentes, classificadas em conformidade com os critérios do Oxford Centre for Evidence-Based Medicine. Quando sintomática, a RSC com pólipos nasais pode afetar a qualidade de vida e as exacerbações pulmonares, já que os seios paranasais podem ser colonizados por bactérias patogênicas, principalmente a Pseudomonas aeruginosa. Essa bactéria tem papel crucial na morbidade e mortalidade após o transplante pulmonar em pacientes com FC. Embora o tratamento clínico das vias aéreas superiores seja indicado no manejo inicial, a indicação é muitas vezes extrapolada de estudos sobre RSC na população geral. A cirurgia é a alternativa quando o quadro nasossinusal é refratário à terapia não invasiva. Mais estudos são necessários para compreender melhor o acometimento das vias aéreas superiores e melhorar o manejo da RSC na FC, a fim de preservar a função pulmonar e evitar procedimentos invasivos desnecessários.

As alterações nasofibroscópicas e tomográficas de seios paranasais são preditoras de gravidade em pacientes com fibrose cística / Nasal endoscopic and CT scan alterations of the paranasal sinuses as predictors of severity in patients with cystic fibrosis

A fibrose cística (FC) resulta de mutação no gene regulador da condutância transmembrana, responsável pelo controle dos processos secretores. As vias aéreas superiores (VAS) geralmente são comprometidas na forma de pansinusite crônica. OBJETIVO: Avaliar as alterações das VAS nos pacientes com FC e determinar a correlação entre os achados tomográficos e endoscópicos nasossinusais e a gravidade da doença. MÉTODO: Estudo transversal, prospectivo com 20 pacientes maiores de 5 anos com diagnóstico de FC avaliando escore de Shwachman-Kulczycki (S-K), tomografia de seios paranasais (TC) (escore de Lund-Mackay) e videonasofibroscopia (escore de Meltzer). RESULTADOS: Alterações tomográficas foram observadas em 94% dos casos. Alterações endoscópicas nas VAS foram encontradas em dez pacientes. Pólipo nasal ocorreu em três pacientes (15%). Observou-se correlação entre a intensidade das alterações da TC e o escore S-K (p = 0,0097) e entre os achados endoscópicos e o escore S-K (p = 0,0318). Observou-se relação positiva entre a presença de colonização crônica e os achados endoscópicos (p = 0,0325), o que não foi observado com os achados tomográficos (p = 0,2941). CONCLUSÃO: Há correlação inversa entre o escore clínico de S-K e os achados de TC e nasofibroscopia. Portanto, os pacientes clinicamente mais graves de acordo com o escore de S-K apresentam maior comprometimento de VAS.

Cystic Fibrosis (CF) results from mutation in the transmembrane conductance regulator gene, responsible for controlling secretory processes. The upper airways (UA) are usually involved in the form of chronic pansinusitis. OBJECTIVE: To evaluate UA changes in patients with CF and to establish the correlations between sinonasal CT and endoscopic endonasal findings and disease severity. METHOD: Cross-sectional and prospective study with 20 patients older than 5 years with CF, assessing the Shwachman-Kulczycki (S-K) score, paranasal sinus tomography (CT) (Lund-Mackay score) and nasal endoscopy (Meltzer score). RESULTS: CT scan alterations were observed in 94% of cases. Endoscopic alterations findings in the upper airways were found in 10 patients. Nasal polyps were found in 3 patients (15%). There was a correlation between the intensity of changes on the CT and S-K score (p = 0.0097), and between endoscopic findings and S-K score (p = 0.0318). There was a positive correlation between the presence of chronic colonization and endoscopic findings (p = 0.0325), which was not observed on the CT (p = 0.2941). CONCLUSION: There is an inverse correlation between the S-K clinical score and nasal endoscopy and CT findings. Therefore, patients who are clinically more severe according to the S-K score have greater UA involvement.

Avaliação endoscópica nasal de crianças e adolescentes com fibrose cística / Nasal endoscopic evaluation of children and adolescents with cystic fibrosis

As principais manifestações otorrinolaringológicas da Fibrose Cística são a rinossinusite crônica e a polipose nasossinusal, com diferentes apresentações clínicas. Objetivo: Caracterizar, do ponto de vista nasossinusal, as crianças e adolescentes com fibrose cística por meio de um questionário, do exame clínico e da endoscopia nasal. Forma de estudo: Clínico descritivo transversal. Material e método: Avaliação de 100 crianças e adolescentes com fibrose cística por meio de um questionário específico, exame físico otorrinolaringológico, endoscopia nasal e estadiamento endoscópico dos pólipos nasais. Resultados: Os sintomas mais frequentes foram: tosse (45 por cento), respiração oral (44 por cento), distúrbios do sono (42 por cento) e obstrução nasal (37 por cento). Vinte e oito pacientes (28 por cento) apresentaram secreção mucopurulenta nasal e 41 por cento apresentaram abaulamento medial da parede lateral do nariz. Os pólipos nasais foram identificados em apenas 14 por cento dos casos, nenhum deles era obliterante. Conclusão: O questionário, o exame clínico e especialmente a endoscopia nasal permitiram uma avaliação detalhada das características nasais das crianças e adolescentes com fibrose cística. Alguns achados foram discordantes da literatura, principalmente a baixa prevalência encontrada de pólipos nasais, e parecem estar relacionados com características próprias da população estudada. A melhor caracterização desse grupo de pacientes, do ponto de vista otorrinolaringológico, contribui para uma adequada abordagem multidisciplinar.

The main otorhinolaryngological manifestations of CF are chronic rhinosinusitis and nasal polyposis, with different clinical presentations. AIM: To characterize children and adolescents with cystic fibrosis through a questionnaire, an ENT clinical examination and nasal endoscopy. Study design: Cross-sectional clinical descriptive. Material and method: Assessment of 100 children and adolescents with cystic fibrosis through a specific questionnaire, ENT physical examination, nasal endoscopy and endoscopic staging of nasal polyps. Results: The most frequent symptoms were: cough (45 percent), oral breathing (44 percent), sleep disorders (42 percent) and nasal obstruction (37 percent). Twenty-eight patients (28 percent) had purulent nasal discharge, and 41 percent had medial bulging of the nasal lateral wall. Nasal polyps were identified in only 14 percent of cases, none were obstructing. Conclusion:The questionnaire, clinical examination and especially nasal endoscopy lead to a detailed assessment of the nasal characteristics of children and adolescents with cystic fibrosis. Some findings were discordant with the literature, particularly the low prevalence of nasal polyps, and appear to be related to specific characteristics of the population studied. The best characterization of this group of patients, from the ENT standpoint, contributes to an appropriate multidisciplinary approach.

Sonotubometry findings in patients with combined airway disease with and without associated eosinophilic otitis media

Active opening of the eustachian tube is accomplished by contraction of the paratubal muscles. Disturbance of any of the ET functions may contribute to the development of otitis media [OM] with effusion and other middle ear diseases. Sonotubometry seems to be the most [physiologic] method for assessment of ET function and has the advantage that it can be performed on ears with an intact tympanic membrane and without the use of a pressure chamber. The aim of this study was to compare the Eustachian tube function using Sonotubometry in patients with combined airway disease associated with Eosinophilic otitis media with that having combined airway disease without otitis media. This study was applied on 45 patients divided into 3 groups each of 15. 1[st] group is the control group, 2[nd] group patients with combined airway disease without Eosinophilic otitis media, 3[rd] group patients with combined airway disease associated with Eosinophilic otitis media. Our results explains that the tubal opening durations were significantly longer in patients of EOM group than in patients with combined airway disease without EOM group and also the normal control group. Sonotubometry can be performed in patients with or, without an intact tympanic membrane and under physiological conditions. Sonotubometry is also inexpensive, painless, and easy to perform in both adults and children. Therefore, it has great potential value as a diagnostic tool for individuals with suspected ET disease

Incidência e evolução da polipose nasal em crianças e adolescentes com fibrose cística / Incidence and evolution of nasal polyps in children and adolescents with cystic fibrosis

A polipose nasal é manifestação clínica de alerta para investigação de fibrose cística (FC). OBJETIVO: Avaliar incidência de pólipos nasais em crianças e adolescentes com FC, sua associação com idade, sexo, sintomas clínicos, achados laboratoriais e genótipo, e sua evolução com corticoterapia tópica. CASUÍSTICA E MÉTODOS: Foram avaliados sintomas clínicos, níveis de cloro no suor e mutações genéticas de 23 pacientes com FC. A polipose nasal foi investigada por exame endoscópico e quando presente, o paciente recebeu 6 meses de tratamento com corticosteróide tópico e foi realizada nova endoscopia depois. Para análise estatística utilizou-se média, desvio padrão e Teste de Fisher. RESULTADOS: 39,1 por cento dos pacientes apresentaram polipose nasal (cinco bilateral, quatro unilateral), todos com mais de seis anos, 82,6 por cento, pneumonias recorrentes, 87 por cento, insuficiência pancreática e 74 por cento, desnutrição. Não houve associação entre polipose e nível de cloro no suor, genótipo, fenótipo clínico e sintomas nasais. Houve melhora da polipose com tratamento clínico em sete pacientes, com regressão completa em seis. CONCLUSÃO: O estudo mostrou elevada incidência de polipose em crianças com FC, sendo encontrada em todos os espectros de gravidade clínica, mesmo na ausência de sintomas nasais. O tratamento com corticosteróide tópico mostrou-se eficaz. A interação de pneumopediatra e do otorrinolaringologista é fundamental para diagnóstico e seguimento.

Nasal polyps are a clinical sign of alert for investigating Cystic Fibrosis (CF). AIMS: To study the incidence of nasal polyps in children and adolescents with cystic fibrosis, its possible association with age, gender, clinical manifestations, genotype and sweat chlorine level, and its evolution with topical steroid therapy. METHODS: Clinical symptoms, sweat chlorine level and genotype were studied in 23 cystic fibrosis patients. Nasal polyps were diagnosed by nasal endoscopy and treated with topical steroids during 6 months, followed by a second nasal endoscopy. Fisher test was used for statistical analysis. RESULTS: Nasal polyps were found in 39.1 percent of the patients (five bilateral, four unilateral), all older than six years, recurrent pneumonia in 82.6 percent, pancreatic insufficiency in 87 percent and malnutrition in 74 percent. No association was seen between nasal polyps and sweat chlorine level, genotype, clinical sings of severity and nasal symptoms. Seven patients improved in their nasal polyps with topical steroids, six showed complete resolution. CONCLUSION: The study showed a high incidence of nasal polyps in older children, who span the entire range of clinical severity, even in the absence of clinical nasal symptoms. Topical steroid therapy showed good results. An interaction among pediatricians and otolaryngologists is necessary for diagnosis and follow-up.

Poliposis nasal en niños / Nasal polyposis in children

Las molestias atribuidas a obstrucción nasal son causa frecuente de consulta, los pediatras deben pensar primero en las etiologías más frecuentes como infección respiratoria alta y alergias, pero no olvidar considerar patologías menos frecuentes como poliposis nasal. En este artículo se realiza una revisión del tema para orientar su correcta sospecha y diagnóstico.

Eotaxinas en asma bronquial y poliposis nasal / The role of eotaxins in bronchial asthma and nasal polyposis

Durante la última década se han descubierto tres péptidos con actividad quimotáctica específica para los eosinófilos y que son miembros de la familia de las quimocinas. Estas citocinas inducen a los eosinófilos a realizar diferentes funciones como quimotaxis, migración transendotelial e inducción de la liberación de radicales de oxígeno. Como los eosinófilos infiltran tanto las vías aéreas de pacientes asmáticos como los pólipos nasales, se ha postulado que las eotaxinas pueden ser responsables del reclutamiento de estas células. Los eosinófilos tienen la propiedad de inducir remodelamiento de la matriz extracelular y daño tisular a través de la liberación de proteasas tóxicas, mediadores inflamatorios, citocinas y radicales de oxígeno. Por lo cual, el desarrollo de estrategias terapéuticas que inhiban el reclutamiento de estas células constituye una esperanza en el tratamiento de las enfermedades alérgicas. Este artículo revisa la función de las eotaxinas en asma y poliposis nasal, además de discutir el posible uso de antagonistas de CCR3, receptor de las eotaxinas, como una nueva modalidad terapéutica de asma y poliposis nasal.

Over the last few years, three specific eosinophil activating peptides, eotaxin-1, -2 and -3, members of the chemokine family have been identified. These cytokines exert a number of functions on eosinophils including chemotaxis, transendothelial migration and induction of the release of reactive oxygen species. Eosinophils are considered to play an important role in allergic disease by causing tissue damage through the release of toxic proteases, lipid mediators, cytokines and oxygen free radicals. This article reviews the role of eotaxins in asthma and nasal polyps. Discussion focuses on therapeutic guidelines, particularly as it has been shown that CCR3, the major chemokine receptor in eosinophils, serves as a eotaxin receptor.

Update on nasal polyps: etiopathogenesis.

PURPOSE OF REVIEW: Nasal polyps is a common ENT disease with high medical failure and recurrence rate, reflecting unknown pathogenesis. The present review is an update on the etiopathogenesis of nasal polyps. RECENT FINDING: Several mechanisms have been proposed for the formation of nasal polyps, including allergy, mucosal allergy, autonomic imbalance, nitric oxide, superantigens, infection, abnormal transepithelial ion transport, mucopolysaccharide abnormality, mechanical obstruction and epithelial rupture. Eosinophils comprises more than 60% of the cell population. Activated T cells, mast cells and plasma cells are also increased compared with the normal nasal mucosa. The stroma has numerous mediators, including cytokines, growth factors, adhesion molecules, and immunoglobulins. Both Th1 and Th2 types of cytokines are upregulated independent of the atopic status. An increased production of GM-CSF, IL5, RANTES and eotaxin can contribute to chronic eosinophilic inflammation by regulating the migration, survival and activation of eosinophils. CONCLUSION: Nasal polyps is a multifactorial disease, with infectious, noninfectious, inflammation, anatomic and genetic abnormalities. Chronic inflammation remains the central major factor in nasal polyps.

Nasal polyps: the relationship to allergy, sinonasal infection and histopathological type.

OBJECTIVE: To evaluate the relationship of nasal polyps to allergy, sinonasal infection and histopathological type by examining the prevalences of these factors among nasal polyps patients. STUDY DESIGN: Prospective descriptive study. MATERIAL AND METHOD: A total of 73 patients were enrolled between October 1st, 1999 and August 31st, 2002 at the Allergy and Rhinology Clinic, Faculty of Medicine, Songklanagarind Hospital. The medical history was recorded. Allergy skin prick test, nasal endoscopy with biopsy and plain film paranasal sinus were performed. Positive allergy skin test was defined by at least 1 aeroallergen with a wheal size > or = 3 mm greater than the negative control. Rhinosinusitis was diagnosed by clinical symptoms, positive nasal endoscopy and/or positive plain film paranasal sinus. Histopathological investigation was classified as eosinophil- or neutrophil-dominated inflammation. RESULTS: 68.5 per cent of patients with nasal polyps had a positive allergy skin test, 67.1 per cent had rhinosinusitis. Eosinophil-dominated inflammation was presented in 69.9 per cent and neutrophil-dominated inflammation in 30.1 per cent, respectively. Within each histopathological type, 62.7 per cent of patients with eosinophil-dominated inflammation and 81.8 per cent of patients with neutrophil-dominated inflammation had a positive allergy skin test. There was no statistically significant difference in prevalence of positive allergy skin test between eosinophil- and neutrophil-dominated inflammations (p = 0.107). 60.8 per cent of patients with eosinophil-dominated inflammation and 81.8 per cent of patients with neutrophil-dominated inflammation had rhinosinusitis. There was no statistically significant difference in prevalence of rhinosinusitis between eosinophil- and neutrophil-dominated inflammations (p = 0.079). CONCLUSION: Nasal polyps had association with positive allergy skin test (68.5%), rhinosinusitis (67.1%) and eosinophil-dominated inflammation (69.9%). There were no statistically significant differences in prevalence of positive allergy skin test and rhinosinusitis between eosinophil- and neutrophil-dominated inflammations (p = 0.107 and p = 0.079, respectively).

Eosinophil Inflammation of Nasal Polyp Tissue: Relationships with Matrix Metalloproteinases, Tissue Inhibitor of Metalloproteinase-1, and Transforming Growth Factor-beta1

Eosinophil and mast cell infiltrations are consistent findings in nasal polyp tissue. Previous studies have shown that matrix metalloproteinases (MMPs) may be involved in eosinophil infiltration in airway mucosa of asthmatic patients, and that transforming growth factor-beta1 (TGF-beta1) induces extracellular matrix deposition in nasal polyp tissue. The aim of this study was to evaluate the role of MMPs and tissue-inhibitor of metalloproteinase-1 (TIMP-1) in association with TGF-beta1, eosinophils and mast cell activation in nasal polyp tissue. Nasal polyp tissues from 20 patients who underwent polypectomies were collected and prepared into tissue homogenate. Eosinophil cationic protein (ECP) and tryptase levels were measured by CAP system (Pharmacia, Sweden). MMP-2, MMP-9, TIMP-1 and TGF-beta1 levels were measured by enzyme-liked immunosorbent assay. MMP-2 was the predominant form of MMPs, followed by MMP-9 and TIMP-1. There were significant correlations between ECP, and MMP-9, MMP-2, TGF-beta1 and tryptase, but not with TIMP-1. Significant correlations were noted between tryptase, and MMP-2, MMP-9, and TGF-beta1, but not with TIMP-1. Close correlations were noted between TGF-beta1, and MMP-9 and MMP-2, but not with TIMP-1. MMP-2, MMP-9, and TGF-beta1 may contribute to eosinophil and mast cell migrations into nasal polyp tissue.

Nasal polyposis: immunohistochemical study [a hypothesis for their development]

Nasal polypi and turbinates were obtained from individuals undergoing surgery for symptomatic nasal obstruction caused by nonspecific rhinosinusitis or allergic rhinosinusitis. Monoclonal antibodies were used to identify macrophages, lymphocytes and plasma cells. Middle turbinates and polyps had more macrophages, lymphocytes, plasma cells and eosinophils than the inferior turbinates. A theory for the pathogenesis of nasal polyps was proposed. Local release of inflammatory mediators could cause sodium absorption and chloride permeability to be higher in polyps than in normal turbinate epithelium

Role of circulating immune complex in aspirin-sensitive asthma

BACKGROUND & OBJECTIVES: The pathogenic mechanism of aspirin-sensitive asthma (ASA-BA) remains to be further defined. To evaluate the role of circulating immune complex (CIC) in ASA-BA. SUBJECTS & METHODS: We measured IgG- and IgA-IC level by ELISA using anti-C3 antibody in 33 ASA-BA patients whose sensitivity was confirmed by lysine-aspirin bronchoprovocation test, and compared with those of 14 allergic, 14 intrinsic asthma patients and 7 healthy controls. RESULTS: There was no significant difference in IgG-IC level among the four groups (p > 0.05), while IgA-IC levels of aspirin-sensitive asthma were higher than those of other groups (p = 0.0035). Patients with nasal polyp had significantly higher IgG-IC than those without it (p = 0.02). No differences were found according to medication and symptom scores, and presence of atopy, rhino-sinusitis, urticaria or concurrent sensitivity to sulfite (p > 0.05). Insignificant correlation was found between IgG-IC level and asthma duration, total IgE level, or circulating eosinophil count. CONCLUSION: These findings suggest a possible contribution of IgG-IC to the development of nasal polyp in ASA-BA. Further study will be needed to clarify the role of IgA-IC in the pathogenesis of ASA-BA.

Allergic fungal sinusitis: incidence and clinical and pathological features of seven cases.

Allergic fungal sinusitis, like allergic bronchopulmonary fungal disease, is a noninvasive inflammatory process. It manifests as recurrent nasal polyposis. Histologically the characteristic feature is the presence of thick mucin with dense collections of degenerating eosinophils and Charcot-Leyden crystals (allergic mucin). Demonstration of fungal hyphae in allergic mucin is diagnostic of the disease. We reviewed 85 cases of nasal polyposis operated upon during a period of four years. Allergic fungal sinusitis was diagnosed in seven (8.2%) cases on the basis of presence of allergic mucin and fungal hyphae. History of previous nasal polypectomy was present in four of the seven cases, and in six of the remaining 78. There were no clinical or radiological features that could distinguish the cases of allergic fungal sinusitis from the rest. Aspergillus fumigatus, Mucor and Cladosporium were cultured from one case each.

Angiofibroma juvenil / Juvenil angiofibroma

El Angiofibroma Juvenil es un tumor benigno, que se presenta con más frecuencia en el sexo masculino, durante la adolescecia; pero vemos como pueden darse casos aislados a mayor edad. La sintomatología clásica de obstrucción nasal y epistaxis aunada a la edad del paciente, sexo y hallazgos físicos, nos permiten orientar el diagnóstico. Con frecuencia pueden recidivar las lesiones tumorales, por lo que es aconsejable los controles periódicos

Tuberculosis of nose, presenting as a polyp

Nasal tuberculosis is a very rare disease. It usually presents as a secondary disease to pulmonary tuberculosis. It commonly destroys the nasal cartilagenous framework of the nose and produces nasal deformity. The present case is being reported because of the non involvement of the cartilaginous framework and an unusual presentation as nasal polyp