Effect of cigarette smoke on counts of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa in young patients with perennial allergic rhinitis / Efeito do tabagismo nas contagens de células imunorreativas a eotaxina-1 e eosinófilos na mucosa nasal em pacientes jovens com rinite alérgica perene

Abstract Introduction: In teenagers with perennial allergic rhinitis, exposure to tobacco cigarette smoke increases the count of eosinophils in the nasal mucosa; the recruitment of eosinophils arises from the combined action of a number of cellular and molecular signals, including eotaxin. Objective: To assess the effect of exposure to tobacco cigarette smoke on the count of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa of children and teenagers with perennial allergic rhinitis. Methods: In a cross-sectional study, forty-four patients were evaluated (aged 7-19 years old): 22 with and 22 with no exposure to tobacco cigarette smoke. After replying to 2 validated questionnaires, on Asthma and Allergies in Childhood and on the severity of nasal symptoms, nasal mucosal samples were obtained by scraping the middle one-third of the inferior turbinates. Then counts of immunoreactive cells to eotaxin-1 and eosinophils were assessed by immunohistochemistry. Results: Patients with exposure to tobacco cigarette smoke showed higher cell counts of both eotaxin-1 and eosinophils than patients with no exposure to the smoke, with no correlation between the two variables. However, both counts, of eotaxin-1 and eosinophils, were related to the cotinine/creatinine ratio. Conclusions: Exposure to tobacco cigarette smoke can increase eotaxin-1 and the count of eosinophils in the nasal mucosa of young patients with perennial allergic rhinitis.

Resumo Introdução: Em adolescentes com rinite alérgica perene, a exposição à fumaça do cigarro de tabaco aumenta a contagem de eosinófilos na mucosa nasal. O recrutamento de eosinófilos surge da ação combinada de alguns sinais celulares e moleculares, inclusive a eotaxina. Objetivo: Avaliar o efeito da exposição à fumaça do cigarro de tabaco na contagem de células imunorreativas a eotaxina-1 e eosinófilos na mucosa nasal de crianças e adolescentes com rinite alérgica perene. Método: Em um estudo transversal, 44 pacientes foram avaliados (entre sete e 19 anos): 22 com e 22 sem exposição à fumaça do cigarro de tabaco. Depois de responder a dois questionários validados, sobre asma e alergias na infância e sobre a gravidade dos sintomas nasais, as amostras de mucosa nasal foram obtidas por meio de raspagem do terço médio das conchas inferiores. Em seguida, as contagens de células imunorreativas para eotaxina-1 e eosinófilos foram avaliadas por imuno-histoquímica. Resultados: Os pacientes com exposição à fumaça do cigarro de tabaco apresentaram contagens de células mais elevadas tanto para eotaxina-1 como para eosinófilos em comparação com os pacientes sem exposição à fumaça, sem correlação entre as duas variáveis. No entanto, ambas as contagens, de eotaxina-1 e eosinófilos foram relacionadas com a razão cotinina/creatinina. Conclusões: A exposição à fumaça do cigarro de tabaco pode aumentar a eotaxina-1 e a contagem de eosinófilos na mucosa nasal de pacientes jovens com rinite alérgica perene.

Co-administration of Chenopodium album allergens and CpG oligodeoxy- nucleotides effects on peripheral blood mononuclear cells of patients with allergic rhinitis treated with intranasal corticosteroids and antihistamines

Allergic Rhinitis [AR] is one of the most common chronic diseases in the developed countries. This study was performed to investigate the effect of CpG-ODN in alteration of T-helper [Th]l/Th2 balance of patients with AR treated with intranasal corticosteroids [INCs] and antihistamines. Peripheral blood mononuclear cells [PBMCs] of 20 patients with AR were isolated before and after 45 days therapy. Cytokine production [IL-4, IL-10, IL-13, IFN-gamma] and specific Ch.a IgE in response to CpG co-administration of natural chenopodium album [CpG/Ch.a] or recombinant Ch.a [CpG/rCh.a] allergen were investigated in supernatants.of cultured PBMCs using ELISA Intracellular IL-10 was also assessed in CD4[+] cells using flow cytometry. Significant increase in production of IFN-y and IL-10 and decrease in production of IL-4 were found in supernatants of cultured PBMCs activated with CPG/ch.a and CPG/rch.a. of both CpG/Ch.a and CpG/rCh.a compared to allergens alone, before and after therapy. After therapy, IFN-gamma production with CpG/Ch.a was significantly increased in comparison with before [237 vs. 44 pg/ml, p=0.001]. IFN-gamma and IL-10 production with CpG/rCh.a was significantly increased after therapy compared to before [407.6 vs. 109 pg/ml, p=0.0l for IFN- gamma; 171.7 vs. 52.6 pg/ml, p=0.008 for IL-10], whilst IL-4 was significantly decreased [2.1 vs. 5.8 pg/ml, p=0.02]. Intracellular IL-10 expression was also significantly increased in response to either CpG/Ch.a or CpG/rCh.a that showed intracellular assay could be more sensitive than ELISA. Also, treatment with intranasal corticosteroids and antihistamines could enhance this CpG effect, in vitro

Exhaled Nitric Oxide is Associated with Allergic Inflammation in Children

Exhaled nitric oxide (eNO) has been proposed as a noninvasive marker of airway inflammation in asthma. In asthmatic patients, exhaled NO levels have been shown to relate with other markers of eosinophilic recruitment, which are detected in blood, sputum, bronchoalveolar lavage fluid and bronchial biopsy samples. The purpose of this study was to assess the possible relationship between eNO and allergic inflammation or sensitization in childhood asthma and allergic rhinitis. Subjects consisted of 118 asthmatic children, 79 patients with allergic rhinitis, and 74 controls. Their age ranged from 6 to 15 yr old. eNO level, peripheral blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE level and specific IgE levels were measured. Methacholine challenge test and allergic skin prick test for common allergens were performed in all subjects. Atopic group (n = 206, 44.48 +/- 30.45 ppb) had higher eNO values than non-atopic group (n = 65, 20.54 +/- 16.57 ppb, P < 0.001). eNO level was significantly higher in patients with asthma (42.84 +/- 31.92 ppb) and in those with allergic rhinitis (43.59 +/- 29.84 ppb) than in healthy controls (27.01 +/- 21.34 ppb, P < 0.001) but there was no difference between asthma and allergic rhinitis group. eNO also had significant positive correlations with Dermatophagoides pteronyssinus IgE level (r = 0.348, P < 0.001), Dermatophagoides farinae IgE level (r = 0.376, P < 0.001), and the number of positive allergens in skin prick test (r = 0.329, P = 0.001). eNO had significant positive correlations with peripheral blood eosinophil count (r = 0.356, P < 0.001), serum total IgE level (r = 0.221, P < 0.001), and ECP (r = 0.436, P < 0.001). This study reveals that eNO level is associated with allergic inflammation and the degree of allergic sensitization.

Rol de los receptores tipo toll en la patogénesis de la rinitis alérgica: [revisión] / Toll like receptors role in the allergic rhinitis: [review]

La rinitis alérgica afecta alrededor de seiscientos millones de personas alrededor del mundo, siendo actualmente la enfermedad recurrente con mayor prevalencia. En su patogénesis participa una compleja red de mediadores humorales y celulares participantes del perfil inmunológico Th2. Junto con el sistema inmune adaptativo, componentes de la inmunidad innata han mostrado jugar un importante rol en enfermedades alérgicas, tales como dermatitis atópica y asma bronquial. En el presente trabajo evaluamos el rol de los receptores tipo Toll en rinitis alérgica, realizando una revisión de avanzada con respecto a la expresión, función y modulación de estos receptores en esta enfermedad.

Allergic rhinitis (AR) affects about six hundred million people worldwide and is now considered the most prevalent recurrent disease. The pathogenesis of AR involves a complex network of cellular and humeral mediators involved in the Th2 immune profile. Together with the adaptive immune system, components of innate immunity have shown to play an important role in allergic diseases such as atopic dermatitis and bronchial asthma. The present review describes the role of Toll-like receptors in allergic rhinitis. We discuss the importance of the receptors expression, function and modulation in this disease.

IgE cross-reactivity between Lolium multiflorum and commercial grass pollen allergen extracts in Brazilian patients with pollinosis

Lolium multiflorum (Lm) grass pollen is the major cause of pollinosis in Southern Brazil. The objectives of this study were to investigate immunodominant components of Lm pollen allergens and the cross-reactivity of IgE with commercial grass pollen allergen extracts. Thirty-eight serum samples from patients with seasonal allergic rhinitis (SAR), 35 serum samples from patients with perennial allergic rhinitis (PAR) and 30 serum samples from non-atopic subjects were analyzed. Allergen sensitization was evaluated using skin prick test and serum IgE levels against Lm pollen extract were determined by ELISA. Inhibition ELISA and immunoblot were used to evaluate the cross-reactivity of IgE between allergens from Lm and commercial grass pollen extracts, including L. perenne (Lp), grass mix I (GI) and II (GII) extracts. IgE antibodies against Lm were detected in 100 percent of SAR patients and 8.6 percent of PAR patients. Inhibition ELISA demonstrated IgE cross-reactivity between homologous (Lm) and heterologous (Lp or GII) grass pollen extracts, but not for the GI extract. Fifteen IgE-binding Lm components were detected and immunoblot bands of 26, 28-30, and 32-35 kDa showed >90 percent recognition. Lm, Lp and GII extracts significantly inhibited IgE binding to the most immunodominant Lm components, particularly the 55 kDa band. The 26 kDa and 90-114 kDa bands presented the lowest amount of heterologous inhibition. We demonstrated that Lm extract contains both Lm-specific and cross-reactive IgE-binding components and therefore it is suitable for measuring quantitative IgE levels for diagnostic and therapeutic purposes in patients with pollinosis sensitized to Lm grass pollen rather than other phylogenetically related grass pollen extracts.

Doença alérgica polínica: polens alergógenos e seus principais alérgenos / Pollen allergic disease: pollens and its major allergens

Pacientes com alergia a pólen de gramíneas, comumente denominada polinose, freqüentemente apresentam reatividade a alérgenos de pólen de inúmeras gramíneas devido às reatividades cruzadas entre anticorpos IgE dirigidos contra proteínas presentes nos polens de gramíneas. Nesse contexto, pólen de Italian ryegrass (Lolium multiflorum), ou azevém anual, gramínea da família Poaceae cultivada no Sul do Brasil, é considerado o principal agente sensibilizante em pacientes com polinose. Nessa região, o azevém é capaz de produzir grande quantidade de pólen. Adicionalmente, outras gramíneas da família Poaceae crescem naturalmente no Sul, entretanto, sem relevância clínica. Extratos de pólen derivados de gramíneas homólogas ou heterólogas são freqüentemente empregados no diagnóstico e tratamento da alergia sazonal a pólen, sendo que para esses fins não se encontra comercialmente disponível no Brasil extrato padronizado de pólen de L. multiflorum. Futuros estudos serão importantes para melhor caracterizar a reatividade cruzada entre alérgenos de pólen de L. multiflorum e alérgenos de outras gramíneas com o objetivo de aprimorar o diagnóstico e imunoterapia de pacientes com alergia a pólen causada por L. multiflorum.

Patients with grass pollen allergy, commonly called pollinosis, often present reactivity to pollen allergens from a number of grass species due to cross-reactivity of IgE antibodies to pollen proteins present in pollen grasses. In this context, Italian rye grass (Lolium multiflorum) pollen of the Poaceae family cultivated in Southern Brazil has been considered a major sensitizing agent in patients with pollinosis. In this region, Italian rye grass is capable of producing a great amount of pollen. In addition to L. multiflorum, other Poaceae grasses are naturally grown as weed in Southern Brazil, but with no clinical relevance. Pollen extracts derived from homologous or heterologous grasses are often used for both diagnosis and treatment of seasonal allergy. However, no standardized L. multiflorum pollen extract is commercially available in Brazil and mixed grass extracts are commonly used for diagnosis and immunotherapy of grass pollen allergy. Further studies are required to better characterize the cross-reactivity between L. multiflorum and other grass pollen allergens for improving the diagnosis and immunotherapy to L. multiflorum pollen allergy.

Quantitative analysis of antigen specific IgE in tears in comparison to serum samples.

We determined pollen specific IgE in tears and compared these results to the concentration of specific IgE in serum samples. We obtained tears (using Schirmer strips) and serum samples from subjects with Japanese cedar (Cryptomeria japonica) pollinosis, and tested for C. japonica pollen specific IgE using a quantitative ELISA. Time kinetic analyses through the pollen season showed that specific IgE levels in tears were found to increase earlier than those in sera and reached their maximum at the end of or after the pollen season, from March to early June. In the C. japonica pollen free season, July to December, the specific IgE levels in tears decreased, although the serum levels remained relatively high. These results indicate that the quantitative assay for specific IgE in tears might be useful to identify specific eye allergens.

Correlation between some parameters in active seasonal allergic rhinitis: a controlled clinico-immunological study

Allergic rhinitis is a global disease with increasing prevalence worldwide. It is characterized by inflammatory cells and mediators of which, eosinophil and IgE, are playing a central role. IgA with its two forms [serum IgA and secretory IgA] is one of the respiratory system defense mechanisms against pathogens, however, its role and its relation to other allergic inflammatory parameters is still under investigation. This study was conducted on twenty allergic rhinitis patients and ten apparently healthy persons as a control to test the correlation between different parameters in allergic rhinitis including; eosinophil count, IgE, IgA levels and symptoms score in active symptomatic seasonal allergic rhinitis. Results showed that blood eosinophil percentage and nasal eosinophil count as well as serum IgE were significantly increased in patients than controls. Secretory IgA [sIgA] in nasal secretion but not serum IgA was significantly increased in patients group indicating excess local production; which is probably a part in the allergic reaction. There was a positive correlation between serum eosinophil percentage and eosinophil count in nasal secretion and serum IgE levels, which may suggest that eosinophil count in nasal secretions; could be a reliable tool in diagnosis of allergic rhinitis. sIgA in nasal secretions increased in patient's group and is found to be positively correlated to nasal eosinophil count, which may suggest a role of sIgA in the pathogenesis of allergic rhinitis. Although there was a positive correlation between nasal obstruction score and nasal eosinophil count, however, as it is a subjective scoring, it can't be relied on until accurate objective scoring is used to measure nasal obstruction. The present study stressed on the importance of meticulous history taking [symptoms score]. The results stressed on the opinion that serum IgE and eosinophil count are good markers for allergic rhinitis, also, nasal cytology for eosinophil count could be used to assist in diagnosis; it is easy, simple and east to help in differentiation of allergic from non allergic rhinitis. The findings of IgA raise the point that it's measurement could be a good tool to be added to the battery of parameters for diagnosis or evaluation of the severity of allergic rhinitis together with follow up of patients. IgE, IgA, IgG: immunoglobulin E, A, G., sIgA: secretory IgA., HDM: House dust mites, Fc: fraction crystalline, ELISA: Enzyme linked Immunosorbent Assay, ECP: eosinophilic cationic protein, PO: eosinophil peroxidase, EDN: eosinophil- derived neurotoxin, TNF-alpha: tumor necrosis factor alpha, SAR=seasonal allergic rhinitis, HPF: high power field

Nasal Eosinophilic Inflammation Contributes to Bronchial Hyperresponsiveness in Patients with Allergic Rhinitis

There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41 +/-3.59 mg/mL vs 10.2 +/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5 +/-132.5 IU/L vs. 389.0 +/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.

Reactividad cutánea a alimentos en pacientes con rinoconjuntivitis alérgica / Food allergens in pacients with allergic rhinoconjunctivitis

La alergia ocular puede ser inducida por alimentos o por alergenos inhalantes; sin embargo, hay pocos estudios pediátricos al respecto. Objetivo: evaluar la relación de reactividad cutánea a alimentos y compararla con la de los inhalantes en pacientes pediátricos con rinoconjuntivitis. Método: se incluyeron 50 pacientes entre 6 y 16 años y se les realizaron pruebas a inhalantes y alimentos, IgE sérico total, citología de mucosa nasal y ocular. Para el análisis estadistico se utilizaron la prueba de T de Student no pareada, análisis de varianza de una vía, Ji cuadrada, medidas de tendencia central y dispersión. Resultados: la edad promedio fue de 9.1 años ñ 2.5 días. Las pruebas cutáneas resultaron positivas en 20 por ciento sólo para alimentos, 50 por ciento para inhalantes y 30 por ciento para ambos. Los alergenos alimentarios más frecuentes fueron mariscos, jitomate, arroz, cacahuate. El de los inhalantes fue Dermatophagoides pteronissinus. Se observó IgE sérica más elevada y citología ocular positiva en el grupo con respuesta positiva a alimentos, con diferencia significativa (p= 0.023) en relación con inhalantes. Conclusiones: en el grupo de estudio se encontraron pacientes con alergia ocular con alta frecuencia de hipersensibilidad a los alimentos (50 por ciento)

Pólenes relevantes para la rinitis alérgica estacional en la ciudad de Bahía Blanca y zona de influencia / The importance of the pollen for seasonal allergic rhinitis in Bahia Blanca city and influence zone

Se estudió la importancia etiológica de diversas especies vegetales en la rinitis y/o asma en Bahía Blanca y zona de influencia, teniendo en consideración los postulados de Thomen. Métodos: se realizaron pruebas cutáneas (prick test) con 55 alérgenos estandarizados en 50 pacientes con rinoconjuntivitis estacional o exacerbada estaciomnalmente, con o sin asma. Los resultados obtenidos fueron cotejados con los registros florísticos, fenológicos y aeropalinológicos de la región en estudio. Resultados: de los alérgenos utilizados cuatro hierbas de la familia Gramineae (Poa pratensis, 70 por ciento; Phalaris arundinacea, 58 por ciento; Agrupyrum repens, 54 por ciento y Agrostis alba, 54 por ciento) son los que produjeron reacciones más intensas, seguidas por Olea europaea (olivo), árbol perteneciente a las Oleaceae. Altos registros aeropalinológicos coincidieron con las especies más alérgenicas, salvo Cupresus spp y Fraxinus que presentaron los mayores volúmenes de polen aéreo y baja sensibilidad (10 por ciento y 6 por ciento). Conclusiones: a) los alérgenos más reactivos no coinciden con la abundancia relativa de la especie homóloga en la zona. Tal desviación de los postulados de Thomen debe explicarse por la existencia de reacciones cruzadas con especies taxonómicamente afines, b) los taxones más relevantes pertenecen a las familias Gramineae tomada en su conjunto, Oleaceae (olivo) y Salicaceae (álamos); c) nuestros resultados revelan semejanzas con los obtenidos por otros autores para países de la cuenca del Mediterráneo, pero se apartan de los correspondientes a América del Norte y Escandinavia

Immunological and clinical evaluation during a 12 month period of immunotherapy.

Serum IgE and IgG4 were evaluated in twenty adult allergic rhinitis subjects during a 12-month immunotherapy (IT) course against common inhalant allergens. The selection criteria for IT were the result of a prolonged history of allergic diseases and a positive skin test for common inhalant allergens. Twenty non-atopic adults served as the control group. By using enzyme-linked immunoassay a normal range of IgE and IgG4 were 78 +/- 40 IU/ml and 180 +/- 54 micrograms/ml, respectively. The changes in IgE and IgG4 levels were compared with significant improvements of symptoms and drug consumption. The clinical and laboratory responses to IT were considered good in 8 cases (40%), moderate in 7 cases (35%), and poor in the remaining 5 cases (25%). A regression analysis revealed a negative simple linear correlation between elevated level of IgG4 and diminished level of clinical symptom scores during 12 months of IT (Pearson's r = -0.7548). The serum IgG4 level after one year IT predicted change in clinical symptom scores.

Arborizaçäo urbana como influência na epidemiologia da polinose na cidade de Caxias do Sul, RS, Brasil / Urban arborization as influence in epidemiology of pollinosis in the city of Caxias do Sul, RS, Brazil

A incidência de polinose no Brasil näo é conhecida, porém existe um aumento recente na regiäo Sul. A cidade de Caxias do Sul, possui uma incidência de 4,8% entre a populaçäo, é considerada regiäo de polinose endêmica. O Ligustrum sp é uma árvore ornamental amplamente distribuída na zona central da cidade. O total de 157 pacientes com "hay fever" foi pesquisado para a presença de sensibilidade cutânea a alergenos. Houve 50,3% de testes cutâneos positivos para o extrato político de Ligustrum. As árvores com pólen alergênico, e, especialmente o Ligustrum lucidum deve ser poribido o plantio nas cidades

Epidemiologia da polinose na populaçäo de algumas cidades do Estado do Rio Grande do Sul / Epidemiology of pollinosis in the population of some cities from the state of Rio Grande do Sul

A incidência de sensibilizaçäo a pólens tem aumentado recentemente na Regiäo Sul do Brasil. Através de entrevistas dirigidas, foi estudada uma populaçäo de 4.207 indivíduos em diferentes cidades do Estado do Rio Grande do Sul. A periodicidade anual da doença, associada aos sintomas característicos, permitiu diagnosticar neste grupo 62 (1,4%) pessoas com provável polinose. A cidade de Caxias do Sul, com uma incidência de 4,8%, somada a pesquisas paralelas nas áreas médica e botânica, constitui regiäo de polinose endêmica, asim como a cidade de Passo Fundo, que apresenta uma incidência média de 2,3%

Análise de 50 casos de polinose por gramíneas / Evaluation of 50 cases pollinosis by grass pollen

A doença polínica era considerada uma raridade no Brasil. Säo apresentados 50 casos de polinoso por gramineas, cuja exteriorizaçäo clínica principal é de rinoconjuntivite alérgica de extrema intensidade. A periodicidade dos sintomas nos meses de Primavera coincide com a presença na atmosfera de pólens de gramíneas. A avaliaçäo através de testes cutâneos revela a gramínea Lolium multiflorum como de maior importância para este grupo de pacientes. Esta observaçäo pioneira deve alertar para a existência do fenômeno também, em outras regiöes com características de clima e flora semelhantes às de Curitiba