Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function.

The level of fractional exhaled nitric oxide (FENO) is significantly elevated in uncontrolled asthma and decreases after anti-inflammatory therapy. The aim of this prospective study was to analyze the behavior of FENO in the follow-up and management of the inflammation in asthmatic pediatric patients treated with inhaled corticosteroids (ICS), compared to sputum cellularity, serum interleukins (IL), and pulmonary function. Twenty-six clinically stable asthmatic children aged from 6 to 18 years, previously treated or not with ICS were included. Following an international consensus (GINA), the patients were submitted to standard treatment with inhaled fluticasone for 3 months according to the severity of the disease. During this period, each patient underwent three assessments at intervals of approximately 6 weeks. Each evaluation consisted of the measurement of FENO, determination of serum interleukins IL-5, IL-10, IL-13, and interferon gamma (INF-gamma), spirometry and cytological analysis of spontaneous or induced sputum. A significant reduction in mean FENO and IL-5, without concomitant changes in FEV1, was observed along the study. There was no significant correlation between FeNO and FEV1 in the three assessments. A significant correlation between FeNO and IL-5 levels was only observed in the third assessment (r = 0.499, P = 0.025). In most patients, serum IL-10, IL-13, and INF-gamma concentrations were undetectable throughout the study. Sputum samples were obtained spontaneously in 11 occasions and in 56 by induction with 3% hypertonic saline solution (success rate: 50.8%), with 39 (69.9%) of them adequate for analysis. Only two of the 26 patients produced adequate samples in the three consecutive evaluations, which impaired the determination of a potential association between sputum cellularity and FeNO levels throughout the study. In conclusion, among the parameters of this study, it was difficult to perform and to interpret the serial analysis of spontaneous or induced sputum. Serum interleukins, which remained at very low or undetectable levels in most patients, were not found to be useful for therapeutic monitoring, except for IL-5 that seems to present some correlation with levels of FeNO exhaled. Monitoring of the mean FEV1 indicated no significant variations during the treatment, demonstrating that functional stability or the absence of obstruction may not reflect the adequate management of asthma. Serial measurement of FeNO seemed to best reflect the progressive anti-inflammatory action of ICS in asthma.

ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens.

OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) is a complicating factor of cystic fibrosis which can result in a devastating combination as lung disease progresses. The overlap between the signs and symptoms of the two conditions makes diagnosis problematic, even if standardized criteria are used. The objective of this study was to identify, in a group of cystic fibrosis patients, cases of ABPA by assaying IgE specific to recombinant Aspergillus fumigatus antigens and to compare the method with the Cystic Fibrosis Foundation diagnostic criteria. METHODS: Fifty-four patients, aged 2 to 20 years, presenting characteristics that could occur with ABPA in isolation, were systematically assessed based on the following: clinical data, a chest CT scan, immediate hypersensitivity skin test for A. fumigatus, total serum IgE assay, RAST for A. fumigatus and serum IgE specific for the recombinant allergens Asp f1, f2, f3, f4 and f6. RESULTS: Thirty-nine patients were eligible for the study. Thirty-two of these were investigated. Sensitization to A. fumigatus was observed in 34%. Both the Cystic Fibrosis Foundation criteria and the recombinant antigen specific IgE assay defined three patients as suffering from ABPA; however, only two of these patients were diagnosed by both methods. CONCLUSIONS: The detection of A. fumigatus recombinant antigen specific IgE was a useful tool for the early detection of sensitization and diagnosis of ABPA. Nevertheless, diagnostic confirmation cannot be divorced from clinical findings, and before this method can be used for ABPA diagnosis, for detecting relapses and for defining cure criteria, longitudinal studies with larger numbers of patients are required.

Diagnóstico de ABPA em pacientes portadores de fibrose cística: utilidade clínica da pesquisa de IgE específica contra alérgenos recombinantes do Aspergillus fumigatus / ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens

OBJETIVO: A aspergilose broncopulmonar alérgica (ABPA) é um fator complicador da fibrose cística que pode determinar uma combinação devastadora na evolução da doença pulmonar. A sobreposição de sinais e sintomas das duas enfermidades dificulta o diagnóstico, mesmo aplicando critérios padronizados. O objetivo deste trabalho foi identificar, em grupo de portadores de fibrose cística, os casos de ABPA através da detecção de IgE específica contra os alérgenos recombinantes do Aspergillus fumigatus e confrontar esse método com os critérios preconizados pela Cystic Fibrosis Foundation. MÉTODOS: Cinqüenta e quatro pacientes de 2 a 20 anos, com características que poderiam estar isoladamente presentes na ABPA, foram avaliados sistematicamente, incluindo: dados clínicos, tomografia computadorizada de tórax, teste cutâneo de hipersensibilidade imediata para A. fumigatus; dosagem de IgE sérica total, RAST para A. fumigatus, e IgE sérica específica para alérgenos recombinantes r Asp f1, f2, f3, f4 e f6. RESULTADOS: Foram elegíveis para o estudo 39 pacientes. Destes, 32 foram investigados. Houve sensibilização ao A. fumigatus em 34 por cento. Ambos os métodos, o critério da Cystic Fibrosis Foundation e a pesquisa de IgE específica contra antígenos recombinantes, determinaram três casos de ABPA; entretanto, o diagnóstico foi concordante em apenas dois pacientes. CONCLUSÃO: A detecção de IgE específica contra antígenos recombinantes do A. fumigatus foi ferramenta útil para detecção precoce da sensibilização e diagnóstico de ABPA. No entanto, a confirmação diagnóstica não pôde ser desvinculada da condição clínica, e sua utilização para diagnóstico, detecção de recidivas e critério de cura ainda requer estudos longitudinais, envolvendo maior número de pacientes.

[Induced sputum in children and adolescents with asthma: safety, clinical applicability and inflammatory cells aspects in stable patients and during exacerbation]. / Escarro induzido em crianças e adolescentes com asma: segurança, aplicabilidade clínica e perfil de células inflamatórias em pacientes estáveis e durante exacerbação.

OBJECTIVES: To determine the safety of sputum induction in asthmatic children and adolescents, to characterize sputum inflammatory cells while clinically stable and during exacerbation and to correlate sputum inflammatory cells with peripheral blood eosinophils, serum IgE and the degree of bronchial obstruction. METHODS: Ninety-six asthmatic patients aged 6 to 18 years were recruited for the present cross-sectional study. Spirometry was performed before and after administration of a bronchodilator. Sputum was collected spontaneously or after induction by the inhalation of saline solution at increasing concentrations. Blood samples were obtained for serum IgE and eosinophil quantification. RESULTS: Sputum samples adequate for analysis were obtained from 68 (70.8%) of the patients recruited. No relevant bronchoconstriction was observed during induction. The presence of a larger number of eosinophils in sputum did not correlate with more clinically severe asthma. No correlation was observed between the degree of bronchial obstruction, measured based on FEV1, and inflammatory cells in sputum, peripheral blood eosinophils or serum IgE. Larger numbers of neutrophils were observed in the asthma exacerbation group (p < 0.05). CONCLUSIONS: Sputum induction was found to be a safe procedure for obtaining clinical samples from children and adolescents even during exacerbations, allowing for clinical and functional limitations. The 67% induction success rate was considered satisfactory. In this group of patients, receiving inhaled corticosteroids, eosinophil quantification did not distinguish between the clinical and functional severity of asthma and was independent of the degree of airway obstruction. A proportional predominance of neutrophils was observed in the sputum of patients with asthma exacerbation.

Escarro induzido em crianças e adolescentes com asma: segurança, aplicabilidade clínica e perfil de células inflamatórias em pacientes estáveis e durante exacerbação / Induced sputum in children and adolescents with asthma: safety, clinical applicability and inflammatory cells aspects in stable patients and during exacerbation

OBJETIVOS: Verificar a segurança da indução de escarro em crianças e adolescentes asmáticos. Caracterizar a citologia do escarro durante a estabilidade clínica e exacerbação. Correlacionar a citologia do escarro com os eosinófilos no sangue periférico, IgE sérica e grau de obstrução brônquica. MÉTODOS: Foram recrutados 96 pacientes asmáticos, de 6 a 18 anos, para um estudo transversal. Foi realizada espirometria antes e, após, broncodilatador. A seguir, foi coletado o escarro, espontaneamente ou após indução com inalação de solução salina em concentrações crescentes. Foi coletada amostra de sangue para quantificar a IgE sérica e os eosinófilos. RESULTADOS: Obtiveram-se amostras adequadas de escarro para análise em 68 (70,8 por cento) dos pacientes recrutados. Não houve broncoconstrição relevante durante a indução. A presença de maior número de eosinófilos no escarro de acordo com a maior gravidade clínica da asma não foi estatisticamente significante. Não houve correlação entre o grau de obstrução brônquica medido pelo VEF1 e as células inflamatórias do escarro. O mesmo foi observado em relação aos eosinófilos no sangue periférico e à IgE sérica. No grupo com exacerbação da asma, observou-se uma quantidade maior de neutrófilos (p < 0,05). CONCLUSÕES: A indução de escarro mostrou-se segura para obtenção de amostras clínicas em crianças e adolescentes, mesmo durante exacerbações, respeitando-se limitações clínicas e funcionais. O índice de sucesso da indução de 67 por cento foi considerado satisfatório. A quantificação dos eosinófilos não discriminou a gravidade clínica e funcional da asma e mostrou-se independente do grau de obstrução das vias aéreas neste grupo de pacientes em tratamento com corticosteróides inalatórios. No escarro de pacientes em exacerbação da asma, houve um predomínio proporcional de neutrófilos.

Educational program for smoke-induced respiratory diseases in Brazilian Amazon: assessing knowledge about asthma.

Economic and cultural considerations underlie the forest clearing by burning that occurs in the Brazilian Amazon region. The prevalence of respiratory diseases markedly increases during the annual burning season. As part of a nongovernmental initiative to reduce forest fires, health professionals received updated training about respiratory diseases aggravated by smoke. The aim of the present study was to describe and evaluate this educational program. A total of 1500 health care professionals received theoretical and practical guidance. Some of the involved community health agents (CHA) and nurse technicians completed a questionnaire that assessed knowledge about asthma before and after training. Asthma was recognized as an inflammatory disease by 274 of 743 (36%) CHA and nurse technicians on the initial questionnaire compared with 542 of 684 (80%) on the final questionnaire (p < 0.0001). The concept that asthma and allergic bronchitis are the same disease was initially acknowledged by 250 of 743 (33%) CHA and nurse technicians compared with 671 of 684 (90%) after the training (p < 0.0001). The usefulness of bronchodilators was identified by 442 of 743 (60%) CHA and nurse technicians before the training vs. 497 of 684 (73%) after the training (p < 0.0001). Training significantly influenced knowledge about asthma in the group studied. The impact of this program on health care remains unknown.