RESUMO
BACKGROUND: The genetic diversity of the Brazilian population results from three ethnic groups admixture: Europeans, Africans and Amerindians, thus increasing the difficulty of performing cystic fibrosis (CF) diagnosis. The nasal potential difference (NPD) evaluates the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity. Despite being a useful CF diagnostic test and a biomarker of CFTR-modulator drugs, it is also highly operator dependent. Therefore, it may be difficult to get accurate results and to interpret them. Wilschanski and Sermet scores were proposed to address these issues. This study aimed to evaluate repeatability and diagnostic value of NPD parameters and Wilschanski and Sermet scores in a CF center in Rio de Janeiro. METHODS: NPD was performed in 78 subjects. Maximal PD, amiloride response, total chloride response, and Wilschanski and Sermet scores were explored as means (confidence interval, CI). One-way ANOVA was used to compare mean differences and Scheffe test was used to pair-wise comparisons. Repeatability was evaluated by scatter and Bland-Altman plots. The Ethics Committee of the CF Center has approved the study protocol. Parents and adult participants signed an informed consent form. RESULTS: Forty-eight healthy-volunteers, 19 non-CF and 11 CF patients were enrolled in this study. Significant differences were found when comparing CF patients' NPD parameters to the other two groups (P = 0.000). Moreover, no significant differences were found when parameters from non-CF patients were compared with those from healthy volunteers (P > 0.05). The means of NPD parameters and diagnostic scores of each group were in concordance with disease/non-disease conditions. The repeatability data - Wilschanski and Sermet and NPD - allow NPD to be performed in this Brazilian CF Center. CONCLUSIONS: The present study gathered consistent data for Bland-Altman plots. The results of Wilschanski and Sermet diagnostic scores suggest that they were concordant with CF/non-CF conditions. More NPD tests should be performed in the Rio de Janeiro CF dynamic cohort to contribute to international NPD validation studies and to provide NPD as a biomarker in Brazil.
RESUMO
Pseudomonas aeruginosa is associated with increased mortality in cystic fibrosis (CF) patients, and expresses type III secretion system proteins (TTSP), which is a common mechanism used by gram-negative pathogens for delivery of anti-host factors. Our aim was to investigate whether or not these antigens (TTSP) would be recognized by CF sera, by Western blot reaction. We have showed herein that all patients (n = 11) not chronically infected by P. aeruginosa had their first serum positive for TTSP (ExoS, ExoT, PopB, and/or PopD). All chronic patients had a strong positive serology to TTSP, although relatively weak reactions to TTSP were observed for some individuals in the negative control group. Therefore, TTSP that were early produced in P. aeruginosa infected CF patients, induced a detectable antibody response in those patients and were easily detected by Western-blot reaction.
Assuntos
Fibrose Cística/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/microbiologia , Adolescente , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/sangue , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/sangue , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Criança , Pré-Escolar , Estudos Transversais , Fibrose Cística/sangue , Fibrose Cística/metabolismo , Humanos , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/metabolismo , Infecções Respiratórias/imunologia , Infecções Respiratórias/metabolismo , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare HRCT findings in cystic fibrosis (CF) patients chronically colonized with Pseudomonas aeruginosa or Staphylococcus aureus using the modified Bhalla CT scoring system, as well as to evaluate intraobserver and interobserver reliability of the method. METHODS: This was a retrospective cross-sectional study involving 41 CF patients, 26 of whom were chronically colonized with P. aeruginosa (Pa group), and 15 of whom were colonized with S. aureus (Sa group).Two independent radiologists evaluated the HRCT scans of these patients using the modified Bhalla CT scoring system in two different moments. Intraobserver and interobserver reliability was calculated using the intraclass correlation coefficient (ICC). RESULTS: There was good intraobserver and interobserver agreement (ICC > 0.8). Scores were higher in the Pa group than in the Sa group for observer 1 (mean, 13.50 ± 3.90; median, 13.5 vs. mean, 5.00 ± 5.28; median, 3.0) and for observer 2 (mean, 11.96 ± 5.07; median, 12.0 vs. mean, 5.07 ± 5.65; median, 5.0). In addition, HRCT findings, such as bronchiectasis, bronchial wall thickening, mucus plugging, generation of bronchial divisions, and mosaic attenuation/perfusion pattern, were more prevalent in the Pa group. CONCLUSIONS: The modified Bhalla CT scoring system was reproducible and reliable for use in the evaluation of HRCT scans, allowing distinctions to be drawn between the two groups of patients under study. The higher scores in the Pa group provided evidence of greater pulmonary impairment in that group.
Assuntos
Bronquiectasia/diagnóstico por imagem , Fibrose Cística/diagnóstico por imagem , Infecções por Pseudomonas/diagnóstico por imagem , Infecções Estafilocócicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Criança , Fibrose Cística/microbiologia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Muco/diagnóstico por imagem , Variações Dependentes do ObservadorRESUMO
OBJETIVO: Comparar achados de TCAR em pacientes com fibrose cística (FC) colonizados cronicamente por Pseudomonas aeruginosa ou Staphylococcus aureus, empregando o escore de Bhalla modificado, e avaliar as confiabilidades intraobservador e interobservador do método. MÉTODOS: Estudo transversal retrospectivo incluindo 41 pacientes portadores de FC, 26 dos quais colonizados cronicamente por P. aeruginosa (grupo Pa) e 15 por S. aureus (grupo Sa). Dois radiologistas analisaram independentemente em duas ocasiões, as imagens de TCAR desses pacientes e aplicaram o escore de Bhalla modificado. As confiabilidades intra e interobservador foram avaliadas segundo o coeficiente de correlação intraclasse (CCI). RESULTADOS: Houve boa concordância intraobservador e interobservador (CCI > 0,8). Os resultados dos escores do grupo Pa foram mais elevados que os do grupo Sa para o observador 1 (média de 13,50 ± 3,90 e mediana de 13,5 vs. média de 5,0 ± 5,28 e mediana de 3,0) e para o observador 2 (média de 11,96 ± 5,07 e mediana de 12,0 vs. média de 5,07 ± 5,65 e mediana de 5,0). Alterações tomográficas, como bronquiectasias, espessamento das paredes brônquicas, formação de tampões mucosos, comprometimento de gerações de divisões brônquicas e padrão de atenuação em mosaico, foram mais prevalentes no grupo colonizado por P. aeruginosa. CONCLUSÕES: O escore de Bhalla modificado se mostrou reprodutível e confiável para a avaliação de TCAR e permitiu a diferenciação entre os pacientes incluídos nos dois grupos. Escores mais altos no grupo Pa evidenciaram maior comprometimento estrutural pulmonar nesse grupo.
OBJECTIVE: To compare HRCT findings in cystic fibrosis (CF) patients chronically colonized with Pseudomonas aeruginosa or Staphylococcus aureus using the modified Bhalla CT scoring system, as well as to evaluate intraobserver and interobserver reliability of the method. METHODS: This was a retrospective cross-sectional study involving 41 CF patients, 26 of whom were chronically colonized with P. aeruginosa (Pa group), and 15 of whom were colonized with S. aureus (Sa group).Two independent radiologists evaluated the HRCT scans of these patients using the modified Bhalla CT scoring system in two different moments. Intraobserver and interobserver reliability was calculated using the intraclass correlation coefficient (ICC). RESULTS: There was good intraobserver and interobserver agreement (ICC > 0.8). Scores were higher in the Pa group than in the Sa group for observer 1 (mean, 13.50 ± 3.90; median, 13.5 vs. mean, 5.00 ± 5.28; median, 3.0) and for observer 2 (mean, 11.96 ± 5.07; median, 12.0 vs. mean, 5.07 ± 5.65; median, 5.0). In addition, HRCT findings, such as bronchiectasis, bronchial wall thickening, mucus plugging, generation of bronchial divisions, and mosaic attenuation/perfusion pattern, were more prevalent in the Pa group. CONCLUSIONS: The modified Bhalla CT scoring system was reproducible and reliable for use in the evaluation of HRCT scans, allowing distinctions to be drawn between the two groups of patients under study. The higher scores in the Pa group provided evidence of greater pulmonary impairment in that group.
Assuntos
Criança , Feminino , Humanos , Masculino , Bronquiectasia , Fibrose Cística , Infecções por Pseudomonas , Infecções Estafilocócicas , Tomografia Computadorizada por Raios X/métodos , Fibrose Cística/microbiologia , Métodos Epidemiológicos , Muco , Variações Dependentes do ObservadorRESUMO
INTRODUÇÃO: As infecções respiratórias agudas (IRAs) constituem importante causa de morbidade e mortalidade em crianças nos países em desenvolvimento. A etiologia viral dessas infecções nem sempre é conhecida no Brasil, e estudos sobre as IRAs virais em crianças com doenças de base (DBs) são escassos. OBJETIVO: Determinar a etiologia viral dessas infecções em menores de 5 anos assistidos no Instituto Fernandes Figueira da Fundação Oswaldo Cruz (IFF/FIOCRUZ), Rio de Janeiro. MÉTODOS: Foram analisadas 285 amostras de aspirado de nasofaringe, obtidas de 204 crianças com IRA, de maio de 2005 a junho de 2006. RESULTADOS: Por meio da imunofluorescência indireta (IFI), 90 amostras (31,6 por cento) foram positivas: 21,4 por cento vírus sincicial respiratório (VSR); 3,5 por cento adenovírus (Ad); 3,1 por cento parainfluenza (PF) 3; 2,5 por cento influenza (Flu) A; 0,7 por cento PF 1; 0,4 por cento Flu B. Das 195 negativas, 156 foram testadas para metapneumovírus humano (MPVh), com 15 positivas (9,6 por cento das amostras testadas). CONCLUSÃO: A prevalência viral nos serviços de ambulatórios foi de 42,8 por cento e nos hospitalizados foi de 30 por cento. Das crianças, 83,3 por cento possuíam uma ou mais DBs associadas às IRAs, resultando em longos períodos de internação. Algumas delas tiveram múltiplas internações e múltiplos diagnósticos clínicos de IRA no período estudado.
INTRODUCTION: Acute respiratory infections (ARIs) are an important cause of morbidity and mortality among children in developing countries. The viral etiology of such infections is not always known in Brazil. Furthermore, studies on viral ARIs in children with underlying diseases (UD) are scanty. OBJECTIVE: The objective of this study was to determine the viral etiology of these infections among children under 5 years of age treated at Instituto Fernandes Figueira/Fundação Oswaldo Cruz (IFF/FIOCRUZ), Rio de Janeiro. METHOD: Two hundred and eighty-five samples of nasopharyngeal aspirate, which had been obtained from 204 children with ARI from May/2005 to June/2006, were analyzed. RESULTS: Samples were tested through indirect immunofluorescence assay and 90 of them (31.6 percent) were positive for the following viral agents: respiratory syncytial virus (21.4 percent), adenovirus (3.5 percent), parainfluenza 3 (3.1 percent), influenza A (2.5 percent), parainfluenza 1 (0.7 percent), and influenza B (0.4 percent). One hundred and ninety-five samples were negative, from which 156 were tested for human metapneumovirus, and 15 of them (9.6 percent) were positive. CONCLUSION: The viral prevalence among outpatients was 42.8 percent and among inpatients it was 30 percent; 83.3 percent of the children were carriers of one or more UD associated with ARI, resulting in long-term admission to hospital. Some children had multiple admissions and multiple clinical diagnoses of ARI during the studied period.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Imunofluorescência , Infecções Respiratórias/etiologia , VirosesRESUMO
SUMMARY BACKGROUND: Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction. PATIENTS AND METHODS: One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T(0)), and at 3 (T(1)), 6 (T(2)), 9 (T(3)), and 12 (T(4)) months of follow-up. Eighteen patients were excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6-11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis. RESULTS: After 1 year of follow-up, there was significant improvement in respiratory symptoms (T(4) - T(0) = 8.1; 95% confidence interval (95% CI) = [2.1;14.0]; effect size (ES) = 0.35; P < 0.001), Emotional Functioning (T(4) - T(0) = 5.6; 95% CI = [1.1;10.1]; ES = 0.31; P < 0.05), Social Functioning (T(4) - T(0) = 6.0; 95% CI = [1.3;11.7]; ES = 0.31; P < 0.05), Body Image (T(4) - T(0) = 11.9; 95% CI = [4.1;19.7]; ES = 0.42; P < 0.05), and Treatment Burden (T(4) - T(0) = 5.3; 95% CI = [0.3;10.3]; ES = 0.24; P < 0.05) domains in the younger group. A significant improvement in Role Functioning (T(4) - T(0) = 6.1; 95% CI = [1.1;11.1]; ES = 0.40; P < 0.05), Body Image (T(4) - T(0) = 12.6; 95% CI = [3.5;21.7]; ES = 0.46; P < 0.05), and Weight (T(4) - T(0) = 11.7; 95% CI = [1.8;21.6]; ES = 0.40; P < 0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T(4) - T(0) = 5.5; 95% CI = [1.5;9.4]; ES = 0.30; P < 0.05), Respiratory Symptoms (T(4) - T(0) = 7.6; 95% CI = [3.9;11.4]; ES = 0.48; P < 0.05), and Weight (T(4) - T(0) = 10.1; 95% CI = [1.6;18.6]; ES = 0.26; P < 0.05) domains. CONCLUSION: The introduction of dornase alfa improved the HRQL of the patients with CF during the first year of treatment.
Assuntos
Fibrose Cística/tratamento farmacológico , Desoxirribonuclease I/uso terapêutico , Expectorantes/uso terapêutico , Qualidade de Vida , Adolescente , Brasil , Criança , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Estudos ProspectivosRESUMO
Cystic fibrosis (CF) is the most frequent life threatening autosomal recessive disease in white subjects. The primary cause of morbidity and mortality in children with CF is chronic pulmonary infection, mainly caused by Pseudomonas aeruginosa. The purpose of this study was to assess the value of the measurement of antibodies to P. aeruginosa in diagnosing lung infection by the bacteria in CF patients. We assessed P. aeruginosa antibody titers in CF patients from Rio de Janeiro, Brazil, using cell lysate antigens as well as recombinant PcrV, a Type III Secretion System protein. Sputum (more than 70% of the specimens) or oropharyngeal swabs were obtained whenever patients were regularly followed for their pulmonary disease. Blood samples were obtained with an average interval of 6 months for a period of 2 years. The ELISA cut-offs were assigned as the positive 95% confidence interval of the mean antibody levels from non-fibrocystic controls. Our data showed that most CF patients (81%) of whom were not chronically infected by P. aeruginosa (Groups I and II), had their first serology positive for rPcrV. Cell-lysate ELISA was able to detect P. aeruginosa antibodies before positive culture in the first serum sample of 44% of the patients from Groups I and II. When serum reactivity to rPcrV and cell lysate were combined, 94% of CF patients from Groups I and II (n = 16) had the first serology positive for P. aeruginosa over a mean time of 20 months before the first isolation of P. aeruginosa. In conclusion, longitudinal P. aeruginosa serology should become part of respiratory care follow-up, in conjunction with other lung parameter functions.
Assuntos
Anticorpos Antibacterianos/sangue , Fibrose Cística/sangue , Fibrose Cística/imunologia , Pseudomonas aeruginosa/imunologia , Adolescente , Brasil , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Fibrose Cística/microbiologia , Diagnóstico Precoce , Feminino , Humanos , Lactente , Masculino , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Valores de ReferênciaRESUMO
Objetivo: avaliar o diagnóstico da infecção e colonização pulmonar por Pseudomonas aeruginosa (Pa), através da detecção de anticorpos séricos específicos em pacientes fibrocísticos.Fontes pesquisadas: foi revisada a base de dados Medline, no período de 1986 a 2007, com os descritores fibrose cística e pseudomonas. Síntese dos dados: as alterações no transporte de íons nas células epiteliais levam à obstruçãocrônica das vias aéreas, com infecções secundárias. A Pa mucóide é o principal agente que aumenta a morbidade e a mortalidade nos pacientes fibrocísticos. A erradicação da bactéria é possível com antibioticoterapia precoce, queaumenta a sobrevida dos pacientes. A cultura de secreções respiratórias apresenta limitação como método diagnóstico, pela dificuldade decoleta da amostra. Parece promissora a detecção de anticorpos específicos no soro para Pa, que, em muitos casos, precede o isolamento bacterianoem cultura. O método mais utilizado é ode ELISA, com pesquisa de IgG ou IgG, IgM, e IgA. A positividade da sorologia não discrimina entre colonização e infecção pulmonar e, a condutaantibiótica não é uniforme nessa situação. Conclusões: a pesquisa sorológica de anticorpos para Pa pode ser útil no tratamento do pacientefibrocístico. Complementa a avaliação clínica, permite reavaliações não invasivas durante a evolução e possibilita a antibioticoterapia precoceem parte dos casos.
Objective: to evaluate the diagnosis of lung infection and colonization by Pseudomonas aeruginosa (Pa) through the detection of specific seric antibodies in fibrocystic patients. Data sources: the Medline database, was searched in the period 1986 to 2007, with the keywords cystic fibrosisand pseudomonas. Data synthesis: the epithelium cells disturb in ion transport cause a chronic airways obstruction, with secondary infections. Themucoid Pa is the main agent that increases morbidity and mortality in fibrocystic patients. The Objective: to evaluate the diagnosis of lung infectionand colonization by Pseudomonas aeruginosa (Pa) through the detection of specific seric antibodies in fibrocystic patients. Data sources: the Medline database, was searched in the period1986 to 2007, with the keywords cystic fibrosis and pseudomonas. Data synthesis: the epithelium cells disturb in ion transport cause a chronic airwaysobstruction, with secondary infections. The mucoid Pa is the main agent that increases morbidity and mortality in fibrocystic patients. The bacteria eradication is possible with early antibiotic therapy, which increases patients survival period. Respiratory secretions culture is limited as a diagnostic method, due to the difficulty incollecting samples. The detection of specific antibodies in serum for Pa, which in many cases precedesthe bacteria isolation in culture, seems to be promising. The most used method is the ELISA, with survey of IgG or IgG, IgM, and IgA. The serological positive result does not make a distinctionbetween lung colonization and infection, and the antibiotic procedure is not uniform in such situation. Conclusions: the serological antibodies survey for Pa can be useful in the treatment of fibrocystic patients. It completes the clinical evaluation, allowing non invasive reevaluations during the evolution as well as an early antibiotictherapy in some cases.
Objetivo: evaluar el diagnostico de la infección y colonización pulmonar por Pseudomonas aeruginosa (Pa) en pacientes con fibrosis cística, mediante la detección de anticuerpos sericosespecíficos. Fuente de los datos: fueron seleccionados los artículos en la base de datos Medline publicados entre 1986 y 2007, con las palabras clave fibrose cistica y pseudomonas. Síntesis delos datos: las alteraciones en el transporte de los iones de las células epiteliales llevan a la obstruccióncrónica de las vias aereas, con infecciones secundarias. La Pa mucoide es el principal agente que aumenta la morbidad y mortalidad de los pacientes fibrocisticos. La eliminación de labacteria es posible con antibióticoterapia precoz, qui determina mayor sobrevida de los pacientes.Lo cultivo de secreciones respiratorias presenta limitación como método diagnóstico, determinada por la dificultad de recolectar la muestra. Ladetección de anticuerpos específicos en el suero para Pa en muchos casos precede el islamiento bacteriano en cultura. Lo metodo más utilizadoes el de ELISA, con pesquisa de IgG, o IgG IgM y IgA. El resultado positivo non discrimina entre la ocurrencia de colonización o infección pulmonary, por lo tanto, a conducta non es uniforme en esta situación. Conclusiones: la pesquisa serologicade anticuerpos para Pa puede ser util en el tratamiento del paciente con fibrose cística. Complementa la evaluación clinica, permite reevaluaciones non invasivas, y posibilita la antibioticoterapia precoz en parte dos casos.
Assuntos
Humanos , Fibrose Cística/genética , Pneumopatias/diagnóstico , Pseudomonas aeruginosa , Condutas Terapêuticas Homeopáticas , Fibrose Cística/epidemiologia , Testes SorológicosRESUMO
Knowledge about the virulence mechanisms of species from the Burkholderia cepacia complex (BCC) is still limited. The genomovar heterogeneity and production of different virulence factors are likely to contribute to the variation in the clinical outcome observed in BCC-infected cystic fibrosis (CF) patients. Therefore, in this study we investigated the genetic polimorphism, the presence of genetic makers associated with virulence and transmissibility in BCC, and the profile of exoenzyme production of 59 BCC isolates obtained from 59 CF patients attending the reference CF centre in Rio de Janeiro, Brazil. The DNA sequence analyses of the recA gene allowed us to identify 40 of these 59 BCC species as being B. cenocepacia, 9 as B. vietnamiensis, 6 as B. multivorans and 4 as B. ambifaria. The assessment of the bacterial genetic polymorphism by PFGE revealed that B. cenocepacia and the B. multivorans isolates belonged to four and two different PFGE profiles with prevalence of two clones, A and B, respectively. All B. vietnamiensis and B. ambifaria belonged to only one PFGE profile (J and E, respectively). None of the isolates exhibited the genetic markers cblA and BCESM, assessed by polymerase chain reaction. In contrast, the profile of enzymatic activity, assessed by phenotypic methods, differed among the BCC species: protease activity was detected only in B. cenocepacia and B. ambifaria isolates, whereas only B. vietnamiensis isolates produced hemolysin. Although the phospholipase C activity was similar among the different species, the level of lipase activity produced by B. multivorans was higher than in the other species. We speculate that the differential characteristics of exoenzyme production may account for the differences in the pathogenic potentials of each BCC species.
Assuntos
Infecções por Burkholderia/microbiologia , Burkholderia cepacia/isolamento & purificação , Burkholderia/isolamento & purificação , Fibrose Cística/microbiologia , Pneumopatias/microbiologia , Proteínas de Bactérias/análise , Técnicas de Tipagem Bacteriana , Biomarcadores/análise , Brasil , Burkholderia/enzimologia , Burkholderia/genética , Burkholderia cepacia/enzimologia , Burkholderia cepacia/genética , Eletroforese em Gel de Campo Pulsado , Enzimas/análise , Humanos , Polimorfismo Genético , Virulência/genéticaRESUMO
Fifteen serial Burkholderia cepacia complex isolates recovered over a period of 4 years from a single cystic fibrosis patient were analysed for genomovar status by means of recA sequence determination, and genetic relatedness by RAPD-PCR. Twelve isolates were assigned as Burkholderia vietnamiensis, two as Burkholderia cenocepacia and one as Burkholderia multivorans. B. vietnamiensis persisted in the airways during 4 years, except in three occasions when B. cenocepacia or B. multivorans were isolated. The patient was chronically colonized by B. vietnamiensis with the RAPD-profile 12 and transiently by the RAPD-profile 15.