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1.
Sci Transl Med ; 10(440)2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743346

RESUMO

Prostaglandin D2 (PGD2) signals through PGD2 receptor 2 (DP2, also known as CRTH2) on type 2 effector cells to promote asthma pathogenesis; however, little is known about its role during respiratory syncytial virus (RSV) bronchiolitis, a major risk factor for asthma development. We show that RSV infection up-regulated hematopoietic prostaglandin D synthase expression and increased PGD2 release by cultured human primary airway epithelial cells (AECs). Moreover, PGD2 production was elevated in nasopharyngeal samples from young infants hospitalized with RSV bronchiolitis compared to healthy controls. In a neonatal mouse model of severe viral bronchiolitis, DP2 antagonism decreased viral load, immunopathology, and morbidity and ablated the predisposition for subsequent asthma onset in later life. This protective response was abolished upon dual DP1/DP2 antagonism and replicated with a specific DP1 agonist. Rather than mediating an effect via type 2 inflammation, the beneficial effects of DP2 blockade or DP1 agonism were associated with increased interferon-λ (IFN-λ) [interleukin-28A/B (IL-28A/B)] expression and were lost upon IL-28A neutralization. In RSV-infected AEC cultures, DP1 activation up-regulated IFN-λ production, which, in turn, increased IFN-stimulated gene expression, accelerating viral clearance. Our findings suggest that DP2 antagonists or DP1 agonists may be useful antivirals for the treatment of viral bronchiolitis and possibly as primary preventatives for asthma.


Assuntos
Bronquiolite Viral/metabolismo , Bronquiolite Viral/patologia , Interferon gama/biossíntese , Prostaglandina D2/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Alérgenos , Animais , Animais Recém-Nascidos , Antivirais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/virologia , Humanos , Imunidade , Lactente , Inflamação/patologia , Inflamação/virologia , Oxirredutases Intramoleculares/metabolismo , Pulmão/patologia , Pulmão/virologia , Camundongos Endogâmicos BALB C , Vírus da Pneumonia Murina , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina/antagonistas & inibidores , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/fisiologia , Regulação para Cima
2.
J Clin Virol ; 102: 101-109, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29549834

RESUMO

BACKGROUND: As the expression of type III IFN receptor is restricted to the mucosal surfaces, its evaluation could be crucial to characterize the role of IFNλs during bronchiolitis. OBJECTIVES: This study was designed to investigate airway type III IFN receptor (IFNLR1/IL10RB) expression during respiratory syncytial virus (RSV) or human rhinovirus (HRV) bronchiolitis. STUDY DESIGN: Seventy-one 1-6 month old infants hospitalized with their first episode of acute RSV or HRV bronchiolitis were selected for this study. Expression of IFNLR1, IL10RB and IFN-stimulated genes (ISGs) MxA and ISG56 in cells of nasopharyngeal washings taken within the first 48 h of admission were determined by a real-time hydrolysis probe RT-PCR assay. The ability of types I and III IFNs to induce the expression of both IFNLR1 and IL10RB in vitro was also evaluated. RESULTS: Airway IFNLR1 transcript levels were significantly higher in HRV bronchiolitis infants compared to those with RSV bronchiolitis. No differences were recorded for IL10RB-mRNA between RSV or HRV infection. IFNLR1 mRNA levels increased significantly in infants infected with the C species of HRV and in those with a higher clinical score index and with an eosinophil count >3%. There were no correlations in vivo between type III IFN receptors and those of ISGs and neither IFNLR1 nor IL10RB were induced in vitro by IFNs. CONCLUSIONS: These results suggest that IFNLR1 are increased in HRV-infected infants with more severe bronchiolitis and blood eosinophilia and in those infected with the HRVC species.


Assuntos
Bronquiolite Viral/imunologia , Bronquiolite Viral/patologia , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/patologia , Receptores de Citocinas/genética , Rhinovirus/isolamento & purificação , Bronquiolite Viral/virologia , Eosinofilia/virologia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringe/imunologia , Nasofaringe/patologia , RNA Mensageiro/metabolismo , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Rhinovirus/classificação , Rhinovirus/genética , Índice de Gravidade de Doença
4.
J Infect Dis ; 217(1): 24-34, 2017 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-29045741

RESUMO

Background: Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles. Methods: A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes. Results: We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes. Conclusions: RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses.


Assuntos
Bronquiolite Viral/patologia , Bronquiolite Viral/virologia , Genótipo , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/imunologia , Bronquiolite Viral/imunologia , Feminino , Perfilação da Expressão Gênica , Variação Genética , Técnicas de Genotipagem , Hospitalização , Humanos , Lactente , Interferons/metabolismo , Tempo de Internação , Masculino , Nasofaringe/virologia , Neutrófilos/imunologia , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Índice de Gravidade de Doença , Carga Viral
5.
Immunity ; 46(2): 301-314, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28228284

RESUMO

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production. In the respiratory tract of neonates with severe RSV-induced acute bronchiolitis, RSV-infected nBreg cell frequencies correlated with increased viral load and decreased blood memory Th1 cell frequencies. Thus, the frequency of nBreg cells is predictive of the severity of acute bronchiolitis disease and nBreg cell activity may constitute an early-life host response that favors microbial pathogenesis.


Assuntos
Linfócitos B Reguladores/imunologia , Bronquiolite Viral/imunologia , Receptores de Quimiocinas/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Linfócitos B Reguladores/virologia , Bronquiolite Viral/patologia , Linfócitos T CD4-Positivos/imunologia , Receptor 1 de Quimiocina CX3C , Ensaio de Imunoadsorção Enzimática , ELISPOT , Perfilação da Expressão Gênica , Humanos , Recém-Nascido , Ativação Linfocitária/imunologia , Análise de Sequência com Séries de Oligonucleotídeos , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sinciciais Respiratórios , Transcriptoma
6.
PLoS One ; 10(11): e0142649, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26587832

RESUMO

Severe infection with respiratory syncytial virus (RSV) during infancy is strongly associated with the development of asthma. To identify genetic variation that contributes to asthma following severe RSV bronchiolitis during infancy, we sequenced the coding exons of 131 asthma candidate genes in 182 European and African American children with severe RSV bronchiolitis in infancy using anonymous pools for variant discovery, and then directly genotyped a set of 190 nonsynonymous variants. Association testing was performed for physician-diagnosed asthma before the 7th birthday (asthma) using genotypes from 6,500 individuals from the Exome Sequencing Project (ESP) as controls to gain statistical power. In addition, among patients with severe RSV bronchiolitis during infancy, we examined genetic associations with asthma, active asthma, persistent wheeze, and bronchial hyperreactivity (methacholine PC20) at age 6 years. We identified four rare nonsynonymous variants that were significantly associated with asthma following severe RSV bronchiolitis, including single variants in ADRB2, FLG and NCAM1 in European Americans (p = 4.6x10-4, 1.9x10-13 and 5.0x10-5, respectively), and NOS1 in African Americans (p = 2.3x10-11). One of the variants was a highly functional nonsynonymous variant in ADRB2 (rs1800888), which was also nominally associated with asthma (p = 0.027) and active asthma (p = 0.013) among European Americans with severe RSV bronchiolitis without including the ESP. Our results suggest that rare nonsynonymous variants contribute to the development of asthma following severe RSV bronchiolitis in infancy, notably in ADRB2. Additional studies are required to explore the role of rare variants in the etiology of asthma and asthma-related traits following severe RSV bronchiolitis.


Assuntos
Asma/genética , Bronquiolite Viral/genética , Estudos de Associação Genética , Receptores Adrenérgicos beta 2/genética , Afro-Americanos/genética , Asma/complicações , Asma/patologia , Asma/virologia , Bronquiolite Viral/complicações , Bronquiolite Viral/patologia , Antígeno CD56/genética , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu/genética , Exoma/genética , Feminino , Humanos , Lactente , Masculino , Vírus Sinciciais Respiratórios/patogenicidade , Proteínas S100/genética
7.
J Clin Invest ; 125(2): 571-82, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25555213

RESUMO

While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-γ ratio in respiratory secretions. The IL-4/IFN-γ ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-γ ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention.


Assuntos
Bronquiolite Viral , Exposição Ambiental/efeitos adversos , Genótipo , Lipopolissacarídeos/toxicidade , Infecções por Vírus Respiratório Sincicial , Vírus Sinciciais Respiratórios , Células Th2/imunologia , Receptor 4 Toll-Like , Animais , Bronquiolite Viral/genética , Bronquiolite Viral/imunologia , Bronquiolite Viral/patologia , Modelos Animais de Doenças , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Humanos , Lactente , Recém-Nascido , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Masculino , Camundongos , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/patologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Células Th2/patologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia
8.
Asian Pac J Allergy Immunol ; 32(3): 226-34, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25268340

RESUMO

BACKGROUD: Children who suffer a viral lower respiratory infection early in life are prone to subsequent wheezing and asthma: RSV and rhinovirus are thought to be the primary causative pathogens. Epidemiologic and long-term data on these pathogens in Thailand are limited. OBJECTIVES: To detect the causative pathogens in children hospitalized with a first episode of acute wheezing and to compare the respective impact on the recurrence of wheezing and development of asthma. METHOD: We conducted a 5-year cohort study of children under 2 hospitalized with acute bronchiolitis at two tertiary hospitals. Nasopharyngeal secretions were collected at admission to determine the causative pathogens by RT-PCR. RESULTS: 145/170 samples (85%) were positive for pathogens. RSV, rhinovirus, influenza, bacteria and hMPV was found in 64.7%, 18.2%, 17.6%, 12.9% and 3.5% of children respectively. The majority (94/152; 62%) of participants reported having recurrent wheezing within the first year of follow-up (mean duration 5.5 ± 7.2 months). Only 16% still had wheezing episodes after 5 years. Asthma was diagnosed in 41 children (45%), most of whom were treated with inhaled corticosteroid. There were no statistically significant differences among the various etiologies. CONCLUSION: Rhinovirus ranked second after RSV as the cause of hospitalizations of children with acute bronchiolitis. More than half of these children had recurrent wheezing which mostly disappeared before the age of 6. Nearly half were subsequently diagnosed with asthma at the 5th year of follow-up. The specific pathogens did not account for a statistically significant difference in subsequent wheezing or asthma development.


Assuntos
Asma , Bronquiolite Viral , Hospitalização , Infecções por Picornaviridae , Sons Respiratórios/fisiopatologia , Rhinovirus , Doença Aguda , Adolescente , Asma/etiologia , Asma/patologia , Asma/fisiopatologia , Asma/terapia , Bronquiolite Viral/etiologia , Bronquiolite Viral/patologia , Bronquiolite Viral/fisiopatologia , Bronquiolite Viral/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Infecções por Picornaviridae/etiologia , Infecções por Picornaviridae/patologia , Infecções por Picornaviridae/fisiopatologia , Infecções por Picornaviridae/terapia , Estudos Prospectivos , Estudos Retrospectivos
9.
PLoS One ; 8(12): e83035, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24349427

RESUMO

INTRODUCTION: Respiratory insufficiency due to severe respiratory syncytial virus (RSV) infection is the most frequent cause of paediatric intensive care unit admission in infants during the winter season. Previous studies have shown increased levels of inflammatory mediators in airways of mechanically ventilated children compared to spontaneous breathing children with viral bronchiolitis. In this prospective observational multi-center study we aimed to investigate whether this increase was related to disease severity or caused by mechanical ventilation. MATERIALS AND METHODS: Nasopharyngeal aspirates were collected <1 hour before intubation and 24 hours later in RSV bronchiolitis patients with respiratory failure (n = 18) and non-ventilated RSV bronchiolitis controls (n = 18). Concentrations of the following cytokines were measured: interleukin (IL)-1α, IL-1ß, IL-6, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α. RESULTS: Baseline cytokine levels were comparable between ventilated and non-ventilated infants. After 24 hours of mechanical ventilation mean cytokine levels, except for MIP-1α, were elevated compared to non-ventilated infected controls: IL-1α (159 versus 4 pg/ml, p<0.01), IL-1ß (1068 versus 99 pg/ml, p<0.01), IL-6 (2343 versus 958 pg/ml, p<0.05) and MCP-1 (174 versus 26 pg/ml, p<0.05). CONCLUSIONS: Using pre- and post-intubation observations, this study suggests that endotracheal intubation and subsequent mechanical ventilation cause a robust pulmonary inflammation in infants with RSV bronchiolitis.


Assuntos
Bronquiolite Viral/metabolismo , Bronquiolite Viral/terapia , Citocinas/metabolismo , Respiração Artificial/efeitos adversos , Infecções por Vírus Respiratório Sincicial/metabolismo , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sinciciais Respiratórios , Bronquiolite Viral/patologia , Bronquiolite Viral/fisiopatologia , Feminino , Humanos , Lactente , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Inflamação/terapia , Masculino , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Estações do Ano
10.
Am J Respir Cell Mol Biol ; 49(5): 808-13, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23763491

RESUMO

Viral illness with wheezing during infancy is associated with the inception of childhood asthma. Small airway dysfunction is a component of childhood asthma, but little is known about how viral illness at an early age may affect the structure and function of small airways. We used a well-characterized rat model of postbronchiolitis chronic airway dysfunction to address how postinfectious small airway lesions affect airway physiological function and if the structure/function correlates persist into maturity. Brown Norway rats were sham- or virus inoculated at 3 to 4 weeks of age and allowed to recover from the acute illness. At 3 to 14 months of age, physiology (respiratory system resistance, Newtonian resistance, tissue damping, and static lung volumes) was assessed in anesthetized, intubated rats. Serial lung sections revealed lesions in the terminal bronchioles that reduced luminal area and interrupted further branching, affecting 26% (range, 13-39%) of the small airways at 3 months of age and 22% (range, 6-40%) at 12 to 14 months of age. At 3 months of age (n = 29 virus; n = 7 sham), small airway lesions correlated with tissue damping (rs = 0.69) but not with Newtonian resistance (rs = 0.23), and Newtonian resistance was not elevated compared with control rats, indicating that distal airways were primarily responsible for the airflow obstruction. Older rats (n = 7 virus; n = 6 sham) had persistent small airway dysfunction and significantly increased Newtonian resistance in the postbronchiolitis group. We conclude that viral airway injury at an early age may induce small airway lesions that are associated quantitatively with small airway physiological dysfunction early on and that these defects persist into maturity.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Asma/etiologia , Bronquíolos/patologia , Bronquiolite Viral/complicações , Fatores Etários , Envelhecimento , Obstrução das Vias Respiratórias/patologia , Obstrução das Vias Respiratórias/fisiopatologia , Resistência das Vias Respiratórias , Animais , Asma/patologia , Asma/fisiopatologia , Bronquíolos/crescimento & desenvolvimento , Bronquíolos/fisiopatologia , Bronquiolite Viral/patologia , Bronquiolite Viral/fisiopatologia , Modelos Animais de Doenças , Medidas de Volume Pulmonar , Masculino , Ratos , Ratos Endogâmicos BN , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de Tempo
11.
Eur J Immunol ; 43(5): 1297-308, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23436183

RESUMO

ROS production is an important effector mechanism mediating intracellular killing of microbes by phagocytes. Inappropriate or untimely ROS production can lead to tissue damage, thus tight regulation is essential. We recently characterized signal inhibitory receptor on leukocytes-1 (SIRL-1) as an inhibitory receptor expressed by human phagocytes. Here, we demonstrate that ligation of SIRL-1 dampens Fc receptor-induced ROS production in primary human phagocytes. In accordance, SIRL-1 engagement on these cells impairs the microbicidal activity of neutrophils, without affecting phagocytosis. The inhibition of ROS production may result from reduced ERK activation, since co-ligation of Fc receptors and SIRL-1 on phagocytes inhibited phosphorylation of ERK. Importantly, we demonstrate that microbial and inflammatory stimuli cause rapid downregulation of SIRL-1 expression on the surface of primary neutrophils and monocytes. In accordance, SIRL-1 expression levels on neutrophils in bronchoalveolar lavage fluid from patients with neutrophilic airway inflammation are greatly reduced. We propose that SIRL-1 on phagocytes sets an activation threshold to prevent inappropriate production of oxygen radicals. Upon infection, SIRL-1 expression is downregulated, allowing microbial killing and clearance of the pathogen.


Assuntos
Monócitos/metabolismo , Neutrófilos/metabolismo , Fagócitos/metabolismo , Espécies Reativas de Oxigênio/imunologia , Receptores Imunológicos/imunologia , Explosão Respiratória/imunologia , Bronquiolite Viral/imunologia , Bronquiolite Viral/patologia , Bronquiolite Viral/virologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Estudos de Casos e Controles , Contagem de Colônia Microbiana , Regulação da Expressão Gênica/imunologia , Humanos , Imunoconjugados/química , Imunoconjugados/genética , Imunoconjugados/imunologia , Lactente , Monócitos/imunologia , Monócitos/microbiologia , Neutrófilos/imunologia , Neutrófilos/microbiologia , Fagócitos/imunologia , Fagócitos/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Receptores Fc/química , Receptores Fc/genética , Receptores Fc/imunologia , Receptores Imunológicos/química , Receptores Imunológicos/genética , Vírus Sinciciais Respiratórios/imunologia , Sistema Respiratório/imunologia , Transdução de Sinais , Staphylococcus epidermidis/crescimento & desenvolvimento , Staphylococcus epidermidis/imunologia
12.
Pediatr Infect Dis J ; 32(1): e8-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22926214

RESUMO

BACKGROUND: Viruses are detected in most hospitalized children admitted for acute respiratory infections. Etiologic understanding is needed to improve clinical management and prevention, particularly in resource-limited tropical countries. METHODS: A 3-year prospective descriptive study was conducted among Cambodian children admitted to 2 provincial hospitals for acute lower respiratory tract infection. Molecular detection for 18 viral pathogens using multiplex polymerase chain reaction/reverse transcription polymerase chain reactions was performed. RESULTS: We enrolled 1006 children less than 5 years of age of whom 423 (42%), 428 (42%) and 155 (16%) had pneumonia, bronchiolitis and unclassified lower respiratory tract infections, respectively. Of the 551 (55%) with documented viral infection, a single virus was detected in 491 (89%), including rhinovirus (n = 169; 34%), respiratory syncytial virus (n = 167; 34%), parainfluenza virus (n = 40; 8%), human metapneumovirus (n = 39; 8%), influenza virus (n = 31; 6%), bocavirus (n = 16; 3%), adenovirus (n = 15; 3%), coronavirus (n = 9; 2%) and enterovirus (n = 5; 1%). Coinfections with multiple viruses were detected in 6% (2 viruses detected in 59 cases; 3 viruses detected in 1 case). CONCLUSION: Similar to other tropical countries, rhinovirus and respiratory syncytial virus were the principal viral pathogens detected among children hospitalized for lower tract respiratory infection in Cambodia.


Assuntos
Bronquiolite Viral/epidemiologia , Pneumonia Viral/epidemiologia , Bronquiolite Viral/patologia , Bronquiolite Viral/virologia , Camboja/epidemiologia , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Estudos Prospectivos , Estações do Ano , Resultado do Tratamento , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificação
13.
Curr Opin Virol ; 2(3): 294-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22709516

RESUMO

Human parainfluenza viruses (HPIVs) are a common cause of acute respiratory illness throughout life. Infants, children, and the immunocompromised are the most likely to develop severe disease. HPIV1 and HPIV2 are best known to cause croup while HPIV3 is a common cause of bronchiolitis and pneumonia. HPIVs replicate productively in respiratory epithelial cells and do not spread systemically unless the host is severely immunocompromised. Molecular studies have delineated how HPIVs evade and block cellular innate immune responses to permit efficient replication, local spread, and host-to-host transmission. Studies using ex vivo human airway epithelium have focused on virus tropism, cellular pathology and the epithelial inflammatory response, elucidating how events early in infection shape the adaptive immune response and disease outcome.


Assuntos
Bronquiolite Viral/patologia , Crupe/patologia , Infecções por Paramyxoviridae/patologia , Infecções por Paramyxoviridae/virologia , Pneumonia Viral/patologia , Respirovirus/patogenicidade , Bronquiolite Viral/imunologia , Bronquiolite Viral/virologia , Pré-Escolar , Crupe/imunologia , Crupe/virologia , Humanos , Evasão da Resposta Imune , Hospedeiro Imunocomprometido , Lactente , Infecções por Paramyxoviridae/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Respirovirus/imunologia
15.
Braz J Infect Dis ; 15(3): 285-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21670932

RESUMO

We report a case of a 67 year-old-male patient admitted to the intensive care unit in the post-coronary bypass surgery period who presented cardiogenic shock, acute renal failure and three episodes of sepsis, the latter with pulmonary distress at the 30th post-operative day. The patient expired within five days in spite of treatment with vancomycin, imipenem, colistimethate and amphotericin B. At autopsy severe adenovirus pneumonia was found. Viral pulmonary infections following cardiovascular surgery are uncommon. We highlight the importance of etiological diagnosis to a correct treatment approach.


Assuntos
Infecções por Adenovirus Humanos/patologia , Bronquiolite Viral/patologia , Complicações Pós-Operatórias/patologia , Idoso , Bronquiolite Viral/virologia , Ponte de Artéria Coronária , Evolução Fatal , Cardiopatias/cirurgia , Humanos , Unidades de Terapia Intensiva , Masculino , Necrose , Complicações Pós-Operatórias/virologia
16.
Braz. j. infect. dis ; 15(3): 285-287, May-June 2011. ilus
Artigo em Inglês | LILACS | ID: lil-589963

RESUMO

We report a case of a 67 year-old-male patient admitted to the intensive care unit in the post-coronary bypass surgery period who presented cardiogenic shock, acute renal failure and three episodes of sepsis, the latter with pulmonary distress at the 30th post-operative day. The patient expired within five days in spite of treatment with vancomycin, imipenem, colistimethate and amphotericin B. At autopsy severe adenovirus pneumonia was found. Viral pulmonary infections following cardiovascular surgery are uncommon. We highlight the importance of etiological diagnosis to a correct treatment approach.


Assuntos
Idoso , Humanos , Masculino , Infecções por Adenovirus Humanos/patologia , Bronquiolite Viral/patologia , Complicações Pós-Operatórias/patologia , Bronquiolite Viral/virologia , Ponte de Artéria Coronária , Evolução Fatal , Cardiopatias/cirurgia , Unidades de Terapia Intensiva , Necrose , Complicações Pós-Operatórias/virologia
17.
Fetal Pediatr Pathol ; 30(1): 64-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21204669

RESUMO

Myocarditis in the pediatric population is commonly caused by viral pathogens, notably entero virus and adeno virus. Respiratory syncytial virus, although widespread among this population, is rarely associated with myocarditis. The incidence of myocarditis is unknown due to the variability of clinical presentation and diagnostic limitations. Data regarding prognosis is lacking in children. Patients should be monitored in a pediatric intensive care unit secondary to the risk of hemodynamic compromise. We present the case of fulminant myocarditis in a seven-month old female in the setting of respiratory syncytial virus bronchiolitis.


Assuntos
Bronquiolite Viral/patologia , Miocardite/patologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Bronquiolite Viral/complicações , Bronquiolite Viral/terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Lactente , Miocardite/fisiopatologia , Miocardite/virologia , Prognóstico , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/terapia , Resultado do Tratamento
18.
J Toxicol Environ Health A ; 74(5): 313-24, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21240731

RESUMO

Epidemiological studies demonstrated that the number of emergency-room visits for respiratory indications increases during periods of Florida Red Tides. The purpose of this study was to examine whether or not repeated brevetoxin inhalation, as may occur during a Florida Red Tide, affects pulmonary responses to influenza A. Male F344 rats were divided into four groups: (1) sham aerosol/no influenza; (2) sham aerosol/influenza; (3) brevetoxin/no influenza; and (4) brevetoxin/influenza. Animals were exposed by nose-only inhalation to vehicle or 50 µg brevetoxin-3/m3, 2 h/d for 12 d. On d 6 of aerosol exposure, groups 2 and 4 were administered 10,000 plaque-forming units of influenza A, strain HKX-31 (H3N2), by intratracheal instillation. Subgroups were euthanized at 2, 4, and 7 d post influenza treatment. Lungs were evaluated for viral load, cytokine content, and histopathologic changes. Influenza virus was cleared from the lungs over the 7-d period; however, there was significantly more virus remaining in the group 4 lungs compared to group 2. Influenza virus significantly increased interleukins-1α and -6 and monocyte chemotactic protein-1 in lung; brevetoxin exposure significantly enhanced the influenza-induced response. At 7 d, the severity of perivascular and peribronchiolar inflammatory cell infiltrates was greatest in group 4. Bronchiolitis persisted, with low incidence and severity, only in group 4 at d 7. These results suggest that repeated inhalation exposure to brevetoxin may delay virus particle clearance and recovery from influenza A infection in the rat lung.


Assuntos
Vírus da Influenza A Subtipo H3N2/crescimento & desenvolvimento , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Toxinas Marinhas/toxicidade , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Oxocinas/toxicidade , Administração Intranasal , Animais , Bronquiolite Viral/imunologia , Bronquiolite Viral/patologia , Bronquiolite Viral/virologia , Citocinas/metabolismo , Suscetibilidade a Doenças , Proliferação Nociva de Algas , Imunidade nas Mucosas/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Pulmão/patologia , Pulmão/virologia , Masculino , Toxinas Marinhas/administração & dosagem , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Oxocinas/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Fatores de Tempo , Carga Viral
19.
Clin Microbiol Infect ; 17(12): 1829-33, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20636429

RESUMO

The objective of this study was to determine the efficacy and safety of frequently inhaled nebulized hypertonic saline (HS) in infants with moderate to severe bronchiolitis. One hundred and twenty-six infants were randomized to receive either nebulized 3% hypertonic saline (HS) or 0.9% normal saline (NS), but only 112 patients completed the whole study. Cough, wheezing, pulmonary physical signs, clinical severity scores and the hospital length of stay (LOS) were recorded. The wheezing remission time was 4.8 ± 1.0 days in the NS group and 3.6 ± 0.9 days in the HS group (p <0.01). The cough remission time was 5.5 ± 0.9 days in the NS group and 4.3 ± 0.7 days in the HS group (p <0.01). The moist crackles disappeared at 6.2 ± 0.7 days in the NS group and at 4.4 ± 0.9 days in the HS group (p <0.01). The clinical severity scores decreased more significantly in the HS group than in the NS group on each day within 96 h after enrolment (p <0.01). The LOS decreased from 6.4 ± 1.4 days in the NS group to 4.8 ± 1.2 days in the HS group (p <0.01). The treatment was well tolerated, with no adverse effects attributable to nebulized HS. The conclusions are that frequently inhaled HS relieved symptoms and signs faster than NS, and shortened LOS significantly for infants with moderate to severe bronchiolitis, without apparent adverse effects.


Assuntos
Aerossóis/administração & dosagem , Bronquiolite Viral/tratamento farmacológico , Solução Salina Hipertônica/administração & dosagem , Aerossóis/efeitos adversos , Bronquiolite Viral/patologia , Feminino , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Masculino , Terapia Respiratória/efeitos adversos , Terapia Respiratória/métodos , Solução Salina Hipertônica/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Zhonghua Bing Li Xue Za Zhi ; 40(12): 825-9, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22336208

RESUMO

OBJECTIVE: To study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection. METHODS: Eight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out. RESULTS: The major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%). CONCLUSION: Necrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/patologia , Pulmão/patologia , Adolescente , Adulto , Idoso , Células Epiteliais Alveolares/patologia , Antígenos Virais/metabolismo , Apoptose , Autopsia , Biópsia por Agulha , Bronquiolite Viral/patologia , Criança , Pré-Escolar , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/metabolismo , Influenza Humana/mortalidade , Influenza Humana/virologia , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/patologia , Adulto Jovem
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