Objective: To investigate the cytokine response pattern (IL 4/IFN γ ) in infants with RSV infections and bronchiolitis during the acute phase. Methods: Four color flow cytometry was used to measure intracellu...Objective: To investigate the cytokine response pattern (IL 4/IFN γ ) in infants with RSV infections and bronchiolitis during the acute phase. Methods: Four color flow cytometry was used to measure intracellular IL 4 and IFN γ expressions in peripheral blood CD3+ and CD8+ lymphocytes from RSV infected and bronchiolitis infants. Serum IL 4 and IFN γ levels were also determined. Results: RSV infected and bronchiolitis infants showed no statistical differences from not RSV infected or pneumonia infants and control in the frequency of IL 4 and IFN γ expressions in CD3+CD8 lymphocytes, showed no obvious Th1/Th2 imbalance, while IFN γ was expressed much more frequently in CD3+CD8+ lymphocytes. Systematically, RSV infected and bronchiolitis infants showed much lower levels of serum IL 4 and IL 4/IFN γ ratios and much higher serum IFN γ levels than control. However, there were no statistical differences in the above three indices between RSV infected and not RSV infected infants or between bronchiolitis and pneumonia infants, except that bronchiolitis infants had a higher level of serum IFN γ than pneumonia infants statistically. Conclusions: There is no type 2 cytokine response predominance in the acute phase of RSV infection and bronchiolitis. IL 4 production is suppressed and IFN γ production upregulated, the latter being most prominent in bronchiolitis infants.展开更多
Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 -...Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 - 36 months and to relate their responses to disease severity. Methods: Nasopharyngeal aspirations (NPAs) were analyzed for RSV and IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-1RA, IL-4R, IFN-γ, sTNFR1, sTNFR2, and TNF-α. Clinical data were collected from the medical records. Results: We included 331 infants of whom 214 were RSV+. In comparison to RSV- infants, they had significantly higher levels of TNF-α, IL-6, IL-1β, and IFN-γ (p α, IL-6, and IL-1β. sTNFR1/2 were significantly increased in RSV+ infants. Hospitalized patients had significantly higher levels of TNF-α, sTNFR2, and IL-10 (p < 0.05) than non-hospitalized patients. The cytokine response could not be related to disease severity. We found no evidence of a skewed Th1/Th2 immune profile. Conclusion: In acute RSV disease, infected infants’ NPAs contain a significant amount of pro-inflammatory cytokines. Whether this response is beneficial or deleterious remains unanswered. Interpersonal variations in cytokine responses might be linked to an inherited tendency to variations in disease severity.展开更多
We studied the RSV specific IgE antibody, histamine and basophil from infants with RSV bronchiolitis and found during the acute phase either the titers of RSV-IgE or the concentration of histamine increased significan...We studied the RSV specific IgE antibody, histamine and basophil from infants with RSV bronchiolitis and found during the acute phase either the titers of RSV-IgE or the concentration of histamine increased significantly, the number of basophil and basophil degranulation in the presence of RSV antigen also increased. In vitro studies revealed hypersensitivity participates in the pathogenesis of RSV bronchiolitis. We also found that infants with RSV bronchiolitis, the RSV-IgE persisted for a long time presumably this plays an important role in recurrent wheezing after RSV infection for years.展开更多
Background:The influence of Mycoplasma pneumoniae(MP)infection on bronchiolitis remains unclear.Additionally,reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been in...Background:The influence of Mycoplasma pneumoniae(MP)infection on bronchiolitis remains unclear.Additionally,reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been inconclusive.Methods:Children with respiratory syncytial virus(RSV)-induced bronchiolitis were divided into two groups:RSV+MP group and RSV group.Each group was randomly divided into two subgroups:one received routine and placebo treatment,while the other received routine and montelukast treatment for 9 months.The cumulative numbers of wheezing episodes and recurrent respiratory tract infections were recorded.Blood parameters were determined.Results:Patients in the RSV+MP group exhibited an older average age,fever,more frequent flaky and patchy shadows in chest X-rays,more frequent extrapulmonary manifestations,and longer hospital stays compared with patients in the RSV group.Additionally,higher baseline blood eosinophil counts,eosinophil cationic protein(ECP),total immunoglobulin E(IgE),interleukin(IL)-4,IL-5,IL-4/interferon-γratios,leukotriene(LT)B4,and LTC4,and lower baseline lipoxin A4(LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the RSV group.Montelukast treatment decreased the cumulative numbers of recurrent wheezing episodes and recurrent respiratory tract infections at 9 and 12 months.This efficacy may be related to the montelukast-induced reductions in peripheral eosinophil counts,ECP and total IgE,as well as the montelukast-dependent recovery in T helper(Th)1/Th2 balance and LXA4/LTB4 ratios in children with bronchiolitis.Conclusions:RSV bronchiolitis with MP infection was associated with clinical and laboratory features that differed from those of RSV bronchiolitis without MP infection.Add-on therapy with montelukast for 9 months was benefi cial for children with bronchiolitis at 9 and 12 months after the initiation of treatment.展开更多
Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respira...Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance.展开更多
Background Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (-1082A/G) polymorph...Background Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (-1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (-3575A/T), rs1800871 (-819C/T) or rs1800872 (-592C/A) either alone or combined with the SNP at rs1800896 (-1082G/A), and the etiology and severity of infant bronchiolitis. Methods Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization. Results Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P=0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than con-trols (65.5%, P=0.009). Twenty-eight infants with bronchiolitis had the variant–variant Grs1800896Trs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures. Conclusion IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and con-trols, but not between infants with respiratory syncytial virus bronchiolitis and controls.展开更多
Background Bronchiolitis is a common acute lower respiratory tract infection(ALRTI)and the most frequent cause of hospitalization of infants and young children with ALRTI.Respiratory syncytial virus is the main pathog...Background Bronchiolitis is a common acute lower respiratory tract infection(ALRTI)and the most frequent cause of hospitalization of infants and young children with ALRTI.Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis.The disease burden is relatively high.To date,few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available.This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China.Methods This study included the face sheet of discharge medical records collected from 27 tertiary children’s hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords(FUTURE)database.The sociodemographic variables,length of stay(LOS)and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests.Results In total,42,928 children aged 0–3 years were hospitalized due to bronchiolitis from January 2016 to December 2020,accounting for 1.5%of the total number of hospitalized children of the same age in the database during the period and 5.31%of the hospitalizations for ALRTI.The male to female ratio was 2.01:1.Meanwhile,more boys than girls were observed in different regions,age groups,years,and residences.The 1–2 year age group had the greatest number of hospitalizations for bronchiolitis,while the 29 days–6 months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group.In terms of region,the hospitalization rate of bronchiolitis was the highest in East China.Overall,the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016.Seasonally,the peak hospitalizations for bronchiolitis occurred in winter.Hospitalization rates in North China in autumn and winter were higher than those in South China,while hospitalization rates in South China were higher in spring and summer.Approximately,half of the patients with bronchiolitis had no complications.Among the complications,myocardial injury,abnormal liver function and diarrhea were more common.The median LOS was 6 days[interquartile range(IQR)=5–8],and the median hospitalization cost was 758 United States dollars(IQR=601.96–1029.53).Conclusions Bronchiolitis is a common respiratory disease in infants and young children in China,and it accounts for a higher proportion of both total hospitalizations and hospitalizations due to ALRTI in children.Among them,children aged 29 days–2 years are the main hospitalized population,and the hospitalization rate of boys is significantly higher than that of girls.The peak season for bronchiolitis is winter.Bronchiolitis causes few complications and has a low mortality rate,but the burden of this disease is heavy.展开更多
文摘Objective: To investigate the cytokine response pattern (IL 4/IFN γ ) in infants with RSV infections and bronchiolitis during the acute phase. Methods: Four color flow cytometry was used to measure intracellular IL 4 and IFN γ expressions in peripheral blood CD3+ and CD8+ lymphocytes from RSV infected and bronchiolitis infants. Serum IL 4 and IFN γ levels were also determined. Results: RSV infected and bronchiolitis infants showed no statistical differences from not RSV infected or pneumonia infants and control in the frequency of IL 4 and IFN γ expressions in CD3+CD8 lymphocytes, showed no obvious Th1/Th2 imbalance, while IFN γ was expressed much more frequently in CD3+CD8+ lymphocytes. Systematically, RSV infected and bronchiolitis infants showed much lower levels of serum IL 4 and IL 4/IFN γ ratios and much higher serum IFN γ levels than control. However, there were no statistical differences in the above three indices between RSV infected and not RSV infected infants or between bronchiolitis and pneumonia infants, except that bronchiolitis infants had a higher level of serum IFN γ than pneumonia infants statistically. Conclusions: There is no type 2 cytokine response predominance in the acute phase of RSV infection and bronchiolitis. IL 4 production is suppressed and IFN γ production upregulated, the latter being most prominent in bronchiolitis infants.
基金Funding has been granted from the Medical Research Foundation in Region III,East-Danish Medical Research Forum(ΦSFF)Frederiks-borg County Research Foundation+5 种基金Rosalie Petersen’s FoundationCaptain Harald Jensen and Wife’s FoundationMrs Olga Bryde Nielsen’s FoundationTvergaard Foundationthe Danish Medical Association’s Research Foundationthe Danish Pediatric Society(DPS).
文摘Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 - 36 months and to relate their responses to disease severity. Methods: Nasopharyngeal aspirations (NPAs) were analyzed for RSV and IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-1RA, IL-4R, IFN-γ, sTNFR1, sTNFR2, and TNF-α. Clinical data were collected from the medical records. Results: We included 331 infants of whom 214 were RSV+. In comparison to RSV- infants, they had significantly higher levels of TNF-α, IL-6, IL-1β, and IFN-γ (p α, IL-6, and IL-1β. sTNFR1/2 were significantly increased in RSV+ infants. Hospitalized patients had significantly higher levels of TNF-α, sTNFR2, and IL-10 (p < 0.05) than non-hospitalized patients. The cytokine response could not be related to disease severity. We found no evidence of a skewed Th1/Th2 immune profile. Conclusion: In acute RSV disease, infected infants’ NPAs contain a significant amount of pro-inflammatory cytokines. Whether this response is beneficial or deleterious remains unanswered. Interpersonal variations in cytokine responses might be linked to an inherited tendency to variations in disease severity.
文摘We studied the RSV specific IgE antibody, histamine and basophil from infants with RSV bronchiolitis and found during the acute phase either the titers of RSV-IgE or the concentration of histamine increased significantly, the number of basophil and basophil degranulation in the presence of RSV antigen also increased. In vitro studies revealed hypersensitivity participates in the pathogenesis of RSV bronchiolitis. We also found that infants with RSV bronchiolitis, the RSV-IgE persisted for a long time presumably this plays an important role in recurrent wheezing after RSV infection for years.
基金supported by a grant from the Priority Academic Program Development of Jiangsu Higher Education Institution(JX10231801).
文摘Background:The influence of Mycoplasma pneumoniae(MP)infection on bronchiolitis remains unclear.Additionally,reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been inconclusive.Methods:Children with respiratory syncytial virus(RSV)-induced bronchiolitis were divided into two groups:RSV+MP group and RSV group.Each group was randomly divided into two subgroups:one received routine and placebo treatment,while the other received routine and montelukast treatment for 9 months.The cumulative numbers of wheezing episodes and recurrent respiratory tract infections were recorded.Blood parameters were determined.Results:Patients in the RSV+MP group exhibited an older average age,fever,more frequent flaky and patchy shadows in chest X-rays,more frequent extrapulmonary manifestations,and longer hospital stays compared with patients in the RSV group.Additionally,higher baseline blood eosinophil counts,eosinophil cationic protein(ECP),total immunoglobulin E(IgE),interleukin(IL)-4,IL-5,IL-4/interferon-γratios,leukotriene(LT)B4,and LTC4,and lower baseline lipoxin A4(LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the RSV group.Montelukast treatment decreased the cumulative numbers of recurrent wheezing episodes and recurrent respiratory tract infections at 9 and 12 months.This efficacy may be related to the montelukast-induced reductions in peripheral eosinophil counts,ECP and total IgE,as well as the montelukast-dependent recovery in T helper(Th)1/Th2 balance and LXA4/LTB4 ratios in children with bronchiolitis.Conclusions:RSV bronchiolitis with MP infection was associated with clinical and laboratory features that differed from those of RSV bronchiolitis without MP infection.Add-on therapy with montelukast for 9 months was benefi cial for children with bronchiolitis at 9 and 12 months after the initiation of treatment.
文摘Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance.
文摘Background Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (-1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (-3575A/T), rs1800871 (-819C/T) or rs1800872 (-592C/A) either alone or combined with the SNP at rs1800896 (-1082G/A), and the etiology and severity of infant bronchiolitis. Methods Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization. Results Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P=0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than con-trols (65.5%, P=0.009). Twenty-eight infants with bronchiolitis had the variant–variant Grs1800896Trs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures. Conclusion IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and con-trols, but not between infants with respiratory syncytial virus bronchiolitis and controls.
基金XZD was supported by the CAMS Innovation Fund for Med‑ical Sciences(2019-I2M-5-026)the National Major Science&Technology Project(2017ZX10103004-004).
文摘Background Bronchiolitis is a common acute lower respiratory tract infection(ALRTI)and the most frequent cause of hospitalization of infants and young children with ALRTI.Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis.The disease burden is relatively high.To date,few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available.This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China.Methods This study included the face sheet of discharge medical records collected from 27 tertiary children’s hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords(FUTURE)database.The sociodemographic variables,length of stay(LOS)and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests.Results In total,42,928 children aged 0–3 years were hospitalized due to bronchiolitis from January 2016 to December 2020,accounting for 1.5%of the total number of hospitalized children of the same age in the database during the period and 5.31%of the hospitalizations for ALRTI.The male to female ratio was 2.01:1.Meanwhile,more boys than girls were observed in different regions,age groups,years,and residences.The 1–2 year age group had the greatest number of hospitalizations for bronchiolitis,while the 29 days–6 months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group.In terms of region,the hospitalization rate of bronchiolitis was the highest in East China.Overall,the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016.Seasonally,the peak hospitalizations for bronchiolitis occurred in winter.Hospitalization rates in North China in autumn and winter were higher than those in South China,while hospitalization rates in South China were higher in spring and summer.Approximately,half of the patients with bronchiolitis had no complications.Among the complications,myocardial injury,abnormal liver function and diarrhea were more common.The median LOS was 6 days[interquartile range(IQR)=5–8],and the median hospitalization cost was 758 United States dollars(IQR=601.96–1029.53).Conclusions Bronchiolitis is a common respiratory disease in infants and young children in China,and it accounts for a higher proportion of both total hospitalizations and hospitalizations due to ALRTI in children.Among them,children aged 29 days–2 years are the main hospitalized population,and the hospitalization rate of boys is significantly higher than that of girls.The peak season for bronchiolitis is winter.Bronchiolitis causes few complications and has a low mortality rate,but the burden of this disease is heavy.