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Professor Matt S.
Zinter and others analyzed the influence of factors such as lung virus infection, microbiome exhaustion, lung inflammation, and epithelial injury on the occurrence of lung injury after HCT in children before HCT, and further explored how to reduce the occurrence of HCT in children.
To improve the overall safety of children's HCT.
Research background and purpose Each year, more than 7500 children in Europe and America require hematopoietic cell transplantation (HCT) for disease treatment.
The incidence of HCT pulmonary toxicity in children is 10%-40%, and the causes include infection, treatment-related toxicity, rejection, and other forms of non-infectious inflammation.
Children undergoing HCT have a poor prognosis after lung injury.
Among them, the mortality rate of children who need to use a ventilator is about 40%, and the mortality rate of children with acute respiratory distress syndrome is more than 60%.
Therefore, it is necessary to determine the factors that cause lung injury after HCT, and promote the development of prevention, early detection, and biological treatment.
Previous related studies have shown that clinical factors related to the development of lung injury after HCT in children include impaired lung function tests before HCT, abnormalities in high-resolution chest tomography (HRCT) before HCT, use of myeloablative preconditioning programs, and/or specific Chemotherapy drugs (such as busulfan, bleomycin), whole body irradiation, and HLA-incompatible transplantation; and the microbiological factor before HCT that is related to lung injury after HCT in children is the respiratory virus (RV) at the time of transplantation Infection, which may be the cause of HCT lung injury, may be due to HCT and/or airway epithelial injury triggering allogeneic immune inflammation; other microbiological factors related to lung injury after HCT include cytomegalovirus seropositivity before HCT, History of bacterial or invasive fungal infection in the lungs.
In order to further determine the pre-HCT biological factors associated with lung damage after HCT, the researchers included children who routinely received bronchoalveolar lavage (BAL) before HCT into the study cohort, and used advanced transcriptomics sequencing technology for sample detection.
Research methods This study analyzed the biological specimens of 181 pediatric HCT candidates who received BAL before routine HCT at Utrecht University Medical Center from 2005 to 2016.
The BAL fluid of the child was subjected to transcriptome sequencing of microbial and human RNA, and unsupervised clustering and generalized linear models were used to correlate the microbial gene expression data with the occurrence of lung injury after HCT.
The correlation between microorganisms and genes has been verified using 18 pediatric HCT candidates in different cohorts.
Results of the study The total incidence of lung injury after HCT in the patients included in the study was 21%, and the incidence of fatal lung injury was 9.
4%.
The results of univariate analysis showed that the recent (2013-2016) HCT lung injury incidence, recurrence rate, and lung injury-related mortality were low.
In addition, the mortality rate and non-recurrent mortality rate of adolescent patients are higher.
The results of routine microbiology testing showed that pathogens were detected in nearly 50% of children with BAL samples before HCT.
Adenoviremia after HCT is related to lung injury after HCT.
The researchers further combined the microbiome data of the children’s BAL samples with standardized human protein coding gene counts, and used the UMAP method to perform dimensionality reduction to generate 4 clusters of distinct HCT pretranscriptomes, of which cluster 1 oropharyngeal microbes are rich.
Cluster group, cluster 2 microbial exhaustion group, cluster 3 oropharyngeal microbial content low group, and cluster 4 virus-enriched group.
The spatial superposition of the total respiratory viral RNA amount and the bacterial RNA amount in each BAL sample shows that these clusters are composed of significantly different microorganisms spanning multiple orders of magnitude.
The results showed that the cumulative incidence of lung injury after HCT in children was significantly different among the four clusters of patients (P<0.
001).
Among them, cluster 3 patients had a higher cumulative incidence of lung injury after HCT than cluster 2 patients (44.
4±0.
6% vs 9.
5±0.
1%, SHR: 5.
6, 95% CI: 2.
5-12.
8, P<0.
001). The cumulative incidence of death after HCT-induced lung injury was also significantly different among the 4 clusters of patients (P=0.
003).
The results of multivariate competitive risk regression analysis showed that the incidence of lung injury after fatal HCT in 4 clusters of patients was significantly different (P=0.
032).
In addition, the fatal lung injury after HCT is related to the activation of epithelial-epidermal differentiation, mucus production, and cell adhesion.
In a separate validation cohort, the researchers confirmed the correlation between lung respiratory viral load, oropharyngeal microbiota and lung gene expression, as well as the correlation with lung injury after HCT.
Research conclusions The research results indicate that for children who need to receive HCT, the microbiome data of BAL fluid can be evaluated before HCT, or high-risk children who can benefit from pathogenic microbiological intervention can be found.
References: Matt S Zinter, Caroline A Lindemans, Birgitta A Versluys, et al.
The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury.
Blood.
2021 Mar 25;137(12):1679-1689.
Click to read Original ", we make progress together
Zinter and others analyzed the influence of factors such as lung virus infection, microbiome exhaustion, lung inflammation, and epithelial injury on the occurrence of lung injury after HCT in children before HCT, and further explored how to reduce the occurrence of HCT in children.
To improve the overall safety of children's HCT.
Research background and purpose Each year, more than 7500 children in Europe and America require hematopoietic cell transplantation (HCT) for disease treatment.
The incidence of HCT pulmonary toxicity in children is 10%-40%, and the causes include infection, treatment-related toxicity, rejection, and other forms of non-infectious inflammation.
Children undergoing HCT have a poor prognosis after lung injury.
Among them, the mortality rate of children who need to use a ventilator is about 40%, and the mortality rate of children with acute respiratory distress syndrome is more than 60%.
Therefore, it is necessary to determine the factors that cause lung injury after HCT, and promote the development of prevention, early detection, and biological treatment.
Previous related studies have shown that clinical factors related to the development of lung injury after HCT in children include impaired lung function tests before HCT, abnormalities in high-resolution chest tomography (HRCT) before HCT, use of myeloablative preconditioning programs, and/or specific Chemotherapy drugs (such as busulfan, bleomycin), whole body irradiation, and HLA-incompatible transplantation; and the microbiological factor before HCT that is related to lung injury after HCT in children is the respiratory virus (RV) at the time of transplantation Infection, which may be the cause of HCT lung injury, may be due to HCT and/or airway epithelial injury triggering allogeneic immune inflammation; other microbiological factors related to lung injury after HCT include cytomegalovirus seropositivity before HCT, History of bacterial or invasive fungal infection in the lungs.
In order to further determine the pre-HCT biological factors associated with lung damage after HCT, the researchers included children who routinely received bronchoalveolar lavage (BAL) before HCT into the study cohort, and used advanced transcriptomics sequencing technology for sample detection.
Research methods This study analyzed the biological specimens of 181 pediatric HCT candidates who received BAL before routine HCT at Utrecht University Medical Center from 2005 to 2016.
The BAL fluid of the child was subjected to transcriptome sequencing of microbial and human RNA, and unsupervised clustering and generalized linear models were used to correlate the microbial gene expression data with the occurrence of lung injury after HCT.
The correlation between microorganisms and genes has been verified using 18 pediatric HCT candidates in different cohorts.
Results of the study The total incidence of lung injury after HCT in the patients included in the study was 21%, and the incidence of fatal lung injury was 9.
4%.
The results of univariate analysis showed that the recent (2013-2016) HCT lung injury incidence, recurrence rate, and lung injury-related mortality were low.
In addition, the mortality rate and non-recurrent mortality rate of adolescent patients are higher.
The results of routine microbiology testing showed that pathogens were detected in nearly 50% of children with BAL samples before HCT.
Adenoviremia after HCT is related to lung injury after HCT.
The researchers further combined the microbiome data of the children’s BAL samples with standardized human protein coding gene counts, and used the UMAP method to perform dimensionality reduction to generate 4 clusters of distinct HCT pretranscriptomes, of which cluster 1 oropharyngeal microbes are rich.
Cluster group, cluster 2 microbial exhaustion group, cluster 3 oropharyngeal microbial content low group, and cluster 4 virus-enriched group.
The spatial superposition of the total respiratory viral RNA amount and the bacterial RNA amount in each BAL sample shows that these clusters are composed of significantly different microorganisms spanning multiple orders of magnitude.
The results showed that the cumulative incidence of lung injury after HCT in children was significantly different among the four clusters of patients (P<0.
001).
Among them, cluster 3 patients had a higher cumulative incidence of lung injury after HCT than cluster 2 patients (44.
4±0.
6% vs 9.
5±0.
1%, SHR: 5.
6, 95% CI: 2.
5-12.
8, P<0.
001). The cumulative incidence of death after HCT-induced lung injury was also significantly different among the 4 clusters of patients (P=0.
003).
The results of multivariate competitive risk regression analysis showed that the incidence of lung injury after fatal HCT in 4 clusters of patients was significantly different (P=0.
032).
In addition, the fatal lung injury after HCT is related to the activation of epithelial-epidermal differentiation, mucus production, and cell adhesion.
In a separate validation cohort, the researchers confirmed the correlation between lung respiratory viral load, oropharyngeal microbiota and lung gene expression, as well as the correlation with lung injury after HCT.
Research conclusions The research results indicate that for children who need to receive HCT, the microbiome data of BAL fluid can be evaluated before HCT, or high-risk children who can benefit from pathogenic microbiological intervention can be found.
References: Matt S Zinter, Caroline A Lindemans, Birgitta A Versluys, et al.
The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury.
Blood.
2021 Mar 25;137(12):1679-1689.
Click to read Original ", we make progress together
