scholarly journals 3439 Role of the Airway Microbiome in Viral Bronchiolitis Associated Respiratory Failure

2019 ◽  
Vol 3 (s1) ◽  
pp. 20-20
Author(s):  
Emily Wasserman ◽  
Stefan Worgall ◽  
Anurag Sharma

OBJECTIVES/SPECIFIC AIMS: This study aims to determine if a bronchiolitis specific microbiome exists and how it evolves through disease course. Objective 1. Determine the microbiome profile of the airway in virus induced bronchiolitis-associated respiratory failure. Objective 2. Identify changes in the airway microbiome profile through the course of virus induced bronchiolitis associated respiratory failure, and the relationship between microbiome composition and clinical respiratory status. Objective 3. Determine the impact of rhinovirus infection on the lung and stool microbiome in a murine asthma model. METHODS/STUDY POPULATION: Objectives 1 &2: We are conducting a single-center prospective case-control study of patients admitted to the Komansky - Weill Cornell Pediatric Critical Care Unit. Infants less than two years of age with a diagnosis of bronchiolitis requiring intubation and mechanical ventilation are enrolled as subjects. Infants less than two years of age intubated and requiring mechanical ventilation without primary lung pathology are enrolled as controls. To evaluate our primary objective, tracheal aspirates will be collected from both subjects and controls on the day of intubation. We will perform 16s RNA sequencing on the tracheal aspirate samples and compare the resulting microbiomes. To evaluate secondary objective, we will collect tracheal aspirates of our study population on a daily basis and map the microbiome in parallel with objective measures of respiratory status including oxygen index and successful extubation. Both subjects and controls are being enrolled as a convenience sample. Objective 3: Mice, heterozygous for the sptlc2 gene (Spltc2 +/−) demonstrate reduced de-novo sphingolipids and increased airway hyperresponsiveness with methacholine challenge. Airway hyper-responsiveness is a cardinal feature of asthma. This airway hyperresponsiveness is exacerbated in the setting of rhinovirus (Figure 1). Using 16s sequencing, we will examine the lung microbiome of Sptlc2 +/− ad Sptlc2 +/+ at 1- and 7-days following rhinovirus infection. RESULTS/ANTICIPATED RESULTS: This clinical study is currently IRB approved and enrollment is ongoing. We have enrolled 12 subjects and 5 controls. Sample analysis will begin following the 2018-2019 respiratory season, with an anticipated cohort of 20 subjects and 20 controls. With regards to the murine studies, we have demonstrated that the lung microbiome of Sptlc2 +/− and Sptlc2 +/+ mice is similar at baseline (Figure 2) and remains similar following 1-day infection with rhinovirus. We do however, see a distinct change in the microbiome profile of the stool of Sptlc2 +/− mice following rhinovirus infection (Figure 3). Lung analysis at day 7 post infection is pending. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will lay the groundwork for detailing the functional role of the airway microbiome in bronchiolitis, with the objective of developing new modalities for disease treatment and prevention. In addition our murine studies allow us to view the microbiome in the context of sphingolipid deficiency, providing a potential mechanistic link to rhinovirus and ORMDL3 associated asthma.

2019 ◽  
Vol 32 (Supplement_1) ◽  
Author(s):  
U Krishnan ◽  
H Singh ◽  
N Kaakoush ◽  
S Leach

Abstract Background Children with esophageal atresia (EA) often suffer from gastroesophageal reflux disease (GERD) and it's complications, including reflux aspiration. Reflux aspiration can be difficult to diagnose in these patients who often have other causes for their respiratory symptoms. Tracheal pepsin has been studied as a marker of reflux aspiration in other conditions but not in EA. The role of the airway microbiome in the diagnosis of reflux aspiration has not been studied previously. Aims The aim of this study was to examine the composition of the airway (tracheal aspirate) microbiome of EA patients and correlate the results of the microbial analysis with the presence of gastric pepsin in the airways as a marker of reflux aspiration. Methods A cohort of children with EA was prospectively recruited at Sydney Children's Hospital in 2018. The EA group were subdivided into children with GERD, eosinophilic esophagitis (EoE), and those with no disease. Tracheal aspirates were collected. The bacterial component (16S rRNA gene) of the microbiome was amplified. Pepsin was assayed using a monoclonal antibody specific for pepsin A by the ELISA technique. Results There were 26 EA patients. The mean age was 6.96 years (0.7–18) and 15 (58%) were female. Eighteen (69%) children were on proton pump inhibitors for GERD and 8 (30%) were on swallowed steroids for EoE. GERD, defined as reflux esophagitis on biopsy and/or abnormal result on pH/impedance testing, was present in 7 (27%) and EoE defined as >15 eosinophils/HPF was seen in 5 (19%) children. Tracheal pepsin was detected in a significant proportion of EA patients and correlation between the pepsin results and the airway microbial analysis was seen in some of the EA patients who were pepsin positive. Conclusions This study is the first to examine the role of the microbiome and pepsin in tracheal aspirates as markers of reflux aspiration in children with EA. These results require validation in larger cohorts.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Junying Lu ◽  
Lingxin Xiong ◽  
Xiaohao Zhang ◽  
Zhongmin Liu ◽  
Shiji Wang ◽  
...  

With the development of culture-independent techniques, numerous studies have demonstrated that the lower airway is not sterile in health and harbors diverse microbial communities. Furthermore, new evidence suggests that there is a distinct lower airway microbiome in those with chronic respiratory disease. To understand the role of lower airway dysbiosis in the pathogenesis of asthma, in this article, we review the published reports about the lung microbiome of healthy controls, provide an outlook on the contribution of lower airway dysbiosis to asthma, especially steroid-resistant asthma, and discuss the potential therapies targeted for lower airway dysbiosis.


Proceedings ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 15
Author(s):  
Hernan Mondani ◽  
Amir Rostami ◽  
Tina Askanius ◽  
Jerzy Sarnecki ◽  
Christofer Edling

This presentation summarizes a register-based study on women who have been identified as belonging to three violent extremist milieus in Sweden: violent Islamic, violent far-right, and violent far-left extremism. We studied the women in these milieus along a number of analytical dimensions, ranging from demographic and educational to criminal background and network relationships, and compared them to three reference groups: (i) non-extremist biological sisters to female extremists in the study population; (ii) men in the respective extremist milieus; and (iii) female members of other antagonistic milieus such as organized crime. Our results showed that there are both similarities and differences between groups. In some cases, like age and region of birth, there are commonalities between violent far-right and violent far-left women. Regarding region of birth and migration background, women affiliated to violent far-right and violent far-left extremism are predominantly born in Sweden. Women affiliated to violent Islamic extremism tend to be born in Sweden to a greater extent than men in the same milieu, but to a much lesser degree than women in the violent far-right and violent far-left. When it comes to education, women in the violent Islamic milieu are closer to women in violent far-right extremism. Women in violent far-left extremism perform best at school, with consistently higher grades. The average score of women in violent far-left extremism is identical to that of their sisters, and women in violent far-left extremism perform on average substantially better than men in the same milieu. Women in violent Islamic extremism, in contrast, perform on average similarly to men in violent far-left extremism, and they perform better than their biological sisters. Regarding labor market attachment, violent Islamic extremists have the weakest attachment and the highest dependency upon financial assistance as well as a low employment share (36 percent in 2016), but also a relatively high share of individuals with a high number of unemployment days, suggesting that women in violent Islamic extremism experience higher social exclusion. We find the highest employment share among women in violent far-left extremism, where 89 percent are gainfully employed in 2016 (80 percent for at least three of the last five years) and about a 20 percent unemployment share. Men in violent far-left extremism have an employment share around 10 percent below that of the women in far-left extremism for 2016. The highest fractions of individuals that have not been in contact with the health system due to mental disorders are among violent Islamic extremism, with the women’s fraction at 84 percent, compared to their non-extremist sisters and men in the same milieu that are just above 79 percent. Women in violent far-left extremism have the highest share of in-patient major mental disorders among the extremist milieus (3 percent), higher than men in the same milieu (less than 1 percent) as well as than women and their sisters in the other categories. During the period 2007–2016, 68 percent of individuals in the extremist milieus are covered by the register of suspected individuals. The coverage is substantially higher for men, 72 percent than for women, 43 percent. Compared to their sisters, women in all three milieus are criminally active to a much higher extent. However, women in all three milieus are less criminally active than women in other antagonistic milieus, among whom 67 percent have been suspected at least once. In all three milieus, the share of men with a criminal record is about twice as large as that of women. As far as the gender aspect is concerned, we know that extremist milieus generally have a conservative view of the role of women in society. In our results, this is reflected in the low rates of crime in women compared to men, and relatively marginal positions in the co-offending networks. The fact that women in violent far-left extremism have stronger positions in their networks than the other women in the study population is expected, given that the ideology of this milieu allows for greater equality. This means that women in violent far-left extremism participate more often than, e.g., women in violent far-right extremism, in political actions where violence is common. This pattern of gender roles and criminal involvement also holds concerning women in violent Islamic extremism. This milieu has a more traditional view of the role of women than views among even violent far-right extremists. Women in violent Islamic extremism are less involved in crime and, in particular, violent crime.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoung-Eun Ko ◽  
Chi Ryang Chung ◽  
Jeong Hoon Yang ◽  
Kyeongman Jeon ◽  
Gee Young Suh ◽  
...  

AbstractAlthough extracorporeal membrane oxygenation (ECMO) is increasingly utilized, only a limited level of experience has been reported in postpartum cardiopulmonary failure. Ten critically ill postpartum patients who received ECMO were included between January 2010 and December 2018 in this retrospective observational study. The main indication for ECMO support was peripartum cardiomyopathy (n = 5), followed by postpartum hemorrhage (n = 2). Nine patients initially received veno-arterial ECMO, and one patient received veno-venous ECMO. Major bleeding occurred in six patients. The median number of units of red blood cells (RBC) transfused during ECMO was 14.5 units (interquartile range 6.8–37.8 units), and most RBC transfusions occurred on the first day of ECMO. The survival-to-discharge rate was 80%. Compared to the survival outcomes in female patients of similar age who received ECMO, the survival outcomes were significantly better in the study population (56% versus 80%, P = 0.0004). Despite the high risk of major bleeding, ECMO for patients with postpartum cardiac or respiratory failure showed excellent survival outcomes. ECMO is feasible in these patients and can be carried out with good outcomes in an experienced centre.


Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 829
Author(s):  
Yana Kogan ◽  
Edmond Sabo ◽  
Majed Odeh

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.


1990 ◽  
Vol 69 (3) ◽  
pp. 880-884 ◽  
Author(s):  
G. L. Jones ◽  
C. G. Lane ◽  
P. M. O'Byrne

Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness.


2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Talvensaari-Mattila Anne ◽  
Turpeenniemi-Hujanen Taina

Background. The role of matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in matrix degradation and metastasis has been described in various tumors. Their action is inhibited by their natural tissue inhibitor molecules TIMP-1 and -2.Methods. The study population consisted of 12 squamous cervical carcinoma patients and 27 healthy volunteer control patients. MMP-9, MMP-2-TIMP-2 complex, TIMP-1, and TIMP-2 were analyzed from serum samples using enzyme-linked immunoassay (ELISA).Results. The mean levels of serum TIMP-2 and of MMP-2-TIMP-2 complex were higher in healthy controls compared to patients with a malignant tumor. Serum TIMP-2 values decreased significantly from healthy controls (median 323 g/l, range 305–342 g/l) to malignant (median 136 g/l, range 120–151 g/l) squamous cervical carcinoma patients . Also, serum proMMP2-TIMP2 complex values decreased from control patients to squamous cervical carcinoma patients .Conclusion. This paper shows that the levels of circulating TIMP-2 and that of MMP-2-TIMP-2 complex are lower in squamous cervical carcinoma patients than in healthy women.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Miira Klemetti ◽  
Leena M. Hiltunen ◽  
Sanna Heino ◽  
Seppo Heinonen ◽  
Eero Kajantie ◽  
...  

Previous studies have demonstrated a common variant of the obesity and fat mass-relatedFTOgene, rs9939609, to be associated with obesity, type 2 diabetes, and elevated blood pressure. We investigated whether theFTOSNP rs9939609 is associated with the risk of preeclampsia (PE) in a Finnish study population. 485 women with prior PE and 449 women who had given birth after a normotensive pregnancy were genotyped (TaqMan) for the SNP rs9939609. The prevalences of genotypes AA, AT, and TT were 15%, 53%, and 32%, respectively, among the PE cases, and 16%, 47%, and 37%, respectively, among the controls (P=0.199). We found no evidence of an association between theFTOSNP rs9939609 and PE. However, our cases were dominated by severe, early-onset PE. Thus, we are unable to exclude an association with the milder, later-onset form of the disease in which the role of maternal metabolic predisposition could be more significant.Erratum to “An Obesity-RelatedFTOVariant and the Risk of Preeclampsia in a Finnish Study Population”


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