Gas exchange mechanisms in preterm infants on HFOV - a computational approach.
Ontology highlight
ABSTRACT:
SUBMITTER: Roth CJ
PROVIDER: S-EPMC6115430 | biostudies-other | 2018 Aug
REPOSITORIES: biostudies-other
Publications
Gas exchange mechanisms in preterm infants on HFOV - a computational approach.
Roth Christian J CJ Förster Kai M KM Hilgendorff Anne A Ertl-Wagner Birgit B Wall Wolfgang A WA Flemmer Andreas W AW
Scientific reports 20180829 1
High-frequency oscillatory ventilation (HFOV) is a commonly used therapy applied to neonates requiring ventilatory support during their first weeks of life. Despite its wide application, the underlying gas exchange mechanisms promoting the success of HVOF in neonatal care are not fully understood until today. In this work, a highly resolved computational lung model, derived from Magnetic Resonance Imaging (MRI) and Infant Lung Function Testing (ILFT), is used to reveal the reason for highly effi ...[more]
Similar Datasets
Project description:Estimation of mortality risk of very preterm neonates is carried out in clinical and research settings. We aimed at elaborating a prediction tool using machine learning methods. We developed models on a cohort of 23747 neonates <30 weeks gestational age, or <1501 g birth weight, enrolled in the Italian Neonatal Network in 2008-2014 (development set), using 12 easily collected perinatal variables. We used a cohort from 2015-2016 (N?=?5810) as a test set. Among several machine learning methods we chose artificial Neural Networks (NN). The resulting predictor was compared with logistic regression models. In the test cohort, NN had a slightly better discrimination than logistic regression (P?<?0.002). The differences were greater in subgroups of neonates (at various gestational age or birth weight intervals, singletons). Using a cutoff of death probability of 0.5, logistic regression misclassified 67/5810 neonates (1.2 percent) more than NN. In conclusion our study - the largest published so far - shows that even in this very simplified scenario, using only limited information available up to 5 minutes after birth, a NN approach had a small but significant advantage over current approaches. The software implementing the predictor is made freely available to the community.
| S-EPMC6137213 | biostudies-literature
Project description:RationaleThe technique used to provide continuous positive airway pressure (CPAP) to the newborn may influence lung function and breathing efficiency.ObjectivesTo compare differences in gas exchange physiology and lung injury resulting from treatment of respiratory distress with either bubble or constant pressure CPAP and to determine if the applied flow influences short-term outcomes.MethodsLambs (133 d gestation; term is 150 d) born via cesarean section were weighed, intubated, and treated with CPAP for 3 hours. Two groups were treated with 8 L/minute applied flow using the bubble (n = 12) or the constant pressure (n = 12) technique. A third group (n = 10) received the bubble method with 12 L/minute bias flow. Measurements at study completion included arterial blood gases, oxygraphy, capnography, tidal flow, multiple breath washout, lung mechanics, static pressure-volume curves, and bronchoalveolar lavage fluid protein.Measurements and main resultsBirth weight and arterial gas variables at 15 minutes were comparable. Flow (8 or 12 L/min) did not influence the 3-hour outcomes in the bubble group. Bubble technique was associated with a higher pH, Pa(O2), oxygen uptake, and area under the flow-volume curve, and a decreased alveolar protein, respiratory quotient, Pa(CO2), and ventilation inhomogeneity compared with the constant pressure group.ConclusionsCompared with constant pressure technique, bubble CPAP promotes enhanced airway patency during treatment of acute postnatal respiratory disease in preterm lambs and may offer protection against lung injury.
| S-EPMC2049065 | biostudies-literature
Project description:Failure of ductus arteriosus closure after preterm birth is associated with significant morbidities. Ductal closure requires and is regulated by a complex interplay of molecular and mechanical mechanisms with underlying genetic factors. In utero patency of the ductus is maintained by low oxygen tension, high levels of prostaglandins, nitric oxide and carbon monoxide. After birth, ductal closure occurs first by functional closure, followed by anatomical remodeling. High oxygen tension and decreased prostaglandin levels mediated by numerous factors including potassium channels, endothelin-1, isoprostanes lead to the contraction of the ductus. Bradykinin and corticosteroids also induce ductal constriction by attenuating the sensitivity of the ductus to PGE2. Smooth muscle cells of the ductus can sense oxygen through a mitochondrial network by the role of Rho-kinase pathway which ends up with increased intracellular calcium levels and contraction of myosin light chains. Anatomical closure of the ductus is also complex with various mechanisms such as migration and proliferation of smooth muscle cells, extracellular matrix production, endothelial cell proliferation which mediate cushion formation with the interaction of blood cells. Regulation of vessel walls is affected by retinoic acid, TGF-β1, notch signaling, hyaluronan, fibronectin, chondroitin sulfate, elastin, and vascular endothelial cell growth factor (VEGF). Formation of the platelet plug facilitates luminal remodeling by the obstruction of the constricted ductal lumen. Vasa vasorum are more pronounced in the term ductus but are less active in the preterm ductus. More than 100 genes are effective in the prostaglandin pathway or in vascular smooth muscle development and structure may affect the patency of ductus. Hemodynamic changes after birth including fluid load and flow characteristics as well as shear forces within the ductus also stimulate closure. Current pharmacological treatment for the closure of a patent ductus is based on the blockage of the prostaglandin pathway mainly through COX or POX inhibition, albeit with some limitations and side effects. Further research for new agents aiming ductal closure should focus on a clear understanding of vascular biology of the ductus.
| S-EPMC7477801 | biostudies-literature
Project description:BackgroundPhotosynthesis of reproductive organs in C3 cereals is generally regarded as important to crop yield. Whereas, photosynthetic characteristics of reproductive organs are much less understood as compared to leaf photosynthesis, mainly due to methodological limitations. To date, many indirect methods have been developed to study photosynthesis of reproductive organs and its contribution to grain yield, such as organ shading, application of herbicides and photosynthetic measurement of excised organs or tissues, which might be intrusive and cause biases. Thus, a robust and in situ approach needs to be developed.ResultsHere we report the development of a custom-built panicle photosynthesis chamber (P-chamber), which can be connected to standard infrared gas analyzers to study photosynthetic/respiratory rate of a rice panicle. With the P-chamber, we measured panicle photosynthetic characteristics of seven high-yielding elite japonica, japonica-indica hybrid and indica rice cultivars. Results show that, (1) rice panicle is photosynthetically active during grain filling, and there are substantial inter-cultivar variations in panicle photosynthetic and respiratory rates, no matter on a whole panicle basis, on an area basis or on a single spikelet basis; (2) among the seven testing cultivars, whole-panicle gross photosynthetic rates are 17-54 nmol s-1 5 days after heading under photon flux density (PFD) of 2000 ?mol (photons) m-2 s-1, which represent some 20-38% of that of the corresponding flag leaves; (3) rice panicle photosynthesis has higher apparent CO2 compensation point, light compensation point and apparent CO2 saturation point, as compared to that of a typical leaf; (4) there is a strong and significant positive correlation between gross photosynthetic rate 5 days after heading on a single spikelet basis and grain setting rate at harvest (Pearson correlation coefficient r?=?0.93, p value?<?0.0001).ConclusionsRice panicle gross photosynthesis is significant, has great natural variation, and plays an underappreciated role in grain yield formation. The P-Chamber can be used as a tool to study in situ photosynthetic characteristics of irregular non-foliar plant organs, such as ears, culms, leaf sheaths, fruits and branches, which is a relatively less explored area in current cereal breeding community.
| S-EPMC7336644 | biostudies-literature
Project description:16S rRNA gene profiling of preterm infants
| PRJEB34372 | ENA
Project description:Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity.Objectives: To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define disease severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks' postmenstrual age best predicts death or serious respiratory morbidity through 18-26 months' corrected age.Methods: We assessed infants born at less than 32 weeks of gestation between 2011 and 2015 at 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.Measurements and Main Results: Of 2,677 infants, 683 (26%) died or developed serious respiratory morbidity. The diagnostic criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks' postmenstrual age, regardless of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support (n = 773); grade 1, nasal cannula ≤2 L/min (n = 1,038); grade 2, nasal cannula >2 L/min or noninvasive positive airway pressure (n = 617); and grade 3, invasive mechanical ventilation (n = 249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33-79%) was observed for death or neurodevelopmental impairment.Conclusions: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks' postmenstrual age, regardless of supplemental oxygen use.
| S-EPMC6775872 | biostudies-literature
Project description:Background: HIV infection is associated with impaired gas transfer in the lung as indicated by a low diffusing capacity (DLCO). Mechanisms for reduced DLCO in the setting of HIV infection are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood gene expression. Methods: A total of 40 HIV-infected (HIV+) and uninfected (HIV-) men with preserved versus reduced DLCO were selected from a larger cohort study of lung function. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from peripheral blood leukocytes (PBLs) and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV+ vs. HIV- subjects with preserved DLCO and those with impaired DLCO to identify differentially activated pathways. Results: Using pathway-based analyses we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and apoptosis. When we applied a similar analysis to subjects with low DLCO, we identified a much broader repertoire of inflammatory and immune-related pathways in HIV+ patients relative to HIV- subjects, with up-regulation of multiple interleukin pathways, interferon signaling, Toll-like receptor signaling, and T cell/B cell receptor signaling. We confirmed elevated circulating levels of IL-6 in HIV+ patients with reduced DLCO relative to the other groups. Conclusions: Our findings reveal that PBLs of subjects with HIV infection and low DLCO are distinguished by widespread enrichment of immuno-inflammatory programs. Activation of these pathways may alter the biology of circulating leukocytes and play a role in the pathogenesis of HIV-associated pulmonary gas exchange impairment. Total RNA was isolated from peripheral blood leukocytes in four subject groups: 1. HIV-, low DLCO (N = 11); 2. HIV+, low DLCO (N = 10); 3. HIV-, preserved DLCO (N = 9); 4. HIV+, preserved DLCO (N = 9). Each sample was hybridized to an Affymetrix PrimeView Human Gene Expression microarray for a total of 39 experiments.
2016-04-01 | E-GEOD-76403 | biostudies-arrayexpress
Project description:Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.
| S-EPMC4529054 | biostudies-literature
Project description:Background Inhaled nitric oxide (iNO) is being increasingly used in preterm infants < 34 weeks with hypoxemic respiratory failure (HRF) and/or pulmonary hypertension (PH). Objective To evaluate the risk factors, survival characteristics, and lung histopathology in preterm infants with PH/HRF. Methods Retrospective chart review was conducted to determine characteristics of 93 preterm infants treated with iNO in the first 28 days and compared with 930 matched controls. Factors associated with survival with preterm HRF and smooth muscle actin from nine autopsies were evaluated. Results Preterm neonates treated with iNO had a higher incidence of preterm prolonged rupture of membrane (pPROM ≥ 18 hours), oligohydramnios and delivered by C-section. In infants treated with iNO, antenatal steroids (odds ratio [OR],3.7; confidence interval [CI], 1.2-11.3; p = 0.02), pPROM (OR, 1.001; CI, 1.0-1.004; p = 0.3), and oxygenation response to iNO (OR, 3.7; CI, 1.08-13.1; p = 0.037) were associated with survival. Thirteen infants with all three characteristics had 100% (13/13) survival without severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL) compared with 48% survival (12/25, p = 0.004) and 16% severe IVH/PVL without any of these factors. Severity of HRF correlated with increased smooth muscle in pulmonary vasculature. Conclusion Preterm infants with HRF exposed to antenatal steroids and pPROM had improved oxygenation with iNO and survival without severe IVH/PVL. Precisely targeting this subset may be beneficial in future trials of iNO.
| S-EPMC5572579 | biostudies-other
Project description:Background: HIV infection is associated with impaired gas transfer in the lung as indicated by a low diffusing capacity (DLCO). Mechanisms for reduced DLCO in the setting of HIV infection are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood gene expression. Methods: A total of 40 HIV-infected (HIV+) and uninfected (HIV-) men with preserved versus reduced DLCO were selected from a larger cohort study of lung function. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from peripheral blood leukocytes (PBLs) and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV+ vs. HIV- subjects with preserved DLCO and those with impaired DLCO to identify differentially activated pathways. Results: Using pathway-based analyses we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and apoptosis. When we applied a similar analysis to subjects with low DLCO, we identified a much broader repertoire of inflammatory and immune-related pathways in HIV+ patients relative to HIV- subjects, with up-regulation of multiple interleukin pathways, interferon signaling, Toll-like receptor signaling, and T cell/B cell receptor signaling. We confirmed elevated circulating levels of IL-6 in HIV+ patients with reduced DLCO relative to the other groups. Conclusions: Our findings reveal that PBLs of subjects with HIV infection and low DLCO are distinguished by widespread enrichment of immuno-inflammatory programs. Activation of these pathways may alter the biology of circulating leukocytes and play a role in the pathogenesis of HIV-associated pulmonary gas exchange impairment.
2016-04-01 | GSE76403 | GEO