Effect of childhood obesity on admissions for respiratory disease.

AIM: The purpose of this study was to assess for an association between higher body mass index and disease severity, morbidity and mortality in children admitted for an acute respiratory distress and failure. METHODS: A single-institution retrospective cross-sectional study performed in the United States evaluating paediatric patients, 2-20 years of age, admitted for diagnoses related to acute respiratory distress and acute respiratory failure. Main outcomes include disease severity as assessed using the respiratory component of the Paediatric Early Warning Score (PEWS) with adjustment for altered mental status (Resp-PEWS + AMS), hospital or intensive care length of stay (LOS) and death. RESULTS: Children with obesity made up 42/334 (13%) of the cohort. There was no significant difference in Resp-PEWS + AMS between obese and non-obese cohorts (mean of 0.93, {standard deviation 1.11} vs. 1.13 {1.35}, range 0-6, rank sum p = 0.46). There was no significant difference in overall hospital LOS or intensive care LOS. Multivariate analysis including diagnosis as a control variable did not change the results. CONCLUSION: We found that body habitus was not an independent factor for illness severity or clinical outcomes.

Comparison of Tidal Volumes at the Endotracheal Tube and at the Ventilator.

OBJECTIVE: Lung protective ventilation for children with acute respiratory distress syndrome requires accurate assessment of tidal volume. Although modern ventilators compensate for ventilator tubing compliance, tidal volume measured at the ventilator may not be accurate, particularly in small children. Although ventilator-specific proximal flow sensors that measure tidal volume at the endotracheal tube have been developed, there is little information regarding their accuracy. We sought to test the accuracy of ventilator measured tidal volume with and without proximal flow sensors against a calibrated pneumotachometer in children. DESIGN: Prospective, observational. SETTING: Tertiary care PICU. PATIENTS: Fifty-one endotracheally intubated and mechanically ventilated children younger than 18 years. INTERVENTIONS: Tidal volumes were measured at the ventilator, using a ventilator-specific flow sensor, and a calibrated pneumotachometer connected to the SensorMedics 2600A Pediatric Pulmonary Function Cart. MEASUREMENTS AND MAIN RESULTS: In a pressure control mode of ventilation: median tidal volume measured with the pneumotachometer (9.5 mL/kg [interquartile range, 8.2-11.7 mL/kg]) was significantly higher than tidal volume measured either at the ventilator (8.2 mL/kg [7.1-9.6 mL/kg]) or at the proximal flow sensor (8.1 mL/kg [7.2-10.0 mL/kg]) (p < 0.001). In pressure regulated volume control mode of ventilation: median tidal volume measured with the pneumotachometer (10.2 mL/kg [8.8-12.4 mL/kg]) was significantly higher than tidal volume measured either at the ventilator (8.0 mL/kg [7.1-9.7 mL/kg]) or at the proximal flow sensor (8.5 mL/kg [7.3-10.4 mL/kg]) (p < 0.001). These findings were consistent when subgrouped by ventilator type and circuit size. CONCLUSIONS: Tidal volume measured either at the endotracheal tube with a proximal flow sensor or at the ventilator with compensation for tubing compliance are both significantly lower than tidal volume measured with a calibrated pneumotachometer. This underestimation of delivered tidal volume may be particularly important when managing children with acute respiratory distress syndrome.

Pulmonary function testing in infants with tetralogy of Fallot and absent pulmonary valve syndrome.

AIM: Absent pulmonary valve syndrome (APVS) is found in 3-6% of patients with Tetralogy of Fallot (TOF). Along with findings of TOF, absence of pulmonary valve tissue results in aneurysmal dilatation of the main and branch pulmonary arteries compressing the trachea, main-stem, and intrapulmonary bronchi leading to obstructive airways disease. Our objective was to review pulmonary function tests (PFT) in TOF-APVS patients. MATERIALS AND METHODS: Eight PFT were performed on five mechanically ventilated TOF-APVS patients in the intensive care unit. Tidal volume, forced vital capacity (FVC), maximal expiratory flow 25%, resistance and compliance of the respiratory system were measured. RESULTS: Pre-operative PFTs showed markedly elevated airways resistance (RRS) (median 0.45 cmH2O/mL/sec, range 0.17-0.66) and marked variability of the static compliance of the respiratory system (CRS) (median 0.6 mL/cmH2O/kg, range 0.25-2.6). Flow-volume loops measured by forced deflation showed flow limitation within the medium to small airways. Post-operative FVC was reduced in four of the five patients (median 46 mL/kg, IQR 42.9 - 48.8 mL/kg). Patients studied with various levels of positive end expiratory pressure (PEEP) showed improvement in tidal volume and reduced obstruction with PEEP greater than 10 cmH2O. For three patients with pre-operative data available, surgical correction resulted in near-normal post-operative CRS and improved, but still elevated RRS (median 0.14 cmH2O/mL/sec, interquartile range [IQR] 0.11-0.31). CONCLUSION: For our patients with TOF-APVS, airway resistance was elevated. Flow limitation was seen in the medium to small airways with a mild reduction of FVC. PFTs may help guide management of mechanical ventilation for TOF-APVS patients.

Micro sensors: linking real-time oscillatory shear stress with vascular inflammatory responses.

The important interplay between blood circulation and vascular cell behavior warrants the development of highly sensitive but small sensing systems. The emerging micro electro mechanical systems (MEMS) technology, thus, provides the high spatiotemporal resolution to link biomechanical forces on the microscale with large-scale physiology. We fabricated MEMS sensors, comparable to the endothelial cells (ECs) in size, to link real-time shear stress with monocyte/EC interactions in an oscillatory flow environment, simulating the moving and unsteady separation point at arterial bifurcations. In response to oscillatory shear stress (tau) at +/- 2.6 dyn/cm2, time-averaged shear stress (tauave) = 0 at 0.5 Hz, individual monocytes displayed unique to-and-fro trajectories, undergoing rolling, binding, and dissociation with other monocyte, followed by solid adhesion on EC. Incorporating with cell-tracking velocimetry, we visualized that these real-time events occurred over a dynamic range of oscillating shear stress between +/- 2.6 dyn/cm2 and Reynolds number between 0 and 22.2 in the presence of activated adhesion molecule and chemokine mRNA expression.

Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit expression: implication for native LDL oxidation.

Shear stress regulates endothelial nitric oxide and superoxide (O2-*) production, implicating the role of NADPH oxidase activity. It is unknown whether shear stress regulates the sources of reactive species production, consequent low-density lipoprotein (LDL) modification, and initiation of inflammatory events. Bovine aortic endothelial cells (BAECs) in the presence of 50 microg/mL of native LDL were exposed to (1) pulsatile flow with a mean shear stress (tau(ave)) of 25 dyne/cm2 and (2) oscillating flow at tau(ave) of 0. After 4 hours, aliquots of culture medium were collected for high-performance liquid chromatography analyses of electronegative LDL species, described as LDL- and LDL2-. In response to oscillatory shear stress, gp91phox mRNA expression was upregulated by 2.9+/-0.3-fold, and its homologue, Nox4, by 3.9+/-0.9-fold (P<0.05, n=4), with a corresponding increase in O2-* production rate. The proportion of LDL- and LDL2- relative to static conditions increased by 67+/-17% and 30+/-7%, respectively, with the concomitant upregulation of monocyte chemoattractant protein-1 expression and increase in monocyte/BAEC binding (P<0.05, n=5). In contrast, pulsatile flow downregulated both gp91phox and Nox4 mRNA expression (by 1.8+/-0.2-fold and 3.0+/-0.12-fold, respectively), with an accompanying reduction in O2-* production, reduction in the extent of LDL modification (51+/-12% for LDL- and 30+/-7% for LDL2-), and monocyte/BAEC binding. The flow-dependent LDL oxidation is determined in part by the NADPH oxidase activity. The formation of modified LDL via O2-* production may also affect the regulation of monocyte chemoattractant protein-1 expression and monocyte/BAEC binding.

Monocyte recruitment to endothelial cells in response to oscillatory shear stress.

Leukocyte recruitment to endothelial cells is a critical event in inflammatory responses. The spatial, temporal gradients of shear stress, topology, and outcome of cellular interactions that underlie these responses have so far been inferred from static imaging of tissue sections or studies of statically cultured cells. In this report, we developed micro-electromechanical systems (MEMS) sensors, comparable to a single endothelial cell (EC) in size, to link real-time shear stress with monocyte/EC binding kinetics in a complex flow environment, simulating the moving and unsteady separation point at the arterial bifurcation with high spatial and temporal resolution. In response to oscillatory shear stress (tau) at +/- 2.6 dyn/cm2 at a time-averaged shear stress (tau(ave))=0 and 0.5 Hz, individual monocytes displayed unique to-and-fro trajectories undergoing rolling, binding, and dissociation with other monocyte, followed by solid adhesion on EC. Our study quantified individual monocyte/EC binding kinetics in terms of displacement and velocity profiles. Oscillatory flow induces up-regulation of adhesion molecules and cytokines to mediate monocyte/EC interactions over a dynamic range of shear stress +/- 2.6 dyn/cm2 (P=0.50, n=10).