Changes in lung volume and ventilation following transition from invasive to noninvasive respiratory support and prone positioning in preterm infants

To minimize secondary lung injury, ventilated preterm infants are extubated as soon as possible. To maximize extubation success, they are often placed in prone position. The effect of extubation and subsequent prone positioning on lung volumes is currently unknown. Changes in end-expiratory lung volume (ΔEELV), tidal volume (VT), and ventilation distribution were monitored during transition from endotracheal to nasal continuous positive airway pressure and following prone positioning using electrical impedance tomography. In addition, the continuous distending pressure (CDP) and oxygen need (FiO₂) were recorded. Twenty preterm infants (GA 28.7 ± 1.7 wk) were included. Following extubation, the CDP decreased from 7.9 ± 0.5 to 6.0 ± 0.2 cmH₂O, while the FiO₂ remained stable. Both ΔEELV and VT increased significantly (P < 0.05) after extubation, without changing ventilation distribution. Prone positioning resulted in a further increase in ΔEELV (P < 0.01) and a decrease in respiratory rate. VT remained stable but its distribution clearly shifted toward the ventral lung regions. Infants who are transitioned from invasive to noninvasive respiratory support are able to maintain their EELV and increase their VT. Prone positioning increases EELV and shifts tidal ventilation to the ventral lung regions. The latter suggests that infants should preferably be placed in prone position after extubatio

Cross-sectional changes in lung volume measured by electrical impedance tomography are representative for the whole lung in ventilated preterm infants

Objective:\ud Electrical impedance tomography measures lung volume in a cross-sectional slice of the lung. Whether these cross-sectional volume changes are representative of the whole lung has only been investigated in adults, showing conflicting results. This study aimed to compare cross-sectional and whole lung volume changes using electrical impedance tomography and respiratory inductive plethysmography.\ud \ud Design:\ud A prospective, single-center, observational, nonrandomized study.\ud \ud Setting:\ud The study was conducted in a neonatal ICU in the Netherlands.\ud \ud Patients:\ud High-frequency ventilated preterm infants with respiratory distress syndrome.\ud \ud Interventions:\ud Cross-sectional and whole lung volume changes were continuously and simultaneously measured by, respectively, electrical impedance tomography and respiratory inductive plethysmography during a stepwise recruitment procedure. End-expiratory lung volume changes were assessed by mapping the inflation and deflation limbs using both the pressure/impedance and pressure/inductance pairs and characterized by calculating the inflection points. In addition, oscillatory tidal volume changes were assessed at each pressure step.\ud \ud Measurements and Main Results:\ud Twenty-three infants were included in the study. Of these, eight infants had to be excluded because the quality of the registration was insufficient for analysis (two electrical impedance tomography and six respiratory inductive plethysmography). In the remaining 15 infants (gestational age 28.0 ± 2.6 wk; birth weight 1,027 ± 514 g), end-expiratory lung volume changes measured by electrical impedance tomography were significantly correlated to respiratory inductive plethysmography measurements in 12 patients (mean r = 0.93 ± 0.05). This was also true for the upper inflection point on the inflation (r = 0.91, p < 0.01) and deflation limb (r = 0.83, p < 0.01). In 13 patients, impedance and inductance data also correlated significantly on oscillatory tidal volume/pressure relationships (mean r = 0.81 ± 0.18).\ud \ud Conclusions:\ud This study shows that cross-sectional lung volume changes measured by electrical impedance tomography are representative for the whole lung and that this concept also applies to newborn infants

Effect of Minimally Invasive Surfactant Therapy on Lung Volume and Ventilation in Preterm Infants

To assess the changes in (regional) lung volume and gas exchange during minimally invasive surfactant therapy (MIST) in preterm infants with respiratory distress syndrome. In this prospective observational study, infants requiring a fraction of inspired oxygen (FiO2) ≥ 0.30 during nasal continuous positive airway pressure of 6 cmH2O were eligible for MIST. Surfactant (160-240 mg/kg) was administered in supine position in 1-3 minutes via an umbilical catheter placed 2 cm below the vocal cords. Changes in end-expiratory lung volume (EELV), tidal volume, and its distribution were recorded continuously with electrical impedance tomography before and up to 60 minutes after MIST. Changes in transcutaneous oxygen saturation (SpO2) and partial carbon dioxide pressure, FiO2, respiratory rate, and minute ventilation were recorded. A total of 16 preterm infants were included. One patient did not finish study protocol because of severe apnea 10 minutes after MIST. In the remaining infants (gestational age 29.8 ± 2.8 weeks, body weight 1545 ± 481 g) EELV showed a rapid and sustained increase, starting in the dependent lung regions, followed by the nondependent regions approximately 5 minutes later. Oxygenation, expressed as the SpO2/FiO2 ratio, increased from 233 (IQR 206-257) to 418 (IQR 356-446) after 60 minutes (P < .001). This change was significantly correlated with the change in EELV (ρ = 0.70, P < .01). Tidal volume and minute volume decreased significantly after MIST, but transcutaneous partial carbon dioxide pressure was comparable with pre-MIST values. Ventilation distribution remained unchanged. MIST results in a rapid and homogeneous increase in EELV, which is associated with an improvement in oxygenatio

Effect of nasal continuous and biphasic positive airway pressure on lung volume in preterm infants

To monitor regional changes in end-expiratory lung volume (EELV), tidal volumes, and their ventilation distribution during different levels of nasal continuous positive airway pressure (nCPAP) and nasal biphasic positive airway pressure (BiPAP) in stable preterm infants. By using electrical impedance tomography and respiratory inductive plethysmography, we measured changes in EELV and tidal volumes in 22 preterm infants (gestational age 29.7 ± 1.5 weeks) during 3 nCPAP levels (2, 4, and 6 cmH2O) and unsynchronized BiPAP (nCPAP = 6 cmH2O; pressure amplitude = 3 cmH2O; frequency = 50/min; inspiration time = 0.5 seconds) at 10-minute intervals. We assessed the distribution of these volumes in ventral and dorsal chest regions by using electrical impedance tomography. EELV increased with increasing nCPAP with no difference between the ventral and dorsal lung regions. Tidal volume also increased, and a decrease in phase angle and respiratory rate was noted by respiratory induction plethysmography. At the regional level, electrical impedance tomography data showed a more dorsally oriented ventilation distribution. BiPAP resulted in a small increase in EELV but without changes in tidal volume or its regional distribution. Increasing nCPAP in the range of 2 to 6 cmH2O results in a homogeneous increase in EELV and an increase in tidal volume in preterm infants with a more physiologic ventilation distribution. Unsynchronized BiPAP does not improve tidal volume compared with nCPA

CD45RB Glycosylation and Ig Isotype Define Maturation of Functionally Distinct B Cell Subsets in Human Peripheral Blood

Glycosylation of CD45RB (RB+) has recently been identified to mark antigen-experienced B cells, independent of their CD27 expression. By using a novel combination of markers including CD45RB glycosylation, CD27 and IgM/IgD isotype expression we segregated human peripheral blood B cell subsets and investigated their IGHV repertoire and in vitro functionality. We observed distinct maturation stages for CD27-RB+ cells, defined by differential expression of non-switched Ig isotypes. CD27-RB+ cells, which only express IgM, were more matured in terms of Ig gene mutation levels and function as compared to CD27-RB+ cells that express both IgM and IgD or cells that were CD27-RB-. Moreover, CD27-RB+IgM+ cells already showed remarkable rigidity in IgM isotype commitment, different from CD27-RB+IgMD+ and CD27-RB- cells that still demonstrated great plasticity in B cell fate decision. Thus, glycosylation of CD45RB is indicative for antigen-primed B cells, which are, dependent on the Ig isotype, functionally distinct

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Suomen virallinen tilasto (SVT

An essential role for the Zn2+ transporter ZIP7 in B cell development

Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn2+ in modulating B cell receptor signal strength and positive selection

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence