First week of life respiratory management and pulmonary ventilation/perfusion matching in infants with bronchopulmonary dysplasia: a retrospective observational study.

OBJECTIVE: To investigate the association between early neonatal respiratory management in infants with bronchopulmonary dysplasia (BPD) and the degree of pulmonary ventilation perfusion-matching (V/Q) at term. METHODS: 30 preterm infants with a diagnosis of BPD who were initially treated with either controlled mechanical ventilation/continuous positive airway pressure (CMV/CPAP) (n = 14) or high-frequency oscillatory ventilation (HFOV) using a high lung-volume strategy (n = 16) were retrospectively included in this study. All infants underwent pulmonary V/Q single photon emission computed tomography at a median postmenstrual age of 37 weeks. RESULTS: Infants treated with HFOV had significantly larger proportion of the lung with matched V/Q as compared to infants treated with CMV/CPAP, median (interquartile range) 60.4% (55.5-66.0%) and 45.8% (37.8-53.1%) respectively (p = 0.01). CONCLUSIONS: In infants who needed mechanical ventilation the first week of life and later developed BPD an association was observed between treatment with a HFOV and better pulmonary V/Q matching at near-term age.

Case Report: Fatal Outcome for a Preterm Newborn With Meningitis Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli Sequence Type 1193.

Introduction: In this case report, we describe an extended-spectrum beta-lactamase (ESBL) - Escherichia coli (E. coli) strain of sequence type (ST) 1193, a novel, virulent, multidrug-resistant (MDR) clone with a rapid global spread. ST 1193 has been more commonly associated with invasive disease than other ESBL-E. coli STs. To our knowledge, this is the first known case in Sweden where a newborn died of an ESBL-E. coli ST 1193 meningitis. We emphasize that the clinical knowledge about the properties of certain MDR-clones should be increased. Case Report: A moderately preterm boy was born after preterm prolonged rupture of membranes. The mother had an ESBL-E. coli urinary tract infection during pregnancy. At 36 h of age he developed signs of infection and was given first-line therapy for early onset sepsis. Thereafter he developed seizures. The treatment was changed to cover suspected meningitis. Culture showed growth of the same ESBL- E. coli ST 1193 strain in the child's blood and cerebrospinal fluid, as well as in the mother's urine. Antibiotics were adapted. His condition deteriorated and he developed fulminant septic shock with treatment-resistant seizures. The boy passed away at 3 days of age. Conclusion: This case highlights the risk of delay in diagnosis when a marking for carriage of MDR-bacteria is falsely removed from a medical record of a pregnant women. Further, it demonstrates that ESBL-E. coli ST 1193 infection in neonates can be fatal. Thus, studies regarding virulence factors of ESBL-E. coli infections in pregnant women and their children are needed to understand the association between this infection and severe invasive disease in newborn children.

A Novel Association between YKL-40, a Marker of Structural Lung Disease, and Short Telomere Length in 10-Year-Old Children with Bronchopulmonary Dysplasia.

Extremely preterm infants are born with immature lungs and are exposed to an inflammatory environment as a result of oxidative stress. This may lead to airway remodeling, cellular aging and the development of bronchopulmonary dysplasia (BPD). Reliable markers that predict the long-term consequences of BPD in infancy are still lacking. We analyzed two biomarkers of cellular aging and lung function, telomere length and YKL-40, respectively, at 10 years of age in children born preterm with a history of BPD (n = 29). For comparison, these markers were also evaluated in sex-and-age-matched children born at term with childhood asthma (n = 28). Relative telomere length (RTL) was measured in whole blood with qPCR and serum YKL-40 with ELISA, and both were studied in relation to gas exchange and the regional ventilation/perfusion ratio using three-dimensional V/Q-scintigraphy (single photon emission computer tomography, SPECT) in children with BPD. Higher levels of YKL-40 were associated with shorter leukocyte RTL (Pearson's correlation: -0.55, p = 0.002), but were not associated with a lower degree of matching between ventilation and perfusion within the lung. Serum YKL-40 levels were significantly higher in children with BPD compared to children with asthma (17.7 vs. 13.2 ng/mL, p < 0.01). High levels of YKL-40 and short RTLs were associated to the need for ventilatory support more than 1 month in the neonatal period (p < 0.01). The link between enhanced telomere shortening in childhood and structural remodeling of the lung, as observed in children with former BPD but not in children with asthma at the age of 10 years, suggests altered lung development related to prematurity and early life inflammatory exposure. In conclusion, relative telomere length and YKL-40 may serve as biomarkers of altered lung development as a result of early-life inflammation in children with a history of prematurity.

Ten-year-old children with a history of bronchopulmonary dysplasia have regional abnormalities in ventilation perfusion matching.

AIM: The ratio of ventilation to blood flow is an important determinant for regional gas exchange in the lung and hypoxemia is one of the clinical hallmarks in infants with bronchopulmonary dysplasia (BPD). We have previously demonstrated ventilation/perfusion ratio (V/Q) abnormalities in infants with BPD at 36 weeks postconceptional age. The status of V/Q matching in older children with a history of BPD in infancy is unknown. In this study, we examined if 10-year-old children with a history of BPD had V/Q impairments. METHODS: Three-dimensional V/Q-scintigraphy (SPECT) was performed in 26 children. RESULTS: In the BPD group, lung volume with mismatch, (V>Q) was larger compared to areas with reverse mismatch (Q>V), 26.2% and 11.8%, respectively, implying that perfusion defects contribute more than ventilation defects in the V/Q mismatch. Also, the mean fractional distribution of V and Q to V/Q in children with BPD was reduced compared to healthy children, 31% and 51% compared to 64% and 89%, respectively (P < 0.01). CONCLUSION: At 10 years of age children with a history of BPD had ventilation/perfusion abnormalities, with prominent perfusion defects. These V/Q abnormalities suggest the presence of residual alveolar-capillary impairment.

Bronchopulmonary dysplasia: clinical grading in relation to ventilation/perfusion mismatch measured by single photon emission computed tomography.

Bronchopulmonary dysplasia (BPD) is a significant cause of morbidity in the preterm population. Clinical severity grading based on the need for supplemental oxygen and/or need for positive airway pressure at 36 weeks postmenstrual age does not yield reproducible predictive values for later pulmonary morbidity. Single photon emission computed tomography (SPECT) was used to measure the distribution of lung ventilation (V) and perfusion (Q) in 30 BPD preterm infants at a median age of 37 weeks postmenstrual age. The V and Q were traced with 5 MBq Technegas and Technetium-labeled albumin macro aggregates, respectively, and the V/Q match-mismatch was used to quantify the extent of lung function impairment. The latter was then compared with the clinical severity grading at 36 weeks, and time spent on mechanical ventilation, continuous positive airway pressure (CPAP) and supplemental oxygen. Of those with mild and moderate BPD 3/9 and 3/11 patients, respectively, showed significant V/Q mismatches. By contrast, 4/10 patients with severe BPD showed a satisfactory V/Q matching distribution. An unsatisfactory V/Q match was not correlated with time spent on supplemental oxygen or CPAP, but was significantly negatively correlated with time spent on mechanical ventilation. SPECT provides unique additional information about regional lung function. The results suggest that the current clinical severity grading can be improved and/or complemented with SPECT.

Postoperative regional distribution of pulmonary ventilation and perfusion in infants with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Advances in management of patients with congenital diaphragmatic hernia (CDH) have improved mortality rates but with a risk of increased pulmonary morbidity. The prognosis for CDH survivors remains difficult to predict owing to the lack of adequate methods. We used single photon emission computed tomography (SPECT) to measure the regional distribution of ventilation and perfusion in CDH infants to quantify the degree of lung function impairment and relate it to neonatal clinical disease severity. METHODS: Single photon emission computed tomography was performed in 12 CDH infants at the mean age of six months. Ventilation and perfusion were traced with 5 MBq Technegas and technetium-labelled albumin macro-aggregates, respectively. Neonatal clinical data collected during the patient's stay in the pediatric intensive care unit was correlated with the SPECT data. RESULTS: Single photon emission computed tomography revealed varying degrees of ventilation-perfusion abnormalities which correlated with the presence of pulmonary artery hypertension, days on ventilator and days on extracorporeal membrane oxygenation. CONCLUSIONS: The grade of clinical disease severity in infants following CDH repair is closely related to the ventilation-perfusion abnormality as seen using SPECT. The persistence of pulmonary artery hypertension into the postoperative neonatal period appears to be an important pathophysiological factor related to ventilation-perfusion abnormalities. Single photon emission computed tomography provides valuable clinical information for patient follow-up.