Search

Introduction: Supplemental oxygen therapy is a mainstay of modern neonatal intensive care for preterm infants. However, both insufficient and excess oxygen delivery are associated with adverse outcomes. Automated or closed loop FiO2 control has been developed to keep SpO2 within a predefined target range more effectively. Methods: The aim of this study was to investigate the feasibility of closed loop FiO2 control by Predictive Intelligent Control of Oxygenation (PRICO) on the Fabian ventilator in maintaining SpO2 within a target range (88/89-95%) in preterm infants on different modes of invasive and noninvasive respiratory support. In two tertiary neonatal intensive care units, preterm infants with an FiO2 >0.21 were included and received an 8 h nonblinded treatment period of closed loop FiO2 control by PRICO, flanked by two 8 h control periods of routine manual control (RMC1 and RMC2). Results: 32 preterm infants were included (median gestational age 26 + 5 weeks [IQR 25 + 5–27 + 6], median birthweight 828 grams [IQR 704–930]). Six patients received invasive respiratory support, while 26 received noninvasive respiratory support (18 CPAP, 4 DuoPAP, and 4 nasal IMV). The time percentage within the SpO2 target range was increased with PRICO (74.4% [IQR 67.8–78.5]) compared to RMC1 (65.8% [IQR 51.1–77.8]; p = 0.011) and RMC2 (60.6% [IQR 56.2–66.6]; p < 0.001) with an estimated median difference of 6.0% (95% CI 1.2–11.5) and 9.8% (95% CI 6.0–13.0), respectively. Conclusion: In preterm infants on invasive and noninvasive respiratory supports, closed loop FiO2 control by PRICO compared to RMC is feasible and superior in maintaining SpO2 within target ranges.

Air-liquid interface (ALI) cultures are frequently used in lung research but require substantial cell numbers that cannot readily be obtained from patients. We explored whether organoid expansion [three-dimensional (3D)] can be used to establish ALI cultures from clinical samples with low epithelial cell numbers. Airway epithelial cells were obtained from tracheal aspirates (TA) from preterm newborns and from bronchoalveolar lavage (BAL) or bronchial tissue (BT) from adults. TA and BAL cells were 3D-expanded, whereas cells from BT were expanded in 3D and 2D. Following expansion, cells were cultured at ALI to induce differentiation. The impact of cell origin and 2D or 3D expansion was assessed with respect to 1) cellular composition, 2) response to cigarette smoke exposure, and 3) effect of Notch inhibition or IL-13 stimulation on cellular differentiation. We established well-differentiated ALI cultures from all samples. Cellular compositions (basal, ciliated, and goblet cells) were comparable. All 3D-expanded cultures showed a similar stress response following cigarette smoke exposure but differed from the 2D-expanded cultures. Higher peak levels of antioxidant genes HMOX1 and NQO1 and a more rapid return to baseline, and a lower unfolded protein response was observed after cigarette smoke exposure in 3D-derived cultures compared to 2D-derived cultures. In addition, TA- and BAL-derived cultures were less sensitive to modulation by DAPT or IL-13 than BT-derived cultures. Organoid-based expansion of clinical samples with low cell numbers, such as TA from preterm newborns is a valid method and tool to establish ALI cultures.

Air-liquid interface (ALI) epithelial cell (EC) cultures are useful for studying the effect of exposure to airborne substances, but require substantial cell numbers that cannot always obtained from patients. Recent studies show that 3D organoid cultures can be initiated from samples with limited EC numbers, such as BAL (Sachs et al, 2019). Aim of the present study was to compare expansion of EC using 3D organoid culture to conventional 2D plastic-basic expansion for establishment of ALI cultures, and whether such cultures can be used for exposure to cigarette smoke (CS). Airway EC were obtained from tracheal aspirates (TA) from preterm newborns and bronchoalveolar lavage (BAL), or from bronchial tissue (BT) from adults. TA and BAL cells were 3D-expanded, whereas cells from BT were expanded in 3D and 2D. Following expansion, EC were cultured at ALI to induce differentiation. The impact of cell origin and 2D or 3D expansion was assessed with respect to (i) cellular composition; (ii) response to CS exposure; (iii) effect of Notch inhibition or IL-13 stimulation on cellular differentiation. Well-differentiated ALI cultures were established from all samples and cellular compositions were comparable. All 3D-expanded cultures showed a similar oxidative stress and unfolded protein response following CS exposure, but different from the 2D-expanded cultures. Additionally, TA- and BAL-derived cultures were less sensitive to modulation by DAPT or IL-13 than BT-derived cultures. We conclude that organoid-based expansion of clinical samples with low epithelial cell numbers, such as tracheal aspirates from preterm newborns, is a valid method and tool to establish ALI cultures.

Introduction: Children with bronchopulmonary dysplasia (BPD) have an increased risk for persistent structural and functional lung abnormalities. The multiple breath washout (MBW) test assesses efficiency of ventilation distribution and the lung clearance index (LCI) is considered a sensitive marker of ventilation inhomogeneity. Aim: To determine LCI and functional residual capacity (FRC) in infants with BPD and assess the correlations of LCI and FRC with lung structure and clinical parameters. We hypothesized that LCI would be elevated in infants with BPD and would correlate with structural changes. Methods: Preterm infants born ≤32 weeks gestational age (GA) with BPD were included. Demographics and clinical parameters were obtained from medical records. LCI and FRC were measured by MBW. Lung structure was assessed on chest CT with the PRAGMA-BPD scoring system. Volumes and percentages of regions with normal appearance, low attenuation, high attenuation and bronchial thickening were determined. Results: 15 infants with a median corrected age [IQR] of 7.0 [2.5] months were included. Median GA was 26.9 [1.3] weeks and birth weight was 907.8 [240] g. 14 infants had severe and one had mild BPD. Mean LCI was 7.2±0.7 and FRC was 162±52 ml. Only in 3 patients MBW was abnormal. Architectural distortion was present in all CTs. Median total lung volume was 238,7 [92.9] ml and healthy lung volume was 226,7 [108] ml. LCI and FRC did not correlate with lung volumes on CT and architectural distortion. FRC % predicted strongly correlated with GA (r=0.726, p Conclusion: LCI and FRC are not useful in the follow-up of patients with BPD.

Background Bronchopulmonary dysplasia (BPD) is the most frequent serious complication in preterm infants. We aimed to describe lung structure and ventilatory function of preterm infants with severe BPD and explored the association between early postnatal growth and these outcomes. Methods We included preterm infants born ≤32 weeks gestational age (GA) with severe BPD. Lung structure was assessed on chest CT with the PRAGMA-BPD scoring system and ventilatory function by polysomnography (PSG) at 6 months corrected age. Postnatal growth was assessed by weight measured at birth, and at 2 and 6 months corrected age. Results We included 49 infants (median [IQR] GA of 25.7 [24.6-26.3] weeks and mean [SD] birth weight of 760 [210] g). A 95.5% of the chest CT scans showed architectural distortion of the lung, and an oxygen desaturation index (ODI) >5 was found in 74% of the infants. An increase in GA of 1 week was associated with higher total and normal lung volume (β coefficient [95% CI]: 1.86 [0.15, 3.57] and 2.03 [0.41, 3.65]), less hypoattenuation (−4.3 [−7.70, −0.90]%) and lower ODI (−36.7 [−64.2, −9.10]%). Higher weight at 6 months was independently associated with higher total and normal lung volume, and with less severe desaturations. Increased weight gain between 2 and 6 months of corrected age was associated with less severe desaturations during sleep (β coefficient [95% CI]: 2.09 [0.49, 3.70]). Conclusion Most preterm infants with severe BPD have structural lung abnormalities and impaired ventilatory function early in life, partly explained by birth characteristics and infant growth.

Background In an experimental mouse model we showed that ceramides play a role in the pathogenesis of bronchopulmonary dysplasia (BPD) and are a potential target for therapeutic intervention. We investigated whether ceramides are detectable in tracheal aspirates (TAs) of preterm infants and differ between infants with or without BPD. Methods Infants born ≤ 32 weeks of gestational age in need of mechanical ventilation in the first week of life were included. TAs were obtained directly after intubation and at day 1, 3, 5, 7, and 14. Ceramide concentrations were measured by tandem mass spectrometry. At 36 weeks postmenstrual age BPD was defined as having had ≥ 28 days supplemental oxygen. Results 122 infants were included, of which 14 died and 41 developed BPD. All infants showed an increase in ceramides after the first day of intubation. The ceramide profile differed significantly between preterm infants who did and did not develop BPD. However, the ceramide profile had no additional predictive value for BPD development over GA at birth, birth weight and total days of mechanical ventilation. Conclusions Ceramides are measurable in TAs of preterm born infants and may be an early marker for BPD development.

Background: Bronchopulmonary dysplasia (BPD) is the most frequent serious complication in preterm infants, resulting in significant respiratory morbidity. Objectives: To compare overnight polysomnography (PSG) findings between preterm infants with severe BPD and term infants. Methods: Infants with severe BPD who underwent PSG at 6 months corrected age were included. Severe BPD was diagnosed in infants born < 32 weeks gestational age (GA) who required at least 28 days of oxygen, and needed ≥ 30% oxygen or positive end expiratory pressure at 36 weeks GA. Controls were term infants without BPD who underwent PSG for non-respiratory diseases,. All PSG signals were recorded and analyzed with BrainRT Shell+ (OSG BVBA, Rumst, Belgium) and scored according to international criteria. Mann-Whitney U test was used for between group comparisons. Results: 13 infants with severe BPD and 12 term infants without BPD (corrected age at PSG: 6.2 vs. 8.1 months) were included. Mean heart rate and breathing frequency did not differ between the groups, but mean SaO2 was lower in the BPD group compared to controls (96% [IQR 94.8;97,5] vs 98% [IQR 97;98],p=0.04). Severe BPD infants had higher apnea hypopnea index (AHI) (7.5 [4.5;10.6] vs 2.3 [0.9; 2.9],p < 0.01), higher oxygen desaturation index (ODI) (7.0 [3.9; 12.7] vs 3.1 [1.3; 3.9],p

Idiopathic infantile arterial calcification (IIAC) is a rare disease characterised by extensive depositions of hydroxyapatite in the internal elastic lamina of medium-sized and large arteries, frequently accompanied by periarticular calcifications. We report on three patients with various presenting signs and symptoms. Diagnostic imaging techniques and therapy with bisphosphonates will be discussed. For the first time long-term follow-up of up to 25 years will be reported.

Aim: To evaluate the practical feasibility for nurses working with neurally adjusted ventilatory assist (NAVA) and assess patient comfort and safety when NAVA is initiated. Background: NAVA is a relatively new mode of ventilation. Its application in neonates and children has been widely documented. However, its practical feasibility from a nursing point of view as well as its safety and comfort in these populations compared with conventional modes of ventilation has not been described. Design: A prospective, observational crossover pilot study. Method: NAVA was compared with the conventional mode of ventilation for 3 h each, and practical feasibility, patient comfort level and safety were assessed. Results: Twenty-one neonates and children were enrolled into the study. There were no reported adverse events. In most patients, the NAVA catheter was placed too shallow, as measured by the distances from the nose, ear, xiphisternum (NEX) method, according to the manufacturer's instructions. Accurate placement was confirmed by visual inspection of the NAVA positioning window. Patients' comfort did not differ between the conventional mode and NAVA. Conclusions: NAVA is feasible, once an accurate signal of the electrical activity of the diaphragm is achieved and seems safe and well tolerated in both neonates and children. Nurses need to gain experience in placing the NAVA catheter and practical recommendations are given. Relevance to clinical practice: NAVA is a promising new mode of ventilation. This article contributes to an increasing body of evidence that NAVA is feasible in neonates and children. There are practical considerations when NAVA is applied in these patient-groups.

DNA from disintegrating neutrophils is thought to be an important determinant of the high viscosity of cystic fibrosis sputum. Recombinant human deoxyribonuclease (DNase), an enzyme which cleaves DNA, has proven to be effective in improving sputum clearance from the airways of patients with cystic fibrosis (CF). Inhaled DNase improves pulmonary function, reduces the frequency of respiratory tract infections and improves general well-being in CF. Primary ciliary dyskinesia (PCD), like CF, is a chronic lung disease in which sputum retention leads to lung damage. Impairment of mucociliary transport results in chronic sinusitis, chronic bronchitis, and subsequently bronchiectasis, and in about 50% to situs inversus. Currently, PCD patients are treated with chest physiotherapy, antibiotics, and bronchodilators. We present here an infant with PCD. His severe respiratory symptoms and hypoxemia did not improve, despite nebulized isotonic NaCl solution, physiotherapy, and aggressive antibiotic treatment. Immediately after starting nebulized DNase therapy the respiratory symptoms, lung function, and overnight oximetry improved. During two readmissions because of acute worsening of dyspnea, the baby again showed overnight improvements on treatment with DNase, antibiotics, and bronchodilators. Withholding DNase during an asymptomatic period caused no worsening. The therapeutic potential of nebulized DNase in PCD should be established by controlled trials.