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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.

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.

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.