Right ventricular function in infants with bronchopulmonary dysplasia and pulmonary hypertension: a pilot study.

Premature birth and bronchopulmonary dysplasia (BPD) are risk factors for the development of echocardiographic signs of pulmonary hypertension (PH) and are associated with changes in cardiac structure and function. It is unclear whether this association persists beyond early infancy. The aims of this study are to prospectively investigate the prevalence of PH in children with severe BPD and to investigate the effect of BPD and PH on myocardial structure and function at six months corrected age. Preterm infants (gestational age ≤ 32 weeks) with severe BPD were included. Echocardiography was used to define PH and to measure speckle tracking derived longitudinal and circumferential strain of the left ventricle (LV) and right ventricle (RV). Sixty-nine infants with a median (interquartile range [IQR]) gestational age of 25.6 (24.9-26.4) weeks and a median birthweight of 770 (645-945) gram were included. Eight (12%) infants had signs of PH at six months corrected age. RV fractional area change was lower in infants with severe BPD and PH at six months compared to infants without PH (35% ± 9% vs. 43% ± 9%, P = 0.03). RV mean longitudinal systolic strain was lower in infants with severe BPD and PH compared to infants without PH (17.6% [-19.5%/-16.1%] vs. -20.9% [-25.9%/-17.9%], P = 0.04). RV size and LV longitudinal and circumferential strain in children with BPD with or without PH were similar. Signs of PH were found in 12% of infants with severe BPD at six months corrected age and the presence of PH is associated with reduced RV systolic function.

Ceramides in tracheal aspirates of preterm infants: Marker for bronchopulmonary dysplasia.

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.

Structural and functional ventilatory impairment in infants with severe bronchopulmonary dysplasia.

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 (ß 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 (ß 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.

Lung CT imaging in patients with bronchopulmonary dysplasia: A systematic review.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common respiratory complication of preterm birth and associated with long-term respiratory sequelae. Chest computed tomography (CT) is a sensitive tool to obtain insight in structural lung abnormalities and may be a predictor for later symptoms. OBJECTIVES: To give an overview of chest CT scoring methods that are used to evaluate chest CT scans of BPD patients. To review which structural lung abnormalities are described in children and adults with BPD and whether these are related to clinical outcomes. METHODS: An extensive literature search was conducted for relevant studies on chest CT imaging in patients born preterm with BPD. RESULTS: We retrieved 316 original papers of which 16 articles and three abstracts fulfilled our inclusion criteria. Overall, we identified nine different semi-quantitative scoring methods. Chest CT scans revealed structural abnormalities in >85% of BPD patients. These abnormalities are decreased pulmonary attenuation, opacities, bronchial wall thickening, and consolidations. Some have been found to be negatively correlated with lung function and respiratory symptoms. CONCLUSIONS: None of the currently described scoring systems are appropriately validated or superior over another. Future studies are needed to generate a validated and universal chest CT quantitative scoring method for patients with BPD. Pediatr Pulmonol. 2016; 51:975-986. © 2016 Wiley Periodicals, Inc.

The clinical utility of reticular basement membrane thickness measurements in asthmatic children.

OBJECTIVE: Reticular basement membrane (RBM) thickness is one of the pathological features of asthma and can be measured in endobronchial biopsies. We assessed the feasibility of endobronchial biopsies in a routine clinical setting and investigated the clinical value of RBM thickness measurements for asthma diagnosis in children. METHODS: We included all children who underwent bronchoscopy with endobronchial mucosal biopsies for clinical reasons and divided them into three subgroups: (1) no asthma, (2) mild-moderate asthma, and (3) problematic severe asthma. RESULTS: In 152/214 (71%) patients, mean age 9.5 years (SD 4.6; range 0.1-18.7) adequate biopsies were retrieved in which RBM thickness could be measured. Mean (SD) RBM thickness differed significantly among children without asthma, with mild-moderate asthma, and with problematic severe asthma (p = 0.04), 4.68 (1.24) µm, 4.56 (0.89) µm, and 5.21 (1.10) µm respectively. This difference disappeared after adding exhaled nitric oxide to the multivariate model. CONCLUSIONS: This study confirms the difference in RBM thickness between children with and without asthma and between asthma severities in a routine clinical care setting. However, quantifying the RBM thickness appeared to have no added clinical diagnostic value for asthma in children.

Tidal breathing FeNO measurements: a new algorithm.

OBJECTIVE: International guidelines recommend measuring fractional exhaled nitric oxide (FeNO) during a single slow exhalation with a constant flow of 50 ml/sec. We developed a new algorithm to compute FeNO at 50 ml/sec from tidal breathing measurements. The main objective is to assess the correlation and agreement of this algorithm with the conventional single breath FeNO measurements. METHODS: We recruited children aged 6-18 years, who performed both a single breath and a tidal breathing FeNO measurement in random order. Both maneuvers were performed on the Eco Medics NO-analyser (Eco Physics AG, Duernten, Switzerland). RESULTS: We included 109 patients between January 2011 and April 2011. Geometric mean (95% CI) FeNO values did not differ significantly between single breath and tidal breathing technique: 21.0 (17.7-24.8) ppb and 20.0 (17.0-23.6) ppb (P = 0.18), respectively. We found an excellent intraclass correlation coefficient of 0.96 (0.94-0.97) and moderate agreement with a mean difference of 4% (95% limits of agreement -43% and +90%). CONCLUSION: Tidal breathing FeNO values could be transformed with a new algorithm to match single breath FeNO at a constant flow of 50 ml/sec. This algorithm opens the way to standardized FeNO measurements in preschool children and uncooperative patients.

Exhaled nitric oxide in infants--what is a nice test like FENO doing in a place like this?

In adults and older children the measurement of fractional exhaled nitric oxide (FENO) has been shown to be useful as a tool to diagnose and monitor eosinophilic airway inflammation. However, the recommended method to measure FENO in school-age children is not suited for use in preschool children and infants. This article reviews the data on FENO measurements in infants. In the first year of life, measurement of FENO can be done during tidal breathing or during a single forced passive expiration. Several technical factors, including contamination with nasal and ambient NO, and the influence of expiratory flow influence FENO levels in infants. Because asthma is uncommon in infants and wheezing is often related to viral infections, considerable differences in clinical utility of FENO between older children and infants could be expected. From the available data FENO could potentially be useful to identify early-onset asthma, to diagnose primary ciliary dyskinesia (PCD), and to monitor the effect of various treatments. In conclusion, there is still much uncertainty about the potential clinical utility of FENO in infants. There is a need for clinical studies showing the merits and limitations of different methodologies, to standardize FENO measurements in infants, and to obtain normal reference values for this age group.