The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis. RESULTS: Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.

Changing patterns of infectious diseases in children during the COVID-19 pandemic.

Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the "off-season," "see-saw," and "upsurge" patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.

Kawasaki disease in children with Bacillus Calmette-Guérin scar reactivity: Focus on coronary outcomes.

BACKGROUND: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes. METHODS: This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019-2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups. RESULTS: BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2-3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2-3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2-3 months in children with incomplete KD. CONCLUSION: BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2-3 months.

Epicardial Adipose Tissue Was Highly Associated with Reduction in Left Ventricular Diastolic Function as Early as in Adolescence.

Background: Epicardial adipose tissue (EAT) is increased in adolescents with obesity and may play a role in early cardiovascular pathophysiological changes. There is a lack of evidence focusing on the association between EAT and cardiac function in adolescents. This study explored associations between EAT, left ventricle (LV) geometric, and LV functional changes in adolescents. Methods: Adolescent volunteers between 10 and 20 years of age were included. Body mass index (BMI) was presented as age- and sex-specific BMI z-scores. Blood samples for glucose metabolism, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were obtained. EAT thickness, LV hypertrophy, and LV diastolic function were measured by echocardiography. Results: The mean age of the 276 adolescents was 13.51 ± 2.44 years. BMI z-score was strongly associated with EAT thickness (r = 0.77; p < 0.001). Multivariable analysis revealed that age, insulin resistance, total cholesterol to high-density lipoprotein cholesterol ratio, and hs-CRP were independent predictors of increased EAT thickness. After adjusting for sex, age, and BMI z-score by multivariable analysis, EAT thickness was a strong predictor of higher LV mass indexed to height2.7, higher relative wall thickness, lower mitral annulus e'/a', and higher E/e' of the mitral annulus. There was no association between EAT and LV ejection fraction. Conclusions: EAT was highly associated with LV hypertrophy and reduction in LV diastolic function, independent of BMI z-score in the enrolled adolescents. Of note, the negative impacts of EAT on LV geometry and diastolic function occurred as early as in adolescence. This highlights the importance of preventing obesity and EAT deposition early in life.

Similarities and Differences Between COVID-19-Related Multisystem Inflammatory Syndrome in Children and Kawasaki Disease.

In December 2019, the first case of coronavirus disease (COVID-19) was first reported in Wuhan, China. As of March 2021, there were more than 120 million confirmed cases of COVID-19 and 2.7 million deaths. The COVID-19 mortality rate in adults is around 1-5%, and only a small proportion of children requires hospitalization and intensive care. Recently, an increasing number of COVID-19 cases in children have been associated with a new multisystem inflammatory syndrome. Its clinical features and laboratory characteristics are similar to those of Kawasaki disease (KD), KD shock syndrome, and toxic shock syndrome. However, this new disorder has some distinct clinical features and laboratory characteristics. This condition, also known as multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, has been observed mostly in Europe and the United States. This emerging phenomenon has raised the question of whether this disorder is KD triggered by SARS-CoV-2 or a syndrome characterized by multisystem inflammation that mimics KD. This narrative review is to discuss the differences between MIS-C and KD with the aim of increasing pediatricians' awareness of this new condition and guide them in the process of differential diagnosis.

A Rare Complication During Transcatheter Closure of Double Atrial Septal Defects With Incomplete Cor Triatriatum Dexter: A Case Report.

The cor triatiatum dexter is an embryologic remnant derived from the right atrium and totally separate from the right atrium. An incomplete cor triatiatum dexter (iCTD) means a partially obstructive remnant at the right atrium. It is usually formed by a remnant of the Eustachian valve (EV), Thebesian valve (ThV), or Chiari network (CN). This anatomic variant is usually asymptomatic but is often associated with other heart abnormalities including atrial septal defects (ASDs), and has the potential to hamper percutaneous heart procedures such as electrophysiological study or ASD closure. Herein, we report a rare complication, transient heart ischemia, in transcatheter closure of double ASDs in a 55-year-old woman with EV. This rare complication was thought to be caused by coronary sinus obstruction during device placement. The ischemic change was resolved spontaneously after we withdrew the device. For a second attempt, we adjusted the position of the device to avoid coronary sinus obstruction under transesophageal echocardiogram guidance and the device was smoothly deployed in a good position with a minimal residual shunt. This case suggests that anatomy details in percutaneous heart procedures are important, and this rare and dangerous complication, heart ischemia, should be identified immediately during the procedure.

Initial Experience With Patent Ductus Arteriosus Ligation in Pre-term Infants With Bidirectional Shunt Pattern.

Background: Patent ductus arteriosus (PDA) with a bidirectional shunt reflects critical clinical conditions. The operability of PDA with a bidirectional shunt in pre-term infants is still not clearly clarified. This study aimed to investigate the feasibility and the outcomes of PDA ligation in pre-term infants with a bidirectional shunt PDA. Methods: All pre-term infants receiving PDA ligation between 2013 and 2019 were enrolled in this prospective study. Patients were allocated into two groups based on the shunting direction of PDA, which were the left-to-right group (group A) and the bidirectional group (group B). Clinical characteristics and pre-op comorbidities were analyzed. Intraoperative complications, post-op neurological sequelae, necrotizing enterocolitis, survival, and mortality were compared between these two groups. Results: Thirty-seven pre-term infants were enrolled (18 in group A, 19 in group B). The mean post-menstrual age at PDA surgery was 32.0 ± 1.3 and 32.8 ± 1.5 weeks, respectively. Before surgery, 44.4 and 89.5% (group A vs. B) of the patients were using invasive mechanical ventilator (p < 0.01). The requirement of high-frequency oscillatory ventilatory support was significantly higher in group B. PDA rupture-related bleeding during exposing PDA or ligating PDA occurred in four infants, and all were all in group B, including one with delayed hemothorax. Early surgical mortality within 30 days of surgery was higher in group B (0 vs. 21.1%, p < 0.05), but only one death could be attributed to the surgery, which was caused by a pain-induced pulmonary hypertension crisis. The 5-year survival was 100% in group A, and 73.7% in group B (p < 0.05). Conclusion: We did not recommend routine PDA ligation in pre-term infants with a bidirectional shunt. However, a bidirectional shunt should not be an absolute contraindication if they fulfill indications of PDA closure. Unexpected intraoperative PDA rupture and delayed hemothorax in a bidirectional shunt PDA should be carefully monitored. Aggressive post-op pain control is also warranted to avoid pulmonary hypertension crisis. The post-op early mortality rate was higher in the bidirectional group, which could be inherent to their poor pre-operative lung condition. Only one death was directly related to the surgery.

Ascending Aortic Aneurysm After Repair of Aortico-Left Ventricular Tunnel.

Ascending aortic aneurysm following aortico-left ventricular tunnel (ALVT) repair is an uncommon but life-threatening complication. A 27-year-old man had received patch closure for ALVT at infancy. Eighteen years later, aortic valve replacement for severe aortic regurgitation and direct suture for recurrent slit tunnel were performed. Another 9 years later, ascending aortic replacement was performed because of ascending aortic aneurysm. Thus we report an uncommon case of ascending aortic aneurysm 27 years after the repair of an ALVT.

Serum apoptotic marker M30 is positively correlated with early diastolic dysfunction in adolescent obesity.

PURPOSE: Obesity in adolescence has been shown to be related to cardiac geometric and functional changes. Cardiac dysfunction in adults with obesity could be attributed to chronic low-grade inflammation, apoptosis of cardiomyocyte, and glucose metabolic disorder. The aforementioned association in adolescents with obesity have never been well studied. Our aim was to determine the types of cardiac dysfunction in adolescents with obesity and survey the association between cardiac dysfunction and chronic low-grade inflammation, apoptosis, and glucose dysregulation in adolescents with obesity. METHODS: Adolescents aged between 10 and 20 years were enrolled in this study. Body mass index, waist-to-hip ratio, blood pressure, glucose metabolism, and high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), and apoptosis marker M30 levels were measured. Echocardiographic indices were also measured. The association between serum biomarkers and echocardiographic function parameters was analyzed. RESULTS: Diastolic dysfunction was the major finding in the cardiac functional assessment. The main changes in glucose metabolism were elevated C-peptide level and insulin resistance. Hs-CRP, IL-6, and M30 levels also increased with adolescent obesity. M30 was the major biomarker that was highly correlated to diastolic dysfunction indices in adolescents with obesity. CONCLUSIONS: Diastolic dysfunction was the main change in adolescent obesity. Insulin resistance, apoptotic marker M30, hs-CRP, and IL-6 were all elevated in adolescents with obesity. Only M30 was related to indices of left ventricular diastolic dysfunction among adolescents with obesity, rather than inflammation or insulin resistance.

B-type natriuretic peptide prevents postnatal closure of ductus arteriosus by both vasodilation and anti-remodeling in neonatal rats.

The physiologic process of postnatal ductus arteriosus (DA) closure consists of vasoconstriction followed by vascular remodeling. We have recently reported that B-type natriuretic peptide (BNP), a potent vasodilator, also has anti-remodeling effects in pulmonary vasculature. However, its effects on DA have not been elucidated. We investigated whether BNP can prevent DA closure, and if so, the underlying mechanisms. Using in vivo studies, we examined effects of BNP (10 mg/kg, ip at birth) on DA closure in neonatal rats within 4 h after birth. We found that in control rats, the DA spontaneously closed at 4 h with a decreased DA diameter, enhanced intimal thickening, and luminal occlusion. BNP prevented DA closure at 4 h with a preserved DA diameter, attenuated intimal thickening, and preserved luminal patency. Ex vivo, BNP attenuated oxygen-induced vasoconstriction of isolated DA rings of newborn rats. These vasodilating effects were blunted by Rp-8-Br-PET-cGMPS, a cGMP inhibitor. In vitro, BNP inhibited angiotensin II (Ang II)-induced proliferation and migration of DA smooth muscle cells (DASMCs). BNP inhibited Ang II-induced mitochondrial reactive oxygen species (ROS) production and calcium overload in DASMCs. Finally, BNP inhibited Ang II-induced ERK1/2 activation. These in vitro effects were antagonized by Rp-8-Br-PET-cGMPS. In conclusion, BNP prevents postnatal DA closure by both vasodilation and anti-remodeling through the cGMP pathway. The mechanisms underlying anti-remodeling effects include anti-poliferation and anti-migration, with attenuation of mitochondrial ROS production and intracellular calcium and ERK1/2 signaling. Therefore, the BNP/cGMP pathway can be a promising therapeutic target for clinical management of DA patency.

Recent review of transcatheter closure of atrial septal defect.

Atrial septal defect (ASD) is one of the two most common congenital heart diseases in children and adult. After the application of catheter intervention for ASD, this became an alternative treatment other than surgery from late 1990. In 2001, the procedure was further approved by the US Food and Drug Administration (FDA), and become the first choice for most cases of secundum type of ASD worldwide. The success rate is more than 98% in literature reviews, with low complication rates in percutaneous ASD closure. Major complications are around 1%, including device embolization, cardiac erosions, new-onset atrial arrhythmia, and other comorbidities. We reviewed indications for percutaneous secundum type ASD closure, technique, successful rate and major complications in this article. To complete the catheter intervention with difficult ASD conditions, various procedural techniques have been developed recently. We also report a challenging case by a current balloon-assisted technique for huge ASD closure.

The role of transthoracic ultrasonography in predicting the outcome of community-acquired pneumonia in hospitalized children.

CONCLUSION: TUS findings of fluid bronchogram, multifocal involvement, and pleural effusion were associated with adverse outcomes, including longer hospital stay, ICU admission, and tube thoracotomy in hospitalized CAP children. Therefore, TUS is a novel tool for prognostic stratifications of CAP in hospitalized children.

Nasal Airflow Measured by Rhinomanometry Correlates with FeNO in Children with Asthma.

BACKGROUND: Rhinitis and asthma share similar immunopathological features. Rhinomanometry is an important test used to assess nasal function and spirometry is an important tool used in asthmatic children. The degree to which the readouts of these tests are correlated has yet to be established. We sought to clarify the relationship between rhinomanometry measurements, fractional exhaled nitric oxide (FeNO), and spirometric measurements in asthmatic children. METHODS: Patients' inclusion criteria: age between 5 and 18 years, history of asthma with nasal symptoms, and no anatomical deformities. All participants underwent rhinomanometric evaluations and pulmonary function and FeNO tests. RESULTS: Total 84 children were enrolled. By rhinomanometry, the degree of nasal obstruction was characterized as follows: (1) no obstruction in 33 children, (2) slight obstruction in 29 children, and (3) moderate obstruction in 22 children. FeNO was significantly lower in patients without obstruction than those with slight or moderate obstruction. Dividing patients according to ATS Clinical Practice Guidelines regarding FeNO, patients < 12 years with FeNO > 20 ppb had a lower total nasal airflow rate than those with FeNO < 20 ppb. Patients ≥ 12 years with FeNO > 25 ppb had a lower total nasal airflow rate than those with FeNO < 25 ppb. CONCLUSIONS: Higher FeNO was associated with a lower nasal airflow and higher nasal resistance. This supports a relationship between upper and lower airway inflammation, as assessed by rhinomanometry and FeNO. The results suggest that rhinomanometry may be integrated as part of the functional assessment of asthma.

Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways.

Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated its effects on rats with monocrotaline (MCT)-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells (PASMCs). Liraglutide was investigated for both prevention and treatment of MCT-induced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immune-reactivity of endothelial nitric oxide synthase (eNOS), endothelin-1 and cyclic guanosine monophosphate (cGMP) levels, protein expressions of eNOS, soluble guanylyl cyclase (sGCα), protein kinase G (PKG) and Rho kinase (ROCK) II pathway were measured in both in vivo and in vitro. Cell migration and cell cycle were also determined. Liraglutide both prevented and reversed MCT-induced PAH, right ventricle hypertrophy and pulmonary vascular wall remodeling. Protein expression of ROCK II was increased while eNOS, sGC and PKG were decreased. Pretreatment with liraglutide inhibited platelet-derived growth factor (PDGF)-BB stimulated PASMCs migration, which were associated with cell-cycle arrest at G0/G1 phase. Liraglutide may have both preventive and therapeutic effects on MCT-induced PAH, through the eNOS/sGC/PKG and Rho kinase pathways. Thus, liraglutide may have a therapeutic role in pulmonary vascular remodelling.

Gamma-secretase Inhibitor Prevents Proliferation and Migration of Ductus Arteriosus Smooth Muscle Cells through the Notch3-HES1/2/5 Pathway.

Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA closure. Notch signaling is an important mediator of vascular remodelling but its role in DA is unkonwn. We investigated the effects and underlying mechanisms of γ-secretase inhibitor DAPT, a Notch signaling inhibitor on angiotensin II (Ang II)-induced proliferation and migration of DASMCs. Proliferation and migration of DASMCs cultured from neonatal Wistar rats were induced by Ang II, with or without DAPT pre-treatment. In addition, potential underlying mechanisms including cell cycle progression, Ca(2+) influx, reactive oxygen species (ROS) production, signal transduction of MAPK and Akt, and Notch receptor with its target gene pathway were examined. We found that DAPT inhibited Ang II-induced DASMCs proliferation and migration dose dependently. DAPT also arrested the cell cycle progression in the G0/G1-phase, and attenuated calcium overload and ROS production caused by Ang II. Moreover, DAPT inhibited nuclear translocation of Notch3 receptor intracellular domain, with decreased expression of its down-stream genes including HES1, HES2 and HES5. Finally, Ang II-activated ERK1/2, JNK and Akt were also counteracted by DAPT. In conclusion, DAPT inhibits Ang II-induced DASMCs proliferation and migration. These effects are potentially mediated by decreased calcium influx, reduced ROS production, and down-regulation of ERK1/2, JNK and Akt, through the Notch3-HES1/2/5 pathway. Therefore, Notch signaling has a role in DA remodeling and may provide a target pathway for therapeutic intervention of PDA.

Activation of endothelial NO synthase by a xanthine derivative ameliorates hypoxia-induced apoptosis in endothelial progenitor cells.

OBJECTIVES: Endothelial damage is strongly associated with cardiovascular diseases such as atherosclerosis, thrombosis and hypertension. Endothelial progenitor cells (EPCs) are primitive bone marrow (BM) cells that possess the capacity to mature into endothelial cells and play a role in neovascularization and vascular remodelling. This study aimed to investigate whether KMUP-1, a synthetic xanthine-based derivative, atorvastatin and simvastatin, can prevent endothelial dysfunction and apoptosis induced by hypoxia and to elucidate the underlying mechanisms. METHODS: Mononuclear cells were separated and were induced to differentiate into EPCs. KMUP-1, atorvastatin or simvastatin were administered prior to hypoxia. KEY FINDINGS: We found that EPCs exposed to hypoxia increased apoptosis as well as diminished proliferation. Pretreatment with KMUP-1, atorvastatin and simvastatin significantly prevented hypoxia-induced EPCs death and apoptosis, with associated increased of the Bcl-2/Bax ratio, and reduced caspase-3 and caspase-9 expression. We also assessed the nitrite production and Ser(1177)-phospho-eNOS expression and found that KMUP-1, atorvastatin and simvastatin not only increased the secretion of NO compared with the hypoxia group but also upregulated the eNOS activation. CONCLUSIONS: KMUP-1 inhibited hypoxia-induced dysfunction and apoptosis in EPCs, which may be mediated through suppressing oxidative stress, upregulating eNOS and downregulating the caspase-3 signalling pathway.

Life-threatening Dilated Cardiomyopathy Induced by Late-onset Neonatal Hypocalcemia.

Neonatal seizures caused by hypocalcemia may be associated with cardiopulmonary dysfunction and may require specific management other than calcium supplementation. Severe dilated cardiomyopathy is an extremely rare complication in neonatal hypocalcemia and often results in high morbidity and mortality. We report here a 14-day-old neonate presenting with a gradually increasing frequency of tonic seizures. After admission, arterial desaturation was found despite supplying oxygen (4 L/min) through nasal prongs and the patient developed life-threatening respiratory distress and heart failure secondary to dilated cardiomyopathy. His critical cardiopulmonary derangements rapidly improved after respiratory support, the administration of diuretic and inotropic drugs, and the correction of his hypocalcemia and hypomagnesemia. The patient responded to treatment and was well during the 1-year follow-up period. We present this unique case history of seizure, respiratory distress, and heart failure induced by transient hypocalcemia to remind clinicians about the importance of this rare, life-threatening, but reversible, disorder.

Lung function in very preterm infants with patent ductus arteriosus under conservative management: an observational study.

BACKGROUND: Persistent patent ductus arteriosus (PDA) during hospitalization is thought to be associated with adverse pulmonary outcomes in very preterm infants. This observational study aimed to compare the lung function in very preterm infants with and without PDA at discharge. METHODS: Very preterm infants, admitted to our neonatal intensive unit, who required respiratory support soon after birth and had undergone a lung function test at discharge, were enrolled. Infants with a need for positive-pressure support (either an invasive ventilator, or nasal continuous positive airway pressure without oxygen) or supplemental oxygen at a postmenstrual age of 36 weeks were defined as having bronchopulmonary dysplasia (BPD). Echocardiography was performed weekly for each of the very preterm infants with PDA to confirm closure of the PDA. The data were collected retrospectively. RESULTS: Fifty-two very preterm infants received lung function tests before discharge during the study period, 28 of whom had PDA and received conservative management, and 20 who did not. The other 4 infants who were given active treatment for PDA were excluded. Gestational age was significantly smaller in the PDA group than in the no-PDA group (27.1 ± 2.0 vs. 28.6 ± 1.6 weeks, p = 0.009). Birth weight did not differ significantly in those with and those without PDA (0.98 ± 0.26 vs. 1.12 ± 0.26 kg, p = 0.074). Significantly more infants with PDA had BPD (p = 0.002) and required respiratory support for a longer period (p = 0.001) than those without PDA. However, functional residual capacity (ml/kg) at discharge was comparable between the two groups after adjusting for gestational age and postmenstrual age at testing (21.6 ± 8.4 vs. 21.5 ± 6.7 ml/kg, p = 0.894). Other lung function test parameters were also comparable. CONCLUSION: Under a definition of BPD (including infants needing CPAP but without oxygen) other than the conventional definition, the very preterm infants in our study who received conservative management for PDA had a higher percentage of BPD than the infants without PDA. The parameters of the lung function test and lung clearance index were comparable between these two groups at discharge.