Diagnostic value of nasal nitric oxide for children with primary ciliary dyskinesia / 中华儿科杂志

Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U=143.00, 2.00, both P<0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min,U=1.00, 9.00, 133.00, 0, all P<0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95%CI 0.95-1.00, P<0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.

Congenital pulmonary alveolar proteinosis in a neonate / 中国当代儿科杂志

The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.

Progressesin endothelial progenitor cells derived extracellular vesicles / 医学研究生学报

Endothelial progenitor cells (EPCs) play an important role in angiogenesis and tissue repair, which have been used to treat various kinds of diseases associated with poor perfusion or organ dysfunction. In recent years, researches had shown that extracellular vesicles(EVs) are the important paracrine components of cells. They carry the protein, mRNA, miRNA and other bioactive substances from the original cells to the target cells, yielding a similar effect to stem cell transplantation. The effects of extracellular vesicles derived from endothelial progenitor cells (EPCs-EVs) have been explored in cardiovascular diseases, diabetes mellitus, and renal injury et al. This review covers the biological characteristics of EVs, the application and mechanism of EPCs-EVs in these studies.

Diagnostic Value of Nasopharyngeal Aspirates in Children with Lower Respiratory Tract Infections / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The accuracy of nasopharyngeal aspirate (NPA) specimens in detecting lower respiratory pathogens remains controversial. The objective of this study was to evaluate the diagnostic accuracy of aspirates (NPAs) specimen in lower respiratory tract infections (LRTIs) in children.</p><p><b>METHODS</b>The prospective study was designed to collect the data of paired NPAs and bronchoalveolar lavage fluids from children with acute LRTIs from January 2013 to December 2015. All specimens were subjected to pathogen detection: bacterial detection by culture, Mycoplasma pneumoniae (Mp) detection by polymerase chain reaction assay and virus (influenza A and B viruses, parainfluenza virus [PIV] Types 1 and 3, respiratory syncytial virus, and adenovirus) detection by immunofluorescence assay. The diagnostic accuracy analysis of NPAs was stratified by age ≤3 years (n = 194) and >3 years (n = 294).</p><p><b>RESULTS</b>We collected paired specimens from 488 children. The positive rate of pathogen was 61.6%. For Streptococcus pneumoniae, NPA culture had the specificity of 89.9% and negative predictive value of 100% in age ≤3 years, the specificity of 97.2% and negative predictive value of 98.9% in age >3 years. For Mp, the positive predictive values of NPA was 77.4% in children ≤3 years, and 89.1% in children >3 years. For PIV III, NPA specimen had the specificity of 99.8% and negative predictive value of 96.5% in children ≤3 years. For adenovirus, NPA had the specificity of 97.8% and negative predictive value of 98.4% in age ≤3 years, the specificity of 98.9% and negative predictive value of 99.3% in age >3 years.</p><p><b>CONCLUSIONS</b>NPAs are less invasive diagnostic respiratory specimens, a negative NPA result is helpful in "rule out" lower airway infection; however, a positive result does not reliably "rule in" the presence of pathogens.</p>

Exhaled nitric oxide in neonates with or without hypoxemic respiratory failure / 世界急诊医学杂志（英文）

BACKGROUND: Exhaled nitric oxide (eNO) is one of the airway condensate derived markers, reflecting mainly airway inflammation in asthma and other lung diseases. The changes of eNO levels as pathophysiology of neonatal hypoxemic respiratory failure (HRF) in early postnatal life have not been thoroughly studied. The present study was to establish a method for measuring eNO concentrations in neonates with or without HRF. METHODS: Twenty-two newborn infants with HRF and 26 non-NRF controls were included within the first 24 hours of postnatal life. Their eNO levels were detected with a rapid-response chemiluminescence analyzer daily during the first week of their postnatal life, and lung mechanics and gas exchange efficiency were monitored at the same time, such as pulse oxygen saturation (SpO2), inspired fraction of oxygen (FiO2) and other parameters. RESULTS: During the first two days of postnatal life, eNO values of HRF neonates were significantly higher than those of the control neonates (day 1, 7.9±3.2 vs. 5.8±1.8 parts per billion [ppb], P<0.05; day 2, 8.8±3.2 vs. 6.0±2.4 ppb, P<0.05), but there were no significant differences in the following days. With SpO2/FiO2 increasing, difference of eNO values between the HRF and non-HRF neonates became narrowed, but there was still a two-fold difference of eNO/[SpO2/(FiO2×100)] on days 5-7. CONCLUSION: We established a method for measuring eNO and found difference in neonates with or without HRF, which diminished with prolonged postnatal days, reflecting pathophysiological characteristics of HRF.

Current status of neonatal acute respiratory disorders: a one-year prospective survey from a Chinese neonatal network / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>We conducted a prospective, multicenter investigation of incidence, management and outcome of neonatal acute respiratory disorders (NARD), and evaluated related perinatal risk factors and efficacy of respiratory therapies in neonatal intensive care units (NICUs) in a Chinese neonatal network.</p><p><b>METHODS</b>Data were prospectively collected in 2004 - 2005 from infants with NARD defined as presence of respiratory distress and oxygen requirement during the first 3 days of life.</p><p><b>RESULTS</b>A total of 2677 NARD was classified (20.5% of NICU admissions). There were 711 (5.44%) with respiratory distress syndrome (RDS), 589 (4.51%) pulmonary infection, 409 (3.13%) meconium aspiration syndrome, 658 (5.03%) aspiration of amniotic fluid and 239 (1.83%) transient tachypnoea. Meconium aspiration syndrome had the highest rate with fetal distress, transient tachypnoea from cesarean section, and RDS with maternal disorders. Assisted mechanical ventilation was applied in 53.4% of NARD, and in above five disorders with 84.7%, 52.3%, 39.8%, 24.5%, and 53.6%, respectively. Corresponding mortality in these disorders was 31.4%, 13.6%, 17.8%, 4.1% and 5.0%, respectively. Surfactant was provided to 33.9% of RDS. In all RDS infants, the survival rate was 78.8% if receiving surfactant, and 63.4% if not (P < 0.001).</p><p><b>CONCLUSIONS</b>This study provided NICU admission-based incidence and mortality of NARD, reflecting efficiency of advanced respiratory therapies, which should be a reference for current development of respiratory support in NICU at provincial and sub-provincial levels, justifying efforts in upgrading standard of care in emerging regions through a collaborative manner.</p>

Engraftment of bone marrow stromal cells in lipopolysaccharide-injured mouse lungs / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore a feasibility of engraftment of systemically transplanted bone marrow stromal cells (BMSCs) and differentiation into lung epithelial cells in lipopolysaccharides (LPS)-injured lungs.</p><p><b>METHODS</b>BMSCs were isolated from bone marrow of transgenic green fluorescent protein (GFP) C57BL/6J mice and systemically administered to bone marrow-suppressed wild-type C57BL/6J mice. A mouse model of lung injury was prepared by intratracheal instillation of LPS. Recipients were assigned to four groups: intratracheal PBS + BMSCs transplantation (CM), intratracheal LPS + BMSCs transplantation (LM), intratracheal PBS + irradiation + BMSCs transplantation (CIM) and intratracheal LPS+ irradiation + BMSCs transplantation (LIM). BMSCs engraftment in recipient lungs was determined by immunofluorescent staining 14 days after BMSCs administration. Alveolar epithelial type II cells were isolated from recipient lungs and the rate of GFP positive cells was measured by flow cytometry. Expression of surfactant protein (SP)-A, SP-C and aquaporin (AQP)-5 mRNA in the lungs was evaluated by real-time PCR.</p><p><b>RESULTS</b>GFP and cytokeratin positive cells were observed in lung parenchyma of the CIM and the LIM groups, but not in the CM and the LM groups. The LIM group had more positive cells than the CIM group. The rates of GFP positive cells were higher in the CIM (11.10+/- 3.19%) and the LIM groups (14.40+/- 2.40%) than those in the CM and the LM groups (2.82+/- 1.03% and 3.81+/- 0.93%, respectively; P< 0.05). The LIM group had higher mRNA expression of SP-C than the CM group (2.09+/- 0.18 vs 1.38+/- 0.30; P< 0.05).</p><p><b>CONCLUSIONS</b>Donor derived BMSCs can engraft in LPS-injured lungs and differentiate into lung epithelial cells, suggesting BMSCs transplantation might contribute to lung repair.</p>

Effects of conventional mechanical ventilation with low tidal volume on the expression of growth factors and inflammatory mediators in developing porcine lungs / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of conventional mechanical ventilation (CMV) with low tidal volume on developmental porcine lungs by examining the expression of growth factors and inflammatory mediators.</p><p><b>METHODS</b>Twelve preterm piglets born at 99 days of gestational age, 12 term neonatal piglets and 11 young piglets (4-5-weeks old) were randomly placed on CMV or were not ventilated (control group). The ventilator settings were adjusted to provide a tidal volume of 6-8 mL/kg in order to maintain a normal blood-gas value. After 6 hrs (preterm piglets) or 24 hrs (neonatal and young piglets) of mechanical ventilation, the mRNA expression of growth factors PDGF-B, IGF-I, KGF, HGF, VEGF and TGF-beta1 and proinflammatory cytokines IL-1beta, IL-6, IL-8 and TNF-alpha in the lung tissue was measured using RT-PCR. Growth factor protein expression was measured with immunohistochemistry.</p><p><b>RESULTS</b>In preterm piglets, the CMV group had increased mRNA expression of PDGF-B (5.11+/-0.10 vs 4.88+/-0.01), IL-1beta (4.95+/-0.27 vs 4.08+/-0.37), IL-6 (4.76+/-0.27 vs 4.00+/-0.28) and IL-8 (5.31+/-0.57 vs 4.15+/-0.46), but decreased IGF-I mRNA expression (3.54+/-0.13 vs 3.80+/-0.11) compared with those in the control group (P<0.05 or 0.01). In term neonatal piglets and young piglets, there were no significant differences in the mRNA expression of growth factors and proinflammatory cytokines between the CMV and control groups.</p><p><b>CONCLUSIONS</b>CMV caused inflammatory injury in immature lungs by increasing the expression of proinflammatory cytokines and PDGF-B and decreasing IGF-I expression. However, CMV had no effects on pulmonary expression of growth factors and inflammatory mediators in term neonatal piglets and young piglets.</p>