Chang-Ryul Kim

Analysis of induced sputum to examine the effects of inhaled corticosteroid on airway inflammation in children with asthma

BACKGROUND Analysis of induced sputum can be performed safely in children with asthma and is useful for both cellular and biochemical markers of inflammation. Glucocorticosteroid inhalation has become the first line therapy for chronic asthma by suppressing airway inflammation, which produces the decrease of bronchial hyperreactivity and reduces the number of eosinophil in bronchial submucosa. OBJECTIVE To determine the characteristics of the inflammatory cells and their markers in sputum and to examine the pharmacokinetic effects of glucocorticoid within 3 hours after inhalation therapy on FEV1 and sputum inflammatory indices in children with clinically defined chronic asthma. METHODS Thirty subjects with asthma included 14 current symptomatic asthmatics and 14 normal controls inhaled 4.5% hypertonic saline for 10 minutes by nebulizer. The expectorated sputum were collected from all asthmatics before and 3 hours after corticosteroid inhalation for children with asthma and were reduced by dithiotreitol. Total cell counts and differentials were determined. ECP was measured by CAP system. Interleukin-5, GM-CSF and albumin were measured by double sandwich ELISA. RESULTS The mean eosinophil percentage and ECP in induced sputum of asthmatics were significantly higher than that of controls. The induced sputum samples obtained after glucocorticoid inhalation showed a significant reduction in mean eosinophil percentage, but FEV1, IL-5, GM-CSF, albumin, and ECP values were not significantly decreased. CONCLUSION The present results in induced sputum may be interpreted to reflect direct steroid action on airways and lack of effect on bone marrow effectors at 3 hours after glucocorticoid inhalation.

Alterations in irregular and fractal heart rate behavior in growth restricted fetuses

OBJECTIVES To determine whether irregularity, and short- and long-term fractal correlation reflecting smoothness of heart rate behavior are changed in intrauterine growth restricted fetuses. STUDY DESIGN Fetal heart rate data of 192 normal fetuses and 86 intrauterine growth restricted fetuses between 31 and 42 weeks of gestation were studied. Approximate entropy to quantify irregularity, and short-term (< or =80 beats, alpha1) and long-term (>80 beats, alpha2) fractal scaling exponents to quantify the short- and long-term fractal correlation were calculated. RESULTS In the intrauterine growth restricted fetuses, the approximate entropy was significantly lower (P<0.001). The alpha2 value was significantly higher (P=0.0001) than in the normal fetuses, which performed better (F=34.2, P<0.0001) than other heart rate variability indexes in differentiating the intrauterine growth restricted fetuses from the normal fetuses in stepwise discriminant analysis. CONCLUSIONS Compared to normal fetuses, intrauterine growth restricted fetuses show a difference in that the irregularity of the fetal heart is decreased. A more apparent difference is that the long-term fractal correlation of the fetal heart is increased and the fetal heart is smoother in the long-term scale.

Neurological and Muscular Manifestations Associated With Influenza B Infection in Children

BACKGROUND Influenza viruses have been associated with various neurological and muscular symptoms. The aim of this study was to evaluate the pediatric neurological and muscular manifestations of influenza B during a 5-month epidemic at a single center. METHODS We retrospectively reviewed the medical records of 355 pediatric patients with laboratory-confirmed influenza B infection. RESULTS Neurological and muscular symptoms were exhibited by 28 patients (7.9%). The mean age was 48.7 ± 25.2 months. The mean time between respiratory symptoms and neurological symptoms was 2.2 ± 1.5 days. The most common symptom was seizure (19/28, 67.9%), followed by myositis (5/28, 17.9%), increased intracerebral pressure (1/28, 3.6%), delirium (1/28, 3.6%), and severe headache (1/28, 3.6%). There was one severe case of meningitis with myocarditis (1/28, 3.6%). All seizures were febrile: 15 simple febrile seizures (78.9%), three complex febrile seizures (15.8%), and one febrile status epilepticus (5.3%). The mean age of nine patients with their first seizures was 37.9 ± 22.2 months, which was older than the typical age of onset for febrile seizure. All the patients, except one, were treated with oseltamivir. There were no deaths or chronic debilitating sequelae. CONCLUSIONS The neurological and muscular complications of influenza B infection in children are relatively mild, and febrile seizure is the most common. However, clinicians should be alert to the possibility of rare severe complications during influenza B outbreaks.

Instability and frequency-domain variability of heart rates in fetuses with or without growth restriction affected by severe preeclampsia

This study investigated how the instability and frequency-domain variability in heart rates differ between fetuses affected only by severe preeclampsia and fetuses affected by both severe preeclampsia and growth restriction. From their antepartum fetal heart rates and those of control fetuses, the very short-term intermittency (C1alpha) and the spectral powers were calculated to evaluate the instability and frequency-domain variability, respectively. The fetuses affected only by severe preeclampsia showed abnormally high C1alpha and low- and high-frequency power. The fetuses affected by severe preeclampsia and growth restriction showed even higher C1alpha than that of the fetuses affected by severe preeclampsia and abnormally reduced low-frequency power. Conclusively, when compared to the heart rates of fetuses affected only by severe preeclampsia, the heart rates of fetuses affected by severe preeclampsia and growth restriction showed a greater abnormal instability and an abnormally reduced variability at low-frequency range.

ECP level in nasopharyngeal secretions and serum from children with respiratory virus infections and asthmatic children.

Infection with respiratory virus has been shown to exacerbate asthma in humans. However, the role of a respiratory virus in the pathogenesis of chronic asthma and/or wheezing in young children has not been clearly defined. It has also been debated whether virus-induced wheezing in young children is one entity and allergic asthma another, or whether they are different expressions of the same disease. The present study was done to compare ECP concentrations in nasopharyngeal secretions and serum from 32 nonasthmatic wheezing children with viral infections (RSV in 15 children; influenza B virus in 17 children detected by immunofluorescence antibody technique), 8 asthmatic children without viral infections, and 13 normal children as the controls to understand the role of eosinophil inflammation. The geometric mean of ECP in nasopharyngeal secretions was significantly higher in asthmatic children than in children with virus-induced wheezing (p < 0.05). ECP levels of nasopharyngeal secretions from children with the virus-induced wheezing were significantly greater than those of the controls. However, there were no significant differences in ECP levels in serum among subjects.

Rotavirus infection in neonates at a university hospital in Korea.

To develop measures to prevent neonatal rotavirus infection, we carried out rotavirus surveillance testing on all the newborns who were admitted to a newborn nursery in Korea during 1 year. We investigated the characteristics of neonatal rotavirus infection and found that it occurred throughout the year with the G4P[6] strain exclusively. Most newborns were infected nosocomially and showed no symptoms. We concluded that rotavirus might be transmitted from asymptomatic infected newborns who were born outside the hospital. We recommend isolation and rotavirus surveillance testing for all transfer patients.

Effects of maternal preeclampsia on brain-stem auditory evoked response in very low birth weight infants

OBJECTIVE Because stress in utero may enhance neuromotor maturation, we hypothesized that infants born to mothers with preeclampsia would have a shorter absolute latency V and interpeak latency I-V period (brain-stem conduction time) of brain-stem auditory evoked response (BAER) than infants born to normotensive mothers. STUDY DESIGN A retrospective cohort study was performed to assess the effects of maternal preeclampsia on BAER of very low birth weight infants. The cohort consisted of 24 infants with a birth weight less than 1251 gm born to mothers with preeclampsia, and 48 infants born to normotensive mothers, matched for birth date within 2 months, gestational age, and chronologic age at the time of the BAER test. The BAER test was completed before discharge, with the infant in a quiet state and the use of a 30 dB stimulus. RESULTS The mean latencies of wave V were shortened bilaterally (left 8.60 +/- 0.6 msec vs 9.02 +/- 0.6 msec, p < 0.008; right 8.61 +/- 0.6 msec vs 8.96 +/- 0.6 msec, p < 0.033, and the interpeak latency of I-V was significantly shortened compared with the control subjects on the left (left 4.91 +/- 0.5 msec vs 5.38 +/- 0.6 msec, p < 0.003; right 5.17 +/- 0.5 msec vs 5.37 +/- 0.6 msec, not significant). CONCLUSION These results suggest that the intrauterine stress of maternal preeclampsia accelerates the maturation of the auditory nerve and brain-stem auditory pathway in very low birth weight infants.

Risk Factors for Cause-specific Mortality of Very-Low-Birth-Weight Infants in the Korean Neonatal Network.

This study attempted to assess the risk factors for mortality of very-low-birth-weight (VLBW) infants in the neonatal intensive care unit (NICU, n=2,386). Using data from the Korean Neonatal Network, we investigated infants with birth weights <1,500 g and gestational ages (GAs) of 22-31 weeks born between January 2013 and June 2014. Cases were defined as death at NICU discharge. Controls were randomly selected from live VLBW infants and frequency matched to case subjects by GA. Relevant variables were compared between the cases (n=236) and controls (n=236) by Cox proportional hazards regression to determine their associations with cause-specific mortality (cardiorespiratory, neurologic, infection, gastrointestinal, and others). In a Cox regression analysis, cardiorespiratory death were associated with a foreign mother (hazard ratio, HR, 4.33; 95% confidence interval, CI, 2.08-9.02), multiple gestation (HR, 1.65; 95% CI, 1.07-2.54), small for gestational age (HR, 2.06; 95% CI, 1.25-3.41), male gender (HR, 1.69; 95% CI, 1.10-2.60), Apgar score ≤3 at 5 min (HR, 1.97; 95% CI, 1.18-3.31), and delivery room resuscitation (HR, 2.60; 95% CI, 1.53-4.40). An Apgar score ≤3 at 5 min was also associated with neurological death (HR, 2.95; 95% CI, 1.29-6.73). Death due to neonatal infection was associated with outborn delivery (HR, 5.09; 95% CI, 1.46-17.74). Antenatal steroid and preterm premature rupture of membranes reduced risk of cardiorespiratory death (HR, 0.43; 95% CI, 0.27-0.67) and gastrointestinal death (HR, 0.30; 95% CI, 0.13-0.70), respectively. In conclusion, foreign mother, multiple gestation, small gestation age, male gender, Apgar score ≤3 at 5 min, and resuscitation in the delivery room are associated with cardiorespiratory mortality of VLBW infants in NICU. An Apgar score ≤3 at 5 min and outborn status are associated with neurological and infection mortality, respectively.

Serial Changes in Serum Eosinophil-associated Mediators between Atopic and Non-atopic Children after Mycoplasma pneumoniae pneumonia

Purpose Mycoplasma pneumoniae pneumonia (MP) is associated with the exacerbation, timing, and onset of asthma. The goal of this study was to elucidate the impact of MP on eosinophil-related hyper-reactive amplification in atopic children. Methods We studied 48 patients with MP (26 atopic, 22 non-atopic), between 3 and 12 years of age. Serial changes in blood eosinophil counts, serum interleukin-5 (IL-5), and serum eosinophil cationic protein (ECP) levels were measured in atopic and non-atopic children with MP upon admission, recovery, and at 2 months post-recovery. Serum IL-5 and ECP levels were measured by enzyme-linked immunosorbent assays; eosinophil counts were measured using an autoanalyzer. Results Serial changes in serum IL-5, ECP, and total eosinophil counts were significantly higher in atopic patients, relative to non-atopic controls (P≤0.001). Serum IL-5 and ECP levels were significantly higher in atopic patients at all three time points tested, while eosinophil counts were higher in the clinical recovery and follow-up phases, but not in the acute phase. Furthermore, among atopic patients, serum ECP levels were significantly higher in the recovery and follow-up phases than in the acute phase. Conclusions The present study demonstrated significant differences in eosinophil counts, serum IL-5, and serum ECP levels between atopic and non-atopic children with MP at admission, recovery, and 2 months after clinical recovery. These outcomes are suggestive of eosinophil-related hyperreactivity in atopic children, with this status maintained for at least 2 months after MP.

Haemolytic disease of newborn due to anti-Jka and the duration of antibody persistence.

Whereas Jk(b)-related haemolytic disease of the newborn (HDN) is relatively common, HDN due to anti-Jk(a) is very rare, with the total number of cases with complete laboratory findings being just three. Moreover, case reports that occurred in Asia are even rarer due to the low Jk(a) allelic frequency. Therefore, we were unable to find any data about how long the antibody would persist, when the haemolysis would resolve or how long we should follow-up after discharge. Although it is clear that the causative alloantibodies would eventually become undetectable, this phenomenon could result in a delayed haemoglobin recovery and might require close serological follow-up. Here, we describe a Korean neonate with severe anaemia, early-onset hyperbilirubinaemia, low haemoglobin and spherocytosis due to anti-Jk(a) antibodies (Table 1). The infant was delivered to a gravida 1, live birth 1, woman without any history of transfusions. On admission at 2 days of life, the patient appeared healthy with the exception of a generalised palor and mild jaundice, but jaundice progressively worsened. Numerous spherocytes were also found on peripheral blood smears. Further serological testing revealed a strongly positive direct antiglobulin test (DAT) and a weakly positive indirect antiglobulin test (IAT). Additionally, the infant’s DAT was found to be moderately reactive with both monospecific immunoglobulin G and C3d present on red blood cells (RBCs). Anti-Jk(a) was able to be identified in the patient’s serum via irregular antibody identification studies using 11 panels of RBCs. Consequently, Jk(a) antigen of the neonate’s RBCs was confirmed using monoclonal anti-Jk(a) antibodies. To clearly show that the DAT positivity was caused by anti-Jk(a), the antibodies adherent to patient’s RBCs were eluted and secondarily confirmed by antibody identification panels. Anti-Jk(a) antibodies were also isolated from the maternal serum. Antigen typing of paternal RBCs was then performed by monoclonal antibodies, revealing a positive Jk(a) antigen. Following intensive phototherapy from day 3 to 5, the total bilirubin had dropped to 5.7 mg/dL by the 12th day. Nonetheless, the haemoglobin level had dropped to 7.5 g/dL at this time without transfusion. At a follow-up visit on the 51st day, his haemoglobin level was still relatively low, probably because anti-Jk(a) antibodies were still found to adhere to the patient’s RBCs despite IAT negativity. In the case of alloimmunization (i.e. not passive transfer from mother to fetus), the persistence rates were observed to be 57%, even after a relatively long follow-up period. In the case described here, the passively transferred antibody disappeared from the neonate’s blood by day 51. However, the antibodies adherent to the RBC membrane remained detectable until that time. Therefore, we contend that in such cases, it is necessary to monitor haemoglobin levels during the first months of life after discharge.