Clinical characteristics of bronchiolitis obliterans without preceding severe lower respiratory tract infection

Purpose@#We investigated young children who developed bronchiolitis obliterans (BO) without preceding severe lower respiratory tract infection (LRTI). @*Methods@#Twenty patients referred for chronic respiratory symptoms and diagnosed with BO were enrolled and divided into 2 age groups: group 1 ( < 2 years, n = 12) and group 2 ( ≥ 2, < 6 years, n = 8). A diagnosis of BO was made based on clinical and radiologic findings: (1) persistent cough or abnormal breath sounds which were not responsive to any treatment for more than 6 weeks; and (2) mosaic perfusion on high-resolution computed tomography. None of the subjects had experienced LRTI since birth, and those who had any underlying problems were excluded. The clinical characteristics and disease course were examined retrospectively. @*Results@#Mean age of the patients was 6.8 months and 3.4 years in group 1 and 2, respectively. All patients presented with chronic cough and the most common type of cough was mixed (wet and dry), 67% in group 1 and 50% in group 2. Persistent stridor was the major respiratory sign in group 1 (67%), but 63% of group 2 patients showed no abnormal breath sounds. Chest x-ray finding was nonspecific in 75% each of both groups. The respiratory symptoms and signs resolved rapidly in most patients treated with pulse corticosteroid therapy. Bronchial hyperresponsiveness and decreased forced expiratory volume in 1 second were observed in 3 of group 2 children at age 6, during the follow-up. @*Conclusion@#Our study shows that BO could develop without preceding severe LRTI. It also suggests that BO should be considered in the infants with persistent stridor accompanied by chronic cough.

Effect of overweight or obesity on lung function and asthma severity in prepubertal asthmatic children

Purpose@#Cluster analysis on pediatric asthma identifying a cluster characterized by obesity, females, and puberty showed that obesity is an independent risk factor for severe asthma in this cluster. In the present study, we aimed to investigate the effect of overweight/obesity on lung function and asthma severity in prepubertal asthmatic children. @*Methods@#One hundred fifty-five prepubertal children (aged 6–10) with asthma were enrolled and divided into 2 groups: the overweight/obese group (body mass index [BMI] ≥ 85th percentile, n = 44) and the normal BMI group ( < 85th percentile, n = 111). We reviewed their medical records and analyzed whether there were any differences in clinical features, lung function and degree of bronchial hyperresponsiveness (BHR) between the 2 groups. The clinical factors associated with asthma severity were also investigated. @*Results@#There was no difference in clinical features between the 2 groups. Pulmonary function tests showed that only forced vital capacity in 1 second/forced vital capacity (FEV1/FVC) was significantly lower in the overweight/obese group than in the normal BMI group (P = 0.032). There was no difference in dysanapsis and BHR between the 2 groups. There were significantly more children with moderate-to-severe asthma in the overweight/obese group compared to the normal BMI group (P = 0.018). In multivariate logistic regression analysis, overweight/obesity has been identified as an independent risk factor of affecting asthma severity (odds ratio, 2.44; P = 0.018), in addition to the already known risk factor, FEV1. @*Conclusion@#Our study showed that overweight/obese prepubertal asthmatic children had lower FEV1/FVC than those with normal BMI. It also suggests that overweight/obesity may be an independent risk factor for severe asthma before puberty.

Relationships between lung function and clinical findings in school-agesurvivors of preterm birth

Purpose@#Survivors of preterm birth are at high risk of chronic pulmonary disease. We examined lung function in the school-age children born preterm and investigated the relationship between lung function and clinical parameters. @*Methods@#Thirty children born preterm were enrolled and divided into 2 groups: 14 very preterm (< 32-week gestational age [GA]) and 16 moderate-to-late preterm (32- to 36-week GA). Pulmonary function tests (PFTs) were performed repeatedly during schoolage and PFT parameters were compared with age-matched controls. The relationship between PFT and clinical parameters was also studied. @*Results@#PFT parameters in the very preterm group were persistently reduced compared with age-matched controls (P< 0.05). Half of the children had been diagnosed with asthma at the visit for the first PFT. Seventy-seven percent of patients in the very preterm group had bronchial hyperresposiveness. Birth weight, duration of oxygen therapy and mechanical ventilation in the neonatal intensive care unit, and body weight at age 1 were associated with forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC), or forced expiratory flow between 25% and 75% of expired vital capacity (FEF 25%–75%) z-scores. Multiple regression analysis revealed that body weight at age 1 was an independent predictor of FEV 1 and FVC z-scores, and duration of oxygen therapy was independently associated with FEF 25%–75% z-scores (P< 0.01 for all). @*Conclusion@#No catch-up in lung function was observed in school-age children born very preterm. Lower body weight at age 1 might be an independent risk factor for reduced FEV 1 and FVC, whereas long-term oxygen therapy might be associated with reduced FEF 25%–75%

Pharmacological treatment of the patients with croup

Croup is a respiratory illness usually caused by acute viral infection of the larynx, trachea, and bronchi, and characterized by the abrupt onset of a barking cough, inspiratory stridor, hoarseness, and respiratory distress due to upper airway obstruction. Croup commonly affects children younger than 6 years of age, with peak incidence between 7 and 36 months. Although the disease is usually self-limited, it may occasionally become life threatening, and can, on rare occasion, lead to respiratory failure.Current Concepts: Treatment of viral croup depends on the severity of symptoms as denoted by Westley croup score (i.e., mild, moderate, or severe). A single dose of oral or intramuscular dexamethasone (0.15-0.6 mg/kg) is the mainstay of treatment for viral croup, irrespective of severity. A single dose of nebulized budesonide (2 mg) is equally effective as systemically administered dexamethasone, and is considered when a patient is unable to take a medicine orally. Nebulized L-epinephrine (1:1,000, 3-5 mL) causes vasoconstriction in the mucosa, rapidly reducing airway edema. Addition of nebulized L-epinephrine is indicated in the patients with croup of at least moderate severity, displaying chest retraction and signs of labored breathing.Discussion and Conclusion: The most effective pharmacological treatments for patients with viral croup are oral or intramuscular dexamethasone, and nebulized L-epinephrine. Especially, corticosteroids can significantly decrease the intensity of croup symptoms and reduce hospital admissions, return visits to emergency department and length of stay in the hospital.

Pharmacological treatment of the patients with croup

Croup is a respiratory illness usually caused by acute viral infection of the larynx, trachea, and bronchi, and characterized by the abrupt onset of a barking cough, inspiratory stridor, hoarseness, and respiratory distress due to upper airway obstruction. Croup commonly affects children younger than 6 years of age, with peak incidence between 7 and 36 months. Although the disease is usually self-limited, it may occasionally become life threatening, and can, on rare occasion, lead to respiratory failure.Current Concepts: Treatment of viral croup depends on the severity of symptoms as denoted by Westley croup score (i.e., mild, moderate, or severe). A single dose of oral or intramuscular dexamethasone (0.15-0.6 mg/kg) is the mainstay of treatment for viral croup, irrespective of severity. A single dose of nebulized budesonide (2 mg) is equally effective as systemically administered dexamethasone, and is considered when a patient is unable to take a medicine orally. Nebulized L-epinephrine (1:1,000, 3-5 mL) causes vasoconstriction in the mucosa, rapidly reducing airway edema. Addition of nebulized L-epinephrine is indicated in the patients with croup of at least moderate severity, displaying chest retraction and signs of labored breathing.Discussion and Conclusion: The most effective pharmacological treatments for patients with viral croup are oral or intramuscular dexamethasone, and nebulized L-epinephrine. Especially, corticosteroids can significantly decrease the intensity of croup symptoms and reduce hospital admissions, return visits to emergency department and length of stay in the hospital.

Real-world treatment pattern of mycoplasma pneumonia in hospitalized children: A multicenter retrospective study

Purpose@#Macrolide-refractory Mycoplasma pneumoniae pneumonia (MP) has markedly increased since 2003 and corticosteroids or second-line antibiotics, such as fluoroquinolones or tetracyclines, was considered an alternative treatment modality in macrolide-refractory MP. We aimed to show the real-world treatment pattern of MP in hospitalized children and compared clinical and laboratory findings between children with and without steroid treatment. @*Methods@#We reviewed the medical records of 384 children diagnosed with MP from 6 hospitals in Korea from August 2015 to March 2016. We investigated the clinical, laboratory and radiologic findings, and medications used for the treatment of the subjects. @*Results@#The corticosteroids and second-line antibiotics were administered in 55.5% and 7.0%, respectively. The percentages of steroid administration varied from 17% to 69% in each hospital. The mean start date of corticosteroid administration was 3.4 hospital days. Patients with corticosteroid treatment had a longer length of hospital stay than those without corticosteroid. They exhibited higher rates of lobar pneumonia and pleural effusion, and required longer days until improvement in chest X-ray findings. They also had higher rates of allergic diseases and showed higher C-reactive protein levels at admission. @*Conclusion@#In the real-world practice studied in the 6 hospitals, corticosteroids were more frequently administered than second-line antibiotics to hospitalized children with MP. Children with corticosteroid adjuvant therapy had more severe pneumonia than those without. Randomized controlled trials are needed to make appropriate guidelines for macrolide-refractory MP.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Seasonal patterns and etiologies of croup in children during the period 2010–2015: A multicenter retrospective study

PURPOSE: Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of parainfluenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to examine the seasonal/annual patterns and etiologies of childhood croup in Korea during a consecutive 6-year period. METHODS: Pediatric croup data were collected from 23 centers in Korea from 1 January 2010 to 31 December 2015. Electronic medical records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical information were cross-sectionally reviewed and analyzed. RESULTS: Overall, 2,598 childhood croup patients requiring hospitalization were identified during the study period. Among them, a total of 927 who underwent RT-PCR were included in the analysis. Males (61.5%) predominated, and most (63.0%) of them were younger than 2 years of age (median, 19 months; interquartile range, 11–31 months). Peak hospitalization occurred in 2010 and 2012 in even-numbered years, and parainfluenza virus (PIV, 39.7%) was the most common cause of childhood croup requiring hospitalization, followed by respiratory syncytial virus (14.9%), human rhinovirus (12.5%), Mycoplasma pneumonaie (10.6%), and human coronavirus (7.3%). CONCLUSION: It is concluded that croup hospitalization has a biennial pattern in even-numbered years. PIV may be the most common cause of childhood croup; however, croup epidemics could be attributed to other viruses.

Indoor pet ownership in infancy is a risk factor for the development of sensitization to pets and asthma in childhood

PURPOSE: It is controversial whether indoor pet exposure is either a risk or protective factor developing sensitization to pet allergens or asthma. Therefore, we investigated whether indoor pet ownership entails a risk for the development of asthma and sensitization in childhood. METHODS: The Panel Study of Korean Children (PSKC) is a general-population-based birth cohort study that recruited 2,078 mother-baby dyads in Korea between April and July of 2008. Among 1,577 children who were followed up in 2015, 559 underwent skin prick tests, spirometry and bronchial provocation tests using Provocholine. Having a cat or a dog and the prevalence of asthma were evaluated by using self-reported questionnaires and physicians’ medical records. RESULTS: During infancy, the rate of dog ownership was 4.5% (71 of 1,574) and that of cat ownership was 0.5% (8 of 1,574). Of the subjects, 7.9% (n=109) currently had at least 1 dog and 2.5% (n=34) had at least 1 cat. Pet ownership during infancy was associated with sensitization to cats or dogs (adjusted odds ratio [aOR], 4.24; 95% confidence interval [CI], 1.29–13.98), wheezing within 12 months (aOR, 5.56; 95% CI, 1.65–18.75) and current asthma (wheezing episode in the last 12 months+diagnosed asthma by physicians) (aOR, 6.36; 95% CI, 1.54–26.28). In contrast, pet ownership during the last 12 months was not associated with sensitization to cats or dogs or current asthma. CONCLUSION: Indoor pet exposure during infancy can be critical for developing sensitization to cats or dogs and asthma in childhood. Avoidance of pet exposure in early life may reduce sensitization to cats or dogs and development of asthma.

A novel compound heterozygous mutation in DNAH5 in a Korean neonate with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease affecting motile cilia. A female neonate was hospitalized with respiratory distress 72 hours after birth and showed concurrent situs inversus. She was identified to have compound heterozygous mutations in DNAH5: c.5647C>T, p.Arg1883Ter (nonsense mutation) and c.10810dupA, p.Ile3604AsnfsTer2 (frameshift mutation). Sanger sequencing confirmed that they were inherited from her father and mother, respectively, and she was diagnosed with PCD. The c.10810dupA is a novel DNAH5 mutation that has never been reported. To the best of our knowledge, this is the first report describing DNAH5 mutations in a Korean patient with PCD.

Multicenter Adherence Study of Asthma Medication for Children in Korea

PURPOSE: Adherence is a major component of successful medical treatment. However, non-adherence remains a barrier to effective delivery of healthcare worldwide. METHODS: Twenty healthcare facilities (secondary or tertiary hospitals) belonging to the Korean Academy of Pediatric Allergy and Respiratory Diseases (KAPARD) participated. Questionnaires were given to patients currently receiving treatment in the form of inhalant useor oral intake or transdermal patch for mild to moderate asthma. RESULTS: A total of 1,838 patients responded to the questionnaire. Mean age was 5.98 ± 3.79 years (range: 0-18 years). With help from their caregivers, the percentage of patients that answered “taking as prescribed” was 38.04% for inhalant users, 50.09% for oral medication users and 67.42% for transdermal users. Transdermal patch users had significantly greater adherence compared to the other 2 groups (P < 0.001). The 34.15% of inhalant users, 70.33% of oral medication users and 93.00% of transdermal patch users felt that their medication delivery system was “Easy” or “Very easy” to use (P < 0.001). “Method of administration” was deemed to be the most difficult part of the treatment regimen to follow, and 76.7% of patients preferred once-daily administration (i.e., “Frequency of administration”). CONCLUSIONS: Asthma medication adherence in young children was found to be better in the transdermal patch group. This may be due to requiring fewer doses and easy to follow instructions. From an adherence point of view, the transdermal patch seems more useful for long-term asthma control in children compared to oral or inhaled medicine.

Literature review and future strategies of childhood respiratory diseases in Korea

Thirty years have passed since the Korean Association of Pediatric Allergy and Respiratory Disease was founded. There have been great changes in the pattern of respiratory diseases in Korean children during the last 30 years with economic development in the country. Pneumonia remains the leading cause of childhood morbidity, despite advances in the prevention and management. The incidence and mortality of pneumonia caused by typical bacterial pathogens have been reduced. However, the predominance of Mycoplasma pneumoniae or virus-associated diseases is emerging, which suggests that novel diagnostic and therapeutic strategies are needed. Viral bronchiolitis is one of the most substantial health burdens for infants and young children worldwide. Although respiratory syncytial virus is the most common pathogen, molecular diagnostic techniques have identified many other viruses including human rhinovirus causing bronchiolitis. Bronchiectasis is a chronic respiratory condition characterized by chronic infection, airway inflammation, and progressive lung function decline. Research into the interactions between early life respiratory infections and development of bronchiectasis is imperative to halt the disease in its origin and improve adult outcomes. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening lung disease with diffuse inflammatory lung injury leading to pulmonary edema and hypoxia. Although many modalities to treat ARDS have been studied, supportive therapies and lung protective ventilator support remains the mainstay. This review focuses on the current trends in research on these childhood respiratory diseases through literature review and aims to investigate the impact of Korean study results in this field.

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children

BACKGROUND: A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS: Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS: The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS: BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis / 소아과

PURPOSE: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes. METHODS: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05). CONCLUSION: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.

Bee Venom Exerts Neuroprotective Effects on Neuronal Cells and Astrocytes under Hypoxic Conditions Through MAPK Signaling Pathways

PURPOSE: Hypoxic-ischemic brain injuries influence the mechanisms of signal transduction, including mitogen-activated protein kinase (MAPK) that regulates gene expression through transcription factor activity. Several attempts have been made to use bee venom (BV) to treat neurological diseases. However, limited data are available for brain injuries such as neonatal hypoxic-ischemic encephalopathy (HIE) and neurodegenerative disorders. The purpose of this study was to investigate the neuroprotective effects of BV by determining the expression of activated MAPK pathways. METHODS: We examined activation and cell viability in hypoxia (1% O2, 5% CO2, 94% N2) in low glucose-treated (H+low G) neuronal cells and astrocytes in the presence and absence of BV. After they were subjected to hypoxic conditions and treated with low glucose, the cells were maintained for 0, 6, 15, and 24 h under normoxic conditions. RESULTS: Extracellular-signal-regulated kinases 1/2 (ERK1/2), p38 MAPK, and stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) were activated in H+low G conditions. Particularly, phosphorylation of ERK1/2 was maximized 6 h after exposure to H+low G condition. BV specifically inhibited the phosphorylation of ERK1/2. However, BV had no effect on p38 MAPK or SAPK/JNK. In addition, BV improved neuronal cell and astrocytes viability following exposure to H+low G. CONCLUSION: ERK inactivation is known to mediate protective effects in hypoxic brain injury. Taken together, these results suggest that treatment with BV may be helpful in reducing hypoxic injury in neonatal HIE through the ERK signaling pathway.

Significance of total serum IgE in children with lower respiratory infections due to respiratory syncytial virus

PURPOSE: Respiratory syncytial virus (RSV) is known to induce Th2 immune response with increased IgE production. We investigated serum IgE levels in RSV bronchiolitis/pneumonia (RSV-LRI) in relation to disease severity. METHODS: One hundred seven children admitted with RSV-LRI were enrolled. The patients were divided into 2 groups according to serum IgE levels: the high IgE (n=39, more than 2 standard deviations from the mean levels for age-matched controls) and low IgE groups (n=68). We investigated if there were any differences in clinical and laboratory findings, and recurrence of wheezing between the 2 groups. The difference in IgE levels between severe (severity score≥3) and nonsevere groups was also studied. RESULTS: More frequent and prolonged fever was observed in the high IgE group than in the low IgE group (P<0.05). Patients showing severe symptoms or respiratory difficulties were more frequently seen in the high IgE group (P=0.01). There was no difference in parental allergy and atopic sensitization. The nearly same findings were observed in reanalysis of data from patients with the first RSV-LRI, but recurrence of wheezing was significantly higher in the high IgE group than in the low IgE group (P=0.04). Patients with high IgE levels were more frequently seen in severe patients than in nonsevere patients (P=0.01). CONCLUSION: Our study showed that children who presented with high serum IgE levels during RSV infections had more severe symptoms compared to those with low IgE levels. It suggests that measurement of total serum IgE levels might be helpful in evaluating disease severity and recurrent wheezing in children admitted with RSV-LRI.

Clinical characteristics related to onset age of wheeze in school-age children and adolescents with asthma

PURPOSE: We aimed to investigate the clinical characteristics and their relationship with the onset age of wheeze in school-age children and adolescents with asthma. METHODS: Three hundred twenty-six patients, aged 6 to 19 years, diagnosed with asthma at 6 hospitals from Seoul, Gyeonggi, Daegu, and Busan were enrolled. They were categorized into 3 groups by the onset age of wheeze: group A, early onset (age or =6 years). Clinical characteristics including atopic sensitization, family history, combined allergic diseases, severity of asthma, and influence of asthma on daily life were examined. A history of hospitalization for early lower respiratory infection (LRI) and environmental tobacco smoking were studied and lung function tests were also performed. RESULTS: There was no difference in demographics, prevalence of atopy, combined allergic diseases, and family history of allergy between 3 groups. A history of sever LRI in early life was more common in groups A and B compared with group C. Sensitization to Dermatophagoides pteronyssinus was more prevalent in groups A and B than in group C. Forced expiratory flow between 25% to 75% (FEF(25%-75%)) was lower in groups A and B than in group C, and methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) was lowest in group B. Significantly lower FEF(25%-75%) and methacholine PC20 were observed in the patients who had been hospitalized with LRI in early life. CONCLUSION: Our study shows significant difference in lung function and atopic sensitization in relation to the onset age of wheeze in school-age children and adolescents with asthma, and suggests that early LRI might contribute to the development of asthma in early life.

ERRATUM: Affiliation Correction. Evaluation of the association of vegetation of allergenic plants and pollinosis with meteorological changes

According to the author's request, in this paper, the eighth author's (Bong-Seong Kim) affiliation should be corrected.

Clinical significance of increased vascular endothelial growth factor, transforming growth factor-beta1, and YKL-40 in the serum of children with asthma

PURPOSE: Vascular endothelial growth factor (VEGF), transforming growth factor beta1 (TGF-beta1), and platelet derived growth factor (PDGF) are known to be involved in the pathogenesis of inflammation and remodeling in asthmatic airways. YKL-40, a chitinase-like protein, and clusterin have been reported to be biomarkers for severe asthma. We examined the serum levels of growth factors, YKL-40, and clusterin in children with acute asthma or stable asthma, and investigated their correlation with clinical findings and lung function parameters. METHODS: Forty-one children (> or =6 years of age) with asthma were enrolled, and 2 groups were defined: 23 patients admitted with acute asthma (acute asthma group) and 18 patients with stable asthma (stable asthma group). The serum levels of VEGF, TGF-beta1, PDGF-BB, YKL-40, and clusterin were measured using enzyme-linked immunosorbent assay and assessed in relation to clinical manifestations and spirometric parameters. Fifteen age-matched controls were also studied. RESULTS: The serum levels of VEGF, TGF-beta1, and YKL-40 were significantly elevated in children with acute asthma compared to controls. The serum levels of VEGF and YKL-40 were higher in the stable asthma group than in controls. The serum levels of VEGF, TGF-beta1, and YKL-40 were not different between the acute asthma and stable asthma groups. The serum VEGF levels in the acute asthma group correlated significantly with asthma severity. The serum TGF-beta1 levels in stable asthma group showed a significant inverse correlation with (FEV1) forced expiratory volume in one second and FEF(25%-75%) (forced expiratory flow between 25 and 75 percent of expired vital capacity). Serum YKL-40 had no significant relationship with clinical manifestations and spirometric parameters. CONCLUSION: Our study suggests that increased serum levels of VEGF and YKL-40 might affect asthmatic airways not only during acute exacerbation but also in stable state and that serum TGF-beta1 might be a biomarker for airway obstruction in children with asthma.

Effects of Dizocilpine (MK-801) via Up-modulation of N-methyl-D-aspartate (NMDA) Receptors on Hypoxic-Ischemic Brain Injury in Neonatal Rats / 대한주산의학회잡지

OBJECTIVE: Several studies have demonstrated the neuroprotective effects of (+)-MK-801 hydrogen maleate (dizocilpine), in various animal models of hypoxic-ischemic (HI) brain injury. However limited data are available on the neonatal model of HI brain injury. The aim of the present study was to investigate the effects of dizocilpine and its mechanisms associated with NMDARs expression in neonatal rat model of HI brain injury. METHODS: In in vivo model, 7d-old rat pups underwent permanent unilateral carotid ligation. The animals were divided into six groups: N, normoxia; H, hypoxia without operation; HS, hypoxia with Sham operation; HO, hypoxia with operation; HV, HO treated with vehicle; HD, HO treated with dizocilpine. Dizocilpine (10 mg/kg) was administered intracerebrally to the rats 30 min before HI brain injury. Rat pups were exposed to hypoxia by placing them for 2 hours in hypoxic incubator (92% N2, 8% O2). In in vitro model, embryonic cortical neuronal cell cultures (from SD rats of embryonic days of 18) were done. The normoxia (N) group was prepared in 5% CO2 incubators. The hypoxia (H), and hypoxia treated with dizocilpine (HD) groups were placed in 1% O2 incubators (94% N2, 5% CO2) for 16 hours. In order to estimation of cell viability and growth, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was done. The degree of neuronal death was evaluated by morphometric method and the protein expression of each NMDARs was quantified by Real Time-PCR and Western blot. RESULTS: Both in the in vitro and in vivo models, the expressions of NMDAR subunits were lower in the hypoxia group than in the normoxia group, whereas they increased in the hypoxia treated with dizocilpine group compared to the hypoxia group. In vitro model, however, the expressions of NR1, NR2A mRNAs decreased in the H group when compared to the N group, whereas they increased a little in the HD group when compared to the H group. CONCLUSION: Dizocilpine was modulated the degeneration of neuronal cell death in neonatal rat model of HI by preservation of NR expression.