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Asthma exacerbation (AE) leads to social and economic costs and long-term adverse outcomes. We aimed to predict exacerbation-prone asthma (EPA) in children.The Korean childhood Asthma Study (KAS) is a prospective nationwide pediatric asthma cohort of children aged 5-15 years followed every 6 months. Patients with AE during the 6 months prior to all three visits, with AE prior to one or two visits, and without AE prior to any visit were defined as having EPA, exacerbation-intermittent asthma (EIA), and exacerbation-resistant asthma (ERA), respectively. Risk factors and prediction models of EPA were explored.Of the 497 patients who completed three visits, 42%, 18%, and 15% had exacerbations prior to visits 1, 2, and 3 and 5%, 47%, and 48% had EPA, EIA, and ERA, respectively. Univariate and multivariable logistic regression revealed forced expiratory volume in 1 s (FEV1) z-score, forced vital capacity (FVC) z-score, white blood cell (WBC) count, and asthma control test (ACT) score as relevant EPA risk factors. The EPA prediction model comprised FVC z-score, WBC count, ACT score, sex, and parental education level (area under the receiver operating characteristic curve [AUROC] 0.841 [95% confidence interval (CI): 0.728-0.954]).With appropriate management, AE decreases over time, but persistent AEs may occur. Apart from asthma control level, baseline lung function and WBC count predicted EPA.

Background: Asthma is a heterogeneous disease, characterized by chronic airway inflammation. Asthma exacerbations (AE) are episodes characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing, or chest tightness with a decrease in lung function. There have been previous studies that examined the role of eosinophil-derived neurotoxin (EDN) in asthma, but there have been no studies of the role of EDN in children experiencing AE. Objective: In this study, we aimed to examine the association of EDN with lung function and prognosis in children admitted for severe AE. Methods: We enrolled 82 children who were admitted for severe AE at two different university hospitals in South Korea between January 2018 and December 2019. Blood tests, including white blood cell count, myeloperoxidase (MPO), total eosinophil count, EDN, C-reactive protein (CRP) level, and interleukin (IL) 4, IL-5, IL-10 values, and lung function were measured on admission and at discharge in each patient. Results: We observed significant decreases in the levels of MPO, EDN, CRP, and IL-4, with significant improvement in lung function after treatment. We then classified the subjects into two groups of different clinical phenotypes: eosinophilic asthma exacerbation (EAE) group and non-EAE group. EDN levels were higher and lung functions were lower in the EAE group. Also, we found that the EDN level was a significant biomarker useful for predicting the number of days for hospital stay. Conclusion: We found that EDN can act as a biomarker that reflects lung function, and that EDN could act as a prognostic biomarker, which demonstrated the complex role of EDN in children experiencing AE.

Patient education is important for successful management of atopic dermatitis; however, due to limited time and resources, patient education remains insufficient. This study aimed to investigate the current state of education provided by Korean dermatologists, pediatric allergists, and allergists to patients with atopic dermatitis. A questionnaire survey consisting of items regarding educational programs for patients with atopic dermatitis was conducted via e-mail. In total, 153 participants responded to the questionnaires, and 26.8% indicated that they have had separate educational programs. The workforce involved in the educational program included nurses, residents or fellows, dieticians, pharmacists, and clinical psychologists. Most education protocols addressed the characteristics and natural course of atopic dermatitis and environmental management. Overall, 96.7% of the participants replied that an additional charge is needed for education; moreover, additional assistance from an academic society or association, in the form of medical staff, organized data, and advertisement, is required to develop and provide a well-structured educational program. A standardized education protocol will effectively provide appropriate education for patients with atopic dermatitis. Arrangement of education fees, covered by the National Health Insurance Service, will lead to the establishment of a structured educational program and participation of an additional medical workforce.

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Background Acute urticaria is a common cutaneous disease encountered in children, while anaphylaxis can show cutaneous symptoms as well as systemic symptoms. One study found that urticaria tends to precede anaphylaxis, but studies on the different role of eosinophils and related cytokines in anaphylaxis and urticaria are lacking. Objective The aim of this study was to compare the clinical features, total eosinophil count, serum levels of interleukin (IL)-18, IL-18 binding protein (BP), IL-1 receptor-like (RL) 1, and IL-33 and compare with tryptase to examine if any differences could be found between patients who experienced anaphylaxis and urticaria. Methods We included 63 patients with urticaria and 52 patients with anaphylaxis. We measured total eosinophil count and the serum levels of total IgE, tryptase, IL-18, IL-18BP, IL-1RL1, and IL-33, and we compared the differences between the groups. Lastly, receiver operating characteristic curves were constructed to determine which factors accurately diagnosed anaphylaxis. Results No significant differences were observed in the clinical characteristics or sensitization between urticaria group and anaphylaxis group. Laboratory findings showed that total eosinophil count and IL-18BP were significantly lower in the anaphylaxis group, compared with the urticaria group. IL-18BP showed significant correlation with tryptase. The receiver operating characteristic curve for IL-18BP for diagnosing anaphylaxis had an area under the curve of 0.530. Conclusion IL-18BP level was significantly different in patients with anaphylaxis compared to those with urticaria. Serum IL-18BP level may be used to differentiate between the patients with urticaria or anaphylaxis.

OBJECTIVES: Aspiration of foreign bodies into the tracheobronchial tree is a common accident in children. This study aimed to evaluate the safety and outcome of foreign body removal by flexible bronchoscopy using a retrieval basket in children. METHODS: This was a retrospective study of children treated for foreign bodies in the airway via flexible bronchoscopy using a retrieval basket at a tertiary hospital in Korea between February 2014 and October 2017. The medical records of the patients were retrospectively reviewed and analyzed. RESULTS: A total of 20 children underwent foreign body removal from the airway via flexible bronchoscopy using a retrieval basket. The median age of the patients was 16 (range, 10–21.5) months, and 12 (60%) were male. Foreign bodies removed included 16 (80%) organic items including peanuts, almond, and beans, and 4 (20%) inorganic items including a plastic bag, metal screw, spring, and Lego brick. The locations of the foreign bodies included the central airway (n = 5; trachea, n = 4; subglottic area, n = 1), right bronchial tree (n = 9), and left bronchial tree (n = 6). Successful removal was observed in 18 (90%) cases. The only complication that occurred was mild laryngeal edema (n = 2) after the procedure; both improved with corticosteroid administration. CONCLUSION: Flexible bronchoscopic extraction of a foreign body in the airway using a retrieval basket in children can be performed successfully with minimal complications.

Objectives Lidocaine, a local anaesthetic is a treatment option in uncontrolled asthma due to its immunomodulatory effects. In the present study, proparacaine (PPC), a derivative of lidocaine was examined for its therapeutic application in a mouse model of allergic rhinitis. Methods The mice were grouped into 4 groups: control group, allergic rhinitis (AR) group, ciclesonide (CIC) group, and PPC group. Nasal symptom scores, eosinophil counts, goblet cell counts, and mast cells counts in the nasal mucosa were measured. Serum ovalbumin (OVA)-specific immunoglobulin (Ig) E, OVA-specific IgG1, OVA-specific IgG2a, interleukin (IL)-4, IL-5, and cortisol levels were measured. Results Intranasal administration of PPC significantly decreased nasal symptoms, number of eosinophils, goblet cells, and mast cells in the lamina propria of the nasal mucosa. Serum OVA-specific IgE, OVA-specific IgG1, OVA-specific IgG2a was significantly higher in the AR compared with the control group. Serum level of IL-4 was significantly lower in the CIC group and PPC group in comparison with AR group. Serum IL-5 showed no significant difference among all groups. No significant difference in serum cortisol levels was observed among the 4 groups. Conclusion PPC appears to have a therapeutic potential in treatment of allergic rhinitis in a mouse model by reducing eosinophil, goblet cell, and mast cell infiltration in the nasal mucosa.

Background Eosinophils are encountered in many skin diseases, but the role of eosinophils in atopic dermatitis (AD) remains uncertain. Objective To examine the role of serum eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and total IgE as a biomarker of disease severity and relapse in severe recalcitrant AD. Methods We enrolled 99 patients with AD: 37 with severe recalcitrant AD, 20 with severe AD, and 42 with mild to moderate AD. We examined the difference in serum level of total IgE, ECP, and EDN between the groups and whether any correlation existed between disease severity and ECP or EDN. Lastly, difference in levels of ECP or EDN between those who experienced relapse was examined in the severe recalcitrant group. Results Serum levels of total IgE, ECP, and EDN were significantly higher in the severe recalcitrant AD group and severe AD group compared with the mild to moderate AD group. No significant difference was found in serum levels of total IgE, ECP, and EDN between the severe recalcitrant group and severe group. EDN had a significant positive correlation with the SCORing Atopic Dermatitis. No significant correlation was found between EDN and ECP. In the severe recalcitrant group, 29.7% of patients experienced relapse, and EDN was significantly higher in those who experienced relapse. The cutoff value of EDN for predicting relapse was 64.5. Conclusion EDN correlated with the disease severity of AD. EDN may predict relapse in severe recalcitrant AD. The EDN serum level could be considered a candidate molecule as a clinical biomarker for evaluating AD disease activity and a predictor of relapse.

Purpose Asthma is a heterogeneous airway disease occurring in children, and it has various clinical phenotypes. A clear differentiation of the clinical phenotypes can provide better asthma management and prediction of asthma prognosis. Little is currently known about asthma phenotypes in Korean children. This study was designed to identify asthma phenotypes in school-aged Korean children. Methods This study enrolled 674 children with physician-diagnosed asthma from the Korean childhood Asthma Study (KAS) cohort. The physicians verified the relevant histories of asthma and comorbid diseases, as well as airway lability and hyper-responsiveness from the results of pulmonary function tests and bronchial provocation tests. Questionnaires regarding the participants' baseline characteristics, their environment and self-rating of asthma control were collected at the time of enrollment. Laboratory tests were performed to assess allergy and airway inflammation. Children with asthma were classified by hierarchical cluster analysis. Results Of the 674 patients enrolled from the KAS cohort, 447 were included in the cluster analysis. Cluster analysis of these 447 children revealed 4 asthma phenotypes: cluster 1 (n = 216, 48.3%) which was characterized by male-dominant atopic asthma; cluster 2 (n = 79, 17.7%) which was characterized by early-onset atopic asthma with atopic dermatitis; cluster 3 (n = 47, 10.5%) which was characterized by puberty-onset, female-dominant atopic asthma with the low lung function; and cluster 4 (n = 105, 23.5%) which was characterized by early-onset, non-atopic dominant asthma. Conclusions The asthma phenotypes among Korean children can be classified into 4 distinct clusters. Long-term follow-up with these phenotypes will be needed to define their prognosis and response to treatment.

Background: Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality and its disease burden is affected by age and etiologies with time-dependent changes. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. Methods: We conducted a retrospective study in 30,994 children (0-18 years old) with CAP between 2010 and 2015 at 23 nationwide hospitals in Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified into macrolide-sensitive MP, macrolide-less effective MP (MLEP) and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. Results: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.36% of the total MP pneumonia. In children less than 2 years of age, RSV (34.01%) was the most common cause of CAP, followed by MP (9.44%), whereas MP was the most common cause of CAP in children 2-18 years of age. Systemic corticosteroid was most commonly administered in MP pneumonia. The rate of hospitalization in intensive care unit was highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. Conclusions: The present study provides fundamental data for establishment of public health policies to decrease disease burden due to CAP as well as for improvement of pediatric health.

Purpose Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. Methods This study was performed on 667 children aged 5-15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. Results Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. Conclusions Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.

Objective: Various numerical asthma control tools have been developed to distinguish different levels of symptom control. We aimed to examine whether the asthma control test (ACT) is reflective of objective findings such as lung function, fractional exhaled nitric oxide (FeNO) and laboratory data in patients with stable asthma. Methods: We included patients who were enrolled in the Korean Childhood Asthma Study. ACT, spirometry, blood tests and FeNO were performed in patients after stabilization of their asthma. We examined differences among spirometry parameters, blood tests and FeNO according to control status as determined by ACT and investigated for any significant correlations. Results: The study population consisted of 441 subjects. Spirometry showed that forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity and FEV1/forced vital capacity were all significantly higher in the controlled asthma group. Likewise, FeNO and percent-change in FEV1 were both significantly lower in the controlled asthma group. In blood tests, the eosinophil fraction was significantly lower in the controlled asthma group while white blood cell count was significantly higher in the controlled asthma group. Lastly, among the various factors analyzed, only provocative concentration of methacholine causing a 20% fall in FEV1 significantly correlated with ACT score. Conclusion: ACT is useful as part of the routine evaluation of asthmatic children and should be used as a complement to existing tools such as spirometry and FeNO measurement.

Background Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. Methods We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects’ baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. Discussion Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects’ personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

PURPOSE Although anaphylaxis is recognized as an important, life-threatening condition, data are limited regarding its triggers in different age groups. We aimed to identify anaphylaxis triggers by age in Korean children. METHODS We performed a retrospective review of medical records for children diagnosed with anaphylaxis between 2009 and 2013 in 23 secondary or tertiary hospitals in South Korea. RESULTS A total of 991 cases (mean age=5.89±5.24) were reported, with 63.9% involving patients younger than 6 years of age and 66% involving male children. Food was the most common anaphylaxis trigger (74.7%), followed by drugs and radiocontrast media (10.7%), idiopathic factors (9.2%), and exercise (3.6%). The most common food allergen was milk (28.4%), followed by egg white (13.6%), walnut (8.0%), wheat (7.2%), buckwheat (6.5%), and peanut (6.2%). Milk and seafood were the most common anaphylaxis triggers in young and older children, respectively. Drug-triggered anaphylaxis was observed more frequently with increasing age, with antibiotics (34.9%) and nonsteroidal anti-inflammatory drugs (17.9%) being the most common causes. CONCLUSIONS The most common anaphylaxis trigger in Korean children was food. Data on these triggers show that their relative frequency may vary by age.

Background Bronchiectasis is a chronic pulmonary disease characterized by progressive and irreversible bronchial dilatation. The aim of the present study was to investigate the etiologies and clinical features of bronchiectasis in Korean children. Methods We performed a retrospective review of the medical records for children diagnosed with bronchiectasis between 2000 and 2017 at 28 secondary or tertiary hospitals in South Korea. Results A total of 387 cases were enrolled. The mean age at diagnosis was 9.2 ± 5.1 years and 53.5% of the patients were boys. The most common underlying cause of bronchiectasis was preexisting respiratory infection (55.3%), post-infectious bronchiolitis obliterans (14.3%), pulmonary tuberculosis (12.3%), and heart diseases (5.6%). Common initial presenting symptoms included chronic cough (68.0%), recurrent pneumonia (36.4%), fever (31.1%), and dyspnea (19.7%). The most predominantly involved lesions were left lower lobe (53.9%), right lower lobe (47.1%) and right middle lobe (40.2%). No significant difference was observed in the distribution of these involved lesions by etiology. The forced expiratory volume in 1 s (FEV1) levels were lowest in cases with interstitial lung disease-associated bronchiectasis, followed by those with recurrent aspiration and primary immunodeficiency. Conclusions Bronchiectasis should be strongly considered in children with chronic cough and recurrent pneumonia. Long-term follow-up studies on pediatric bronchiectasis are needed to further clarify the prognosis and reduce the disease burden in these patients.

Background Metabolic syndrome and dyslipidemia contribute to the development of a pro-inflammatory state in asthma. However, studies investigating the association between asthma and dyslipidemia have reported conflicting results. This study aimed to uncover the relationship between asthma and lipid profiles in adolescents using a national health and nutrition survey. Methods This cross-sectional study analyzed the 2010–2012 Korea National Health and Nutrition Examination Survey data and included 2841 subjects aged 11–18 years with fasting blood sample data. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed. We compared asthma prevalence between high-risk and low-risk lipid groups. Results There were 123 adolescents with asthma and 2718 without asthma (controls). The TC/HDL-C ratio, LDL-C/HDL-C ratio, and non-HDL-C levels were significantly higher in the asthma group than in the non-asthma group (P

Background/purpose Differences exist among racial and ethnic groups in the prevalence and severity of allergic diseases. However, influence of population admixing on allergic disease has not been studied. We examined the effect of population admixing on the occurrence of allergic disease. Methods We reviewed the data of 68,043 adolescents who participated in the 11th Korea Youth Risk Behavior Web-based Survey, which provides a sample that is representative of the entire Korean middle school and high school student population. Multi-ethnic status was determined by using parental country of birth and prevalence of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) was determined by questionnaire. Results Multi-ethnic adolescents accounted for approximately 0.9% of the total adolescents. Prevalence of asthma was significantly higher in multi-ethnic group than non multi-ethnic group while that of AR and AD was significantly higher in non multi-ethnic group than multi-ethnic group. Parental region of country at birth showed a significant difference in prevalence of allergic disease. Univariate analysis found that urbanity, perceived economic status (PES), parental region of country at birth, and environmental tobacco smoke (ETS) showed a significant odds ratio (OR) in asthma, AR, and AD. Body mass index (BMI) showed a significant OR in asthma and AD. After adjusting for urbanity, PES, BMI and ETS, multiethnicity showed significantly lower OR in AR and AD. Conclusion Population admixing appears to have significant effect on the prevalence of allergic disease. Further study will be needed to clarify the effect of population admixing on prevalence of allergic disease.

Background House dust mites (HDMs) are important sources of indoor allergens. Seventeen components have been identified from Dermatophagoides pteronyssinus (Der p). Objective Our aim was to define the prevalence of specific IgE to components of Der p in Korea and investigate the clinical features of them in children with allergic disease. Methods We performed a prospective evaluation of 80 HDM sensitized patients with history of allergic rhinitis (AR), atopic dermatitis (AD), asthma and urticaria (UC). Patients underwent ImmunoCAP for total IgE, Der p, Der f, Der p 1, Der p 2, and Der p 10. Results Seventy-nine patients had detectable serum IgE to Der p, 80 patients were sensitized to Der f, 66 patients were sensitized to Der p 1, 63 patients to Der p 2, and 7 patients were sensitized to Der p 10. Der p 1 specific IgE was significantly lower in the UC group compared with the AD and AR group. Total IgE was significantly higher in the Der p 10 sensitized group. Der p 10 serum IgE level was highly correlated with crab and shrimp specific IgE. There was a significant positive correlation between total IgE and specific IgE to Der p and its components and Der f. Conclusion Sensitization to HDM and its components in Korea is similar to previous studies from temperate climate. The determination of Der p 1, Der p 2, and Der p 10 specific IgE helps in obtaining additional information in regards to allergic disease.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis (CRS) is a commonly diagnosed disease that has a significant impact on a child's quality of life. However, no useful biomarker is available to identify antibiotic-responsive CRS. We determined the significance of eosinophil-related markers and total IgE levels in childhood CRS with regard to antibiotic response. DESIGN AND SETTING: This was a case-control study of patients admitted to Uijeongbu St. Mary's Hospital between November 2010 and November 2011 and diagnosed with CRS. PATIENTS AND METHODS: In this analytical cross-sectional study, we identified children whose symptoms and radiologic abnormalities did not resolve after 12 weeks despite appropriate antibiotics (non-responder CRS group), children whose symptoms and radiologic abnormalities resolved after 12 weeks with appropriate antibiotics (responder CRS group), and healthy controls selected from clinic patients. Skin prick tests were performed along with serum total IgE, total eosinophil count (TEC), serum eosinophil cationic protein (ECP) level, and ImmunoCAP analysis for common allergens. RESULTS: This study included 36 responders, 22 nonresponders and 22 healthy controls. The prevalence of allergic diseases, atopy, and a family history of allergic diseases were significantly higher in the non-responder group than in the responder and control groups. TEC, ECP, and total IgE levels were significantly higher in the non-responder group than in the responder and control groups (all P

Summary Background Pentraxin 3 (PTX-3) is an acute-phase protein that increases in the plasma during inflammation. Objective We aimed to evaluate the usefulness of PTX-3 as a clinical marker in children with lower respiratory tract infection (LRTI) and examine the correlation of PTX-3 with other biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). Methods We enrolled 117 consecutive patients admitted to Seoul St. Mary's Hospital with LRTI using the WHO criteria. We recorded data on fever duration and peak temperature before admission, duration of fever after admission, respiratory rate, heart rate, oxygen saturation upon admission, duration of oxygen supplementation, and duration of hospital stay. Upon admission, white blood cell (WBC) count, erythrocyte sedimentation rate, CRP level were measured. Multiplex respiratory virus polymerase chain reaction was performed using nasal swabs. PTX-3, PCT, and various cytokines were measured after the study had been completed. Results We found that there was no significant difference in the level of PTX-3 according to the type of viral infection. PTX-3 levels showed a significant correlation with PCT levels, but not with levels of CRP. The level of PTX-3 showed a significant correlation with peak temperature and duration of fever before admission as well as interleukin (IL)-6 levels. PCT levels showed a significant correlation with IL-6 and granulocyte-colony stimulating factor levels, peak temperature, and duration of fever before admission, and duration of hospital stay. CRP levels showed a significant correlation with duration of fever before admission, total WBC count, and neutrophil count. PCT levels significantly predicted a hospital stay of 7 days or more. PTX-3, PCT, and CRP levels showed no correlation with any other clinical features. Conclusion PTX-3 reflected disease severity but failed to predict length of hospital stay. Further studies evaluating the use of PTX-3 as a biomarker in mild LRTI would be useful. Pediatr Pulmonol. 2016;51:42–48. © 2015 Wiley Periodicals, Inc.

Purpose: Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of para influenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to ex amine 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 medi cal records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical informa tion 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 hos pitalization, 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 com mon cause of childhood croup; however, croup epidemics could be attributed to other viruses. (Allergy Asthma Respir Dis 2019;7:78-85)

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.

Purpose: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. Methods: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df ) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. Results: RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P

Background: Hematopoietic stem cell transplantation (HSCT) has been a life-saving treatment for malignant and nonmalignant pediatric diseases. Its success is often restricted by pulmonary complications (PCs). Methods: A retrospective chart review of 174 pediatric patients of aged between 4 to 18 years, receiving HSCT between 2009 and 2012 was performed. Results: Eighty three PCs developed in 66 patients (37.9%): 57 infectious (24.7%), 26 noninfectious (14.9%), and 3 both infectious and noninfectious (1.7%). The cumulative incidence of infectious PCs was increased earlier than noninfectious PCs after HSCT ( P =0.027). The main infectious PCs were unspecified pneumonia (18 [10.3%]), fungal pneumonia (14 [8%]), acute bronchitis (7 [4%]) and viral pneumonia (7 [4%]). Bronchiolitis obliterans, air trapping, cryptogenic organizing pneumonia were the common noninfectious complications. Independent factors associated with PCs included cell source of HSCT and severity of chronic graft versus host dieases (GvHD, P 0.001). Moderate and severe chronic GVHD showed an association with noninfectious PCs at subdistribution hazard ratios of 6.05 and 11.90, respectively, compared with none chronic GVHD. The mortality risk following noninfectious PCs was much increased during the first year and relatively stable thereafter. Whereas, the mortality risk following infectious PCs showed continuous increase until second year. Conclusion: The development of infectious complications was more related to decreased survival. Knowing the patient9s timeline after HSCT may be helpful for early recognition and treatment of PCs.

This study investigated the preventive therapeutic effects of Hataedock (HTD) treatment on inflammatory regulation and skin protection in AD-induced NC/Nga mice under high-fat diet conditions. Before inducing AD, the extract ofCoptidis RhizomaandGlycyrrhiza uralensiswas administered orally to the 3-week-old mice. After that, AD-like skin lesions were induced by applying DNFB. All groups except the control group were fed a high-fat diet freely. We identified the effects of HTD on morphological changes, cytokine release and the induction of apoptosis through histochemistry, immunohistochemistry, and TUNEL assay. HTD downregulated the levels of IL-4 and PKC but increased the levels of LXR. HTD also suppressed the mast cell degranulation and release of MMP-9, Substance P. The levels of TNF-α, p-IκB, iNOS, and COX-2 were also decreased. The upregulation of inflammatory cell’s apoptosis is confirmed by our results as increase of apoptotic body and cleaved caspase-3 and decrease of Bcl-2. HTD also reduced edema, angiogenesis, and skin lesion inflammation. Our results indicate HTD suppresses various inflammatory response on AD-induced mice with obesity through the regulation of Th2 differentiation and the protection of lipid barrier. Therefore, HTD could be used as an alternative and preventive therapeutic approach in the management of AD.

We investigated the effects of sodium sulfite (Na(2)SO(3)) on rhinovirus (RV)-induced chemokine production in A549 airway epithelial cells. Our results demonstrated that the treatment of A549 cells with 2,500 μM Na(2)SO(3) enhanced the mRNA expression of RV-induced interleukin (IL)-8 1.8 fold (p = 0.025); and regulated on activation, normal T cell expressed and secreted (RANTES), 2.9 fold (p = 0.025). Moreover, the secretion of IL-8, RANTES, and interferon-γ-inducible protein (IP)-10 was increased in a statistically significant manner without affecting cell viability and RV replication. Our results suggest that Na(2)SO(3) may potentiate RV infection by enhancing chemokine production.

Background Nonasthmatic subjects with allergic rhinitis often have bronchial hyperresponsiveness (BHR), characteristic of asthma. The presence and degree of atopy is suggested to be important for BHR in patients with asthma. We aimed to assess BHR to methacholine (direct stimulus) and to adenosine 5′-monophosphate (AMP; indirect stimulus) in preschool children with allergic rhinitis and to investigate their relationship with the degree of atopy. Methods Methacholine and AMP bronchial challenges were performed in preschool children with allergic rhinitis (n = 96), using a modified auscultation method. The end point concentration, resulting in audible wheezing and/or oxygen desaturation, was determined for each challenge. The degree of atopy was assessed using serum total IgE levels, the number of positive skin-prick tests, and atopic scores (sum of graded wheal size). Results BHR to methacholine (end point concentration, ≤ 8 mg/mL) and to AMP (end point concentration, ≤ 200 mg/mL) was observed in 32 (33.3%) and 26 (27.1%) subjects, respectively. No significant relationship was observed between BHR to methacholine and any atopy parameter. In contrast, the atopic scores were higher in the AMP–BHR+ group compared with the AMP–BHR− group, and a significant association was found between the degree of atopic scores and the frequency of BHR to AMP (score for trend, p = 0.006). Such a relationship was not observed for serum total IgE levels and the number of positive SPTs. Conclusion BHR to methacholine and BHR to AMP were detected in a significant proportion of preschool children with allergic rhinitis. The degree of atopy in terms of atopic scores seems to be an important factor for BHR to AMP but not for BHR to methacholine.

Exercise and inhaled mannitol are thought to cause bronchoconstriction through a similar mechanism in asthma. The response to exercise becomes refractory with repeated challenges. This study aimed to investigate whether repeated challenge with mannitol induces refractoriness, as with exercise. Forty-one children with asthma underwent two consecutive dose–response mannitol challenges (Phase 1); the second challenge proceeded after recovery (FEV1: 95% or more of baseline value) from the first. The response to mannitol was expressed as a provocative dose causing a 15% fall in FEV1 (PD15) and the response–dose ratio (RDR) (% fall in FEV1/cumulative dose). In 18 subjects who were deemed to have mannitol refractoriness in Phase 1, a mannitol challenge was performed before and after a methacholine challenge (Phase 2). In Phase 1, the time taken for the FEV1 to recover after the first mannitol challenge ranged from 20 to 100 min with a median of 50 min. In the 23 subjects with a measurable mannitol PD15 in both challenges, the geometric mean (95%CI) PD15 in the second challenge (163 mg [114–232]) was significantly higher than that in the first challenge (66 mg [50–88], P

Background. Airway remodeling has been assumed to cause bronchial hyperresponsiveness (BHR). A low postbronchodilator FEV1/FVC ratio has been suggested to be a functional surrogate marker of airway remodeling in asthma. BHR is commonly assessed by bronchial challenges using direct or indirect stimuli. Objective. The aim of this study was to compare BHR to methacholine and adenosine 5′-monophosphate (AMP) with regard to their relationship with a marker of airway remodeling in children with asthma. Methods. Methacholine and AMP challenge tests were performed in 129 children with asthma, aged 12 years, and a provocative concentration causing a 20% fall in FEV1 (PC20) was calculated for each challenge. All subjects also underwent pre- and postbronchodilator spirometry. A postbronchodilator FEV1/FVC ratio below the lower limits of normal was used as a marker of airway remodeling. Results. A low postbronchodilator FEV1/FVC ratio was found in 17 subjects (13.2%). These subjects had a significantly lower methacho...