Publications by authors named "Hyo-Bin Kim"

88 Publications

Prenatal PM exposure and vitamin D-associated early persistent atopic dermatitis via placental methylation.

Ann Allergy Asthma Immunol 2020 12 21;125(6):665-673.e1. Epub 2020 Sep 21.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 μm to 2.5 μm (PM) and vitamin D on atopic dermatitis (AD) phenotypes have not been evaluated. DNA methylation and cord blood (CB) vitamin D could represent a plausible link between prenatal PM exposure and AD in an offspring.

Objective: To determine the critical windows of prenatal PM exposure on the AD phenotypes, if vitamin D modulated these effects, and if placental DNA methylation mediated these effects on AD in offspring.

Methods: Mother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PM was estimated by land-use regression models, and CB vitamin D was measured by chemiluminescence immunoassay. AD was identified by the parental report of a physician's diagnosis. We defined the following 4 AD phenotypes according to onset age (by the age of 2 years) and persistence (by the age of 3 years): early-onset transient and persistent, late onset, and never. Logistic regression analysis and Bayesian distributed lag interaction model were used. DNA methylation microarray was analyzed using an Infinium Human Methylation EPIC BeadChip (Illumina, San Diego, California) in placenta.

Results: PM exposure during the first trimester of pregnancy, especially during 6 to 7 weeks of gestation, was associated with early-onset persistent AD. This effect increased in children with low CB vitamin D, especially in those with PM exposure during 3 to 7 weeks of gestation. AHRR (cg16371648), DPP10 (cg19211931), and HLADRB1 (cg10632894) were hypomethylated in children with AD with high PM and low CB vitamin D.

Conclusion: Higher PM during the first trimester of pregnancy and low CB vitamin D affected early-onset persistent AD, and the most sensitive window was 6 to 7 weeks of gestation. Placental DNA methylation mediated this effect.
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http://dx.doi.org/10.1016/j.anai.2020.09.008DOI Listing
December 2020

Is it necessary to evaluate urinary tract infection in children with lower respiratory tract infection?

J Paediatr Child Health 2020 Dec 8;56(12):1924-1928. Epub 2020 Aug 8.

Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, South Korea.

Aim: Although the incidence of urinary tract infection (UTI) in children with lower respiratory tract infection (LRTI) has been reported as 3.1-10.0%, the exact concomitant prevalence is questionable. Here, we evaluated the prevalence and related risk factors of UTI associated with LRTI in children under 36 months of age.

Methods: We retrospectively reviewed the medical charts of 1574 patients under 36 months of age who were hospitalised with LRTI from January 2017 to December 2019 in a single centre, Seoul, South Korea. Among them, we analysed 278 patients who showed fever and performed urine evaluation. Urine was collected by catheterisation in children under 24 months of age and by voided urine between 24 and 36 months of age.

Results: The prevalence of concomitant UTI and LRTI was 13.6% in children under 24 months of age. Mean age was significantly younger in the UTI versus non-UTI group (6.93 ± 7.26 months vs. 12.61 ± 11.70 months; P < 0.001). When the participants were stratified by age, the prevalence of UTI was significantly higher in children younger than 24 months of age compared to older ones (P = 0.006). UTIs were more prevalent in boys than in girls (14.6% vs. 5.8%, P = 0.018). Peak body temperature, fever duration, premature birth and detected respiratory virus type did not differ between groups.

Conclusions: It is not uncommon for children with LRTI with fever to be accompanied by UTI. When evaluating for UTI in children with febrile LRTI, age and sex must be considered.
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http://dx.doi.org/10.1111/jpc.15080DOI Listing
December 2020

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 2. Management of H1-Antihistamine-Refractory Chronic Urticaria.

Allergy Asthma Immunol Res 2020 Sep;12(5):750-770

Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H₁-antihistamines, even though the dose of H₁-antihistamines is increased up to 4-fold. CSU that is not controlled with H₁-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H₁-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.
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http://dx.doi.org/10.4168/aair.2020.12.5.750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346997PMC
September 2020

Prenatal maternal anxiety promotes atopic dermatitis in offspring via placental DNA methylation changes.

Asian Pac J Allergy Immunol 2020 May 17. Epub 2020 May 17.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Maternal anxiety during pregnancy has been previously reported to be associated with atopic dermatitis (AD) in offspring. The potential mechanism is not yet proven but epigenetic change may be suggested.

Objective: We examined whether maternal anxiety during pregnancy may alter placental DNA methylation, then develop AD in the offspring.

Methods: We evaluated maternal anxiety at 36 weeks of gestation by self-reported questionnaires, the State-Trait Anxiety Inventory-Trait subscale (STAI-T), in the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) study. AD was diagnosed at 6 months of age by pediatric allergists. We stratified the subjects into four groups according to the STAI score of mothers and diagnosis of AD in children. Placental genome-wide methylation microarray was analyzed using Infinium 450K BeadChip and selected genes were validated by pyrosequencing.

Results: From microarray, several differential methylation sites were identified in AD and healthy subjects and in total subjects, regarding to the STAI scores. Among differential methylation sites in microarray, six sites were selected for pyrosequencing. And site of matrix metalloproteinases 27 (MMP27) among 6 sites showed decreased methylation in AD infants with high STAI mothers compared to healthy infants with low STAI mothers.

Conclusions: Epigenetic change in placenta can be a suggesting mechanism for the development of AD in offspring at 6 months of age associated with maternal anxiety during pregnancy and MMP27 may be a candidate gene.
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http://dx.doi.org/10.12932/AP-221119-0699DOI Listing
May 2020

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management.

Allergy Asthma Immunol Res 2020 Jul;12(4):563-578

Department of Dermatology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
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http://dx.doi.org/10.4168/aair.2020.12.4.563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224993PMC
July 2020

Effectiveness and safety of electroacupuncture and its cotreatment with electronic moxibustion in the treatment of patients with moderate benign prostatic hyperplasia using alpha blocker: Study protocol for an assessor-blinded, randomized controlled clinical trial.

Medicine (Baltimore) 2020 Apr;99(15):e19678

Clinical Medicine Division, Korea Institute of Oriental Medicine.

Background: Benign prostatic hyperplasia (BPH) is a medical condition that affects the quality of life by causing lower urinary tract symptoms (LUTS) in 40% to 70% of men aged ≥60 years. Medication treatment is primarily recommended for patients with BPH if their symptom score based on the International Prostate Symptom score (IPSS) is above the moderate level. However, electroacupuncture (EA) and electronic moxibustion (EM), one of the most recent complementary and alternative treatments, are suggested as adjuvant treatments in the improvement of LUTS caused by BPH with respect to the limitations of medication treatments, such as side effects or no improvement in LUTS despite treatment. Therefore, this study aimed to evaluate the effectiveness and safety of EA and its cotreatment with EM for the improvement of LUTS in patients diagnosed with BPH using an alpha blocker but with moderate symptoms on the basis of IPSS.

Methods/design: This protocol is a 2-arm parallel-design, randomized, controlled assessor-blinded clinical trial. Seventy-eight patients diagnosed with BPH are randomized to one of the following groups: [EA and its cotreatment with EM + alpha blocker group] and [alpha blocker group]. [EA and its cotreatment with EM + alpha blocker group] continues to use the previously prescribed alpha blocker and visits the study institution 3 times a week for 6 weeks to receive the cotreatment of EA and EM. [Alpha blocker group] continues to use the previously prescribed alpha blocker for 6 weeks. To evaluate the effectiveness of the EA and its cotreatment with EM, the followings are measured: total score of the IPSS, IPSS quality of life assessment, EuroQol-Five dimension, maximum and average urinary flow rate (Qmax and Qave), and prostate size at the baseline, 3rd, 6th, and 12th weeks. The primary effectiveness endpoint measures the average change in the total score of the IPSS at the 6th week. Side effects are recorded at each visit.

Discussion: The results of this study are expected to provide useful information on the effectiveness and safety of the EA and its cotreatment with EM for patients with BPH with regard to the improvements in LUTS.

Trial Registration: Clinical Research Information Service of Republic of Korea (CRIS-KCT0004411), October 31, 2019.
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http://dx.doi.org/10.1097/MD.0000000000019678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220246PMC
April 2020

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BMC Infect Dis 2020 Feb 12;20(1):132. Epub 2020 Feb 12.

SCH Biomedical Informatics Research Unit, Soonchunhyang University Seoul Hospital, Seoul, South Korea.

Background: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. 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 (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as 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 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia.

Conclusions: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.
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http://dx.doi.org/10.1186/s12879-020-4810-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017508PMC
February 2020

Asthma predictive index as a useful diagnostic tool in preschool children: a cross-sectional study in Korea.

Clin Exp Pediatr 2020 Mar 8;63(3):104-109. Epub 2019 Nov 8.

Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children.

Purpose: This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children.

Methods: We performed a population-based cross-sectional study in 916 preschool children aged 4-6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma.

Results: The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed.

Conclusion: The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.
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http://dx.doi.org/10.3345/kjp.2019.00640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073380PMC
March 2020

Imbalance of Gut , , and Determines the Natural Course of Atopic Dermatitis in Infant.

Allergy Asthma Immunol Res 2020 03;12(2):322-337

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: The roles of gut microbiota on the natural course of atopic dermatitis (AD) are not yet fully understood. We investigated whether the composition and function of gut microbiota and short-chain fatty acids (SCFAs) at 6 months of age could affect the natural course of AD up to 24 months in early childhood.

Methods: Fecal samples from 132 infants were analyzed using pyrosequencing, including 84 healthy controls, 22 transient AD and 26 persistent AD subjects from the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort. The functional profile of the gut microbiome was analyzed by whole-metagenome sequencing. SCFAs were measured using gas chromatography-mass spectrometry.

Results: Low levels of and high amounts of were evident in transient AD cases, and low , and high were found in children with persistent AD. The relative abundance of positively correlated with scoring of AD (SCORAD) score, whereas that of negatively correlated with SCORAD score. The persistent AD group showed decreased gut microbial functional genes related to oxidative phosphorylation compared with healthy controls. Butyrate and valerate levels were lower in transient AD infants compared with healthy and persistent AD infants.

Conclusions: Compositions, functions and metabolites of the early gut microbiome are related to natural courses of AD in infants.
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http://dx.doi.org/10.4168/aair.2020.12.2.322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997289PMC
March 2020

Prenatal particulate matter exposure with skin barrier dysfunction affects offspring's atopic dermatitis: COCOA study.

J Allergy Clin Immunol Pract 2020 06 29;8(6):2062-2065.e5. Epub 2020 Jan 29.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.01.040DOI Listing
June 2020

Particulate matter at third trimester and respiratory infection in infants, modified by GSTM1.

Pediatr Pulmonol 2020 01 20;55(1):245-253. Epub 2019 Nov 20.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Objectives: To investigate the association between particulate matter with an aerodynamic diameter of less than 2.5 μm (PM ) exposure during each trimester of pregnancy and development of lower respiratory tract infections (LRTIs) during the first 3 years of life and whether GSTM1 gene polymorphisms modify these effects.

Methods: This study included 1,180 mother-child pairs from the Cohort for Childhood Origin of Asthma and allergic diseases. The PM levels during pregnancy were estimated by residential address using land-use regression models based on a national monitoring system. A diagnosis of LRTIs was based on a parental report of a physician's diagnosis. Real-time polymerase chain reaction was used for GSTM1 genotyping.

Results: Higher PM exposure during the third trimester was associated with LRTIs at 1 year of age (aRR, 1.06; 95% CI, 1.00-1.13). This result did not change after adjusting for PM exposures during the first and second trimesters (aRR, 1.06; 95% CI, 0.99-1.13). This association was significant after adjusting for PM exposures during first year of age (aRR, 1.08; 95% CI, 1.02-1.15) and exposures to NO and ozone at the third trimester (aRR, 1.07; 95% CI, 1.00-1.16). In addition, PM exposure during the third trimester increased the risk of LRTIs at 1 year of age in cases with the GSTM1 null genotype (aRR, 1.26; 95% CI, 1.01-1.57; P for interaction .20).

Conclusion: Higher PM exposure during the third trimester of pregnancy may increase the susceptibility to LRTIs at 1 year of age. This effect is modified by GSTM1 gene polymorphisms.
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http://dx.doi.org/10.1002/ppul.24575DOI Listing
January 2020

The Korean Version of the Test for Respiratory and Asthma Control in Kids (TRACK): Reliability and Validity.

J Korean Med Sci 2019 Jan 9;34(3):e25. Epub 2019 Jan 9.

Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

Background: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaires were developed and validated in various languages to monitor respiratory control in preschool-aged children. We aimed to assess the reliability and validity of the Korean version of the TRACK questionnaire.

Methods: We administered the linguistically validated TRACK questionnaires to caregivers of asthmatic preschool children on two separate visits 4-6 weeks apart. Each physician graded the level of the guideline-based asthma control, assessed the timing of symptoms, and adjusted the therapeutic level at each visit.

Results: A total of 137 children were enrolled in the study. Cronbach's alpha was 0.65 for a questionnaire as a whole. The test-retest reliability was 0.72. The median TRACK scores were significantly different between asthma control status categories, with the lowest scores in children classified as poorly controlled and the highest in the well-controlled group ( < 0.001). They were different among groups classified according to the physician adjusted therapeutic levels, with the lowest values in children prescribed step-up therapy ( < 0.001), and according to the recency of respiratory symptoms ( < 0.001). Finally, the changes in TRACK scores between visits were highest in subjects showing improved control, followed by unchanged, and worsened control. When we applied the traditional cut-off of 80 for a well-controlled condition, a sensitivity of 75.6% and a specificity of 70.9% were calculated.

Conclusion: The Korean translated version of the TRACK questionnaire is valid and reliable to assess respiratory and asthma control in Korean preschool children with asthma symptoms.
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http://dx.doi.org/10.3346/jkms.2019.34.e25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335117PMC
January 2019

Multicenter Adherence Study of Asthma Medication for Children in Korea.

Allergy Asthma Immunol Res 2019 Mar;11(2):222-230

Department of Pediatrics, College of Medicine, Seoul National University, Seoul, 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 ( < 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 ( < 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 (, "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.
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http://dx.doi.org/10.4168/aair.2019.11.2.222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340803PMC
March 2019

Drug eruption by antihistamine mistaken for chronic urticaria in a child.

Korean J Pediatr 2019 Feb 30;62(2):75-78. Epub 2018 Oct 30.

Department of Pediatrics, Kangwon National University Hospital, chuncheon, Korea.

Although rare, antihistamines can cause adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after administration of antihistamines, (e.g., ucerax [hydroxyzine] or leptizine [levocetirizine]), for cholinergic rashes; he did not have pruritus. Skin prick, intradermal, and drug provocation tests were performed to determine the relationship between the antihistamines and eruptions. Levocetirizine induced wheals in the skin prick test and a rash in the oral drug provocation test. In contrast, ketotifen induced no reaction in the skin prick test but showed a positive reaction in the oral provocation test. Our case report highlights that children can experience the same types of adverse reactions as seen in adults, and cross-reactivity between various antihistamines can occur.
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http://dx.doi.org/10.3345/kjp.2018.06695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382964PMC
February 2019

Prenatal particulate matter affects new asthma via airway hyperresponsiveness in schoolchildren.

Allergy 2019 04 19;74(4):675-684. Epub 2018 Nov 19.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: The most relevant time of PM exposure to affect airway hyperresponsiveness (AHR) and new development of asthma in school-aged children is unclear. The aims of this study were to investigate the most critical time of PM exposure to affect AHR and new diagnosis of asthma from AHR in school-aged children.

Methods: Elementary schoolchildren (n = 3570) have been enrolled in a nationwide prospective 4-year follow-up survey in Korea from 2005 to 2006. Individual annual PM exposure was estimated by using an ordinary kriging method from the prenatal period to 7 years of age. AHR at 7 years was defined by a methacholine PC ≤8 mg/mL.

Results: PM exposure during pregnancy and at 1 year of age showed significant effects on AHR (aOR: 1.694, 95% CI: 1.298-2.209; and aOR: 1.750, 95% CI: 1.343-2.282, respectively). PM exposure during pregnancy was associated with the risk of a new diagnosis of asthma (aOR: 2.056, 95% CI: 1.240-3.409), with the highest risk in children with AHR at age 7 (aOR: 6.080, 95% CI: 2.150-17.195). PM exposure in the second trimester was associated with the highest risk of a new diagnosis of asthma in children with AHR at age 7 (aOR: 4.136, 95% CI: 1.657-10.326).

Conclusions: Prenatal PM exposure in the second trimester is associated with an increased risk of a new diagnosis of asthma in school-aged children with AHR at 7 years. This study suggests that PM exposure during a specific trimester in utero may affect the onset of childhood asthma via AHR.
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http://dx.doi.org/10.1111/all.13649DOI Listing
April 2019

KAAACI Evidence-Based Clinical Practice Guidelines for Chronic Cough in Adults and Children in Korea.

Allergy Asthma Immunol Res 2018 Nov;10(6):591-613

Department of Pediatrics, Inha University School of Medicine and Environmental Health Center for Allergic Disease, Inha University Hospital, Incheon, Korea.

Chronic cough is common in the community and causes significant morbidity. Several factors may underlie this problem, but comorbid conditions located at sensory nerve endings that regulate the cough reflex, including rhinitis, rhinosinusitis, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease, are considered important. However, chronic cough is frequently non-specific and accompanied by not easily identifiable causes during the initial evaluation. Therefore, there are unmet needs for developing empirical treatment and practical diagnostic approaches that can be applied in primary clinics. Meanwhile, in referral clinics, a considerable proportion of adult patients with chronic cough are unexplained or refractory to conventional treatment. The present clinical practice guidelines aim to address major clinical questions regarding empirical treatment, practical diagnostic tools for non-specific chronic cough, and available therapeutic options for chronic wet cough in children and unexplained chronic cough in adults in Korea.
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http://dx.doi.org/10.4168/aair.2018.10.6.591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182199PMC
November 2018

Association of Genetic Polymorphisms with Atopic Dermatitis, Clinical Severity and Total IgE: A Replication and Extended Study.

Allergy Asthma Immunol Res 2018 Jul;10(4):397-405

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan Collage of Medicine, Seoul, Korea.

Purpose: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease affecting up to 20% of children and 3% of adults worldwide. Although previous reports including genome-wide association study (GWAS) approaches have identified several risk factors that appear to be associated with AD development, replication studies are lacking. In our current study, we replicated the associations between candidate susceptibility loci and AD.

Methods: A total of 885 Korean subjects (425 AD patients and 460 unaffected controls) were genotyped for 17 single nucleotide polymorphisms (SNPs) from previous GWASs and meta-analyses of AD and from immune-related genes.

Results: Several SNPs showed significant associations with AD in the case-control analysis (minimum P=0.005 at rs17389644), suggesting that these polymorphisms may be related to this disease. In addition, several SNPs showed significant signals (minimum P=0.004 at rs6473227) in severe AD compared to unaffected controls. In additional linear regression analysis, a few genotypes appeared to have potential effects on the SCORing AD (SCORAD) values (minimum P=0.003 at rs13361382 on TMEM232) and immunoglobulin E (IgE) levels (minimum P<0.0001 at rs4713555 near HLA-DRB1 and HLA-DQA1) in AD patients.

Conclusions: Our replication and extended study provide additional supporting information on the genetic associations (especially, variants in TMEM232 and nearby to IL21 and HLA-DRB1/HLA-DQA1) related to AD, its clinical severity and IgE involvement.
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http://dx.doi.org/10.4168/aair.2018.10.4.397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021591PMC
July 2018

Clinical phenotypes of bronchial hyperresponsiveness in school-aged children.

Ann Allergy Asthma Immunol 2018 10 8;121(4):434-443.e2. Epub 2018 Jun 8.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background: Bronchial hyperresponsiveness (BHR), one of the key features of asthma, has a diverse natural course in school-aged children, but studies on BHR phenotypes are lacking.

Objective: To classify BHR phenotypes according to onset age and persistence in children and investigate the characteristics and factors associated with each phenotype in a longitudinal study.

Methods: This study analyzed 1,305 elementary school children from the Children's Health and Environmental Research (CHEER) study, a 4-year, prospective, follow-up study with 2-year intervals starting at a mean age of 7years. Total serum IgE levels and blood eosinophil counts were measured, and allergy workup, including methacholine challenge tests with the International Study of Asthma and Allergies in Childhood questionnaire, was performed at each survey.

Results: The 4 BHR phenotypes were classified as non-BHR (n = 942 [72.2%]), early-onset transient BHR (n = 201 [15.4%]), late-onset BHR (n = 87 [6.7%]), and early-onset persistent BHR (n = 75 [5.7%]). Early-onset persistent BHR is characterized by an increased eosinophil count, total serum IgE level, sensitization rate, decreased lung function, and increased risk of newly diagnosed asthma during follow-up (adjusted odds ratio, 3.89; 95% confidence interval, 1.70-8.88). The 2 early-onset phenotypes were associated with peripheral airway dysfunction. The late-onset BHR phenotype was related to increased risks of allergic rhinitis symptoms at baseline and later sensitization against inhalant allergens.

Conclusion: The early-onset persistent BHR phenotype in school-aged children is associated with high atopic burden and increased risk of newly diagnosed asthma, whereas the late-onset BHR phenotype related with later sensitization and allergic rhinitis symptoms. Diverse BHR phenotypes in children have specific characteristics that require targeted follow-ups.
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http://dx.doi.org/10.1016/j.anai.2018.05.033DOI Listing
October 2018

Effect of inhaled allergens and air pollutants on childhood rhinitis development.

Ann Allergy Asthma Immunol 2018 02 6;120(2):212-214. Epub 2017 Dec 6.

Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2017.10.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803404PMC
February 2018

Recurrent wheeze and its relationship with lung function and airway inflammation in preschool children: a cross-sectional study in South Korea.

BMJ Open 2017 Oct 8;7(10):e018010. Epub 2017 Oct 8.

Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Relationship between recurrent wheeze and airway function and inflammation in preschool children is not fully known.

Objective: To investigate the relationship between recurrent wheeze and airway inflammation, lung function, airway hyper-reactivity (AHR) and atopy in preschool children.

Design: Observational study, comparing forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and mid-forced expiratory flow (FEF), dose-response slope (DRS), exhaled nitric oxide (eNO) and atopic sensitisation between children with recurrent wheeze and those without.

Setting: Population-based, cross-sectional study in Seoul and the Gyeonggi province of Korea conducted as a government-funded programme to perform standardised measurement of the prevalence of allergic diseases, and related factors, in preschool children.

Participants: 900 children aged 4-6 years. PRIMARY AND SECONDARY OUTCOME MEASURES: eNO, FEV/FVC, FEF, DRS, atopic sensitisation and allergic diseases.

Methods: Children completed the modified International Study of Asthma and Allergies in Childhood questionnaire and underwent eNO assessments, spirometry, methacholine bronchial provocation tests and skin prick tests. Recurrent wheeze was defined as having a lifetime wheeze of more than three episodes, based on the questionnaire. The frequency of hospitalisation and emergency room visits was also obtained by means of the questionnaire. 'Current' wheeze was defined as having symptoms or treatments within the past 12 months.

Results: The prevalence of recurrent wheeze was 13.4%. Children with recurrent wheeze showed a higher prevalence of lifetime or current allergic rhinitis (p=0.01 and p=0.002, respectively) and lifetime atopic dermatitis (p=0.007). Children with recurrent wheeze showed lower FEV/FVC (p=0.033) and FEF (p=0.004), and higher eNO levels (p=0.013) than those without recurrent wheeze. However, the DRS, prevalence of atopic sensitisation and serum IgE levels were not significantly different between the two groups.

Conclusions: Recurrent wheeze in preschool children may be associated with airway inflammation and diminished airway function, but not with AHR or atopy.
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http://dx.doi.org/10.1136/bmjopen-2017-018010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640071PMC
October 2017

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO.

Allergy Asthma Immunol Res 2017 Jul;9(4):314-321

Department of Pediatrics, Childhood Asthma Atopy Center, Research Center for the Standardization of Allergic Diseases, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Purpose: The nature of allergic rhinitis (AR) in preschool aged children remains incompletely characterized. This study aimed to investigate the prevalence of AR and its associated risk factors in preschool-aged children and to assess the clinical utility of fractional exhaled nitric oxide (FeNO).

Methods: This general population-based, cross-sectional survey included 933 preschool-aged (3- to 7-year-old) children from Korea. Current AR was defined as having nasal symptoms within the last 12 months and physician-diagnosed AR.

Results: The prevalence of current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI, 0.35-0.75) reduced the risk. Children with current atopic AR had significantly higher geometric mean levels of FeNO compared to those with non-atopic rhinitis (12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62-12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38, P<0.001). The FeNO levels were higher in children with current atopic AR compared with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083).

Conclusions: Mold exposure and use of antibiotics during infancy increases the risk of current AR, whereas having an older sibling reduces it. Children with current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis cases, suggesting that FeNO levels may be a useful discriminatory marker for subtypes of AR in preschool children.
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http://dx.doi.org/10.4168/aair.2017.9.4.314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446946PMC
July 2017

Association of atopy phenotypes with new development of asthma and bronchial hyperresponsiveness in school-aged children.

Ann Allergy Asthma Immunol 2017 05 30;118(5):542-550.e1. Epub 2017 Mar 30.

Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Sonapa-gu, Seoul, Korea. Electronic address:

Background: Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood.

Objective: To identify atopy phenotypes in school-age children and to evaluate the association between atopy phenotypes and allergic diseases.

Methods: We enrolled 616 children with atopy defined as 1 or more positive allergen responses on skin prick tests and 665 children without atopy from the Children's Health and Environmental Research (CHEER) study. All children were followed up for 4 years at 2-year intervals. Atopy phenotypes were classified using latent class analysis.

Results: Four atopy phenotypes were characterized: later sensitization to indoor allergens (cluster 1); multiple early sensitization (cluster 2); early sensitization to outdoor allergens, especially Alternaria, and later sensitization to indoor allergens, including Aspergillus (cluster 3); and early sensitization to indoor allergens and later sensitization to outdoor allergens (cluster 4). New cases of asthma during follow-up were increased in clusters 2 and 3 (adjusted odds ratio [aOR], 2.76 and 4.25, respectively). The risk of new-onset bronchial hyperresponsiveness was highest in cluster 3 (aOR, 5.03). Clusters 2 and 4 had an increased risk of allergic rhinitis (aOR, 7.21 and 2.37, respectively).

Conclusion: Identification of atopy phenotypes facilitates prediction of the development of asthma and bronchial hyperresponsiveness in school-age children. Our study suggests prevention of additional sensitization is required to modify the progression of allergic diseases.
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http://dx.doi.org/10.1016/j.anai.2017.02.008DOI Listing
May 2017

Different cutoff values of methacholine bronchial provocation test depending on age in children with asthma.

World J Pediatr 2017 Oct 8;13(5):439-445. Epub 2017 Mar 8.

Department of Pediatrics, Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Bronchial hyperresponsiveness (BHR) is a fundamental pathophysiological characteristic of asthma. Although several factors such as airway caliber can affect BHR, no study has established age-dependent cutoff values of BHR to methacholine for the diagnosis of asthma in children. We investigated the cutoff values of the methacholine challenge test (MCT) in the diagnosis of asthma according to age.

Methods: A total of 2383 individuals aged from 6 to 15 years old were included in this study. MCTs using the five-breath technique were performed in 350 children with suspected asthma based on symptoms by pediatric allergists and in 2033 healthy children from a general population-based cohort. We determined the provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in 1 second from baseline (PC). A modified Korean version of the International Study of Asthma and Allergies in Childhood questionnaire was used to distinguish asthmatics and healthy subjects. Receiver-operator characteristic curve analysis was used to assess the cutoff value of PC for the diagnosis of asthma.

Results: Cutoff values of methacholine PC, which provided the best combination of diagnostic sensitivity and specificity, showed an increasing pattern with age: 5.8, 9.1, 11.8, 12.6, 14.9, 21.7, 23.3, 21.1, 21.1, and 24.6 mg/mL at ages 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 years, respectively.

Conclusion: The application of different cutoff values of methacholine PC depending on age might be a practical modification for the diagnosis of asthma in children and adolescents with asthmatic symptoms.
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http://dx.doi.org/10.1007/s12519-017-0026-5DOI Listing
October 2017

Persistent asthma phenotype related with late-onset, high atopy, and low socioeconomic status in school-aged Korean children.

BMC Pulm Med 2017 Feb 23;17(1):45. Epub 2017 Feb 23.

Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, South Korea.

Background: Treatment guidelines for asthma have been established based on asthma severity; there are limitations in the identification of underlying pathophysiology and prediction of prognosis in heterogeneous phenotypes of asthma. Although the complex interactions between environmental and genetic factors affect the development and progression of asthma, studies on asthma phenotypes considering environmental factors are limited. This study aimed to identify asthma phenotypes using latent class analysis including environmental factors in school-age children.

Methods: We included 235 children (6-8 years) with parent-reported, physician-diagnosed asthma from the Children's HEalth and Environmental Research (CHEER) study, which is a 4-year prospective follow-up study with 2-year intervals. At every survey, pulmonary function tests, methacholine challenge tests and blood tests with questionnaire were conducted.

Results: Four asthma phenotypes were identified. Cluster 1 (22% of children) was characterized by high prevalence of atopy and mild symptoms; subjects in cluster 2 (17%) consisted of less atopy and normal lung function, but intermittent troublesome; cluster 3 (29%) experienced late-onset atopic troublesome asthma with decreased lung function in combination with low socioeconomic status; and cluster 4 was associated with early-onset and less-atopic infrequent asthma.

Conclusions: Late-onset, high atopy, and low socioeconomic status are associated with troublesome persistent asthma phenotype in school-age children. Environmental factors might be implicated in the clinical heterogeneity of asthma. Asthma phenotypes considering diverse factors might be more helpful in the identification of asthma pathogenesis and its prevention.
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http://dx.doi.org/10.1186/s12890-017-0387-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324247PMC
February 2017

Comorbidities and Phenotypes of Rhinitis in Korean Children and Adolescents: A Cross-sectional, Multicenter Study.

Allergy Asthma Immunol Res 2017 Jan;9(1):70-78

Department of Pediatrics, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea.

Purpose: Rhinitis is a nasal inflammatory disease in children and adolescents. However, little is known about the phenotypes and characteristics of allergic rhinitis (AR) in Korean children and adolescents. The objective of this study was to analyze the symptoms and comorbidities of rhinitis, to compare AR to non-allergic rhinitis (NAR), and to reveal the phenotypes and features of AR in a Korean pediatric population.

Methods: Patients under 18 years of age with rhinitis symptoms were recruited from January 2013 to January 2015 by pediatric allergists. We analyzed symptoms, phenotypes, comorbidities, and allergen sensitization in this cross-sectional, multicenter study.

Results: Medical records were collected from 11 hospitals. The AR group has 641 (68.3%) patients, with 63.2% of boys and 7.5 (±3.4) years of mean age. The NAR group has 136 (14.5%) patients, with 55.1% of boys and 5.5 (±2.9) years of mean age. Moderate-severe persistent AR affected 41.2% of AR patients. Nasal obstruction was more common in NAR patients (P<0.050), whereas AR patients sneezed more (P<0.050) and more commonly had conjunctivitis, asthma, and otitis media (P<0.050). Sinusitis was the most common comorbidity in both groups. Allergen sensitization was caused by house dust mites (HDMs) (90.2%), pollen (38.7%), and animal dander (24.8%) in AR patients. Pollen and animal dander sensitization significantly increased age-dependently (P<0.050), but 91.9% of AR patients were already sensitized to HDMs before 5 years old.

Conclusions: Our study revealed that AR was more prevalent than NAR and that 41.2% of AR presented with moderate-severe disease in Korean pediatric populations. Sinusitis was the most common comorbidity, and sleep disturbance was associated with the severity of rhinitis. The majority of AR patients were sensitized to HDMs in preschool ages. Further studies, including nationwide and longitudinal data, will help understand the relationship between these diseases.
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http://dx.doi.org/10.4168/aair.2017.9.1.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102838PMC
January 2017

Asthma Severity and the Controller Prescription in Children at 12 Tertiary Hospitals.

Allergy Asthma Immunol Res 2017 Jan;9(1):52-60

Department of Pediatrics, Inha University Hospital, Incheon, Korea.

Purpose: Guidelines need to be tailored to where they are applied. We aimed to describe the distinctive asthma severity profile and the pattern of controller prescription in Korean children.

Methods: Twelve pediatric allergists from tertiary medical centers reviewed medical records of all asthmatic children who visited their clinics between September 1 and November 30 of 2013. Controller prescriptions were re-classified into 4 categories, then the prevalence of each asthma severity category and the controller prescription patterns according to asthma severity assessed by a Western (Global Initiative for Asthma, GINA) and an Asia-Pacific (Japanese Pediatric GuideLine, JPGL) guideline were evaluated.

Results: A total of 840 cases were reviewed. Both GINA and JPGL revealed that 328 (39.0%) and 249 (29.6%) subjects had intermittent asthma whereas 24 (2.9%) and 21 (2.5%) subjects had severe persistent asthma, respectively. Although higher category controllers tended to be prescribed to those who had more severe asthma, there was much overlap in categories of prescribed controllers between groups with regard to asthma severities. Leukotriene receptor antagonists (LTRA) was the most frequently prescribed as a single controller (40%) or as an add-on medication (19%) in the group of asthmatic children <6 years.

Conclusions: Korean children have distinctive patterns of asthma severity and management strategies with a lower prevalence of severe asthma and a preference toward LTRA rather than low dose inhaled corticosteroids (ICS) alone or add-on long-acting beta-agonist (LABA) in the group of <6 year-old asthmatics that has not been predicted in Western countries. Thus, strategies tailored to regional situations need to be developed and recommended.
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http://dx.doi.org/10.4168/aair.2017.9.1.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102836PMC
January 2017

Dynamics of Gut Microbiota According to the Delivery Mode in Healthy Korean Infants.

Allergy Asthma Immunol Res 2016 Sep;8(5):471-7

Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Microbial colonization of the infant gut is unstable and shows a wide range of diversity between individuals. Gut microbiota play an important role in the development of the immune system, and an imbalance in these organisms can affect health, including an increased risk of allergic diseases. Microbial colonization of young infants is affected by the delivery mode at birth and the consequent alterations of gut microbiota in early life affect the development of allergic diseases. We investigated the effects of the delivery mode on the temporal dynamics of gut microbiota in healthy Korean infants. Fecal samples were collected at 1-3 days, 1 month, and 6 months after birth in six healthy infants. Microbiota were characterized by 16S rRNA shotgun sequencing. At the first and third days of life, infants born by vaginal delivery showed a higher richness and diversity of gut microbiota compared with those born by cesarean section. However, these differences disappeared with age. The Bacteroides genus and Bacteroidetes phylum were abundant in infants born by vaginal delivery, whereas Bacilli and Clostridium g4 were increased in infants born by cesarean section. The Firmicutes phylum and Bacteroides genus showed convergent dynamics with age. This study demonstrated the effect of delivery mode on the dynamics of gut microbiota profiles in healthy Korean infants.
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http://dx.doi.org/10.4168/aair.2016.8.5.471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921703PMC
September 2016

A rhinitis phenotype associated with increased development of bronchial hyperresponsiveness and asthma in children.

Ann Allergy Asthma Immunol 2016 07 13;117(1):21-28.e1. Epub 2016 May 13.

Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background: Allergic rhinitis (AR) has a wide range of clinical features and may be accompanied by comorbid allergic diseases.

Objective: To identify rhinitis phenotypes in school aged children and to predict the prognosis for developing bronchial hyperresponsiveness (BHR) and asthma.

Methods: This prospective follow-up study involved schoolchildren from the Children's Health and Environment Research cohort with current rhinitis, which was defined based on parental-reported, physician-diagnosed rhinitis and symptoms of rhinitis in the previous 12 months. All participants were followed up at 2 and 4 years later. Rhinitis clusters were identified by latent class analysis that used demographic, clinical, and environmental variables.

Results: In 512 eligible children (age range, 6-8 years), 4 rhinitis phenotypes were identified: cluster 1 (25% of children) was associated with nonatopy and a low socioeconomic status; cluster 2 (36%) was associated with a high-atopic burden but normal lung function; cluster 3 (22%) was associated with a high-atopic burden and impaired lung function; and cluster 4 (17%) was associated with low atopy and a high socioeconomic status. Cluster 3 was associated with the highest total serum IgE levels and blood eosinophil percentages at enrollment and the highest incidence of new cases of BHR (P = .04) and asthma symptoms (P = .005) during follow-up.

Conclusion: The rhinitis cluster of schoolchildren with atopy and impaired lung function is associated with allergic march. This identification of distinct rhinitis phenotypes in affected children may help to prevent allergic march in children with rhinitis.
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http://dx.doi.org/10.1016/j.anai.2016.04.016DOI Listing
July 2016

Interaction between 25-hydroxyvitamin D and variants at 17q12-21 on respiratory infections.

Pediatr Pulmonol 2016 09 25;51(9):958-67. Epub 2016 Apr 25.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objectives: 25-hydroxyvitamin D (25[OH]D) deficiency and genetic variants at the 17q12-21 locus are independent risk factors for respiratory tract infections (RTIs). We aimed to investigate whether the effect of 25(OH)D at birth and 1 year of age and the polymorphism at the 17q12-21 locus, or interactions between these two factors, increase susceptibility to RTIs in the first year of life.

Methods: We tested cord-blood (CB) 25(OH)D at birth and 1 year of age and genotypes of a variant at the 17q12-21 locus for associations with RTIs, particularly lower respiratory tract infections (LRTIs), and determined whether there exist interactions between 25(OH)D and 17q12-21 genotypes in a birth cohort of 473 infants.

Results: The levels of CB 25(OH)D inversely associate with development of RTIs and LRTIs during the first year of life. There exists an inverse association of 25(OH)D at birth, but not at 1 year, with the risk of acquiring LRTIs in early infancy (adjusted odds ratio [aOR], 2.37; 95% confidence interval [CI]: 1.23-4.60; P = 0.010 and aOR, 0.50; 95%CI: 0.23-1.12; P = 0.094). We have also found a significant interaction between CB 25(OH)D and a variant at the 17q12-21 locus with respect to the development of early LRTIs, such that associations between a variant at the 17q12-21 locus and LRTIs are restricted to infants with low CB 25(OH)D concentrations (P for interaction = 0.013). In addition, when infants with a variant at the 17q12-21 locus had been exposed to chronic 25(OH)D deficiency over the first year, their risk of LRTIs was increased.

Conclusion: CB 25(OH)D deficiency during fetal life contribute to the development of LRTIs in genetically susceptible infants. Pediatr Pulmonol. 2016; 51:958-967. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ppul.23421DOI Listing
September 2016

Association between menarche and increased bronchial hyper-responsiveness during puberty in female children and adolescents.

Pediatr Pulmonol 2016 10 22;51(10):1040-1047. Epub 2016 Apr 22.

Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Bronchial hyper-responsiveness (BHR) is a key feature of asthma. The degree of BHR in children may be altered by several factors. We evaluated the prevalence of BHR according to age and gender in pediatric and adolescent population and analyzed the associated factors for gender differences.

Methods: Among the 2,067 subjects, methacholine challenge tests were performed in 1,820 children from one elementary and one middle school in Seoul, Korea. A total of 1,725 subjects between 6 and 14 years old were included in the analysis. The prevalence of BHR, defined as a provocative concentration that induced a 20% reduction of FEV (PC ) that was less than 8 mg/ml, was evaluated according to age and gender. Gender differences associated with BHR prevalence at each age were calculated and multiple logistic regression analyses were performed to identify factors associated with BHR by gender.

Results: The prevalence of BHR (PC  ≤ 8 mg/ml) for each gender decreased with age (P < 0.001). Although the prevalence of BHR linearly decreased in males with age, females showed an increase after 11 years of age. BHR in males was associated with a younger age (aOR, 0.797; 95%CI, 0.678-0.925), a higher blood eosinophil counts (%) (aOR, 1.160; 95%CI, 1.047-1.284), atopy (aOR, 2.091; 95%CI, 1.003-4.359), and a lower FEV /FVC ratio (aOR, 0.947; 95%CI, 0.901-0.995), and FEF (aOR, 0.980; 95%CI, 0.961-0.999). In females, BHR was significantly associated with a younger age (aOR, 0.845; 95%CI, 0.747-0.957), lower FEV (%) (aOR, 0.961; 95%CI, 0.938-0.984), and menarche (aOR, 3.674; 95%CI, 1.226-11.012).

Conclusion: BHR declined with age in the Korean pediatric population. A younger age and reduced lung function were common factors related to BHR in both genders. Additionally, atopy was related to BHR in males, whereas sexual maturation was related to BHR in females. These findings have important clinical implications for evaluating of childhood BHR and asthma related to gender. Pediatr Pulmonol. 2016;51:1040-1047. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ppul.23433DOI Listing
October 2016