Outcome prediction of pediatric drowning

Purpose@#Despite the well-known mortality of pediatric drowning, there is a paucity of evidence on the implications of an initial evaluation on the relevant outcome of drowning. This study aimed to investigate the association of initial clinical findings with outcome of children undergoing drowning. @*Methods@#This retrospective study was conducted using the medical records of 56 children undergoing drowning who visited 3 Korean academic hospitals from January 2000 through May 2020. We analyzed information regarding the prehospital resuscitation, drowning time, a 4-tiered chest radiographic grade, and the baseline characteristics. The grade was defined based on the findings of initial chest radiographs. The poor outcomes were defined as the need for intensive care unit care or death aftercare. We analyzed the association of the prehospital resuscitation, submersion time, and the radiographic grade with the poor outcomes using binary logistic regression. @*Results@#Among the 56 children, 31 (55.4%) were aged 1-4 years. Prehospital resuscitation and 1-5 minutes of submersion time were noted in the 25 (44.6%) and 30 children (53.6%), respectively. The chest radiographic grades 1 through 4 accounted for 17 (30.4%), 20 (35.7%), 12 (21.4%), and 3 children (5.4%), respectively. Poor outcomes occurred in 17 children (30.4%), including 3 deaths (5.4%). The association with the poor outcomes was noted in the submersion time of longer than 5 minutes (adjusted odds ratio, 21.49; 95% confidence interval, 1.11-415.73; compared with < 1 minute) while not in the submersion time and chest radiographic grade. @*Conclusion@#This study confirms that submersion time is an outcome predictor of drowning.

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

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.

Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study

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.

Clinical characteristics of allergic rhinitis and nonallergic rhinitis in Korean children

PURPOSE: Recently, the prevalence of allergic rhinitis (AR) in Korean children has been increased. The aim of this study was to investigate the clinical characteristics of rhinitis and to compare clinical parameters between AR and nonallergic rhinitis (NAR) in children.METHODS: We retrospectively reviewed the medical records of 1,034 children under 18 years of age who visited Korea University Anam Hospital for rhinitis symptoms from January 2008 to December 2017. Clinical data, including clinical features, comorbidities, blood test results, allergen sensitization profile, and pulmonary function test parameters, were collected.RESULTS: Among the 1,034 children with rhinitis, 737 (71.3%) were AR and 297 (28.7%) were NAR. The prevalence of AR gradually increased with age. The median levels of eosinophil count (4.1%), serum total IgE (204.4 IU/L), eosinophil cationic protein (ECP) concentration (17.9 µg/L), and fractional exhaled nitric oxide (FeNO) (22.0 ppb) were significantly higher in children with AR than in those with NAR. The sensitization rate to the inhalant allergens increased with age; however, food allergen sensitization rate tended to decrease. Median levels of eosinophil count, total IgE, ECP, and FeNO were significantly higher in the poly-sensitized group than in the mono-sensitized and nonsensitized groups.CONCLUSION: More than 70% of Korean children who have rhinitis symptoms are AR. Children with AR more likely to have higher levels of FeNO and bronchial asthma. Poly-sensitized children showed increased rates of atopic dermatitis and bronchial asthma.

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

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.

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

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

The Effects of Short-Term and Very Short-Term Particulate Matter Exposure on Asthma-Related Hospital Visits: National Health Insurance Data

PURPOSE: The purpose of this study was to investigate the effects of short-term and very short-term exposure to particulate matter (PM) exceeding the daily average environmental standards for Korea (≤100 µg/m³ for PM₁₀ and ≤50 µg/m³ for PM(2.5)) on on asthma-related hospital visits. MATERIALS AND METHODS: This was a population-based, case-crossover study using National Health Insurance and air pollution data between January 1, 2014 and December 31, 2016. The event day was defined as a day when PM exceeded the daily average environmental standard (short-term exposure) or daily average environmental standard for 2 hours (very short-term exposure). The control day was defined as the same day of the week at 1 week prior to the event day. RESULTS: Compared with control days, asthma-related hospital visits on the 24-hr event days and 2-hr event days increased by 4.10% and 3.45% for PM₁₀ and 5.66% and 3.74% for PM(2.5), respectively. Asthma-related hospital visits increased from the 24-hr event day for PM₁₀ to 4 days after the event day, peaking on the third day after the event day (1.26, 95% confidence interval, 1.22–1.30). Hospitalizations also increased on the third day after the event. While there was a difference in magnitude, PM(2.5) exposure showed similar trends to PM₁₀ exposure. CONCLUSION: We found a significant association between short-term and very short-term PM exposure exceeding the current daily average environmental standards of Korea and asthma-related hospital visits. These results are expected to aid in establishing appropriate environmental standards and relevant policies for PM.

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

Low levels of 25-hydroxyvitamin D in children and adolescents with type 1 diabetes mellitus: a single center experience

PURPOSE: Low vitamin D level is common in adults with diabetes mellitus (DM). We assessed vitamin D level and its associated factors in Korean youth with type 1 DM. METHODS: Type 1 DM cases (n=85) and healthy controls (n=518) aged < 20 years were included and grouped into 3 categories according to vitamin D level: deficiency ( < 20 ng/mL), insufficiency (20–30 ng/mL), or sufficiency (≥30 ng/mL). RESULTS: The mean serum vitamin D level was significantly lower (21.6±8.5 ng/mL vs. 28.0±12.0 ng/mL, P < 0.001) and vitamin D deficiency prevalence was significantly higher (48% vs. 26%, P < 0.001) in type 1 DM cases than in healthy controls. Logistic regression analysis revealed that type 1 DM cases were more likely to have vitamin D deficiency (P=0.004), independent of sex, age, and body mass index. Type 1 DM cases with vitamin D deficiency/insufficiency were mainly diagnosed in winter (November to April) (P=0.005), and the duration of diabetes was longer than in those with vitamin D sufficiency (P=0.046). However, season of diagnosis, duration of diabetes, prescribed daily insulin dose, and glycosylated hemoglobin and C-peptide levels were not associated with 25-hydroxyvitamin D (25(OH)D) level in type 1 DM cases after adjustment for other factors. CONCLUSIONS: We recommend assessment of serum 25(OH)D level in type 1 DM cases and to treatment if findings indicate insufficiency. Further studies investigating the mechanisms underlying vitamin D deficiency in youth with type 1 DM are needed.

Clinical and laboratory profiles of hospitalized children with acute respiratory virus infection / 소아과

PURPOSE: Despite the availability of molecular methods, identification of the causative virus in children with acute respiratory infections (ARIs) has proven difficult as the same viruses are often detected in asymptomatic children. METHODS: Multiplex reverse transcription polymerase chain reaction assays were performed to detect 15 common respiratory viruses in children under 15 years of age who were hospitalized with ARI between January 2013 and December 2015. Viral epidemiology and clinical profiles of single virus infections were evaluated. RESULTS: Of 3,505 patients, viruses were identified in 2,424 (69.1%), with the assay revealing a single virus in 1,747 cases (49.8%). While major pathogens in single virus-positive cases differed according to age, human rhinovirus (hRV) was common in patients of all ages. Respiratory syncytial virus (RSV), influenza virus (IF), and human metapneumovirus (hMPV) were found to be seasonal pathogens, appearing from fall through winter and spring, whereas hRV and adenovirus (AdV) were detected in every season. Patients with ARIs caused by RSV and hRV were frequently afebrile and more commonly had wheezing compared with patients with other viral ARIs. Neutrophil-dominant inflammation was observed in ARIs caused by IF, AdV, and hRV, whereas lymphocyte-dominant inflammation was observed with RSV A, parainfluenza virus, and hMPV. Monocytosis was common with RSV and AdV, whereas eosinophilia was observed with hRV. CONCLUSION: In combination with viral identification, recognition of virus-specific clinical and laboratory patterns will expand our understanding of the epidemiology of viral ARIs and help us to establish more efficient therapeutic and preventive strategies.

Mechanism of resistance acquisition and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children / 소아과

Mycoplasma pneumoniae pneumonia (MPP) is one of the most common forms of community-acquired pneumonia in children and adolescents. Outbreaks of MPP occur in 3- to 7-year cycles worldwide; recent epidemics in Korea occurred in 2006–2007, 2011, and 2015–2016. Although MPP is known to be a mild, self-limiting disease with a good response to macrolides, it can also progress into a severe and fulminant disease. Notably, since 2000, the prevalence of macrolide-resistant MPP has rapidly increased, especially in Asian countries, recently reaching up to 80%–90%. Macrolide-resistant Mycoplasma pneumoniae (MRMP) harbors a point mutation in domain V of 23S rRNA with substitutions mainly detected at positions 2063 and 2064 of the sequence. The excessive use of macrolides may contribute to these mutations. MRMP can lead to clinically refractory pneumonia, showing no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. Refractory MPP is characterized by an excessive immune response against the pathogen as well as direct injury caused by an increasing bacterial load. A change of antibiotics is recommended to reduce the bacterial load. Tetracyclines or quinolones can be alternatives for treating MRMP. Otherwise, corticosteroid or intravenous immunoglobulin can be added to the treatment regimen as immunomodulators to down-regulate an excessive host immune reaction and alleviate immune-mediated pulmonary injury. However, the exact starting time point, dose, or duration of immunomodulators has not been established. This review focuses on the mechanism of resistance acquisition and treatment options for MRMP pneumonia.

Macrolide Resistance and Its Impacts on M. Pneumoniae Pneumonia in Children: Comparison of Two Recent Epidemics in Korea

PURPOSE: The aim of this study was to investigate the change in macrolide resistance rate in pediatric Mycoplasma pneumoniae pneumonia and to evaluate the influence of macrolide-resistant M. pneumoniae (MRMP) on the clinical course of disease, by comparing 2 recent, consecutive epidemics in Korea. METHODS: A total of 250 patients with M. pneumoniae pneumonia admitted to a single tertiary hospital were enrolled in this study. Detection of MRMP was based on specific point mutations in domain V of the 23S rRNA gene. The medical records of enrolled patients were reviewed retrospectively, and the clinical courses and laboratory data were compared. RESULTS: The macrolide resistance rate of M. pneumoniae was 51.1% (48/94) in the 2011 epidemic, and 87.2% (136/156) in the 2015 epidemic. All MRMP isolates had the A2063G point mutation. In comparison of 2 epidemics, the mean age of patients with M. pneumoniae pneumonia was increased, and the total febrile days and febrile days after initiation of macrolides were prolonged in the 2015 epidemic. Overall severity of MRMP or macrolide-susceptible M. pneumoniae (MSMP) pneumonia over 2 epidemics was not significantly changed. However, the proportion of patients who had a fever lasting more than 72 hours after initiation of macrolides and who received corticosteroid treatment were higher in MRMP pneumonia during 2 epidemics. CONCLUSIONS: The macrolide resistance rate of M. pneumoniae has risen rapidly over 2 recent, consecutive epidemics, and this has been associated with a prolonged clinical course and increased use of corticosteroids to treat pediatric M. pneumoniae pneumonia.

CCR3 Monoclonal Antibody Inhibits Eosinophilic Inflammation and Mucosal Injury in a Mouse Model of Eosinophilic Gastroenteritis

PURPOSE: Although the role of eosinophils in eosinophilic gastroenteritis (EGE) is not fully understood, they are believed to be a principal effector cell. Previous studies have demonstrated that eotaxin and its specific receptor, cysteine-cysteine chemokine receptor-3 (CCR3), play a central role in eosinophil trafficking into the gastrointestinal (GI) tract. Thus, we examined the targeting of CCR3 as a potential therapeutic intervention for EGE in a mouse model. METHODS: Eight- to 10-week-old BALB/c mice were intraperitoneally sensitized and intragastrically challenged with ovalbumin (OVA). Different groups of mice were administered either an anti-CCR3 antibody or a control IgG by intraperitoneal injection 1 hour before each OVA challenge. Eosinophilic inflammation in the intestinal mucosa, mucosal injury, and severity of diarrhea were compared between different groups at 1 hour after final OVA challenge. RESULTS: Anti-CCR3 antibody reduced the number of eosinophils in peripheral blood and intestinal mucosa, but not in bone marrow. This reduction was associated with restoration of reduced villous crypt ratio, increased intestinal epithelial cell proliferation, and weight loss induced by OVA challenge. However, Anti-CCR3 antibody had no effect on the level of OVA specific immunoglobulin E (IgE) and the expression of critical chemokines or cytokines in eosinophil trafficking into the GI tract, such as eotaxin-1, interleukin (IL)-5, and IL-13. CONCLUSIONS: Anti-CCR3 antibody significantly reduced the severity of eosinophilic inflammation, mucosal injury, and diarrhea in a mouse model of food allergen-induced GI eosinophilic inflammation. CCR3 may be a novel therapeutic target for treatment of EGE and other GI eosinophil-mediated diseases.

Clinical characteristics of respiratory viral coinfection in pediatric Mycoplasma pneumoniae pneumonia

PURPOSE: Bacterial/viral coinfection is not uncommon in children with community acquired pneumonia. However, the data about viral coinfection in Mycoplasma pneumoniae pneumonia is limited. The aim of this study was to investigate the frequency and clinical characteristics of respiratory viral coinfection in pediatric M. pneumoniae pneumonia. METHODS: A retrospective cross sectional study was performed in 432 children hospitalized with M. pneumoniae pneumonia in a tertiary teaching hospital between June 2015 and May 2016. RESULTS: One hundred forty patients (32.4%) were coinfected with M. pneumoniae and respiratory viruses. Among coinfected viruses, rhinovirus (44.4%) was most commonly detected. Viral coinfection was more likely to occur under the age of 5 years in winter and spring. As compared with patients infected with M. pneumoniae monoinfection, patients coinfected with respiratory viruses showed a lower mean age and shorter total febrile days. Although total leukocyte count was higher, relative proportion of neutrophils and C-reactive protein level were significantly lower in these patients. CONCLUSION: Viral coinfection was common in pediatric M. pneumoniae pneumonia, especially in patients under the age of 5 years, and this was associated with shorter total febrile days and lower level of acute phase response as compared with M. pneumoniae monoinfection.

Rhinovirus and childhood asthma: an update / 소아과

Asthma is recognized as a complex disease resulting from interactions between multiple genetic and environmental factors. Accumulating evidence suggests that respiratory viral infections in early life constitute a major environmental risk factor for the development of childhood asthma. Respiratory viral infections have also been recognized as the most common cause of asthma exacerbation. The advent of molecular diagnostics to detect respiratory viruses has provided new insights into the role of human rhinovirus (HRV) infections in the pathogenesis of asthma. However, it is still unclear whether HRV infections cause asthma or if wheezing with HRV infection is simply a predictor of childhood asthma. Recent clinical and experimental studies have identified plausible pathways by which HRV infection could cause asthma, particularly in a susceptible host, and exacerbate disease. Airway epithelial cells, the primary site of infection and replication of HRV, play a key role in these processes. Details regarding the role of genetic factors, including ORMDL3, are beginning to emerge. This review discusses recent clinical and experimental evidence for the role of HRV infection in the development and exacerbation of childhood asthma and the potential underlying mechanisms that have been proposed.

Chronic cough in children

Cough is one of the common symptoms, which is usually related to respiratory infections for children. This symptom is not considered crucial. Published data reported that the community prevalence of chronic cough in primary school children is 5%-10%, while the prevalence is likely to be higher in younger children. The cause of persistent cough should be investigated. There were significant differences in the causes and management for cough according to age. Chronic cough is defined as duration of 4 weeks or longer. Common culprits for chronic cough in children are different from those in adults. The authors reviewed articles about chronic cough of children to help improve the understanding and management for pediatric chronic cough.

Translation and linguistic validation of Korean version of the Test for Respiratory and Asthma Control in Kids instrument

PURPOSE: We aimed to translate the Test for Respiratory and Asthma Control in Kids (TRACK) instrument into Korean, with subsequent linguistic validation. METHODS: The multistep process of forward translation, reconciliation, back-translation, cognitive debriefing, and proofreading of the Korean version of the TRACK was completed. RESULTS: Two bilingual medical personnel independently translated the original English version of the TRACK into Korean one. After moderating the translation into a single reconciled one, 4 other bilingual persons were invited to translate the Korean draft back into an English one. Discrepancies between the original English version and the back-translated one were reviewed, and the need to modify the reconciled Korean draft was discussed. Twenty caregivers of asthmatic children took part in interviews that examine the appropriateness of the Korean version of the TRACK. The feedback from caregivers were then reviewed by a panel of pediatric allergists and reflected in the final Korean version. The document was finally proofread to check the spelling, grammar, layout and formatting. CONCLUSION: Translation and linguistic validation of the Korean version of the TRACK instrument were completed.

Prenatal Particulate Matter/Tobacco Smoke Increases Infants' Respiratory Infections: COCOA Study

PURPOSE: To investigate whether prenatal exposure to indoor fine particulate matter (PM2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects. METHODS: The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician's diagnosis. Indoor PM2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase-mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis. RESULTS: Prenatal exposure to indoor PM2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM2.5 and ETS exposure were not found for upper RTIs. CONCLUSIONS: Prenatal exposure to both indoor PM2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species-related genes.

Clinical Application of Exhaled Nitric Oxide Measurements in a Korean Population

Nitric oxide (NO) is a biologic mediator of various physiologic functions. Recent evidence suggests the clinical utility of fractional exhaled NO (FeNO) as a biomarker for assessing asthma and other respiratory diseases. FeNO methodologies have been recently standardized by international research groups and subsequently validated in several Korean population studies. Normal ranges for FeNO have been reported for various ethnic groups, and the clinical utility has been widely evaluated in asthma and various respiratory diseases. Based on current evidence including most of Korean population data, this position paper aims to introduce the methodological considerations, and provide the guidance for the proper clinical application of FeNO measurements in Korean populations.

Association Between Antibiotic Exposure, Bronchiolitis, and TLR4 (rs1927911) Polymorphisms in Childhood Asthma

PURPOSE: The complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studies have yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis during early life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphism on the development of childhood asthma. METHODS: This cross-sectional study involved 7,389 middle school students who were from 8 areas of Seoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 was genotyped in 1,395 middle school students from two areas using the TaqMan assay. RESULTS: Bronchiolitis in the first 2 years of life, antibiotic exposure during the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibiotic use and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P value for interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma was increased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87). CONCLUSIONS: Early-life antibiotic exposures and a history of bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptible subjects.