A Phase II Trial of Osimertinib as the First-Line Treatment of Non–Small Cell Lung Cancer Harboring Activating EGFR Mutations in Circulating Tumor DNA: LiquidLung-O-Cohort 1 / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for both EGFR-activating and T790M resistant mutation. The treatment efficacy of osimertinib was assessed in previously untreated patients with metastatic non–small cell lung carcinoma (NSCLC) harboring activating EGFR mutations in circulating tumor DNA (ctDNA) as well as tumor DNA. @*Materials and Methods@#Patients with activating EGFR mutations in their tumor DNA underwent screening with ctDNA analysis using Mutyper and Cobas v2 assays. Enrolled subjects received osimertinib 80 mg, once daily. Primary endpoint was objective response rate (ORR) and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety. @*Results@#Among 39 screened patients, 29 were ctDNA positive for activating EGFR mutations and 19 were enrolled (ex19del, n=11; L858R/L861Q, n=7; G719A, n=1). Median age was 70 and most patients had brain metastases (15/19, 79%). ctDNA test sensitivity for activating EGFR mutations was 74% using both methods and 62% (Mutyper) or 64% (Cobas v2) for individual methods. ORR was 68% (13/19), median PFS was 11.1 months (95% confidence interval [CI], 0.0 to 26.7), and median DoR was 17.6 months (95% CI, 3.5 to 31.7). ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9). One patient discontinued the drug because of drug-related interstitial pneumonitis. @*Conclusion@#Osimertinib had favorable efficacy in the first-line treatment of metastatic NSCLC harboring activating EGFR mutations in ctDNA as well as tumor DNA.

NOTCH1 Pathway is Involved in Polyhexamethylene Guanidine-Induced Humidifier Disinfectant Lung Injuries

0.2 and p<0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (p=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.

Imbalance of Gut Streptococcus, Clostridium, and Akkermansia Determines the Natural Course of Atopic Dermatitis in Infant

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 Streptococcus and high amounts of Akkermansia were evident in transient AD cases, and low Clostridium, Akkermansia and high Streptococcus were found in children with persistent AD. The relative abundance of Streptococcus positively correlated with scoring of AD (SCORAD) score, whereas that of Clostridium 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.

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

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

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

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

A Phase II Trial of Osimertinib in the Second-Line Treatment of Non-small Cell Lung Cancer with the EGFR T790M Mutation, Detected from Circulating Tumor DNA: LiquidLung-O-Cohort 2 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Administering the best treatment after failure of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy requires knowledge of resistance status. In this trial, treatment efficacy of osimertinib was assessed in patients with non-small cell lung carcinoma (NSCLC) harboring the T790M resistance mutation, detected from circulating tumor DNA (ctDNA) with unknown tumor mutation status. MATERIALS AND METHODS: To extract ctDNA from plasma, 15 mL of peripheral blood was withdrawn and centrifuged immediately before storage. Cobas ver. 2 and PANA Mutyper were used for ctDNA genotyping. Patients with T790M, detected from ctDNA, were enrolled and they received a once-daily administration of osimertinib 80 mg. The primary endpoint was objective response rate (ORR), and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety. RESULTS: Eighty patients with acquired resistance to prior EGFR-TKI therapies were screened. ctDNA of 21 patients showed T790M positivity, and 19 patients were enrolled. In the response-evaluable population (n=15), ORR was 66.7% (10/15). Median PFS was 8.3 months (95% confidence interval [CI], 7.9 to 8.7) and median DoR was 6.8 months (95% CI, 5.3 to 8.3) in the intent-to-treat population (n=19). No subject experienced drug-related adverse event of grades ≥ 3 or required dose reduction. The sensitivity of the ctDNA tests was 56.8% using both methods and 45.9% with either method from the estimated T790M-positive cases. CONCLUSION: Osimertinib has favorable efficacy in patients with NSCLC harboring T790M, detected from ctDNA with unknown tumor mutation status, in whom disease had progressed during prior EGFR-TKI therapy.

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

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

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

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.

Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction

PURPOSE: Drug provocation tests (DPT) are the gold standard for confirming the diagnosis of drug hypersensitivity reactions (DHRs). However, there are little studies of DPT in children. The purpose of this study was to evaluate DPT results and safety as diagnostic methods of DHR in Korean children. METHODS: We reviewed the medical records of 39 children under 18 years of age with a suspected DHR and performed DPT between January 2010 and May 2016 at Asan Medical Center. RESULTS: Total 110 DPT were performed in 39 children (20 boys and 19 girls) with a history of DHR. Clinical presentation of DHR included skin rash (n=7), pruritus (n=3), urticaria (n=18), angioedema (n=19), dyspnea (n=5), hoarseness (n=1), hypothermia (n=1), and anaphylaxis (n=5). The median age at the time of DPT was 9 years. Positive DPT were observed in 21 of 39 children (53.8%) and 28 of 110 cases (25.5%). Drugs causing positive reactions were acetaminophen in 50% (9 of 18), nonsteroidal anti-inflammatory drugs in 29.2% (14 of 48), cephalosporin in 9.1% (1 of 11), trimethoprim/sulfamethoxazole in 50% (1 of 2), local anesthetics in 10% (1 of 10), and others (levodropropizine and idursulfase) in 15.4% (2 of 13). There was no statistical difference between children who had positive and negative results in sex, age, personal and parental history of allergic disease, eosinophil count, or total IgE level. Children with positive DPT did not develop anaphylaxis during the DPT procedure. CONCLUSION: Drug provocation test is safe, and it can be considered in children with suspected DHRs.

Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated Toxic Lung Injury

Previous animal studies have not conclusively determined the association between exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and development of HD-associated lung injuries. Nonetheless, patients exposed to HDs containing only CMIT and/or MIT showed clinically similar lung injuries to those exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2-ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of age, a younger twin sister presented with the 3-day history of cough, sputum, and respiratory difficulty. Chest radiography revealed multiple patchy consolidation and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy was performed due to pneumothorax at admission and she was discharged at 11 days of hospitalization. At 5 years of age, multiple tiny nodules and faint centrilobular ground-glass opacities were observed with the small pneumatocele. The elder sister visited a tertiary hospital due to dyspnea at 12 months of age. Chest radiography showed consolidation, pneumomediastinum, and pulmonary interstitial emphysema. There was no response to the administration of immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT revealed ground-glass opacity and multiple tiny centrilobular ground-glass opacities nodules in both lungs with exercise intolerance.

Efficacy of Afatinib in a Previously-Treated Patient with Non-Small Cell Lung Cancer Harboring HER2 Mutation: Case Report

Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing of the tumor tissue revealed a HER2 exon 20 mutation (c.2437A > G), which has never been reported. The patient was treated with afatinib for more than four months. She showed rapid radiologic response within a month, and maintained stable state until the last dose of afatinib.

Prevalence and clinical manifestations of macrolide resistant Mycoplasma pneumoniae pneumonia in Korean children / 소아과

PURPOSE: Macrolide resistance rate of Mycoplasma pneumoniae has rapidly increased in children. Studies on the clinical features between macrolide susceptible-M. pneumoniae (MSMP) and macrolide resistant-M. pneumoniae (MRMP) are lacking. The aim of this study was to identify the macrolide resistance rate of M. pneumoniae in Korean children with M. pneumoniae penupmonia in 2015 and compare manifestations between MSMP and MRMP. METHODS: Among 122 children (0–18 years old) diagnosed with M. pneumoniae pneumonia, 95 children with the results of macrolide sensitivity test were included in this study. Clinical manifestations were acquired using retrospective medical records. RESULTS: The macrolide resistant rate of M. pneumoniae was 87.2% (82 of 94 patients) in children with M. pneumoniae pneumonia. One patient showed a mixed type of wild type and A2063G mutation in 23S rRNA of M. pneumoniae. There were no significant differences in clinical, laboratory, and radiologic findings between the MSMP and MRMP groups at the first visit to our hospital. The time interval between initiation of macrolide and defervescence was significantly longer in the MRMP group (4.9±3.3 vs. 2.8±3.1 days, P=0.039). CONCLUSION: The macrolide resistant rate of M. pneumoniae is very high in children with M. pneumoniae pneumonia in Korea. The clinical manifestations of MRMP are similar to MSMP except for the defervescence period after administration of macrolide. Continuous monitoring of the occurrence and antimicrobial susceptibility of MRMP is required to control its spread and establish strategies for treating second-line antibiotic resistant M. pneumoniae infection.

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

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.

The Different Clinical Aspects of Pediatric Primary Airway Tumors in the Larynx, Trachea, and Bronchi

Primary airway tumors are rare in children and no literature reviewed their characteristics each location. We evaluate the clinical characteristics and outcomes of Korean children with primary airway tumors, from the larynx to bronchi. A retrospective chart review of children with primary tumors of the larynx, trachea, and bronchi at Asan Medical Center from January 2000 to July 2016 was conducted. Nineteen children were diagnosed with primary airway tumors of the larynx (47.4%), trachea (10.5%), and bronchi (42.1%). Median follow-up duration was 2.8 years and there were recurrences in 21.1%. Laryngeal tumors were associated with a younger median age at onset (2 months) and diagnosis (4 months), and most were relatively small (median size = 5.3 mm) and symptomatic. Tracheal and bronchial tumors were found in older children (age at onset and diagnosis > 11 years) and large (> 15.0 mm). Most (75%) patients with bronchial tumors were asymptomatic and all the patients with tracheal tumors were symptomatic. This study suggests that we should consider different the locations in primary airway tumor based on the age at onset and diagnosis, initial symptoms or signs, and size of tumor.

Pediatric adverse drug reactions collected by an electronic reporting system in a single tertiary university hospital

PURPOSE: The incidence of adverse drug reactions (ADRs) is increasing. However, studies on the prevalence of ADRs in children are rare. The aim of this study was to investigate the causative drugs and clinical features of ADRs for children in a tertiary university hospital of Korea. METHODS: We retrospectively collected ADRs by a computerized self-reporting system in Asan Medical Center. ADRs of children under the age 18 were collected from January 2005 to August 2015, and we analyzed only ADRs containing current symptoms among total ADR data. RESULTS: A total of 1,408 ADR cases were reported, There were 764 male (54.3%) and 644 female patients (45.7%), and the mean age was 11.5±5.8 years (range, 0–18 years). Antibiotics (n=479, 34.0%) were the most common causative drugs, followed by tramadol (n=173, 12.3%), nonsteroidal anti-inflammatory agents (NSAIDs) and acetylsalicylic acid (n=103, 7.3%), narcotics (n=91, 6.5%), antineoplastics (n=87, 6.2%), and sedatives (n=82, 5.8%). The most common clinical features were skin manifestations (n=500, 34.4%). Gastrointestinal symptoms (n=435, 29.9%) were the second most common clinical features, followed by neuropsychiatric symptoms (n=155, 10.7%) and respiratory symptoms (n=123, 8.5%). Among antibiotics, glycopeptides (n=110, 23.0%), third-generation cephalosporins (n=83, 17.3%), and penicillin/β-lactamase inhibitors (n=60, 12.7%) were the most frequently reported causative drugs. CONCLUSION: Antibiotics were the most reported common causative drugs of ADRs in children, followed by tramadol, NSAID, and narcortics. Compared with adults, the prevalence of contrast medium-induced ADR was lower in children with a higher prevalence of sedative-associated ADR. Greater attention to possible ADRs in children is needed among medical personnel.

The change in food allergy prevalence of elementary school children in Seoul since the last 20 years and the risk factor analysis

PURPOSE: There are many reports that the prevalence of food allergy (FA) is globally increasing. We investigated the change in FA prevalence since the last 20 years in elementary school children, in Seoul, Korea. METHODS: A modified International Study of Asthma and Allergies in Childhood questionnaire survey was done to elementary school children in Seoul, Korea in 1995, 2000, 2005, 2008, and 2012. The numbers of subjects included in the analysis were 7,963, 7,971, 7,131, 3,975, and 3,307, respectively. Blood and skin prick tests were done in 2008 and 2012. RESULTS: The prevalence rates of FA diagnosis ever were 4.6% (95% confidence interval [CI], 4.1-5.1), 5.2% (95% CI, 4.7-5.7), 6.4% (95% CI, 5.9-7.0), 5.5% (95% CI, 4.8-6.3), and 6.6% (95% CI, 5.8-7.6) in 1995, 2000, 2005, 2008, and 2012, respectively (P-value for trend <0.001). Asthma (adjusted odds ratio [aOR], 2.209; 95% CI, 1.589-3.072), allergic rhinitis (aOR, 1.874; 95% CI, 1.473-2.384), and atopic dermatitis (aOR, 4.288; 95% CI, 3.340-5.506) were associated with FA diagnosis. Parental allergic disease history (aOR, 2.191; 95% CI, 1.666-2.881), antibiotics use in infancy (aOR, 1.484; 95% CI, 1.170-1.883), and house mold exposure in infancy (aOR, 1.540; 95% CI, 1.172-2.024) were risk factors for FA diagnosis. Sensitization to inhalant allergens (aOR, 1.867; 95% CI, 1.091-3.194) and increased serum total IgE (aOR, 2.014; 95% CI, 1.081-3.752) were associated with FA diagnosis. CONCLUSION: The prevalence of FA diagnosis is likely to be increasing since the last 20 years in Seoul. Antibiotics use in infancy and house mold exposure in infancy were risk factors for FA diagnosis.

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

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.

Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma

PURPOSE: Asthma is a chronic airway inflammatory disease characterized by bronchial hyperresponsiveness and reversible airway obstruction. Bronchial challenge with methacholine or adenosine-5'-monophosphate (AMP) has been used to diagnose asthma. Recently, measurement of exhaled nitric oxide (eNO) can also be used for the diagnosis of asthma. The aim of this study was to compare the diagnostic value for asthma between challenge with methacholine or AMP and eNO in children with chronic nonspecific respiratory symptoms. METHODS: One hundred thirty-three children who have chronic nonspecific respiratory symptoms were enrolled. Bronchial challenge with methacholin and AMP were performed, and eNO was measured in all subjects. Subjects were defined as asthma based on the clinical symptoms and bronchodilator response during follow-up of at least 3 months after test. RESULTS: Thirty-three subjects (34%) were finally diagnosed as asthma among 97 patients after 3-month follow-up. The area under the receiver operating characteristic curves for the diagnosis of asthma were 0.903 (95% confidence interval [CI], 0.838-0.969; P<0.001) for methacholline challenge, 0.867 (95% CI, 0.783-0.950; P<0.001) for AMP challenge, and 0.588 (95% CI, 0.467-0.709, P=0.156) for eNO measurement. The cutoff values of these tests were methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) 12.0 mg/mL (sensitivity, 87.9%; specificity, 82.8%), AMP PC20 566.2 mg/mL (sensitivity, 84.8%; specificity, 85.9%), and eNO 18.5 ppb (sensitivity, 45.5%; specificity, 71.9%). CONCLUSION: Measurement of eNO may be inferior to challenge with methacholine and AMP for the diagnosis of asthma in children.

The prevalence and risk factors of allergic rhinitis from a nationwide study of Korean elementary, middle, and high school students

PURPOSE: We investigated the prevalence and risk factors of allergic rhinitis (AR), nationwide in random children and adolescents of Korea. METHODS: A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire survey was done in 1,820 children from elementary, middle, and high school nationwide in Korea. The subjects were selected by the stratifying sampling method by school grade and five regions. Current AR was defined as having AR symptoms during the last 12 months with a history of physician-diagnosed AR. Skin prick tests for 18 common allergens were performed. RESULTS: The number of males was 945, and that of females was 875. The mean age of the patients was 12.61+/-3.40 years. The prevalence of current AR and atopic current AR were 29.0% and 18.7%, respectively. Risk factors for current AR were male (adjusted odds ratio [aOR], 1.486; 95% confidence interval [CI], 1.189-1.856), family history of paternal AR (aOR, 3.208; 95% CI, 2.460-4.182), family history of maternal AR (aOR, 3.138; 95% CI, 2.446-4.025), antibiotic use in infancy (aOR, 1.547; 95% CI, 1.228-1.949), mold exposure during infancy (aOR, 1.416; 95% CI, 1.103-1.819), mold exposure during the last 12 months (aOR, 1.285; 95% CI, 1.012-1.630), and sensitization on skin prick tests (aOR, 2.596; 95% CI, 2.055-3.279). Risk factors for atopic current AR were the same as those of current AR, whereas breast-milk feeding (aOR, 0.720; 95% CI, 0.530-0.976) was a protective factor. Sensitized allergens as risk factors for current AR were Dermatophagoides pteronyssinus, Dermatophagoides farina, ragweed, mugwort, oak, alder, birch, Japanese hop, cat, and dog. CONCLUSION: The prevalences of current AR and atopic current AR were 29.0% and 18.7%, respectively. Male, sex parental AR, antibiotic use in infancy, mold exposure during the last 12 months, mold exposure during infancy, and atopic sensitization were risk factors for current AR. Breast-milk feeding was a protective factor for atopic current AR. Aeroallergen sensitization was an important risk factor for AR.

High degree of supervision improves adherence to inhaled corticosteroids in children with asthma / 소아과

PURPOSE: Adherence to treatment with inhaled corticosteroids (ICS) is a critical determinant of asthma control. The objective of this study was to assess factors that determine adherence to ICS therapy in children with asthma. METHODS: Fifty-eight children with asthma, aged 5 to 16 years, used ICS with or without a spacer for 3 months. Adherence rates as measured from questionnaires and canisters, asthma symptom scores, and inhalation technique scores were assessed every 30 days. The degree of supervision by caregivers was assessed at day 30. RESULTS: Adherence rates measured using canisters were lower at day 60 than at day 30 (P=0.044) and did not change thereafter (74.4%+/-17.4% at day 30, 66.5%+/-18.4% at day 60, and 67.4%+/-22.2% at day 90). Adherence rates at days 60 and 90 and during the total study period were significantly different when measured by using questionnaires versus canisters (P<0.001, P=0.022, and P=0.001, respectively). In the comparison of adherence rates repeatedly measured at days 30, 60, and 90 and adherence rates during the total study period among the 3 groups, adherence rates in the high-degree supervision group were significantly higher than those in the low-degree supervision group (82.0+/-16.0 vs. 66.1+/-14.5, 75.4+/-14.4 vs. 56.2+/-18.4, 75.0+/-18.3 vs. 55.0+/-19.7 [P=0.027]; 77.9+/-12.2 vs. 59.1+/-11.4 [P=0.021]) after adjustment for sex and age. CONCLUSION: The level of caregiver supervision is an important factor affecting adherence to ICS therapy in children with asthma. Therefore, a high degree of supervision may be required to increase adherence to ICS therapy in children with asthma.