Comparison of Finasteride and Dutasteride on Risk of Prostate Cancer in Patients with Benign Prostatic Hyperplasia: A Pooled Analysis of 15 Real-world Databases.

PURPOSE: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. MATERIALS AND METHODS: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. RESULTS: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44-1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67-1.14; p=0.310). CONCLUSIONS: Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in South Korea.

INTRODUCTION: Children's rare lung diseases are a heterogeneous group of rare lung diseases with significant morbidity and mortality. There is very limited information on the incidence and prevalence of children's rare lung diseases in Asia. We investigated the nationwide incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in Korea. METHODS: We studied patients who were diagnosed with rare lung diseases coded per International Statistical Classification of Diseases and Related Health Problems, 10th Edition and registered in the national rare diseases database of confirmed patients. Data was extracted from the Korean National Health Insurance Service Claims database over 2019-2021. RESULTS: Average incidence rate was 12.9 new cases per million children per year, and average prevalence rate was 60.2 cases per million children during the study period of 2019-2021. We found that more than 65% of new cases were diagnosed before 2 years of age. ChILD, primary ciliary dyskinesia, and cystic fibrosis were usually diagnosed after 6 years of age. Congenital airway and lung anomalies were often diagnosed before 2 years of age. Busan and Gyeongsangnam-do residents tended to visit hospitals near their place of residence, while residents of other areas tended to visit hospitals in Seoul regardless of their area of residence. CONCLUSIONS: We examined the epidemiology of rare lung diseases in children in South Korea. Our estimation of the incidence and prevalence could be used for sustainable health care and equitable distribution of health care resources.

Evidence-based management guidelines for noncystic fibrosis bronchiectasis in children and adolescents.

Noncystic fibrosis bronchiectasis is a chronic respiratory disease that carries high socioeconomic and medical burdens and is caused by diverse respiratory illnesses. To improve clinical outcomes, early recognition, active treatment of exacerbations, and prevention of further exacerbations are essential. However, evidence for the treatment and prevention of acute exacerbation of noncystic fibrosis bronchiectasis, especially in children, is lacking. Therefore, the evidence- and consensus-based guidelines for medical and nonmedical treatment strategies for noncystic fibrosis bronchiectasis in children and adolescents were developed by the Korean Academy of Pediatric Allergy and Respiratory Disease using the methods recommended by the Grading of Recommendations Assessment, Development, and Evaluation working group with evidence published through July 2, 2020. This guideline encompasses evidence-based treatment recommendations as well as expert opinions, addressing crucial aspects of the treatment and management of non-cystic fibrosis bronchiectasis in children. This includes considerations for antibiotics and airway clearance strategies, particularly in areas where evidence may be limited. Large, well-designed, and controlled studies are required to accumulate further evidence of management strategies for noncystic fibrosis bronchiectasis in children and adolescents.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in Non-pharmacological Management.

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

Long-term Outcomes of Turbinate Surgery in Patients With Allergic Rhinitis: A Systematic Review and Meta-analysis.

Importance: Turbinate surgery is an effective treatment for allergic rhinitis (AR) refractory to medical treatment. However, the long-term outcomes of turbinate surgery are still unclear and have not yet been confirmed by a meta-analysis and systematic review of the literature. Objective: To investigate the long-term outcomes and safety of turbinate surgery in AR by performing a meta-analysis. Data Sources: MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through April 2021. Study Selection: Studies that analyzed turbinate surgery alone, had a follow-up period of more than 1 year, examined long-term efficacy of turbinate surgery, used current turbinate surgery methods, and were published in a peer-reviewed journal were included. Full-text reviews were performed by 2 independent reviewers. Conflicts were resolved by a third reviewer. Data Extraction and Synthesis: Descriptive and quantitative data were extracted; weighted mean difference (WMD) was synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and the I2 metric. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Main Outcomes and Measures: The long-term outcomes of turbinate surgery on subjective nasal symptoms and objective parameters. Results: Of the 3962 citations retrieved, 18 studies comprising 1411 patients were included. Findings showed significantly decreased symptom scores in nasal obstruction (WMD, 4.60, 95% CI, 3.43-5.76), rhinorrhea (WMD, 3.12; 95% CI, 1.97-4.28), sneezing (WMD, 2.64; 95% CI, 1.74-3.54), itching (WMD, 1.75; 95% CI, 1.20-2.30), and nasal resistance (WMD, 0.16; 95% CI, 0.08-0.24) and a significant increased total nasal volume (WMD, 0.96; 95% CI, 0.73-1.19). There was no significant difference in the occurrence of any complication. More than 1 year after surgery, the improvements in nasal obstruction (WMD, 5.18; 95% CI, 3.00-7.37), rhinorrhea (WMD, 3.57; 95% CI, 1.78-5.37), and sneezing (WMD, 2.95; 95% CI, 1.58-4.32) were maintained. Conclusions and Relevance: In this systematic review and meta-analysis, turbinate surgery was associated with positive outcomes in AR and maintained the association during long-term follow-up. The rate of complications is also low. These findings can guide the preoperative counseling of patients with AR being considered for turbinate surgery.

Long-term macrolide treatment for non-cystic fibrosis bronchiectasis in children: a meta-analysis.

Recurrent bacterial infection causes frequent bronchiectasis (BE) exacerbations. The effectiveness and safety of long-term administration of macrolides in BE remain controversial, especially in children who require minimal treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide use in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) which elucidated long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged < 18 years. The primary outcome was frequency of acute exacerbation; secondary outcomes included changes in pulmonary function, sputum scores, and adverse events including bacterial resistance. We included four RCTs. Long-term macrolide treatment showed a significant decrease in the frequency of exacerbation (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.10-0.87), mean number of exacerbations per patient (mean difference, - 1.40; 95% CI, - 2.26 to - 0.54), and sputum purulence score (mean difference, - 0.78; 95% CI, - 1.32 to - 0.24). However, long-term macrolide treatment was accompanied by an increased carriage of azithromycin-resistant bacteria (OR, 7.13). Long-term macrolide administration prevents exacerbation of BE in children; however, there are risks of increasing antibiotic resistance. Benefits and risks should be weighed and determined on a patient-by-patient basis.

Association between the use of allopurinol and risk of increased thyroid-stimulating hormone level.

Allopurinol is the first-line agent for patients with gout, including those with moderate-to-severe chronic kidney disease. However, increased thyroid-stimulating hormone (TSH) levels are observed in patients with long-term allopurinol treatment. This large-scale, nested case-control, retrospective observational study analysed the association between allopurinol use and increased TSH levels. A common data model based on an electronic medical record database of 19,200,973 patients from seven hospitals between January 1997 and September 2020 was used. Individuals aged > 19 years in South Korea with at least one record of a blood TSH test were included. Data of 59,307 cases with TSH levels > 4.5 mIU/L and 236,508 controls matched for sex, age (± 5), and cohort registration date (± 30 days) were analysed. An association between the risk of increased TSH and allopurinol use in participants from five hospitals was observed. A meta-analysis (I2 = 0) showed that the OR was 1.51 (95% confidence interval: 1.32-1.72) in both the fixed and random effects models. The allopurinol intake group demonstrated that increased TSH did not significantly affect free thyroxine and thyroxine levels. After the index date, some diseases were likely to occur in patients with subclinical hypothyroidism and hypothyroidism. Allopurinol administration may induce subclinical hypothyroidism.

Prediction of COVID-19-related Mortality and 30-Day and 60-Day Survival Probabilities Using a Nomogram.

BACKGROUND: Prediction of mortality in patients with coronavirus disease 2019 (COVID-19) is a key to improving the clinical outcomes, considering that the COVID-19 pandemic has led to the collapse of healthcare systems in many regions worldwide. This study aimed to identify the factors associated with COVID-19 mortality and to develop a nomogram for predicting mortality using clinical parameters and underlying diseases. METHODS: This study was performed in 5,626 patients with confirmed COVID-19 between February 1 and April 30, 2020 in South Korea. A Cox proportional hazards model and logistic regression model were used to construct a nomogram for predicting 30-day and 60-day survival probabilities and overall mortality, respectively in the train set. Calibration and discrimination were performed to validate the nomograms in the test set. RESULTS: Age ≥ 70 years, male, presence of fever and dyspnea at the time of COVID-19 diagnosis, and diabetes mellitus, cancer, or dementia as underling diseases were significantly related to 30-day and 60-day survival and mortality in COVID-19 patients. The nomogram showed good calibration for survival probabilities and mortality. In the train set, the areas under the curve (AUCs) for 30-day and 60-day survival was 0.914 and 0.954, respectively; the AUC for mortality of 0.959. In the test set, AUCs for 30-day and 60-day survival was 0.876 and 0.660, respectively, and that for mortality was 0.926. The online calculators can be found at https://koreastat.shinyapps.io/RiskofCOVID19/. CONCLUSION: The prediction model could accurately predict COVID-19-related mortality; thus, it would be helpful for identifying the risk of mortality and establishing medical policies during the pandemic to improve the clinical outcomes.

The nationwide retrospective cohort study by Health Insurance Review and Assessment Service proves that asthma management decreases the exacerbation risk of asthma.

Medical costs have recently increased in South Korea due to the rising rate of asthma. Primary clinics serve an important role in asthma management, as they are the first stop for patients presenting with symptoms. The Health Insurance Review and Assessment Service (HIRA) in South Korea has assessed asthma-management quality since 2013, but studies are lacking on whether these assessments have been performed properly and contribute toward reducing asthma exacerbations. Therefore, we investigated whether the HIRA's quality assessments have decreased asthma exacerbations using national health insurance claims data from 2013 to 2017 of 83,375 primary-clinic and 15,931 tertiary-hospital patients with asthma. These patients were classified into four groups based on disease severity according to the monthly prescribed amount of asthma medication using K-means clustering. The associations between HIRA assessments and asthma exacerbation were analyzed using a generalized estimating equation. Our results showed that exacerbation odds gradually decreased as the HIRA assessments progressed, especially in the mild-severity group, and that exacerbation risk among patients with asthma decreased in the order of assessment grades: "Unsatisfactory," "Satisfactory," and "Tertiary." Therefore, we may conclude that asthma exacerbations may decrease with high quality asthma management; appropriate quality assessment could be helpful in reducing asthma exacerbations.

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

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 and etiologies of bronchiectasis in Korean children: A multicenter retrospective study.

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

Transfusion trends in hip arthroplasty in Korea: a nationwide study by the Korean National Health Insurance Service.

BACKGROUND: Hip arthroplasties are strongly associated with blood transfusion to compensate for perioperative bleeding. The purpose of this study was to evaluate the trends in transfusion associated with hip arthroplasties, using nationwide data supplied by the National Health Insurance Service. STUDY DESIGN AND METHODS: We used data from nationwide claims database of the Health Insurance Review Assessment Service. The data managed by the National Health Insurance Service were used to identify 161,934 hip arthroplasties under three categories, including bipolar hemiarthroplasty, total hip arthroplasty, and revision arthroplasty, from 2007 to 2015. The transfusion rates, transfusion amounts, the proportion of transfusion, and cost associated with each type of operation were investigated and stratified according to age, sex, hospital type, and region. RESULTS: The proportion of patients receiving any allogeneic transfusion was 81.1% in 9 years. The overall proportion of transfusion was 7% fresh frozen plasma, 12% platelets, and 77% RBCs. The average count of transfusions was 4.1 in bipolar hemiarthroplasty (343,815/83,729), 4.3 in total hip arthroplasty (196,869/46,097), and 8.7 in revision arthroplasty (35,044/4,024) from 2007 to 2015. CONCLUSION: In this nationally representative study of trends in transfusion associated with hip arthroplasty, we observed significantly high rates of blood transfusion among patients undergoing hip arthroplasties. Although the overall amount of transfusion declined, the allogeneic transfusion rate was still high from 2007 to 2015 in Korea, and higher than other countries are reporting.

Genome-wide assessment of gene-by-smoking interactions in COPD.

Cigarette smoke exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) and its interactions with genetic variants could affect lung function. However, few gene-smoking interactions have been reported. In this report, we evaluated the effects of gene-smoking interactions on lung function using Korea Associated Resource (KARE) data with the spirometric variables-forced expiratory volume in 1 s (FEV1). We found that variations in FEV1 were different among smoking status. Thus, we considered a linear mixed model for association analysis under heteroscedasticity according to smoking status. We found a previously identified locus near SOX9 on chromosome 17 to be the most significant based on a joint test of the main and interaction effects of smoking. Smoking interactions were replicated with Gene-Environment of Interaction and phenotype (GENIE), Multi-Ethnic Study of Atherosclerosis-Lung (MESA-Lung), and COPDGene studies. We found that individuals with minor alleles, rs17765644, rs17178251, rs11870732, and rs4793541, tended to have lower FEV1 values, and lung function decreased much faster with age for smokers. There have been very few reports to replicate a common variant gene-smoking interaction, and our results revealed that statistical models for gene-smoking interaction analyses should be carefully selected.

Surveillance and compensation claims for adverse events following immunization from 2011 to 2016 in the Republic of Korea.

PURPOSE: In recent years, research on reported adverse events following immunization (AEFI) and claims filed for compensation has been lacking. We reviewed reported AEFIs and compensation claims in Korea from 2011 to 2016. MATERIALS AND METHODS: We listed all of the AEFI registered in the Integrated Management System of Disease and Public Health and reviewed the list of claims filed and serious AEFIs reported from 2011 to 2016. RESULTS: An average of 278 AEFI cases was reported annually from 2011 to 2016. Of these, 31 deaths were reported. However, there was no association found between these deaths and vaccinations when evaluating vaccine lot, reviewing autopsies, and considering underlying diseases. AEFI reporting rate was as high as 20.8 cases for bacillus Calmette-Guérin (BCG) vaccine, 7.3 cases for 23-valent pneumococcal polysaccharide vaccine (PPV23), and 5.4 cases for human papillomavirus vaccine per 100,000 vaccination doses in 2016. Of the 469 total cases that claimed vaccine injury compensation from 2011 to 2016, the BCG vaccine was most commonly involved, with 235 cases (50%), followed by influenza vaccine and PPV23, with 90 and 55 cases, respectively. Of these cases, 96% of BCG-related AEFI were compensated, while only 31% and 49% of AEFI following influenza and PPV23 vaccination, respectively, were compensated. Common characteristics of uncompensated cases included the elderly subjects, receiving influenza vaccine, having underlying disease, or a very short time interval between vaccination and symptoms. CONCLUSION: We have maintained vaccine safety management system through both rapid response to serious AEFI and vaccine injury compensation in order to sustain public trust in the National Immunization Program.

Impact of perinatal environmental tobacco smoke on the development of childhood allergic diseases.

Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear. Thus, it is important to identify and control risk factors in the susceptible individual for the best prevention and management. Genetic susceptibility or environments may be a potential background for the development of allergic disease, however they alone cannot explain the rising prevalence worldwide. There is growing evidence that epigenetic change depends on the gene, environment, and their interactions, may induce a long-lasting altered gene expression and the consequent development of allergic diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure during critical period (i.e., during pregnancy and early life) are considered as a potential cause of the development of childhood allergic diseases. However, the causal relationship is still unclear. This review aimed to highlight the impact of ETS exposure during the perinatal period on the development of childhood allergic diseases and to propose a future research direction.

Association of symptom control with changes in lung function, bronchial hyperresponsiveness, and exhaled nitric oxide after inhaled corticosteroid treatment in children with asthma.

BACKGROUND: A key therapeutic approach to asthma, which is characterized by chronic airway inflammation, is inhaled corticosteroid (ICS). This study evaluated the association of symptom control with changes in lung function, bronchial hyperresponsiveness (BHR), and exhaled nitric oxide (eNO) after ICS treatment in asthmatic children. METHODS: A total of 33 children aged between 5 and 12 years with mild to moderate persistent asthma were treated with 160 µg ciclesonide per day for 3 months. At days 0 and 90, the following parameters were assessed: asthma symptom scores; lung function, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%); BHR to methacholine and adenosine 5-monophosphate (AMP); and eNO. RESULTS: Asthma symptom scores, lung function parameters, BHR to methacholine and AMP, and eNO levels at day 90 were significantly improved versus day 0 (all p < 0.001). Symptom scores at day 90 were not correlated with changes in lung function and BHR to methacholine during the follow-up period, whereas those at day 90 were more closely correlated with changes in BHR to AMP (r = 0.511, p = 0.003) than with eNO (r = -0.373, p = 0.035). Additionally, changes in PC20 AMP were correlated with changes in PC20 methacholine (r = 0.451, p = 0.011) and eNO (r = -0.474, p = 0.006). CONCLUSIONS: Changes in the BHR to AMP, and to a lesser extent eNO, correlate with asthma symptom control after ICS treatment. BHR to AMP may better reflect the relationship between improved airway inflammation due to ICS treatment and asthma symptoms.

Early diagnosis based on clinical history and BALF for successful management of smoking-induced acute eosinophilic pneumonia without unnecessary antibiotic usage: a case report.

INTRODUCTION: Acute eosinophilic pneumonia (AEP) is a rapid onset and severe respiratory illness characterized by acute febrile respiratory insufficiency, eosinophilic infiltration in the lungs and unique findings on chest imaging. Difficulty in differentiating from other respiratory distress caused by community-acquired pneumonia may result in a delayed diagnosis or treatment with empirical antibiotics. CASE STUDY: Sixteen-year-old boy who developed AEP with marked eosinophilia in bronchoalveolar lavage fluid (BALF, 36.6%), decreased diffusion capacity of the lung for carbon monoxide (62%) and unique radiological findings. Although he initially denied tobacco use, on repeated thorough clinical history questioning, he eventually admitted beginning smoking 19 days before the onset of symptoms with gradually increasing frequency. RESULTS: His symptoms resolved quickly without use of antibiotics after cessation of tobacco and treatment with corticosteroids. CONCLUSION: Careful clinical history taking regarding tobacco use combined with early examination of BALF and recognition of unique radiological findings are critical for proper management of AEP.

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.

The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods.

BACKGROUND: This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. METHODS/DESIGN: The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child's neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child's genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child's exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child's neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child's microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures. DISCUSSION: The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.