Association between inflammation-based prognostic markers and mortality of non-cardiac surgery / 대한마취과학회지

Background@#To evaluate the association between inflammation and nutrition-based biomarkers and postoperative outcomes after non-cardiac surgery. @*Methods@#Between January 2011 and June 2019, a total of 102,052 patients undergoing non-cardiac surgery were evaluated, with C-reactive protein (CRP), albumin, and complete blood count (CBC) measured within six months before surgery. We assessed their CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS). We determined the best cut-off values by using the receiver operating characteristic (ROC) curves. Patients were divided into high and low groups according to the estimated threshold, and we compared the one-year mortality. @*Results@#The one-year mortality of the entire sample was 4.2%. ROC analysis revealed areas under the curve of 0.796, 0.743, 0.670, and 0.708 for CAR, NLR, PLR, and mGPS, respectively. According to the estimated threshold, high CAR, NLR, PLR, and mGPS were associated with increased one-year mortality (1.7% vs. 11.7%, hazard ratio [HR]: 2.38, 95% CI [2.05, 2.76], P < 0.001 for CAR; 2.2% vs. 10.3%, HR: 1.81, 95% CI [1.62, 2.03], P < 0.001 for NLR; 2.6% vs. 10.5%, HR: 1.86, 95% CI [1.73, 2.01], P < 0.001 for PLR; and 2.3% vs. 16.3%, HR: 2.37, 95% CI [2.07, 2.72], P < 0.001 for mGPS). @*Conclusions@#Preoperative CAR, NRL, PLR, and mGPS were associated with postoperative mortality. Our findings may be helpful in predicting mortality after non-cardiac surgery.

Survey of Public Attitudes toward the Secondary Use of Public Healthcare Data in Korea / 대한의료정보학회지

Objectives@#Public healthcare data have become crucial to the advancement of medicine, and recent changes in legal structure on privacy protection have expanded access to these data with pseudonymization. Recent debates on public healthcare data use by private insurance companies have shown large discrepancies in perceptions among the general public, healthcare professionals, private companies, and lawmakers. This study examined public attitudes toward the secondary use of public data, focusing on differences between public and private entities. @*Methods@#An online survey was conducted from January 11 to 24, 2022, involving a random sample of adults between 19 and 65 of age in 17 provinces, guided by the August 2021 census. @*Results@#The final survey analysis included 1,370 participants. Most participants were aware of health data collection (72.5%) and recent changes in legal structures (61.4%) but were reluctant to share their pseudonymized raw data (51.8%). Overall, they were favorable toward data use by public agencies but disfavored use by private entities, notably marketing and private insurance companies. Concerns were frequently noted regarding commercial use of data and data breaches. Among the respondents, 50.9% were negative about the use of public healthcare data by private insurance companies, 22.9% favored this use, and 1.9% were “very positive.” @*Conclusions@#This survey revealed a low understanding among key stakeholders regarding digital health data use, which is hindering the realization of the full potential of public healthcare data. This survey provides a basis for future policy developments and advocacy for the secondary use of health data.

Accuracy of Cloud-Based Speech Recognition Open Application Programming Interface for Medical Terms of Korean

Background@#There are limited data on the accuracy of cloud-based speech recognition (SR) open application programming interfaces (APIs) for medical terminology. This study aimed to evaluate the medical term recognition accuracy of current available cloud-based SR open APIs in Korean. @*Methods@#We analyzed the SR accuracy of currently available cloud-based SR open APIs using real doctor–patient conversation recordings collected from an outpatient clinic at a large tertiary medical center in Korea. For each original and SR transcription, we analyzed the accuracy rate of each cloud-based SR open API (i.e., the number of medical terms in the SR transcription per number of medical terms in the original transcription). @*Results@#A total of 112 doctor–patient conversation recordings were converted with three cloud-based SR open APIs (Naver Clova SR from Naver Corporation; Google Speech-toText from Alphabet Inc.; and Amazon Transcribe from Amazon), and each transcription was compared. Naver Clova SR (75.1%) showed the highest accuracy with the recognition of medical terms compared to the other open APIs (Google Speech-to-Text, 50.9%, P < 0.001; Amazon Transcribe, 57.9%, P < 0.001), and Amazon Transcribe demonstrated higher recognition accuracy compared to Google Speech-to-Text (P< 0.001). In the sub-analysis, Naver Clova SR showed the highest accuracy in all areas according to word classes, but the accuracy of words longer than five characters showed no statistical differences (Naver Clova SR, 52.6%; Google Speech-to-Text, 56.3%; Amazon Transcribe, 36.6%). @*Conclusion@#Among three current cloud-based SR open APIs, Naver Clova SR which manufactured by Korean company showed highest accuracy of medical terms in Korean, compared to Google Speech-to-Text and Amazon Transcribe. Although limitations are existing in the recognition of medical terminology, there is a lot of rooms for improvement of this promising technology by combining strengths of each SR engines.

Coronavirus Disease 2019 Vaccine / 계명의대학술지

Coronavirus disease 2019 (COVID-19) vaccination is necessary to prevent infection, morbidity, and mortality. In addition to the usual post-inoculation hypersensitivity reactions including headaches, muscle and joint pain, and fever, especially after the second shot, the mRNA vaccine has risk of inflammation in the heart and heart lining of some recipients, mostly younger people. And the adenovirus vector vaccine can induce rare immune thrombocytopenia. Vaccination should be encouraged according to the information about the effectiveness and safety in individual situation.

Contrecoup Injury associated with Fatal Portal Vein Bleeding:A Case Report

A 64-year-old male visited our emergency department due to severe right flank pain after falling from a 2-meter height. Contrast-enhanced CT revealed a right hemothorax with multiple fractures in the right ribs and iliac bone. A small hematoma in the right perihepatic space was noted, but there was no hepatic laceration on CT. Initial surgical management led to continuous uncontrolled bleeding around the porta hepatis, and subsequent arterial angiography could not demonstrate a bleeding focus. However, immediate follow-up CT showed contrast extravasation on the left side of abdomen, and a percutaneous transhepatic portal venogram revealed active bleeding from the left portal vein. Although the wound was embolized with a glue, the patient suffered from a cardiac arrest and finally expired. In conclusion, during evaluation of abdominal trauma patients, portal vein bleeding and contrecoup injuries should be considered when hepatic arteriography findings are unremarkable.

Preoperative 2D-echocardiographic assessment of pulmonary arterial pressure in subgroups of liver transplantation recipients

Background@#The clinical efficacy of preoperative 2D-echocardiographic assessment of pulmonary arterial pressure (PAP) has not been evaluated fully in liver transplantation (LT) recipients. @*Methods@#From October 2010 to February 2017, a total of 344 LT recipients who underwent preoperative 2D-echocardiography and intraoperative right heart catheterization (RHC) was enrolled and stratified according to etiology, disease progression, and clinical setting. The correlation of right ventricular systolic pressure (RVSP) on preoperative 2D-echocardiography with mean and systolic PAP on intraoperative RHC was evaluated, and the predictive value of RVSP > 50 mmHg to identify mean PAP > 35 mmHg was estimated. @*Results@#In the overall population, significant but weak correlations were observed (R = 0.27; P 50 mmHg identifying mean PAP > 35 mmHg were 37.5% and 49.9%, respectively. In the subgroup analyses, correlations were not significant in recipients of deceased donor type LT (R = 0.129; P = 0.224 for systolic PAP, R = 0.163; P = 0.126 for mean PAP) or in recipients with poorly controlled ascites (R = 0.215; P = 0.072 for systolic PAP, R = 0.21; P = 0.079 for mean PAP). @*Conclusion@#In LT recipients, the correlation between RVSP on preoperative 2D-echocardiography and PAP on intraoperative RHC was weak; thus, preoperative 2D-echocardiography might not be the optimal tool for predicting intraoperative PAP. In LT candidates at risk of pulmonary hypertension, RHC should be considered.

Could real-time ultrasonography guidance be useful for the effective deployment of FemoSeal in common femoral arteriotomy?

A vascular closure device is used for hemostasis after a procedure involving an arterial puncture. The increasing frequency of endovascular arterial interventions has caused these devices to play a more important role in clinical practice. FemoSeal is a popular vascular closure device, and its safety and effectiveness have been verified. However, complications still occur in some cases, including even disastrous complications on occasion. Even with little experience, it is possible to reduce the complication rate by using real-time ultrasonography monitoring during the deployment of this device. Based on our experiences, presented herein, we suggest that complications related to FemoSeal could be reduced by using our method.

Diagnosis of Coronavirus Disease 2019 / 계명의대학술지

The first massive outbreak of coronavirus disease 2019 (COVID-19) in Korea was controlled by fast diagnosis, isolation and triage systems. The development of therapeutic agents and vaccinations are going on, but many studies clarified the nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we will discuss the characteristics and spreading of SARS-CoV-2, and prognostic factors and diagnosis of COVID-19.

Mildly Elevated Cardiac Troponin below the 99th-Percentile Upper Reference Limit after Noncardiac Surgery

Background and Objectives@#In patients with perioperative cardiac troponin (cTn) I below the 99th-percentile upper range of limit (URL), mortality according to cTn I level has not been fully evaluated. This study evaluated the association between postoperative cTn I level above the lowest limit of detection but within the 99th-percentile URL and 30-day mortality after noncardiac surgery. @*Methods@#Patients with cTn I values below the 99th-percentile URL during the perioperative period were divided into a no-elevation group with cTn I at the lowest limit of detection (6 ng/L) and a minor elevation group with cTn I elevation below the 99th percentile URL (6 ng/L < cTn I < 40 ng/L). The primary outcome was 30-day mortality. @*Results@#Of the 5,312 study participants, 2,582 (48.6%) were included in the no-elevation group and 2,730 (51.4%) were included in the minor elevation group. After propensity scorematching, the minor elevation group showed significantly increased 30-day mortality (0.5% vs. 2.3%; hazard ratio, 4.30; 95% confidence interval, 2.23–8.29; p<0.001). The estimated cutoff value of cTn I to predict 30-day mortality was 6 ng/L with the area under the receiver operating characteristic curve 0.657. @*Conclusions@#A mild elevation of cTn I within the 99th-percentile URL after noncardiac surgery was significantly associated with increased 30-day mortality as compared with the lowest limit of detection.

Coronavirus Disease 2019 (COVID-19): Pandemic and the Challenge of Public Health

Infectious diseases caused by the novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), the first outbreak in China, are currently pandemic in the world, including in Korea. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has not been proven and there has been no proper target medicine and vaccine, so it is virtually unprotected and is a serious health problem. A mitigation strategy that lowers and slows the peak of the epidemic is required to ensure efficient distribution of medical resources and time to development of therapeutic medicines and preventive vaccine. For this, close cooperation between the government and medical practitioners are required, and national prevention and prevention of the spread of the community and preparation for inflow from abroad will be required. In addition, large-scale studies on drugs including hydroxychloroquine, remdesivir, etc., which are known to be effective as therapeutic agents for COVID-19, are required to develop a vaccine for prevention. The authors hope that this review will assist primary care physicians currently engaged in patient care.

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.

Antibiotics-Induced Dysbiosis of Intestinal Microbiota Aggravates Atopic Dermatitis in Mice by Altered Short-Chain Fatty Acids

PURPOSE: Alterations in the intestinal microbiota in early life affects the development of atopic dermatitis (AD) in humans. This study aimed to further investigate the effects of gut dysbiosis in early life in an ovalbumin (OVA)-induced mouse model of AD. METHODS: The AD mouse model was developed by serial OVA sensitization and mice were treated with an antibiotic cocktail in their drinking water for 2 weeks before primary sensitization. Probiotics (Lactobacillus rhamnosus, 1 × 10⁹ CFU) or 100 µL of fresh fecal supernatant were orally administered daily from 1 week before the first sensitization until the end of the study. RESULTS: The AD mice which received antibiotics had significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. Total systemic immunoglobulin E production and skin interleukin (IL) 4 levels were significantly increased in the antibiotic-treated mice compared to the other groups. Antibiotic treatment also increased the levels of IL17 and group 3 innate lymphoid cells (ILC3) in the gut and significantly suppressed the production of short-chain fatty acids (SCFAs) and decreased the number FOXP3⁺ cells. CONCLUSIONS: Our results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4⁺IL17⁺/CD4⁺FOXP3⁺ regulatory T cells and ILC3s.

Protease-Activated Receptors 2-Antagonist Suppresses Asthma by Inhibiting Reactive Oxygen Species-Thymic Stromal Lymphopoietin Inflammation and Epithelial Tight Junction Degradation

PURPOSE: Protease-activated receptor 2 (PAR2) reportedly triggers the immune response in allergic asthma. We aimed to investigate the mechanism on allergic inflammation mediated by PAR2. METHODS: Human lung epithelial cells (A549 cells) were used for in vitro, and the German cockroach extract (GCE)-induced mouse model was developed for in vivo studies. RESULTS: In A549 cells, the levels of reactive oxygen species (ROS) and thymic stromal lymphopoietin (TSLP) were significantly increased by GCE treatment, but were suppressed by PAR2-antagonist (PAR2-ant) or N-acetylcysteine (NAC) treatment. Claudin-1 was degraded by GCE, and was restored by PAR2-ant or NAC in the cells. In the mouse model, the clinical appearance including bronchial hyperresponsiveness, bronchoalveolar lavage fluid analysis and total immunoglobulin E were significantly suppressed by PAR2-ant or NAC. Moreover, TSLP levels in the lung were suppressed by the same treatments in the lung. Claudin-1 was also degraded by GCE, and was restored by PAR2-ant or NAC. CONCLUSIONS: ROS generation and epidermal tight junction degradation are triggered by protease, followed by the induction of TSLP in allergic asthma. Our findings could suggest that PAR2-ant or anti-oxidants could be considered for allergic diseases as preventive alternatives.

Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3

Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol (0.05 μg/cm²) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of TNF-α, IL-1β, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.

Association Between Exposure to Environmental Tobacco Smoke at the Workplace and Risk for Developing a Colorectal Adenoma: A Cross-Sectional Study

PURPOSE: A colorectal adenoma (CRA) is a well-defined precursor to colorectal cancer (CRC). Additionally, smoking is a potent risk factor for developing a CRA, as well as CRC. However, the association between exposure to environmental tobacco smoke (ETS) and the risk for developing a CRA has not yet been fully evaluated in epidemiologic studies. We performed a cross-sectional analysis on the association between exposure to ETS at the workplace and the risk for developing a CRA. METHODS: The study was conducted on subjects who had undergone a colonoscopy at a health promotion center from January 2012 to December 2012. After descriptive analyses, overall and subgroup analyses by smoking status were performed by using a multivariate logistic regression. RESULTS: Among the 1,129 participants, 300 (26.6%) were diagnosed as having CRAs. Exposure to ETS was found to be associated with CRAs in all subjects (fully adjusted odds ratio [OR], 1.95; 95% confidence interval [CI], 1.08-2.44; P = 0.001). In the subgroup analysis, exposure to ETS in former smokers increased the risk for developing a CRA (fully adjusted OR, 4.44; 95% CI, 2.07-9.51; P < 0.001). CONCLUSION: Exposure to occupational ETS at the workplace, independent of the other factors, was associated with increased risk for developing a CRA in all subjects and in former smokers. Further retrospective studies with large sample sizes may be necessary to clarify the causal effect of this relationship.

Irritable Bowel Syndrome May Be Associated with Elevated Alanine Aminotransferase and Metabolic Syndrome

PURPOSE: Recent studies have revealed close relationships between hepatic injury, metabolic pathways, and gut microbiota. The microorganisms in the intestine also cause irritable bowel syndrome (IBS). The aim of this study was to examine whether IBS was associated with elevated hepatic enzyme [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], gamma-glutamyl transferase (gamma-GT) levels, and metabolic syndrome (MS). MATERIALS AND METHODS: This was a retrospective, cross-sectional, case-control study. The case and control groups comprised subjects who visited our health promotion center for general check-ups from June 2010 to December 2010. Of the 1127 initially screened subjects, 83 had IBS according to the Rome III criteria. The control group consisted of 260 age- and sex-matched subjects without IBS who visited our health promotion center during the same period. RESULTS: Compared to control subjects, patients with IBS showed significantly higher values of anthropometric parameters (body mass index, waist circumference), liver enzymes, gamma-GT, and lipid levels. The prevalences of elevated ALT (16.9% vs. 7.7%; p=0.015) and gamma-GT (24.1% vs. 11.5%; p=0.037) levels were significantly higher in patients with IBS than in control subjects. A statistically significant difference was observed in the prevalence of MS between controls and IBS patients (12.7% vs. 32.5%; p<0.001). The relationships between elevated ALT levels, MS, and IBS remained statistically significant after controlling for potential confounding factors. CONCLUSION: On the basis of our study results, IBS may be an important condition in certain patients with elevated ALT levels and MS.

Correlation Between the Severity of Diabetic Peripheral Polyneuropathy and Glycosylated Hemoglobin Levels: A Quantitative Study

OBJECTIVE: To investigate risk factors for diabetic peripheral polyneuropathy and their correlation with the quantified severity of nerve dysfunction in patients with diabetes mellitus (DM). METHODS: A total of 187 diabetic patients with clinically suspected polyneuropathy (PN) were subclassified into 2 groups according to electrodiagnostic testing: a DM-PN group of 153 diabetic patients without electrophysiological abnormality and a DM+PN group of 34 diabetic patients with polyneuropathy. For all patients, age, sex, height, weight, duration of DM, and plasma glycosylated hemoglobin (HbA1c) level were comparatively investigated. A composite score was introduced to quantitatively analyze the results of the nerve conduction studies. Logistic regression analysis and multiple regression analysis were used to evaluate correlations between significant risk factors and severity of diabetic polyneuropathy. RESULTS: The DM+PN group showed a significantly higher HbA1c level and composite score, as compared with the DM-PN group. Increased HbA1c level and old age were significant predictive factors for polyneuropathy in diabetic patients (odds ratio=5.233 and 4.745, respectively). In the multiple linear regression model, HbA1c and age showed a significant positive association with composite score, in order (β=1.560 and 0.253, respectively). CONCLUSION: Increased HbA1c level indicative of a state of chronic hyperglycemia was a risk factor for polyneuropathy in diabetic patients and a quantitative measure of its severity.

Shoulder Disease Patterns of the Wheelchair Athletes of Table-Tennis and Archery: A Pilot Study

OBJECTIVE: To investigate the shoulder disease patterns for the table-tennis (TT) and archery (AR) wheelchair athletes via ultrasonographic evaluations. METHODS: A total of 35 wheelchair athletes were enrolled, made up of groups of TT (n=19) and AR (n=16) athletes. They were all paraplegic patients and were investigated for their wheelchair usage duration, careers as sports players, weekly training times, the Wheelchair User's Shoulder Pain Index (WUSPI) scores and ultrasonographic evaluation. Shoulders were divided into playing arm of TT, non-playing arm of TT, bow-arm of AR, and draw arm of AR athletes. Shoulder diseases were classified into five entities of subscapularis tendinopathy, supraspinatus tendinopathy, infraspinatus tendinopathy, biceps long head tendinopathy, and subacromial-subdeltoid bursitis. The pattern of shoulder diseases were compared between the two groups using the Mann-Whitney and the chi-square tests RESULTS: WSUPI did not significantly correlate with age, wheelchair usage duration, career as players or weekly training times for all the wheelchair athletes. For the non-playing arm of TT athletes, there was a high percentage of subscapularis (45.5%) and supraspinatus (40.9%) tendinopathy. The percentage of subacromial-subdeltoid bursitis showed a tendency to be present in the playing arm of TT athletes (20.0%) compared with their non-playing arm (4.5%), even though this was not statistically significant. Biceps long head tendinopathy was the most common disease of the shoulder in the draw arm of AR athletes, and the difference was significant when compared to the non-playing arm of TT athletes (p<0.05). CONCLUSION: There was a high percentage of subscapularis and supraspinatus tendinopathy cases for the non-playing arm of TT wheelchair athletes, and a high percentage of biceps long head tendinopathy for the draw arm for the AR wheelchair athletes. Consideration of the biomechanical properties of each sport may be needed to tailor specific training for wheelchair athletes.

Analysis of Protrusio Acetabuli Using a CT-based Diagnostic Method in Korean Patients with Marfan Syndrome: Prevalence and Association with Other Manifestations

A new CT-based diagnostic method of protrusio acetabuli (PA) was introduced. However, prevalence of PA by this method and correlation between PA and other manifestations of Marfan syndrome (MFS) is unknown in Korean MFS patients. This study aimed to investigate the prevalence of PA diagnosed by a CT-based method in Korean patients with MFS, the association of PA with other manifestations of MFS, and the contribution of PA to MFS diagnosis. We retrospectively reviewed the records of 146 MFS patients with the presence of a causative FBN1 mutation and 146 age- and sex-matched controls from a single tertiary care center. All MFS patients underwent a complete assessment of criteria based on the revised Ghent nosology. PA was assessed quantitatively using a CT-based circle-wall distance (CWD) method. PA was diagnosed in 77.4% of patients in the MFS group and in 11.0% of the control group. CWD was significantly different between the two groups (1.50 mm vs. -0.64 mm, P<0.001). The presence of PA did not correlate with the presence of ectopia lentis, aortic root diameter, or history of aortic dissection. The presence of PA did not have a significant impact on the final diagnosis of MFS. Even though the presence of PA does not related to the cardinal clinical features of MFS or influence MFS diagnosis, its presence may be helpful for the suspicion of MFS when aortic dissection or aneurysm is found on CT angiography of the aorta because of the high frequency of PA in MFS patients.

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.