Allergen sensitization trajectories in children with respiratory and allergic diseases

Purpose@#There is a lack of a report about the trajectories of allergen sensitization, although it is important to understand the change of allergen sensitization to manage allergic disease. This study aimed to analyze the change and trajectories of allergen sensitization in children with respiratory and allergic diseases. @*Methods@#From 2006 to 2020, children with respiratory and allergic diseases or screened for allergic sensitization were evaluated. We visualized the alterations and the trajectories of allergen sensitization using stacked area graphs, box plots, and Sankey diagrams. @*Results@#A total of 2,804 subjects were included, and allergic rhino-conjunctivitis was diagnosed in 1,931 children (68.9%). The mean age for the first test was 4.1 years, and that for the second test was 6.5 years. Children sensitized to class 1 food allergen before age 5 showed sensitizations more for other allergens and at a younger age after age 5 than children who were not. The atopic tendency continued once it had been obtained before the early school age in the persistence or the new development of sensitization. @*Conclusion@#Allergen sensitization has changed over time and has shown different patterns according to age. Its trajectory has taken a wide variety of courses in children with respiratory and allergic diseases until the early school age. These changes reflect the allergic diseases and socio-environmental characteristics of children and adolescents.

A case of vocal cord dysfunction diagnosed in a 10-year-old girl with recurrent wheezing and dyspnea

Vocal cord dysfunction is one of the causes of dyspnea and is characterized by paradoxical closure of the vocal cords. The paradoxical movement of the vocal cords produces the limitation of airflow, resulting dyspnea, chest tightening, hoarseness, stridor, or wheezing. These findings are similar to those of other upper airway obstruction diseases or asthma; therefore, a high index of suspicion and clear differential diagnosis are required. Here, we discuss a case of vocal cord dysfunction aged 10 years that presented recurrent wheezing and dyspnea. The abnormal movement of the vocal cords was observed by fiberoptic laryngotracheobronchoscopy, which was correlated with stridor during respiration. Repeated episodic symptoms were controlled by the multidisciplinary team approach; however, surgical treatment was needed to stabilize the symptom.

Current practice of antibiotics skin test in pediatric inpatients:A single-center experience

Background@#Routine practice of antibiotic skin test (AST) before administering antibiotics is with little scientific basis. However, AST is frequently performed in real-world practice. We aimed to explore the current practice status of AST. @*Methods@#All admission cases in Severance Hospital between January 2019 and December 2020 of patients at less than 19 years of age were collected retrospectively. AST results for 4 penicillins (ampicillin, ampicillin-sulbactam, amoxicillin-clavulanate, and piperacillin-tazobactam) and 6 cephalosporins (cefazolin, cefotaxime, cefotiam, cefpiramide, ceftriaxone, and flomoxef) as well as adverse drug reaction (ADR) reports were collected. @*Results@#Among 36,381 hospitalization cases, 7,589 and 16,468 were administered penicillins and cephalosporins, respectively. Penicillins were administered without AST in 2,622 cases (35%), 2 (0.08%) of which showed ADR. Of the remaining 4,967 cases who received AST, 57 (1.1%) showed a positive reaction. For cephalosporins, 15,473 cases (94%) received antibiotics without AST. Among them, 17 cases (0.1%) showed ADRs. For 995 cases that rceived AST, 22 (2.2%) revealed a positive reaction. Among 79 cases who were AST positive, 10 took the original medication. @*Conclusion@#The current practice of AST reveals heterogeneous and inconsistent patterns. This brings the need for a standardized guideline for the safe and effective use of antibiotics.

Delayed Influenza Treatment in Children With False-Negative Rapid Antigen Test: A Retrospective Single-Center Study in Korea 2016–2019

Background@#We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. @*Methods@#This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016–2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. @*Results@#A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2–100.1, P< 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7–187.3/ILI patient. @*Conclusion@#Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.

Changes in allergen sensitization in children with allergic diseases in the 1980 to 2019

Purpose@#Allergen sensitization is constantly changing, and understanding these changes can help manage and prevent allergic diseases. This research analyzed and compared the changes in allergen sensitization in children diagnosed with allergic diseases using the skin test and the multiple allergen simultaneous test. @*Methods@#We retrospectively analyzed the data on children who were diagnosed with allergic diseases and received immunotherapy at Yonsei Medical Center from 1980 to 1998 and they were screened for allergen sensitization at Severance Hospital from 2005 to 2019. @*Results@#Between 1980 and 1998, and between 2005 and 2019, data on 3,205 (male, 70.3%; mean age, 7.2 ± 2.9 years) and 15,318 children (male, 62.8%; mean age, 8.8 ± 4.5 years) were analyzed. The sensitized allergens that appeared in the 1980–1998 included Dermatophagoides farinae (91.0%), Dermatophagoides pteronyssinus (76.3%), cockroach (13.5%), and Alternaria (11.5%), in order of frequency; further, the sensitized allergens that appeared in the 2005–2019 included D. farinae (45.0%), D. pteronyssinus (39.6%), cat dander (12.2%), and dog dander (9.1%), in order of frequency. D. farinae and D. pteronyssinus demonstrated the highest sensitization rates, although the rates decreased gradually. The sensitization to cat dander and dog dander showed a growing trend, and sensitization to Humulus japonicus, Candida, and cockroach decreased after 2005. @*Conclusion@#Over the past 40 years, the allergen sensitization in Korean children with allergic diseases has increased. These changes reflect lifestyle and environmental changes and influence allergic disease management approaches. Thus, changes in allergic sensitization should be monitored continuously.

Delayed-Onset Anaphylaxis Caused by IgE Response to Influenza Vaccination

Influenza vaccine-associated anaphylaxis is a very rare allergic reaction to vaccines, but the most concerning and life-threatening adverse reaction. Although the safety of influenza vaccines has been well documented, occasional cases of anaphylaxis in vaccinated patients have been reported. In this study, we analyzed the immunoglobulin E (IgE) response to whole influenza vaccines in a pediatric case of delayed-onset anaphylaxis after influenza vaccination. The patient showed elevated specific IgE levels against whole influenza vaccines, especially with split virion from egg-based manufacturing process. Specific IgE levels to influenza vaccines showed decreased over. We evaluated a causal relationship between influenza vaccine and anaphylaxis event by enzyme-linked immunosorbent assay. Delayed-onset anaphylaxis after influenza vaccination can occur in children without predisposing allergic diseases. In addition, the results suggested that formulation and production system of influenza vaccines could affect the probability of severe allergic reaction to vaccines.

Organizing pneumonia as the initial presentation of systemic lupus erythematosus in a Korean adolescent

Organizing pneumonia is characterized histologically by the formation of granulation-tissue plugs within the lumens of small airways. It was reported in association with various disorders including infection, drug reactions and collagen vascular diseases. However, there have been only a few reports on organizing pneumonia accompanied by systemic lupus erythematosus (SLE), especially in the pediatric population. Herein, we report a case of an adolescent with SLE who initially developed respiratory illnesses due to organizing pneumonia. A 14-year-old girl was referred to our clinic for protracted cough with fever, dyspnea, and hemoptysis. Her chest x-ray revealed predominant multifocal consolidations in bilateral lung fields with pleural effusion. Computed tomography scan showed patchy consolidations with surrounding ground-glass opacities and a crazy paving appearance with multiple centrilobular nodules. Laboratory tests exhibited pancytopenia, elevated blood urea nitrogen and creatinine, proteinuria, low serum levels of complements, and positivity for antinuclear antibody and anti-double-stranded DNA antibody, which were suggestive of SLE. Lung biopsy was performed to exclude the possibility of vasculitis and other mixed connective tissue diseases, which confirmed focal organizing pneumonia. Systemic steroid therapy, including high-dose methylprednisolone, was started. After the treatment, her respiratory symptoms and radiologic findings showed significant improvements. The patient has been followed up so far, and she has remined disease-free. This pediatric case of organizing pneumonia as the initial presentation of SLE alerts clinicians to consider thorough assessment of pulmonary manifestations of SLE in children.

Usefulness of bronchodilator response as an index of asthma control in children

PURPOSE: Assessing asthma control is important for proper management, and various indices for objective assessment of asthma control, such as fractional exhaled nitric oxide (FeNO) and asthma control test (ACT) score have been proposed. Recently, bronchodilator response (BDR) was reported as a marker of poor asthma control in adults. This study aimed to assess the usefulness of BDR as a biomarker for childhood asthma. METHODS: A total of 305 children diagnosed with asthma were included. Spirometry with bronchodilator test was done at the time of diagnosis and about 14 months after asthma treatment. All children were evaluated by childhood asthma control test (c-ACT) and FeNO after asthma treatment. The patients were divided into 2 groups according to BDR results: the positive and negative BDR groups. Various biomarkers for asthma control, such as c-ACT, FeNO and changes of forced expiratory volume in 1 second (FEV1), were compared between the 2 groups. RESULTS: Of the 305 patients, 143 (46.9%) were positive and 162 (53.1%) were negative for BDR. The BDR-positive group showed lower FEV1. In the BDR positive group, FEV1 was significantly increased after asthma treatment, especially in children with airflow limitation which was defined as below 80% of FEV1 or atopy. In atopic children, BDR showed a significant negative correlation with c-ACT and a positive correlation with FeNO. CONCLUSION: In asthmatic children with airflow limitation at the time of diagnosis, BDR can be a useful index for predicting improvement in lung function by asthma maintenance treatment. BDR could be a reliable marker for the assessment of asthma control in atopic children.

Prescription Patterns and Burden of Pediatric Asthma in Korea

PURPOSE: This study aimed to estimate the prevalence, prescription pattern and burden of pediatric asthma in Korea by analyzing the National Health Insurance (NHI) claims data. METHODS: We retrospectively analyzed the insurance claim records from the Korean NHI claims database from January 2010 to December 2014. Asthmatic patients were defined as children younger than 18 years, with appropriate 10th Revision of the International Classification of Diseases codes (J45 or J46) and a prescription for 1 or more asthma maintenance medications at the same date. Hospitalization and emergency department visits for asthma were defined as use of short-acting beta2-agonists during hospital visits among asthmatic patients. RESULTS: There were 1,172,807 asthmatic children in 2010, which increased steadily to 1,590,228 in 2014 in Korea. The prevalence showed an increasing trend annually for all ages. The mean prevalence by age in those older than 2 years decreased during the study period (from 39.4% in the 2–3 year age group to 2.6% in the 15–18 year age group). In an outpatient prescription, leukotriene receptor antagonists were the most commonly prescribed medication for all ages. Patients older than 6 years for whom inhaled corticosteroids were prescribed comprised less than 15% of asthmatic patients. The total direct medical cost for asthma between 2010 and 2014 ranged from $376 to $483 million. Asthma-related medical cost per person reached its peak in $366 in 2011 and decreased to $275 in 2014. CONCLUSIONS: The prevalence of pediatric asthma increased annually and decreased with age. Individual cost of asthma showed a decreasing trend in Korean children.

Effects of Vacuuming Mattresses on Allergic Rhinitis Symptoms in Children

PURPOSE: To evaluate the effects of daily vacuuming of mattresses on the concentration of house dust mite (HDM) allergens and on allergic rhinitis (AR) symptoms in children sensitized to HDM. METHODS: Forty children between the ages of 6 and 12 years with mild persistent AR and sensitized only to HDM were enrolled and randomly allocated to 2 groups. Caregivers of children in the experimental group cleaned the children's rooms and vacuumed their mattresses daily for 2 weeks. Caregivers of children in the control group cleaned the children's rooms without vacuuming mattresses. Symptoms of AR were checked weekly and dust samples were collected from the mattresses before and after the study. RESULTS: Demographics at the beginning of the study were not significantly different between the 2 groups. In the experimental group, symptoms of AR and dust weight were significantly decreased after 2 weeks (total symptoms of AR, P <0.001; sneezing, P < 0.001; rhinorrhea, P <0.001; nasal obstruction, P < 0.001; itching, P <0.001; and dust weight, P = 0.006). The concentrations of HDM allergens were not changed significantly (Der p1, P = 0.333; Der f1, P = 0.841). In the control group, there were no significant changes in symptoms of AR, dust weight, or the concentration of HDM allergens. CONCLUSIONS: Our findings showed that daily vacuuming of mattresses reduced dust weight and symptoms of AR. However, the concentration of HDM allergens did not significantly decrease.

Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis

PURPOSE: Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. METHODS: ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. RESULTS: We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4+ effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. CONCLUSIONS: These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.

Reduction Rate of Specific IgE Level as a Predictor of Persistent Egg Allergy in Children

PURPOSE: Egg is the most common food allergen in infants. However, the natural course of egg allergy has not been fully elucidated. This study aimed to describe clinical characteristics and to identify prognostic factors associated with tolerance acquisition of immunoglobulin E (IgE)-mediated egg allergy in children.

Cesarean section does not increase the prevalence of allergic disease within 3 years of age in the offsprings

OBJECTIVE: In this study, we evaluated the prevalence of allergic disease in offsprings delivered via the delivery modes of vaginal delivery vs. planned Cesarean section vs. Cesarean section with labor. METHODS: This study included 175 mother-neonate pairs from Severance Hospital who were enrolled in the Cohort for Childhood Origin of Asthma and allergic diseases study. Information regarding prenatal environmental factors, delivery, and diagnosis of allergic diseases was obtained from a questionnaire and medical record review. Patients with at least 3 years of follow-up data were included in this study. Results were adjusted for sex, birth weight, gestational age at birth, season of birth, neonatal intensive care unit admission, parity, breastfeeding, and maternal factors. RESULTS: A total of 175 offsprings were eligible for analysis. Among the subjects, 52.0% were delivered by vaginal delivery, 34.3% by planned Cesarean section, and 16.6% by Cesarean section with labor. Fifty-nine offsprings (33.7%) were diagnosed with allergic disease at a median age of 1 year (range 0.5–3 years). The prevalence of allergic disease was not associated with delivery mode after adjusting for confounding variables. Time period from membrane rupture to delivery, duration of the active phase, and the beginning of the pelvic division prior to Cesarean section were not associated with allergic disease development in offsprings. CONCLUSION: Cesarean section, irrespective of the occurrence of labor before surgery, did not increase the prevalence of allergic disease in infants up to 3 years of age.

Clinical application of the Pediatric Acute Lung Injury Consensus Conference definition of acute respiratory distress syndrome

PURPOSE: Despite improved quality of intensive care, acute respiratory distress syndrome (ARDS) significantly contributes to mortality in critically ill children. As pre-existing definitions of ARDS were adult-oriented standards, the Pediatric Acute Lung Injury Consensus Conference (PALICC) group released a new definition of pediatric ARDS. In this study, we aimed to assess the performance of PALICC definition for ARDS risk stratification. METHODS: Total 332 patients who admitted to the intensive care unit at Severance Hospital from January 2009 to December 2016 and diagnosed as having ARDS by either the PALICC definition or the Berlin definition were retrospectively analyzed. Patient characteristics and mortality rates were compared between the individual severity groups according to both definitions. RESULTS: The overall mortality rate was 36.1%. The mortality rate increased across the severity classes according to both definitions (26% in mild, 37% in moderate and 68% in severe by the PALICC definition [P<0.001]; 20% in mild, 32% in moderate and 64% in severe by the Berlin definition [P<0.001]). The mortality risk increased only for severe ARDS in both definitions (hazard ratio [95% confidence interval]: 2.279 [1.414–3.672], P=0.001 by the PALICC definition; 2.674 [1.518–4.712], P=0.001 by the Berlin definition). There was no significant difference in mortality discrimination between the 2 definitions (difference in integrated area under the curve: 0.017 [−0.018 to 0.049]). CONCLUSION: The PALICC definition demonstrated similar discrimination power on PARDS' severity and mortality as the Berlin definition.

Nutritional Intervention of a Pediatric Patient with Congenital Bronchomalacia and Gastroesophageal Reflux Disease: a Case Report

Gastroesophageal reflux disease (GERD) is closely related to respiratory issues. We reported the case about the nutrition intervention given to a male infant with congenital bronchomalacia, GERD, and recurrent pneumonia. During the first and second pediatric intensive care unit (PICU) stays, his nutrition status and nutrient intake were good. However, during the 18 days of the third PICU admission, his nutrient intake decreased to 75%–80% of his estimated calorie requirement and his Z-score for weight-for-age dropped to −1.4. We conducted nutritional interventions to improve GERD symptoms and nutritional status include avoiding overfeeding by feeding small amounts frequently, using a pre-thickened formula mixed with a high-calorie formula, and feeding through transpyloric tube. As a result, his daily nutrient intakes gradually increased and his Z-score for weight-for-age was normal. In conclusion, it is important to implement individualized intensive nutritional management to ensure adequate nutrition and growth status in infants with lung disease and GERD.

Pediatric Home Mechanical Ventilation in Korea: the Present Situation and Future Strategy

BACKGROUND: The number of children using home mechanical ventilation (HMV) has increased markedly in Europe and North America, but little is known about the situation in Korea. We described the clinical characteristics of children using HMV and investigated the current situation of HMV utilization in children. METHODS: Data on HMV prescriptions in year 2016 for children under the age of 19 was retrieved from the National Health Insurance Service for nationwide information. For more detailed information, data from year 2016 to 2018 was also retrieved from a tertiary center, Severance Children's Hospital. RESULTS: Nationwide, 416 children were prescribed with HMV in 2016, with an estimated prevalence of 4.4 per 100,000 children, of which 64.2% were male and mean age was 6-year-old. The estimated number of patients using invasive ventilators via tracheostomy was 202 (49%). Neuromuscular diseases were the most frequent cause (217; 52%), followed by central nervous system diseases (142; 34%), and cardiopulmonary diseases (57; 14%). In the tertiary center, a total of 62 children were prescribed with HMV (19 [31%] with non-invasive ventilation; 43 [69%] with invasive ventilation]. The number of children with HMV increased from 11 in 2016 to 29 in 2018. The mean age for initiation of HMV was 3.1 years and male patients comprised 65%. The most frequent diagnostic reason for HMV was central nervous system diseases (68%), followed by cardiopulmonary diseases (19%) and neuromuscular diseases (13%). Five patients died during the study period and five patients weaned from HMV. CONCLUSION: This study provides insights on the present situation of HMV utilization in Korean children.

Life-threatening Hemorrhage Caused by Mandibular Arteriovenous Malformation: A Case Report

Arteriovenous malformation (AVM) of the mandible is a rare vascular condition that can manifest as a wide range of symptoms and, on rare occasions, cause fatal hemorrhage. The symptoms of mandibular AVM can range from soft tissue swelling and tooth mobility to severe hemorrhage. The recognition of early symptoms is crucial for the prevention of a fatal hemorrhage and for the proper diagnosis and treatment of mandibular AVM. For emergency hemostasis of a ruptured mandibular AVM, manual compression with gauze, topical thrombin, absorbable hemostat, suturing the lesion, and replanting the extracted tooth is recommended. Multiple treatment options for mandibular AVM are available, such as arterial embolization, venous embolization, direct surgical closure, and bone resection. A combination of treatment options should be considered in complicated cases. We report a case of a 10-year-old girl with a previous history of telangiectasia on the right cheek presented with cardiac arrest resulting from massive bleeding immediately after a tooth extraction.

Dyspnea Perception During Induced Bronchoconstriction Is Complicated by the Inhaled Methacholine in Children With Clinical Asthma

PURPOSE: Dyspnea is not widely utilized as an indicator of asthma provocation despite its universal presentation. We hypothesized that dyspnea severity was proportionate with the lung function decline, methacholine dose-step, and the degree of bronchial hyperresponsiveness (BHR). METHODS: We retrospectively analyzed 73 children's bronchial provocation test data with an assessment of dyspnea at every dose-step. Dyspnea severity was scored using a modified Borg (mBorg) scale. A linear mixed effect analysis was performed to evaluate the relationship between the mBorg scale, the percentage fall in the forced expiratory volume in 1 second (FEV1) (ΔFEV1%), the methacholine dose-step, and the degree of BHR (BHR grade). RESULTS: Subjects were divided into 5 BHR groups based on their last methacholine dose-steps. The mBorg scores did not differ significantly among BHR groups (P=0.596, Kruskal-Wallis test). The linear mixed effect analysis showed that ΔFEV1% was affected by the methacholine dose-step (P < 0.001) and BHR grade (P < 0.001). The mBorg score was affected by the dose-step (P < 0.001) and BHR grade (P=0.019). We developed a model to predict the mBorg score and found that it was affected by the methacholine dose-step and ΔFEV1%, elevating it by a score of 0.039 (χ² [1]=21.06, P < 0.001) and 0.327 (χ² [1]=47.45, P < 0.001), respectively. A significant interaction was observed between the methacholine dose-step and ΔFEV1% (χ² [1]=16.20, P < 0.001). CONCLUSIONS: In asthmatic children, inhaled methacholine, as well as the degree of BHR and lung function decline, may affect dyspnea perception during the bronchial provocation test. If we wish to draw meaningful information from dyspnea perception, we have to consider various complicating factors underlying it.

Isolated pulmonary Langerhans cell histiocytosis in a 10-month-old infant

Langerhans cell histiocytosis (LCH) is characterized by clonal proliferation and accumulation of abnormal dendritic (Langerhans) cells in various organs. Pulmonary involvement, although rare in children, has been reported in 20%–50% of childhood cases of multisystem LCH. Isolated pulmonary LCH in children, especially in infants, is still rarer, but should be suspected in those with cystic lung disease. We report a case of a 10-month-old boy who presented with chronic dyspnea and whose chest computed tomography (CT) scan demonstrated cystic lesions. Lung biopsy established the diagnosis of LCH; microscopy revealed a background of lymphocytes and eosinophils with kidney-shaped abnormal cells. These abnormal cells were positive for S-100, CD207 (Langerin), and CD1a on immunohistochemical staining. Chemotherapy was administered using a cytotoxic agent (vinblastine) and a steroid. After 12 weeks of induction chemotherapy, although no significant change in cyst size was noted on chest CT, clinical symptoms improved. Consolidation chemotherapy was then administered for 1 year. Thereafter, chest CT findings demonstrated a significant decrease in cyst size and a significant increase in the volume of normal lung parenchyma. Therefore, aggressive treatment of isolated pulmonary LCH in infants with severe tissue destruction and symptoms seems warranted.

German Cockroach Extract Induces Matrix Metalloproteinase-1 Expression, Leading to Tight Junction Disruption in Human Airway Epithelial Cells

PURPOSE: Cockroach exposure is a pivotal cause of asthma. Tight junctions are intercellular structures required for maintenance of the barrier function of the airway epithelium, which is impaired in this disease. Matrix metalloproteinases (MMPs) digest extracellular matrix components and are involved in asthma pathogenesis: MMP1 is a collagenase with a direct influence on airway obstruction in asthmatics. This study aimed to investigate the mechanism by which German cockroach extract (GCE) induces MMP1 expression and whether MMP1 release alters cellular tight junctions in human airway epithelial cells (NCI-H292). MATERIALS AND METHODS: mRNA and protein levels were determined using real-time PCR and ELISA. Tight junction proteins were detected using immunofluorescence staining. Epithelial barrier function was measured by transepithelial electrical resistance (TEER). The binding of a transcription factor to DNA molecules was determined by electrophoretic mobility shift assay, while the levels of tight junction proteins and phosphorylation were determined using Western blotting. RESULTS: GCE was shown to increase MMP1 expression, TEER, and tight junction degradation. Both an inhibitor and small interfering RNA (siRNA) of MMP1 significantly decreased GCE-induced tight junction disruption. Furthermore, transient transfection with ETS1 and SP1 siRNA, and anti-TLR2 antibody pretreatment prevented MMP1 expression and tight junction degradation. An extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor also blocked MMP1 release, ETS1/SP1 DNA binding, and tight junction alteration. CONCLUSION: GCE treatment increases MMP1 expression, leading to tight junction disruption, which is transcriptionally regulated and influenced by the ERK/MAPK pathway in airway epithelial cells. These findings may contribute to developing novel therapeutic strategies for airway diseases.