Dae Hyun Lim

Humidifier Disinfectant–associated Children’s Interstitial Lung Disease

RATIONALE Beginning in 2006, epidemics of a fatal lung injury of unknown cause in children were observed in Korea every spring. A recent study demonstrated that this type of childrens interstitial lung disease (chILD) is associated with humidifier disinfectant use. OBJECTIVES To determine the clinical characteristics of this type of chILD and to assess whether the nationwide suspension of humidifier disinfectant sales in the autumn of 2011 affected its incidence. METHODS The clinical characteristics of suspected cases between 2006 and 2011 were determined by a nationwide retrospective study. The potential causal relationship with humidifier disinfectants was examined by a prospective surveillance study after humidifier disinfectant sales were suspended. MEASUREMENTS AND MAIN RESULTS In total, 138 children were diagnosed with this type of chILD, which was characterized by rapid progression, high mortality, predominance in the spring season, and a familial tendency. The annual incidence increased in 2011 and then dropped to zero in 2012. The children were on average 30.4 months old. The most frequent symptoms at admission were cough and dyspnea. As the disease progressed, the typical complication was spontaneous air leak. Eighty children (58%) died. Two years after humidifier disinfectant-sale suspension, no more new cases were found. CONCLUSIONS This study suggests that humidifier disinfectant inhalation causes an idiopathic type of chILD that is characterized by spontaneous air leak, rapid progression, lack of response to treatment, and high mortality. Further safety studies must be performed on common environmental compounds, particularly those that enter the human body by an unusual route.

Beneficial Effect of Anti-Interleukin-33 on the Murine Model of Allergic Inflammation of the Lower Airway

Objective. Interleukin (IL)-33, which mediates the Th2 allergic pathway, may play a key role in allergic airway inflammation. This study was conducted to evaluate the therapeutic potential of anti-IL-33 antibody for treatment of allergic inflammation of the lower airway in a murine model. Methods. Twenty-four BALB/c mice were used in this study. Saline was used for sensitization and challenge of mice in Group A (control group, n = 6). Mice in Group B (ovalbumin (OVA) group, n = 6) received intraperitoneal (ip) and intranasal OVA challenge. In Group C (control IgG group, n = 6), mice received ip injection with control IgG prior to OVA challenge. Mice in Group D (anti-IL-33 group, n = 6) received an ip injection of anti-IL-33 prior to challenge. Measurements of serum total and OVA-specific IgE and the number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid were performed. We performed histopathologic examination to evaluate the degree of eosinophilic infiltration in lung tissue. Airway hyperreactivity was measured according to change of enhanced pause (Penh). Results. A significant decrease in serum total and OVA-specific IgE and the number of eosinophils and neutrophils in BAL fluid was observed in Group D, compared with Group B or Group C (p < .05). In Group D, treatment with anti-IL-33 resulted in a significant decrease in eosinophilic infiltration in lung tissue, compared with Group B and Group C (p < .05). Degree of airway hyperreactivity, measured by Penh, showed a significant decrease in the anti-IL-33 treatment group, compared with the OVA group or the control IgG treatment group (p < .01, at 50 mg/mL of methacholine). Conclusions: Anti-IL-33 has therapeutic potential for treatment of allergic inflammation of the lower airway.

Sensitization rates of airborne pollen and mold in children

Purpose Aeroallergens are important causative factors of allergic diseases. Previous studies on aeroallergen sensitization rates investigated patients groups that had visited pediatric allergy clinics. In contrast, we investigated sensitization rates in a general population group of elementary school to teenage students in Incheon, Jeju, and Ulsan. Methods After obtaining parental consent, skin-prick tests were performed on 5,094 students between March and June 2010. Elementary school students were tested for 18 common aeroallergens, whereas middle and high school students were tested for 25 allergens. The 25 allergens included Dermatophagoides pteronyssinus, Dermatophagoides farinae, pollen (birch, alder, oak, Japanese cedar, pine, willow, elm, maple, Bermuda grass, timothy grass, rye grass, orchard grass, meadow grass, vernal grass, mugwort, Japanese hop, fat hen, ragweed, and plantain), and mold (Penicillatum, Aspergillus, Cladosporium, and Alternaria). Results The sensitization rates in descending order were 25.79% (D. pteronyssinus), 18.66% (D. farinae), 6.20% (mugwort), and 4.07% (willow) in Incheon; 33.35% (D. pteronyssinus), 24.78% (D. farinae), 15.36% (Japanese cedar), and 7.33% (Alternaria) in Jeju; and 32.79% (D. pteronyssinus), 30.27% (D. farinae), 10.13% (alder), and 8.68% (birch) in Ulsan. The dust mite allergen showed the highest sensitization rate among the 3 regions. The sensitization rate of tree pollen was the highest in Ulsan, whereas that of Alternaria was the highest in Jeju. The ragweed sensitization rates were 0.99% in Incheon, 1.07% in Jeju, and 0.81% in Ulsan. Conclusion The differences in sensitization rates were because of different regional environmental conditions and distinct surrounding biological species. Hence, subsequent nationwide studies are required.

Allergen Specific IgE Measurement with Polycheck Allergy: Comparison of Three Multiple Allergen Simultaneous Tests

BACKGROUND The in vivo skin prick test (SPT) or in vitro detection of allergen specific IgE in serum is commonly used for the diagnosis of allergic disease. In this study, we evaluated the usefulness of a new multiple allergen simultaneous test (MAST) immunoblot assay, Polycheck Allergy (Biocheck GmbH, Germany). METHODS A total of 100 patients with clinical findings of allergic diseases were tested by SPT and three different MAST assays: Polycheck Allergy (Biocheck GmbH, Germany), MAST CLA allergy system (Hitachi Chemical Diagnostics, USA) and Allergy Screen (R-biopharm, Germany). The results of MAST assays were compared with those of SPT. RESULTS Concordance rates of MAST assays with SPT were 79-100% for Polycheck Allergy, 88.9-100% for MAST CLA and 72.7-98.3% for Allergy Screen. In ROC curve analysis, significant differences were observed in four of 25 allergens analysed: Alternaria, Birch, Hazelnut and D. farinae. For Alternaria and Birch, Polycheck Allergy (P<0.001) and Allergy Screen (P=0.0075) showed significantly larger AUC (area under the curve) than MAST CLA. For Hazelnut, Polycheck Allergy (P=0.0021), and for D. farinae, MAST CLA (P=0.015) showed significantly larger AUCs than the other two tests. The ROC analysis for overall 16 food allergens showed better results in Polycheck Allergy (P<0.001), and that for overall 21 inhalants did not show significant differences among three MAST assays (P>0.05). CONCLUSIONS Since Polycheck Allergy showed similar or superior result to the others, it can be used for the detection of allergen specific IgE antibodies.

Comparison of air pollution and the prevalence of allergy-related diseases in Incheon and Jeju City

Purpose A high level of air pollutants can increase the number of patients with allergy-related diseases such as asthma and allergic rhinitis (AR). To analyze the association between air pollution and allergic disease, we investigated 2 areas in Korea: Incheon, an industrial area, and Jeju, a non-industrialized area. Methods Second grade students at elementary schools (11 schools in Incheon and 45 schools in Jeju) were examined in a cross-sectional study. A questionnaire was used and a skin prick test was performed. The levels of NO2, CO2, O3, particulate matter (PM) PM10/2.5, formaldehyde, tVOCs, and dust mites in the classrooms and grounds were determined. Results The levels of outdoor CO, PM10, and PM2.5 were significantly higher in Incheon (P<0.01). The levels of indoor CO, CO2, PM10, PM2.5 were significantly higher in Incheon (P<0.01). The prevalence rates of AR symptoms at any time, AR symptoms during the last 12 months, diagnosis of rhinitis at any time, and AR treatment during the last 12 months were significantly higher in Incheon (P<0.01). The prevalence rate of wheezing or whistling at any time, and wheezing during the last 12 months were significantly higher in Incheon (P<0.01). Conclusion We found that the children living in Incheon, which was more polluted than Jeju, had a higher rate of AR and asthma symptoms compared to children in Jeju. To determine the effect of air pollution on the development of the AR and asthma, further studies are needed.

Relationship between silent gastroesophageal reflux and food sensitization in infants and young children with recurrent wheezing.

It is known that early childhood wheezing associated with sensitization to allergens, including food, has an increased risk of developing asthma later during school age. Gastroesophageal reflux (GER) is well known to be associated with asthma. The purpose of this study was to determine whether there is an association between silent GER and food sensitization in infants and young children with recurrent wheezing. Eighty-five infants or young children with recurrent wheezing, and no gastrointestinal symptoms, underwent 24 hr esophageal pH monitoring, as well as total serum IgE and specific IgE testing for eggs and milk. Among the 85 subjects, 48.2% had significant GER. There was no significant difference in the GER between atopic and non-atopic recurrent wheezers (41.7% and 50.8%, respectively). The sensitization rate to food (eggs or milk) was 12.2% and 20.5% in the GER and non-GER groups, respectively and showed no statistically significant difference between the two groups (P=0.34). In conclusion, about half of infants and young children with recurrent wheezing and no gastrointestinal symptoms have silent GER. The silent GER may not contribute to food sensitization in infants and young children with recurrent wheezing.

Prevalence and allergen of allergic rhinitis in Korean children.

Background In recent decades, the amount of data about allergic rhinitis (AR) in Korean National Health Insurance Service has increased. Objective To investigate the prevalence and quality of sensitized allergens of AR in Korean children and adolescents. Methods This study obtained the results of the Korean International Study of Asthma and Allergies in Childhood questionnaires and the skin-prick test (SPT) results of 14,356 students who participated in a health screening from 2010 to 2014. AR was defined as one with current symptoms of AR with at least one or more positive results of an SPT with inhalant allergens. Results The prevalence of AR in children was 20.8%. Positive rates of the allergen group were 87.3% for house-dust mites, 37.0% for pollen, 12.4% for mold, and 8.4% for pets. The common allergens in descending order were Dermatophagoides pteronyssinus, Dermatophagoides farinae, Betula, Humulus, Alnus, and Alternaria. As the children became older, pollen-sensitization rates tended to increase (p value for trends, <0.001). In metropolitan and middle inland areas, weed pollen was the most common pollen. The rates of tree-pollen sensitization were the highest at the seaside and in the southern inland. The most common comorbid allergic diseases associated with AR were pollen allergy and allergic conjunctivitis at 37.0% and 34.5%, respectively. Conclusions This was the first study conducted in Korea to investigate the prevalence of AR in the general population by using both questionnaires and SPTs. The allergens used for the SPTs were chosen based on the common allergens in this study, and this current pollen data will contribute to establish the cause of increasing AR prevalence in Korea.

Development of a Questionnaire for the Assessment of Quality of Life in Korean Children With Allergic Rhinitis

Purpose Korean children have their own unique lifestyle based on their living environment and culture. This study aimed to develop a questionnaire to evaluate the quality of life in Korean children with allergic rhinitis. Methods After a preliminary survey, an initial questionnaire was developed. Questions were modified to be easily understood by young children aged 6 to 7 years. The modified questionnaire was tested on children aged 6 to 12 years old. Item scores, defined as the proportion of children whose answer score was 1 point or higher was multiplied by the average answer score of each question, were used to identify questions that have practical application to the quality of life in Korean children with allergic rhinitis. Differences in answer scores between children with allergic rhinitis and those who were healthy were assessed by a Wilcoxon rank-sum test. The relationship between nasal index scores and quality of life scores was determined by a Spearman rank order test. Results An initial questionnaire was composed of 21 items. We identified 19 questions with item scores above 0.5 in children with allergic rhinitis, many of which were related to nasal symptoms and 10 questions that were different between the allergic rhinitis group and the control group. The final questionnaire included the 10 questions that had both high item scores and a significant difference in the answer scores between the two groups. Conclusions The developed questionnaire is essential and practical for assessing discomfort related to the symptoms felt by Korean children with allergic rhinitis.

Antiallergic effect of anti-Siglec-F through reduction of eosinophilic inflammation in murine allergic rhinitis

Background Sialic acid-binding Ig-like lectin-F (Siglec-F) in mice and its functional paralog Siglec-8 in humans are transmembrane receptors that play a role in the apoptosis of eosinophils. We aimed to evaluate the therapeutic potential of anti-Siglec-F antibodies in a murine model of allergic rhinitis. Methods Twenty-eight BALB/c mice were used. In group A (control group, n = 7), mice were sensitized and challenged with saline. In group B (ovalbumin [OVA] challenge group, n = 7), OVA was used for i.p. sensitization and intranasal challenge. Mice in group C (control IgG group, n = 7) or those in group D (anti-Siglec-F group, n = 7) had been given rabbit control IgG or anti-Siglec-F antibody injections, respectively. We assessed the number of nose-scratching events; serum total/OVA-specific IgE; the number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathological changes in nasal cavity tissues; and the levels of IL-4, IL-5, and IL-13 in BAL fluid. Results Mice in group D had significantly less nose scratching. Serum total and OVA-specific IgE were not significantly changed. The number of eosinophils in BAL fluid and in the lamina propria of the nasal cavity mucosa was significantly decreased with anti-Siglec-F antibody treatment. The levels of Th2 cytokines such as IL-4, IL-5, and IL-13 were also significantly decreased with anti-Siglec-F antibody treatment. Conclusion Anti-Siglec-F antibody has beneficial effects in a mouse model of experimental allergic rhinitis.

A Case of Acute Hepatitis with Mycoplasma pneumoniae Infection and Transient Depression of Multiple Coagulation Factors

We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M. pneumoniae) infection and transient depression of multiple coagulation factors. A 5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae infection was confirmed by serology testing. Liver enzymes were elevated on admission without any past medical history. After treatment with azithromycin for 3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial thromboplastin time (PTT) was prolonged and depression of multiple coagulation factors developed. Liver biopsy revealed features consistent with acute hepatitis. A week later, liver enzymes were nearly normalized spontaneously. Normalization of prolonged PTT and coagulation factors were also observed several months later. This may be the first case of transient depression of multiple coagulation factors associated with M. pneumoniae infection.