• Tuberculosis and Respiratory Diseases
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• v.87 no.3
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• pp.329-337
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• 2024

Background: Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. Methods: We retrospectively analyzed 107 COPD patients without a history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion (ppb) were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. Results: The median FeNO value was 32 ppb (interquartile range, 19 to 45) and 34 (20.0%) patients were classified as high FeNO group (median 74 ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥300 cells/µL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01 to 6.91; p=0.049). Conclusion: High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

• Toxicological Research
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• v.21 no.2
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• pp.151-160
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• 2005

In order to monitor the histological and general profiles of lung after direct expose of p,p-DDE, 1, 5 and 10 mg/ml of p,p-DDE were sprayed to male ICR mouse, and seven days after exposure, changes of body weight, lung weight, clinical signs, histological profiles of lung and total WBC in blood were investigated with changes of total cell number and their differential count in bronchoalveolar lavage fluid (BALF). In the present study, a significant and dosage-dependent decrease of body weight was detected in p,p-DDE exposed groups and body weight gains during observational periods (7 days) were also significantly and dosage-dependently decreased in p,p-DDE exposed groups compared to that of vehicle control group. In addition general depression signs were detected in all p,p-DDE exposed groups with dosage-dependent manners, and lung weights were also increased in p,p-DDE exposed groups. Congestion, hemorrhage and severe exudate were observed in the lung of p,p-DDE exposed groups with sarcomatous changes and these signs were also showed by dosage-dependent manners. In addition, foreign body pneumonia signs were observed in the lung of p,p-DDE exposed groups in histological levels. The percentage of ALSA (Area of luminal surface of alveoli) was also significantly and dosage-dependently decreased in p,p-DDE exposed groups and total blood WBC and BALF cell numbers were significantly and dosage-dependently increased in p,p­DDE exposed groups compared to that of vehicle control group and increase percentage of neutrophil, eosinophil, and lymphocyte in BALF were monitored in p,p-DDE exposed groups compared to that of vehicle control group. In conclusion, severe allergic response and/or foreign body pneumonitic changes were induced by direct exposure of p,p-DDE containing beverage. So it is considered that strong and powerful regulation was need to control production of residence of environmental pollutant especially to p,p-DDE.

• Korean Journal of Clinical Pharmacy
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• v.11 no.1
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• pp.19-29
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• 2001

Teicoplanin, a glycopeptide antibiotic, has potential for use as an alternative to vancomycin in the treatment of gram-positive bacterial infections. However, unlike vancomycin, there is a lack of study on teicoplanin's efficacy and safety and the guideline for its use is not available, yet. The objective of this study was to investigate and evaluate the pattern of teicoplanin usage in a university hospital. A retrospective study was performed on 72 adult patients, who took teicoplanin for 3 continuous days at D. University hospital from 1 January 1999 to 30 June 2000. The microorganisms treated with teicoplanin were methicillin-resistant Staphylocorcus aureus $(69\%)$, coagulase-negative Staphylococci $(12\%)$, Enterococcus $(4\%)$, vancomycin-resistant Enterococci $(2\%)$, Streptococci $(2\%)$, and Bacillus $(1\%)$. The types of infection treated with teicoplanin were surgical wound infection $(58\%)$, lower respiratory infection $(11\%)$, bactremia $(7\%)$, urinary tract infection $(5\%)$, pleural fluid infection $(4\%)$, and peritoneal fluid infection $(2\%)$. The mean duration of teicoplanin usage was 16.5 days and teicoplanin was used with 1.4 other antibiotics, which were aminoglycosides (isepamicin, amikacin, netilmicin, astromicin) or quinolones (ciprofloxacin, tosufloxacin) or the third generation cephalosporin (ceftazidime). Only 24 cases $(28.6\%)$ met with the criteria for the justification of use, and the rest of 60 cases $(71.4\%)$ did not meet the criteria. In 84 cases $(100\%)$, blood culture tests were performed prior to the initial dose of teicoplanin. In 83 cases $(99\%)$, serum creatinine were conducted before the initial doses. In 45 cases $(53.6\%)$, serum creatinine was monitored at least twice weekly. In 55 cases $(65.5\%)$, WBC was tested at least twice weekly. In 84 cases $(100\%)$, body temperature was monitored at least once per nursing shift. In 15 cases out of 56 cases, maximum temperature decreased at least 1 degree within 3 days of teicoplanin use. In 15 case out of 35 cases, WBC values were within the normal range after treatment. In 23 cases $(27.4\%)$, dosage regimen was appropriate. Drug-related adverse effects were reported in 13 cases. Nephrotoxicity (progressively increasing SCr. or sustained SCr increase of $\geq$0.5 mg/dl from baseline) was noted in five cases. Neutropenia (absolute neutrophil count <1,500 $cells/mm^3$) was noted in one case and eosinophilia (total eosinophil count >350 $cells/mm^3$) was noted in seven cases. A more strict control on use of teicoplanin is required, considering that teicoplanin is categorized as one of restricted antibiotics.

• Clinical and Experimental Pediatrics
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• v.54 no.9
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• pp.373-379
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• 2011

Purpose: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, $IgG_1$, and $IgG_{2a}$ levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific $IgG_1$ levels and increased serum $IgG_{2a}$ level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

• Clinical and Experimental Pediatrics
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• v.58 no.3
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• pp.96-101
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• 2015

Purpose: Atopic dermatitis (AD) is a chronic inflammatory relapsing skin disorder. Vitamin D plays a pivotal role in the development of AD, and interleukin (IL) 31 is known to be related to pruritus in AD. The aim of our study was to determine whether 25-hydroxyvitamin D (25(OH)D) levels are related to IL-31 levels or to the severity of AD. Methods: We enrolled 91 children with AD and 32 control subjects without history or symptoms of allergic diseases. Blood was drawn to evaluate complete blood cell count, total eosinophil count (TEC), and total IgE, specific IgE to common allergens, 25(OH)D, and IL-31 levels. Serum 25(OH)D and IL-31 levels were measured using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. The scoring atopic dermatitis (SCORAD) index was used to evaluate the severity of AD. Results: The mean 25(OH)D level was significantly lower in the AD group than in the control group; 25(OH)D decreased greatly in the moderate and severe AD groups compared with the mild AD group. Children with atopic sensitization showed significantly lower 25(OH)D levels than nonatopic children. However, serum IL-31 levels were not related to AD group, SCORAD index, or 25(OH)D levels. The SCORAD index was inversely correlated with serum 25(OH)D level and positively correlated with TECs and total IgE levels. Children with moderate and severe AD had significantly higher TECs than children with mild AD. Conclusion: Vitamin D is related to the severity of AD independently of IL-31.

• Parasites, Hosts and Diseases
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• v.61 no.1
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• pp.60-71
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• 2023

Cockroaches can cause allergic sensitization in humans via contact with their feces or frass. Antibiotics can affect concentration of major allergen and total bacteria production in German cockroaches (Blattella germanica). This study examined the ability of antibiotic-treated German cockroaches to induce allergic airway inflammation and the effect of antibiotics on their lipopolysaccharide and Bla g1, 2, and 5 expression levels. Specifically, we measured the ability of German cockroach extract (with or without prior antibiotic exposure) to induce allergic inflammation in human bronchial epithelial cells and a mouse model of asthma. Bacterial 16S rRNA and lipopolysaccharide levels were lower in ampicillin-treated cockroaches than in the control group. The Bla g1, Bla g2, and Bla g5 expression in ampicillin-treated cockroaches decreased at both the protein and RNA levels. In human bronchial epithelial cell lines BEAS-2B exposed to the ampicillin-treated extract, expression levels of interleukin-6 and interleukin-8 were lower than that in the control group. The total cell count and eosinophil count in bronchoalveolar lavage fluid was also lower in mice exposed to the ampicillin-treated extract than in those exposed to normal cockroach extract. Mouse lung histopathology showed reduced immune cell infiltration and mucus production in the ampicillin group. Our results showed that ampicillin treatment reduced the symbiont bacterial population and major allergen levels in German cockroaches, leading to reduced airway inflammation in mice. These results can facilitate the preparation of protein extracts for immunotherapy or diagnostics applications.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.298-304
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• 2006

Purpose : We compared the asthma predictive index(API) and the modified asthma predictive index (mAPI) of the Tuscon Children's Respiratory Study Group in Korean children with recurrent wheezing. We investigated the atopic profiles and presence of allergen sensitization of each risk group, and ascertained the significant clinical risk factors. Methods : Two hundred and sixty two children, who visited for recurrent wheezing from 1998 to 2005, were enrolled and divided into groups by API and mAPI. We investigated the history of the patients and their families, atopic profiles, and sensitization to aeroallergen and food allergens. Twenty nine children were followed up to 6 years of age and we evaluated the sensitivity, specificity and positive and negative predictive value of both indices. Results : The high risk group of API were of older age, were more likely to be sensitized to aeroallergen(P=0.001) and food allergen(P=0.034) and had higher levels of total eosinophil count, eosinophil percent, serum ECP, total IgE, and D.p-, D.f-specific IgE. High risk group of mAPI showed higher levels of atopic markers such as egg-, milk-, D.p- and D.f-specific IgE. Even though API did not include allergen sensitization, the high risk group was more significantly sensitized to common allergens than the low risk group. Twenty nine children were followed up until 6 years of age; therefore 15 children were diagnosed as asthma, clinically. The sensitivity, specificity, positive and negative predictive values of mAPI were higher than API. Conclusion : Both high risk groups of API and mAPI had higher levels of atopic markers and were more sensitized to common allergens. These findings suggest that sensitization to aeroallergens and food allergens are more objective markers as asthma predictive indices. In addition, mAPI is a more reliable index in predicting asthma in Korean children with recurrent wheezing than is API. But only 29 patients were followed until the age of 6, so we need to include more children with long term follow up for future study.

• Clinical and Experimental Pediatrics
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• v.51 no.5
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• pp.487-491
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• 2008

Purpose : Although Mycoplasma pneumoniae (M. pneumoniae) infection can cause wheezing in non-asthmatic children, the mechanisms of this symptom remain unclear. Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and vascular permeability, and is also known to be elevated in cases of chronic pulmonary disease such as asthma. We hypothesized that VEGF may increase in children with acute M. pneumoniae pneumonia and wheezing. Methods : Nine patients with clinical and laboratory evidence of acute M. pneumoniae pneumonia were enlisted from children admitted to Korea University Hospital. They had had more than one episode of wheezing during the illness, which was confirmed by a physician; they comprised the wheezer group. The individuals with M. pneumoniae pneumonia without wheezing were 63 in number, and they comprised the non-wheezer group. Patients with a history of asthma or who had received asthma medications were excluded. Serum concentrations of VEGF, total IgE, eosinophil cationic protein (ECP), and peripheral blood eosinophil counts were measured. Results : The serum VEGF concentrations were higher in the wheezer group ($mean{\pm}SD$; $650.2{\pm}417.9pg/mL$) than in the non-wheezer group ($376.5{\pm}356.2pg/mL$, P=0.049). M. pneumoniae antibody (1:1,380 vs. 1:596, P=0.048) and serum total IgE (591.8 IU/mL vs. 162.2 IU/mL, P=0.032) were higher in the wheezer group than in the non-wheezer group. There were no differences between the two groups in terms of serum ECP concentration or blood eosinophil count. Conclusion : In the presence of wheezing, serum VEGF concentrations were higher in the children with M. pneumoniae pneumonia. This finding suggests that VEGF may associate with wheeze-related symptoms in children with acute M. pneumoniae pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.63 no.3
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• pp.235-241
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• 2007

Background: Airway mucus hypersecretion plays an important role in the pathogenesis of asthma, and is associated with the induction of MUC5AC expression in airway secretion. The MUC5AC gene is highly polymorphic; however, there are few studies about the association between the polymorphisms of the MUC5AC gene and asthma susceptibility or asthma phenotypes. We have investigated the association of MUC5AC promoter polymorphisms with the risk of asthma and asthma phenotypes. Methods: We determined the genotypes of the MUC5AC promoter (-1274G>A) in 78 asthma patients and in 78 age, sex-matched control individuals in the Korean population. Genomic DNAs from blood were analyzed by PCR and RFLP (restriction fragment length polymorphism) determination. We examined $FEV_1$, total eosinophil count, serum IgE level, $PC_{20}$ and the presence of atopy (by a skin test) in asthma patients. Results: The mean age of the patients was $47.7{\pm}16.1$ years and 38.5% were men, and the mean $FEV_1$ was $84.4{\pm}22.3%$ of predicted in the asthma patients. The -1274G>A polymorphism of the MUC5AC promoter in asthma patients was not significantly different as compared with normal individuals (GG 57.7%, AG 34.6% and AA 7.7% in asthma patients vs. GG 56.4%, AG 38.5% and AA 5.1% in control subject, p = 0.752, Cod). Several clinical parameters in asthma patients such as $FEV_1$, total eosinophil count, serum IgE level, $PC_{20}$ and the presence of atopy, were not associated with the -1274G>A polymorphism of the MUC5AC promoter. Conclusion: The -1274G>A single nucleotide polymorphism (SNP) frequency of the MUC5AC promoter was not associated with asthma in a Korean population.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.221-227
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• 2006

Background : Cough may be a consequence of bronchial hyperresponsiveness or inflammation. Empirical treatment is important in this context because it difficult to verify the obvious cause of cough using laboratory tests, Corticosteroid has a nonspecific anti-inflammatory effect, and can be used for cough management. However, its response rate has not yet been fully elucidated. This study investigated the short- term effects of inhaled corticosteroid on chronic cough Methods : Patients with chronic cough with a normal chest radiograph and a pulmonary function test were enrolled. Cases with a prior respiratory infection within 8 weeks, a history of bronchial asthma, objective wheezing on examination, subjective symptoms of gastroesophageal reflux or taking an ACE inhibitor were excluded. On the first visit, a methacholine bronchial provocation test, spontaneous sputum eosinophil count performed twice and a paranasal sinus radiograph were checked, and the patients were treated with budesonide turbuhaler $800{\mu}g/day$ for ten days. The primary outcome measure was a decrease in the cough score after treatment. Results : Sixty nine chronic coughers were finally analyzed. The final diagnoses by the routine tests were as follows: bronchial asthma 13.0%, eosinophilic bronchitis 18.8%, paranasal sinusitis 23.2% and non-diagnostic cases 53.6%. The following responses to the inhaled corticosteroid were observed: definite responders, 76.8%, possible responders, 2.9% and non-responders, 20.3%. The response rate was not affected by the final diagnosis even in the non-diagnostic cases. There were minimal adverse drug related effects during the empirical treatment. Conclusion : Routine objective tests such as methacholine provocation, sputum eosinophil count and simple radiographs were notare not suitable for diagnosing chronic cough Therefore, empirical treatment is important. Short term inhaled corticosteroid is effective and can guide a further treatment plan for chronic cough.