• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.529-535
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• 1998

Background: Interleukin-4 plays an important role in pathogenesis of asthma, especially in developing atopy by means of switching B lymphocytes to produce IgE. It has been shown that there is polymorphism in the Interleukin-4 promoter region, transversion of cytosine to thymine at-598 from translation initiation site of IL-4 gene. There has also been quite a few works to reveal the role of the polymorphism of IL-4 gene in patients with asthma. We performed this investigation to determine the role of the polymorphism in the severity of symptoms of patients with asthma. We also examined the frequency and the type of the polymorphism in asthmatics compared with non-asthmatics as well. Method: The subjects enrolled in this study were 49 asthmatics and 33 non-asthmatics. All the asthmatics were classified as mild and moderate to severe by the NHLBI/WHO Workshop. DNA from both asthmatics and non-asthmatics was extracted, then performed ARMS(Amplification Refractory Mutation System) as well as RFLP using BsmFl restriction enzyme in order to confirm the polymorphism of Il-4 gene. Results: There was no significant difference in the occurrence of polymorphism of the IL-4 promoter sequence between asthm and non-asthma groups(P=0.7). Among those with polymorphisms, the number of C/C type was slightly more than C/T type in both asthmatics and non-asthmatics, 26 vs 21 in asthmatics and 18 vs 15 in non-asthmatics, which was, however, insignificant statistically. No significant relationship between the severity of asthma and the polymorphism was found(P=0.7). Conclusion: There was no significant difference between the severity of asthma and the IL-4 promoter polymorphism(P=0.709). Interestingly, the frequency of the polymorphism in both asthmatics as well as non-asthmatics was found to be even higher than that occurred in Caucasians. However, no significant difference in the frequency of the polymorphism was found in both groups.

• Tuberculosis and Respiratory Diseases
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• v.51 no.1
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• pp.35-43
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• 2001

Background : The eosinophil chemotactic and activating effects of eotaxin and the known association of eosinophils with asthma suggest that eotaxin expression is increased during an asthma attack. This study was aimed to determine whether the plasma eotaxin levels are higher in patients during an asthma attack and to correlate the eotaxin levels with the disease activity, severity and response to therapy. Method : A case-control study of the plasma eotaxin levels was performed in 100 patients with exacerbated asthma and 48 age- and sex-matched subjects with stable asthma. Results : The plasma eotaxin levels were significantly higher in the 100 patients with exacerbated asthma($233{\pm}175\;pg/mL$) than in the 48 subjects with stable asthma($169{\pm}74\;pg/mL$). A trend toward higher eotaxin levels was observed in asthmatic subjects who were taking oral steroids ($332{\pm}225\;pg/mL$) than in those who were not ($214{\pm}159\;pg/mL$) and higher levels were found in those admitted to the hospital ($275{\pm}212\;pg/mL$) than in those discharged after receiving only emergency treatment ($190{\pm}115\;pg/mL$). The eotaxin levels inversely correlated with the $FEV_$ (r=-0.25, p<0.01). The eotaxin levels were higher in moderate persistent ($323{\pm}256\;pg/mL$) and severe persistent asthmatics ($276{\pm}170\;pg/mL$) than in mild intermittent asthmatics ($l60{\pm}60\;pg/mL$). Conclusion : Eotaxin expression is directly associated with asthma exacerbation, impaired pulmonary function and the disease severity.

• Clinical and Experimental Pediatrics
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• v.49 no.9
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• pp.977-982
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• 2006

Purpose : There has been an increasing amount of literature concerning the association between Mycoplasma pneumoniae and asthma pathogenesis. Interleukin(IL)-6 stimulates the differentiation of monocytes, and can promote Th2 differentiation and simultaneously inhibit Th1 polarization. IL-8 is a potent chemoattractant and, it has been suggested, has a role in asthma pathogenesis. Nitric oxide (NO) synthesized by airway epithelium may be important in the regulation of airway inflammation and reactivity. Vascular endothelial growth factor(VEGF) has been reported to be a mediator of airway remodeling in asthma. We investigated the effects of M. pneumoniae on IL-6, IL-8, NO and VEGF production in human respiratory epithelial cells. Methods : A549 cells were cultured and inoculated with M. pneumoniae at a dose of 20 cfu/cell. After infection, the presence of M. pneumoniae in epithelial cell cultures was monitored by immunofluorescence and confirmed by polymerase chain reaction(PCR) detection. IL-6, IL-8 and VEGF were determined by an enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. NO was measured using the standard Griess reaction. Results : In A549 cells, M. pneumoniaeinduced IL-6, IL-8, NO and VEGF release in time-dependent manners. It also induced mRNA expression of IL-6, IL-8 and VEGF in similar manners. Conclusion : These observations suggest that M. pneumoniae might have a role in the pathogenesis of the allergic inflammation of bronchial asthma.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.832-836
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• 2009

Plastic bronchitis is a rare disorder characterized by the formation of extensive, obstructing endobronchial casts. It is associated with asthma and complex cardiac defects such as those requiring the Fontan procedure. The treatment of plastic bronchitis comprises conventional therapy involving spontaneous expectoration and bronchoscopic removal and specific therapy with several new drugs. Herein, we describe the cases of 2 patients diagnosed with plastic bronchitis accompanied with a different underlying disease, which were treated with inhaled corticosteroid and low-dose oral clarithromycin.

• Tuberculosis and Respiratory Diseases
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• v.55 no.2
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• pp.165-174
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• 2003

Background : Asthma is one of the most prevalent diseases in Korea. Although the guidelines of asthma management were reported in Korea, the present pattern of asthma management by primary physicians has not been studied. The purpose of this study is to elucidate the pattern of asthma management by primary physicians. Methods : In November 2002, 710 primary physicians specializing in internal medicine in Seoul, Korea were provided with two scenarios of asthmatic patients, one mild and the other severe. By mail or interview, the physicians were asked several questions about their present pattern of asthma management for the patients in each scenario. Results : Among 710 primary physicians, we obtained the answers from 325 physicians (response rate 46%). The most preferred prescription was oral theophylline. 71% and 81% of the physicians answered that they would prescribe oral theophylline for the mild and severe asthmatics, respectively. The next prescription preferred were mucolytics and oral ${\beta}_2$-agonist, in that order. However, 36% and 56% of the physicians answered that they would prescribe inhaled steroids for the mild and severe asthmatics, respectively. Among diagnostic tests, physicians preferred pulmonary function test to the rank next to chest radiography. Conclusion : The primary physicians in Seoul prefer oral bronchodilators to inhaled steroids in asthma management. More efforts should be made to reduce the difference between the present pattern of asthma management by primary physicians and the asthma guidelines.

• Clinical and Experimental Pediatrics
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• v.51 no.3
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• pp.323-328
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• 2008

Purpose : Asthma is defined as chronic inflammation of the lower small airways, and bronchial hyperreactivity (BHR) is a pathophysiologic feature of asthma. It has been proposed that although there is no direct variable capable of assessing the small airways, a forced expiratory flow of between 25 and 75 percent ($FEF_{25-75}$) might be considered a more sensitive early marker of small airway obstruction than the forced expiratory volume in 1 second ($FEV_1$). Thus, we proposed that the presence and degree of positive responses to bronchial methacholine testing were related to the difference (DFF) and ratio (RFF) between $FEV_1$ and $FEF_{25-75}$ in asthmatic children. Methods : The subjects were 583 symptomatic children, including 324 children with BHR and 259 controls. Pulmonary function tests, methacholine challenge tests, and skin prick tests were performed, and the total eosinophil count, total serum IgE, and serum eosinophil cationic protein level were measured in all subjects. From a concentration-response curve, the methacholine concentration required to produce a decrease of 20% from post-saline $FEV_1$ was calculated ($PC_{20}$). Results : The median DFF and RFF values decreased in controls compared to subjects with bronchial hyperresponsiveness, and this trend was found in groups ranked by its severity. $PC_{20}$ had a negative correlation with DFF and RFF. Cutoff values of 0.5 for DFF and 1.042 for RFF were identified, and sensitivity and specificity were calculated. Conclusion : This study revealed that DFF and RFF might be predictive of bronchial hyperresponsiveness in the context of normal $FEV_1$ in children.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1012-1021
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• 1998

Background : It is known that airway inflammation is present in most patients with asthma, but the relationship between symptoms and the severity and nature of airway inflammation has not been established. Cough variant asthma is defined as an asthma in which the dominant symptom is cough, and the condition can be successfully treated with inhaled steroids. This study was performed to evaluate the time course of bronchial responsiveness according to an inhaled anti-inflammatory therapy and the factors which affect the resolution of bronchial responsiveness, and an efficacy of nedocromil to cough asthma. Method: A prospective study for the investigation of bronchial responsiveness according to an inhaled anti-inflammatory treatment in sixty-one cough asthmatics was performed. Twenty-three entered budesonide ($400{\mu}g{\times}2/day$), twenty-two entered nedocromil ($4mg{\times}2/day$) and sixteen patients entered combined group. The bronchial hyperresponsiveness (BHR) was estimated by methacholine challenge test using counted breath method. The symptom was estimated by 'symptom score'. Reevaluation of BHR and symptom was performed at 2 month after treatment, and if BHR was not resoluted at this time, regarded as a non-responder, and then follow-up of BHR and symptom was performed at 4- and/or 6 month after treatment. Results: The improvement of BHR and symptom was significant in 2 month (p<0.05), but there was no change of them during follow-up period of 4- and/or 6 month in non-responders. In comparison of allergic markers such as serum total IgE, peripheral eosinophil count and skin test reactivity between responders and non-responders, there was no difference in each other. However, in comparison of other factors such as cumulative pack-years, symptom duration, age, gender, and the initial degree of PC20, there was a significant difference in each other(p<0.05). The percent of patients with the resolution of BHR in 2 month was not different in each group(p=0.95). There was no significant difference in the degree of improvement of BHR and symptom in each group. Conclusion: Bronchial responsiveness and symptom was not significantly improved in non-responders during follow-up period of 4- and/or 6 month. The effect of inhaled nedocromil was equivalent to that of inhaled steroid in cough asthmatics, and the response to combined treatment is not superior to that achieved by either of these agents used alone.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.425-433
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• 2004

Background : Induction of oral tolerance (OT) has been known to prevent allergic inflammation in acute asthma model within 4 weeks. However it is remained whether induction of OT may effectively prevent allergic inflammation in chronic asthma model over 4 weeks. We observed the effect of induction of OT on allergic inflammation and airway remodeling in chronic asthma model up to 8 weeks. Methods : 5-week-old female BALB/c mice divided into 4 groups-control group, asthma group, low dose OT group, and high dose OT group. To induce oral tolerance mice were fed ovalbumin (OVA) before sensitization with OVA and aluminum hydroxide-1 mg for 6 consecutive days in the low dose OT group and 25 mg once in the high dose OT group. Mice in the asthma group were fed phosphate buffered saline instead of OVA. After sensitization followed by repeated challenge with aerosolized 1% OVA during 6 weeks, enhanced pause (Penh), inflammatory cells, IL-13, and IFN-${\gamma}$ levels in bronchoalveolar lavage (BAL) fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum were measured. In addition the degree of goblet cell hyperplasia and peribronchial fibrosis were observed from lung tissues by PAS and Masson's trichrome stain. Results : Both OT groups showed a significant decrease in Penh, inflammatory cells, IL-13, and IFN-${\gamma}$ levels in BAL fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum compared with the asthma group (P<0.05). In addition, the degree of goblet cell hyperplasia and peribronchial fibrosis were significantly attenuated in both OT groups compared with the asthma group (P<0.01). Conclusion : These results suggest that induction of OT may effectively prevent allergic inflammation as well as airway remodeling even in chronic asthma model up to 8 weeks.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1063-1071
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• 1997

Backgroung : The efficacy of oral corticosteroids in the treatment of chronic asthma is undisputed, but their long-term use is associated with adverse side-effects, including supression of the hypothalamic-pituitary adrenal axis function, osteoporosis, weight gain, hypertension and impaired glucose tolerance. The introduction of inhaled corticosteroids in the early 1970's represented a significant therapeutic advance in the management of asthma, since these compounds combined high topical potency with low systemic activity. Fluticasone propionate is a new topically active synthetic glucocorticosteroid that combinds a high degree of efficacy with negligible systemic bioavailability. This study was perfomed to determine the effect of inhaled fluticasone propionate on the adreocortical supression in patients with bronchial asthma or chronic obstructive pulmonary disease. Method : The adrenocortical function was assessed by measurement of plasma cortisol concentration at 8 o'clock in morning and free cortisol in 24 hour urine collection at interval. Absolutely, no steroid was taken during pretreatment period of 10days. There after each subject inhaled fluticasone aerosol, in daily doses of 500 or 1000micrograms for 12days. The dose was delivered by metered dose inhaler(MDI). Results : The serum cortisol and 24hour urinary free cortisol were not decreased during the treatment period in patients with inhaled fluticasone propionate in daily doses of 500 micrograms. In contrast, serum cortisol was significantly decreased on 9th and 12th day(p less than 0.05). And, 24hour urinary free cortisol was also significantly decreased on 3rd and 12th day of treatement period(p less than 0.05) in patients with inhaled fluticasone in daily doses of 1000 micrograms. Conclusion : These results suggested that endogenous cortisol secretion was not supressed after short-term inhalation of fluticasone in daily dose of 500 micrograms, but in daily dose of 1000 micrograms, the endogenous cortisol secretion was supressed.

• 월간산업보건
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• s.328
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• pp.55-59
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• 2015

톨루엔-2,4-디이소시아네이트, 톨루엔-2,6-디이소시아네이트 각각 또는 두 이성체 혼합물(TDI)에 대하여 TLV-TWA는 0.005 ppm, TLV-STEL은 0.02 ppm으로 직업적 노출기준을 권고하고 있다. 본 수치는 호흡기에 대한 영향과 과민성 반응에 대한 높은 발생 가능성을 최소화하기 위한 것이다. 산업현장에서 증기상 TDI 물질은 점막, 호흡기계에 심한 자극을 일으켜 천식과 같은 증후군 등 급성 발작을 유발한다. 고농도에 노출시 심한 기관지 경련, 폐렴, 폐부종, 두통, 불면증과 기관지염으로 이어질 수 있다. TDI에 상당 부분 노출되면 대부분의 사람들은 위와 같은 건강 영향을 경험하게 된다. 심지어 처음 노출되었을 경우에도 발생된다. TDI 노출 관련 연구자들은 일반 근로자들이 0.02 ppm 수준 정도로 가끔 노출되는 경우 건강 영향을 받지 않으나, 0.02 ppm이 무영향 수준으로 간주될 수 있는 그 어떠한 증거도 없다고 결론을 내렸다. TDI에 일단 감작되면 몇몇 근로자들은 노출 중단 후에도 몇 년 동안 건강 영향 증세가 지속된다. 따라서 감작제 표기는 호흡 노출을 통한 알레르기성 감작 증세의 명확한 증거로서 권고된다. A4(비발암성 물질) 표기는 생쥐와 흰쥐들을 대상으로 수행된 위장관 투여 연구와 흡입 연구들을 통해 얻어진 동물 노출 데이터에 근거하여 설정되었다. 불충분한 데이터로 피부 표기는 권고되지 않았다.