• 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.

• Parasites, Hosts and Diseases
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• v.49 no.4
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• pp.373-380
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• 2011

We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific lgE and lgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-${\alpha}$ (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.99-106
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• 1998

Background: Bronchial asthma is a complex disease, which is characterized by spontaneous exacerbations of airway obstruction and persistent bronchial hyperresponsiveness. Animal models have fallen short of reproducing the human disease, particularly in mimicking the spontaneous and persistent airflow obstruction that characterized in asthma. In animals, airflow obstruction is usually assessed by measuring airflow resistance during tidal breathing under such invasive technique as tracheostomy and anesthesia. A noninvasive technique for measuring pulmonary function in small animals is needed to evaluate long-term changes in lung function during the course of experimentally produced disease without sacrificing the animal. Purpose: The purpose of this study was to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness (AR) to inhaled methacholine in nonanethetized, unrestrained guinea pigs. Method: Guinea pig model of asthma was sensitized by subcutaneous injection with ovalbumin and challenged by inhalation of aerosolized ovalbumin(1% wt/vol ovlabumin). Airflow obstruction of conscious guinea pig was measured as specific airway resistance (airway resistance $\times$ thoracic gas volume). Airway resistance and thoracic gas volume of conscious guinea pig were assessed by body plethysmography before challenge and at regular intervals for as long as 30 minutes after challenge. AR to aerosolized methacholine of asthma group was compared with that of control group in body plethysmography. Result: Asthma model<> developed in 13 (65%) among 20 guinea pigs, in which early responses occurred in the airways after the exposure to inhalation with ovalbumin. Airway challenge with ovalbumin caused increase in specific airway resistance, which peaked at 6 minutes and amounted to a $231.5{\pm}30.4%$ increase from baseline. AR to aerosolized methacholine of asthma model increased significantly compared with control group. Conclusion: These results have showed a useful animal model to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness in nonanethetized, unrestrained guinea pigs.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.490-501
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• 1992

Background: Isocyanate is the most significant cause of occupational asthma in this country. The mechanism of isocyanate induced bronchoconstriction is unclear. Subjects and Method: To observe its immunologic and clinical findings, we performed methacholine bronchial challenge test (MBCT), toluene diisocyanate (TDI)-bronchoprovocation test (BPT) and RAST to TDI-, diphenylmethane diisocyanate (MDI)-, and hexamethylene diisocyanate (HDI)-human serum albumin (HSA) conjugate in 22 isocyanate-sensitive asthmatic workers. Results: BPT revealed early (11), dual (5), and late only (6) asthmatic responses. Their latent period ranged from 3 to 120 months (mean:45.9 months). Three cases (13.6%)showed a negative response on initial MBCT, but following MBeT performed 24 hours after TDI-BPT revealed the development of airway hyperresponsivenss. Twelve (54.5%) workers had increased specific IgE to TDI-HSA, seven (31.8%) had to MDI-HSA, and nine (40.9%) had to HDI-HSA conjugate. The prevalence of specific IgE was not associated with latent period, type of asthmatic responses, smoking, and atopic status. After 3 months' avoidance from workplace, airway hyperresponsiveness was improved in 10 (38.3%), among 12 followed cases. Conclusion: It is suggested that isocyanate can induce IgE-mediated bronchoconstriction in 59.1% of isocyanate-sensitive asthmatic workers. Isocyanate-induced asthma can occur even though MBeT showed a negative result, and measurement of the changes of airway hyperresponsivenss after isocyanate-BPT could be helpful to diagnose isocyanate-sensitive asthma.

• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.181-187
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• 2008

Purpose : Asthma is characterized by reversible airway obstruction and bronchial hyperresponsiveness result from airway inflammation. Fraction of nitric oxide in expired air (FeNO) has recently been investigated as a noninvasive measure of airway inflammation. FeNO has been reported to correlate with induced sputum eosinophilia and methacholine challenge test that it is represent severity of asthma. The purpose of this study was to analyze the relationship of FeNO with pulmonary function tests in patients with intermittent asthma. Methods : Eighty children included in this study were diagnosed as asthma from April through August, 2005 in Department of Pediatrics, College of Medicine, Kyunghee University. They aged from 4 to 15 years who were able to conduct spirometry and FeNO monitoring. They did not have upper respiratory tract infection and did not use an asthma controller which contain corticosteroids within 4 weeks. Pulmonary function test was done and FeNO was measured with online tidal breathing method using a chemiluminescence NO analyzer (CLD 88 sp, Eco Medics, Duernten, Switzerland). The correlations between pulmonary function test and FeNO were analyzed using Spearman correlation coefficient method. Results : The mean of FeNO of subject was 16.88 parts per billion (ppb). The mean of forced expiratory volume in 1 second ($FEV_1$) was $0.890{\pm}0.455L$ and forced vital capacity (FVC) was $1.071{\pm}0.630L$. The mean of predicted $FEV_1%$ ($FEV_1%pred$) was $98.39{\pm}34.27%$ and $FEV_1/FVC$ was $88.53{\pm}19.49$. FeNO was significantly correlate with $FEV_1$ (r=0.345, P<0.01) and FVC (r=0.244, P<0.05). FeNO did not correlate with $FEV_1%pred$ or $FEV_1/FVC$. Conclusion : The measurement of FeNO could be a useful marker in the management of childhood asthma and it is evolving to provide a complementary role alongside existing pulmonary function test. We propose that measuring technique and establishment of normal reference range are important area for future research.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.191-202
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• 2000

Background: Bronchial asthma is characterized by airway hyperresponsiveness(BHR) and inflammation. The cyclooxygenase(COX) is believed to be one of the important enzymes in these inflammatory reactions. Recently, the COX was divided into two isoforms, COX1 and COX2. COX2 is induced by lipopolysaccharide and some cytokines at the inflammation site. Prostaglandin E2(PGE2), produced from COX2, may affect airway inflammation. The purpose of this study is to evaluate the effect of COX2 inhibitor on COX2 expression, plasma PGE2, airway resistance and histologic finding in an animal asthma model. Methods : Sprague-Dawley rats were divided into 3 groups. The normal control group did not receive any treatment, but the asthma control group was sensitized by ovalbumin but not treated with the COX2 inhibitor(nimesulide, Mesulid$^{(R)}$). The treatment group was sensitized and treated with nimesulide. Specific airway resistance(sRaw) before and after nimesulide ingestion was investigated. The PGE2 level in the plasma was examined and COX2 immunogold-silver stain on lung tissue was performed. Results: sRaw and eosionophilic infiltration on airway, which increased in the asthma control group, was compared to normal control(p=0.014). However, there was no difference in eosinophilic infiltration between asthma control and treatment groups(p=0.408) and no difference in COX2 expression on bronchiolar epithelium among the three groups. Plasma PGE2 levels were not statically different among the three groups. Conclusion: The role of COX2 in the allergen-induced BHR was not significant The effect of nimesulide was not observed on BHR, COX2 expression, and plasma PGE2 level. Therefore, COX2 may not be a major substance of allergic asthma.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.481-487
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• 2010

Purpose: Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS) and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR) in mouse model of asthma. Methods: Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA), LPS or $1.0{\mu}g$ LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL) fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; $P$ values for significance were set to 0.05. Results: Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL)-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion: These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic responses to OVA in this mouse model of astham. Our data show that early life exposure with OVA and/or LPS may have a protective role in the development of allergic airway inflammation and development of allergen-induced airway responses in mouse model of asthma.

• Journal of Life Science
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• v.16 no.5
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• pp.780-787
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• 2006

Asthma is a chronic inflammatory disorder of the airways, which characterized by bronchial hyperresponsiveness, reversible airflow limitation and respiratory symptoms. Internationally, the prevalence of asthma has been increased over last 3 decades. Recently, several studies of asthma have been reported with gradually increasing importance. To tesify the hypothesis that interleukin (IL)-4 and IL-10 may be an important determinant of the severity of airway inflammation, their expression was studied in mouse model of asthma. BALB/c mouse, IL-4 Knockout (KO) mouse and IL-10 KO mouse were sensitized with intraperitoneal injection of ovalbumin adsorbed to aluminum potassium sulfate, followed by challenges with intranasal ovalbumin on 3 consecutive days. The severity of pulmonary inflammation was assessed by eosinophilia in BAL fluid, number of total BAL cells, histopathological changes in lung tissues, and immunohistochemical staining against IL-4 and IL-10. In BAL fluid, the number of total cells was significantly increased in asthma induced mouse compare to the control. In asthma induced mouse, eosinophil was increased to 56% and neutrophil was 0.2%. In H &E stains, eosinophilic infiltration and epithelium hyperplasia were clearly noticed in asthma induced mouse. In immunohistochemical staining for IL-4 and IL-10, there was no positive reaction in control group. However, very strong reactions were appeared in asthma induced group. In this research, IL-4 and IL-10, which seem to play a central role in allergic asthma, KO mouse was utilized to test the causative relationship between airway inflammation and role of specific cytokine. Asthma induced IL-4 and IL-10 KO mice showed much decreased inflammatory reactions in the number of total BAL cells, in eosinophilic infiltration, and in immunohistochemical stains against diverse inflammatory proteins. These results suggest that IL-4 and IL-10 increase the asthmatic reactions in vivo mice model.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.77-84
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• 2004

Background : We hypothesized that there was a relationship between body weight change and bronchodilator response (BDR) in patients with chronic renal failure (CRF) on hemodialysis (HD). Several mechanisms such as pulmonary edema due to water retention or increased permeability of alveolar capillary may play a important role in pulmonary function impairment and bronchial hyperresponsiveness in patients with CRF on HD. But, no studies have been published concerning BDR in patients with CRF on HD. This study was aimed to know the immediate effect of hemodialysis on pulmonary function and BDR in patients with CRF on HD. Methods : This study included 30 patients with CRF on HD. We collected data including age, sex, height, pretibial and pedal pitting edema, interdialysis weight gain, postdialysis weight loss, underlying diseases, duration of HD, $FEV_1$, FVC, $FEV_1/FVC$, and BDR before and after HD. Results : Interdialysis weight gain of the patients was $3.4{\pm}1.0kg$, and postdialysis weight loss was $3.2{\pm}0.7kg$. Before HD,$FEV_1$, FVC, and $FEV_1/FVC$ of the patients were $89{\pm}22%$, $86{\pm}19%$ of predicted, and $87{\pm}10%$. After bronchodilator inhalation, these parameters were changed to $95{\pm}22%$, $90{\pm}19%$ of predicted, and $88{\pm}9%$ respectively. BDR was positive in 15 patients. After HD, $FEV_1$, FVC, and $FEV_1/FVC$ of the patients were $100{\pm}23%$, $94{\pm}18%$ of predicted, and $88{\pm}11%$. After bronchodilator inhalation, these parameters were changed to $102{\pm}23%$, $96{\pm}18%$ of predicted, and $89{\pm}8%$ respectively. BDR was positive in 9 patients. Conclusion : First, HD increases $FEV_1$, FVC, and $FEV_1/FVC$ but little affects BDR. Second, there is no correlation between postdialysis weight loss and increases in $FEV_1$, FVC, and $FEV_1/FVC$ after HD. Third, there is also no correlation not only between interdialysis weight gain and BDR before HD but between postdialysis weight loss and BDR after HD.