Background : Chronic obstructive pulmonary disease(COPD) is one of the major contributors to morbidity and mortality among the adult population. Cigarette smoking(CS) is undoubtedly the single most important factor in the pathogenesis of COPD. However, its mechanism is unclear. The current hypothesis regarding the pathogenesis of COPD postulates that an imbalance between proteases and antiproteases leads to the destructive changes in the lung parenchyma. This study had two aims. First, to evaluate the effect of CS exposure on histologic changes of the lung parenchyme, and second, to evaluate the effect of CS exposure on the expression of the gelatinolytic enzymes in BAL fluid cells in guinea pigs. Methods : Two groups of five guinea pigs were exposed to the whole smoke of 20 commercial cigarettes per day, 5 hours/day, 5 days/week, for 6weeks, and 12 weeks, respectively, using a smoking apparatus. Five age-matched guinea pigs exposed to room air were used as controls. Five or more sections were microscopically extamined(${\times}400$) and the number of cellular infiltration of the alveolar wall was measured in order to evaluate the effect of CS exposure on the histologic changes of lung parenchyme. The statistical significance was analyzed by a linear regression method. To evaluate the expression of the gelatinolytic enzymes in intraalveolar cells, BAL fluid was obtained and the intraalveolar cells were separated by centrifugation (500 g for 10 min at $4^{\circ}C$). Two sets of culture plates were loaded with $1{\times}10^6$ intraalveolar cells. One plate, contained O.1mM EDTA, a inhibitor of matrix metalloproteases(MMPs), and the other plate had no EDTA. Both plates were incubated for 48 hours at $37^{\circ}C$. After incubation, gelatinolytic protease expression in the supernatants was analyzed by gelatin zymography. Results : At the end of CS exposure, the level of blood carboxy Hb had increased significantly(4.1g/dl in control group, 24g/dl immediately after CS exposure, 18g/dl 30 min after CS exposure, 15g/dl 1 hour after CS exposure). Alveolar inflammatory cells were identified in the CS exposed guinea pigs. The number of alveolar cellular cells observed in a microscopic field ($400{\times}$) was $121.4{\pm}7.2$, $158.0{\pm}20.2$, $196.8{\pm}32.8$, in the control, the 6 weeks, and the 12 weeks group, respectively. The increased extent of inflammatory cellular infiltration of the lung parenchema showed a statistically significant linear relationship with the duration of CS exposure(p=0.001, $r^2=0.675$). Several types of gelatinolytic enzymes in the intraalveolar cells of CS exposed guinea pigs were expressed, of which some were inhibited by EDT A. However, the gelatinolytic enzymes were not expressed in the control groups. Conclusion : CS exposure increases inflammatory cellular infiltration of the alveolar wall and the expression of gelatinolytic proteases in guinea pigs. EDTA inhibits some of the gelatinolytic proteases. These findings suggest a possibility that CS exposure may increase MMP expression in the lungs of guinea pigs.
Jung, Eun Jung;Kim, Yang Ki;Lee, Young Mok;Kim, Ki-Up;Uh, Soo-Taek;Kim, Yong Hoon;Kim, Do Jin;Park, Choon Sik;Hwang, Jung Hwa
Tuberculosis and Respiratory Diseases
/
v.66
no.4
/
pp.288-294
/
2009
Background: A lung hyperinflation, or air trapping, caused by expiratory flow-limitation contributes to dyspnea in patients with chronic obstructive pulmonary disease (COPD). Forced expiratory volume in 1 second ($FEV_1$) has served as an important diagnostic measurement of COPD, but does not correlate with patient-centered outcomes such as dyspnea. Therefore, this study was performed to investigate the role of radiologic quantity in evaluating the dyspnea in patients with COPD by measuring lung hyperinflation in chest x-ray and high resolution chest tomography (HRCT). Methods: Fifty patients with COPD were enrolled in this study. Their subjective dyspnea score (modified Borg scale dyspnea index), spirometry, and lung volume were measured. Simultaneous hyperinflations of chest x-ray score ("chest score") and degree of emphysema of HRCT ("HRCT score") were measured. The "chest score" were composed of lung length, retrosternal space width, and height of the arc of the diaphragm and "HRCT score" were composed of severity and extent of emphysema. Results: The mean age of patients was 69 years old and their mean $FEV_1$ was 51.7%. The Borg score significantly correlated with parameters of spirometry and lung volume, including FVC, $FEV_1$, $FEV_1$/FVC, RV, RV/TLC, and DLCO. The Borg score correlated well with "HRCT score", but did not correlate with "chest score". Also, the Borg scale correlates inversely with body mass index. Conclusion: The quantity of emphysema on chest HRCT may serve as an objective marker of dyspnea in patients with COPD.
Kim, J.E.;Choi, S.S.;Lee, J.H.;Yoo, Y.S.;Yu, H.S.;Park, M.H.;Park, H.S.
Journal of Chest Surgery
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v.9
no.1
/
pp.78-82
/
1976
Bullous emphysema is usually associated with extensive chronic obliterative pulmonary disease. It is the disease of old age but rare in children or infancy. The bulla in this disease is acquired one. In general the symptoms are due to not the mere presence of the bulla but the extent of underlying lung pathology as emphysema or bronchitis. Occassionally giant bulla of great size may cause symptoms and in this occassion it should be differentiated from other diseases. Especially in children or infancy pneumothorax, congenital pulmonary cyst of lobar obstructive-emphysema should be excluded. Recently we experienced 2 cases of bullous emphysema in infancy with severe respiratory symptoms because of bullae of great size. We felt difficulties in differentiating with other conditions. The purpose of this report is to review our cases thoroughly and enhance considerations of this disease.
Pulmonary diseases distress millions of people worldwide. Numerous studies have shown an association between pulmonary disease and psychiatric disorders. Despite this, little is known about the treatment of psychiatric disorder in patients with pulmonary disease. The three main goals of this article are 1) to discuss the major disorders such as asthma, chronic obstructive pulmonary disease, hyperventilation, tuberculosis, lung cancer that most clinicians see in practice, 2) to provide an information about psychiatric treatment such as anxiety, depression, psychosis in pulmonary disease, and 3) to provide some clinically relevant suggestions about pharmacologic interactions between pulmonary and psychotropic drugs.
Journal of Physiology & Pathology in Korean Medicine
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v.25
no.1
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pp.122-131
/
2011
The object of this study was to evaluate the single dose toxicity of Yukmijihwangtanggamibang (YMJHTGMB), a polyherbal formula have been traditionally used as prevention or treatment agent for various lung diseases including chronic obstructive pulmonary disease (COPD), in male and female mice. Aqueous extracts of YMJHTGMB (Yield = 16.33%) wasadministered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changesin the body and organ weight except for soft feces restricted to YMJHTGMB 2,000 mg/kg treated two male mice (2/5; 40%) at 1 day after administration. In addition, no YMJHTGMB-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of YMJHTGMB aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines.
Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches.
Park, Hun Pyo;Park, Soon Hyo;Lee, Sang Won;Seo, Yong Woo;Lee, Jeong Eun;Seo, Chang Kyun;Kwak, Jin Ho;Jeon, Young June;Lee, Mi Young;Chung, In Sung;Kim, Kyung Chan;Choi, Won-Il
Tuberculosis and Respiratory Diseases
/
v.57
no.2
/
pp.143-147
/
2004
Background : It is important to predict the exercise capacity and dyspnea, as measurements of lung volume, in patients with COPD. However, lung volume changes in response to an improvement in airflow limitation have not been explored in detail. In the present study, it is hypothesized that lung volume responses might not be accurately predicted by flow responses in patients with moderate to severe airflow limitations. Methods : To evaluate lung volume responses, baseline and follow up, flow and lung volumes were measured in moderate to severe COPD patients. The flow response was defined by an improvement in the $FEV_1$ of more than 12.3%; lung volume changes were analyzed in 17 patients for the flow response. Results : The mean age of the subjects was 66 years; 76% were men. The mean baseline $FEV_1$, $FEV_1$/FVC and RV were 0.98L (44.2% predicted), 47.5% and 4.65 L (241.5%), respectively. The mean follow up duration was 80 days. The mean differences in the $FEV_1$, FVC, TLC and RV were 0.27 L, 0.39 L, -0.69 L and -1.04 L, respectively, during the follow up periods. There was no correlation between the delta $FEV_1$ and delta RV values(r=0.072, p=0.738). Conclusion : To appropriately evaluate the lung function in patients with moderate to severe airflow limitations; serial lung volume measurements would be helpful.
Background: Due to the irreversible nature of chronic obstructive pulmonary disease (COPD), the treatment aim in patients with COPD is not to cure but to reduce the symptoms, increase lung function, and improve the quality of life. It has been suggested that depression is a common emotional disturbance in patients with COPD who are faced with a major physical impairment and embarrassing symptoms. This study evaluated the prevalence and risk factors of depression in patients with chronic obstructive pulmonary disease. Methods: A total of 59 patients with a registered diagnosis of chronic obstructive pulmonary disease were selected. Depression was assessed using the Centers for Epidemiologic Studies Depression (CES-D) scale. The quality of life was assessed using the Korean version of the St. George's Respiratory Questionnaire. Results: The prevalence of depression was 17.0%. In the correlation model, the interaction of the $FEV_1%$ over predicted value and SGRQ score(symptom, activity, impact, overall score) was statistically significant. The interaction of the $FEV_1%$ over predicted value and depression scale(CES-D) was also statistically significant. There was a positive correlation between the SGRQ scores(symptom, activity, impact, overall score) and the depression scale. Conclusion: The prevalence of depression in patients with chronic obstructive pulmonary disease is relatively high. The pulmonary function and the living standards were found to be significant risk factors for depression.
Kim, Yeon-Jae;Park, Jae-Yong;Won, Jun-Hee;Kim, Chang-Ho;Kang, Duk-Sik;Jung, Tae-Hoon
Tuberculosis and Respiratory Diseases
/
v.46
no.4
/
pp.489-499
/
1999
Background: The patient with bronchiectasis may have obstructive ventilatory impairment combined with mild restrictive ventilatory impairment due to fibrosis of surrounding lung parenchyme and pleural adhesions caused by chronic recurrent pulmonary infections. Since hyperinflation or emphysematous change can be occured in bronchiectasis, pulmonary functions such as lung volumes and diffusing capacity may also vary with associated emphysema. Methods: For the evaluation of lung volumes and diffusing capacity in bronchiectasis with respect to the anatomic types and severity of bronchiectasis, a total of 40 cases comprising 24 cases of tubular, and 16 cystic type of bronchiectasis were analyzed retrospectively. Correlation between lung functions and extent of bronchiectasis or associated emphysema detected in HRCT were also evaluated. Results: Vital capacity(VC) tended to decrease in cystic type than in tubular type. As the severity of bronchiectasis became serious, the VC were significantly reduced, whereas the total lung capacity(TLC), residual volume(RV) and its ratio to the total lung capacity(RV/TLC) had no significant difference. Lung clearance index(LCI) was significantly increased in cystic type than in tubular type, whereas the slope of phase III in single breath nitrogen curve($\triangle$N2/L) was not significantly changed regard to the type and severity of bronchiectasis. DLCO and DLCO/VA reflecting diffusing capacity were significantly decreased in cystic type and also as the severity of bronchiectasis became serious. The correlation coefficient of VC, DLCO and LCI with the extent of bronchiectasis were -0.322, -0.339 and 0.487, respectively, whereas other parameters were not significantly correlated with the extent of bronchiectasis. VC and DLCO correlated negatively with the extent of emphysema while RV, RV/TLC, LCI and $\triangle$N2/L correlated positively. Conclusion: These findings suggest that the reduction of VC and diffusing capacity or uneven distribution of inspired gas in bronchiectasis are related to both the extent of bronchiectasis and associated emphysema while increased residual volume be related to the extent of associated emphysema alone.
Some kinds of newer fluoroquinolone antibiotics are known to interact with theophylline, which is widely used as a potent bronchodilator in asthma or chronic obstructive lung disease. To evaluate the effect of enoxacin and ciprofloxacin on the metabolism of theophylline, aminophylline was administered intravenously in bolus (6 mg/kg) over 30 minutes to 6 healthy volunteers (age: $23.3{\pm}4.2$ year, body weight: $63.2{\pm}9.0\;kg$, height: $169.0{\pm}6.5\;cm$, female 3, male 3) before and after per oral 5-day medication of enoxacin and ciprofloxacin, respectively and we measured the level of theophylline in serum. The results were as follows: 1) Enoxacin and ciprofloxacin did not influence the volume of distribution significantly. 2) Enoxacin decreased the clearance of theophylline significantly (from $42.9{\pm}14.6\;ml/min$ to $30.1{\pm}6.3\;ml/min$: p<0.05), but ciprofloxacin did not cause significant decrease (to $32.8{\pm}6.2\;ml/min$: p>0.005). 3) Enoxacin increased the elimination half life of theophylline significantly (from $496{\pm}83\;min$ to $693{\pm}32\;min$: p<0.001), but ciprofloxacin did not cause significant increase (to $687{\pm}222\;min$: p>0.05). These results suggested that enoxacin influenced clearance and elimination half life significantly and thorough monitoring of the level of theophylline in patients with coadminstration of enoxacin and theophylline was necessary. In case of ciprofloxacin, the influence on the metabolism of theophylline was not statistically significant, but one exceptionally large decrease of the clearance and increase of the elimination halflife of theophylline suggested the necessity of monitoring of theophylline level during coadministration of ciprofloxacin and theophylline.
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