• Tuberculosis and Respiratory Diseases
• /
• v.63 no.4
• /
• pp.337-345
• /
• 2007

Backgrounds: Although glucocorticoids are one of the most potent anti-inflammatory agents, they have limited effect on cysteinyl leukotriene biosynthesis. In addition, the response to inhaled corticosteroids (ICS) and inhaled long-acting ${\beta}_2-agonists$ (LABA) combination therapy in moderate to severe persistent asthmatics varies. Additional therapy with leukotriene receptor antagonists (LTRA) in patients with moderate to severe asthma suboptimally controlled with ICS and LABA combination therapy would be complementary to asthma control. Methods: One hundred and ninety eight asthmatics entered a 2 month, open-label descriptive study. Patients suffering from persistent asthma and suboptimally controlled on a combination therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as an add-on therapy. The level of asthma control was assessed using the Asthma Control Questionnaire (ACQ) including $FEV_1%$ predicted at the baseline and after a 2-month treatment with montelukast. A global evaluation of the treatment was also made by the patients and physicians. Results: The mean ACQ score decreased significantly on montelukast ($11.5{\pm}5.4$ at baseline vs. $6.7{\pm}5.0$), with a significant improvement in all individual symptom scores (p<0.01). The $FEV_1%$ predicted values did not show any significant change. 59.9% of patients and 59.4% of physicians reported global improvement in their asthma (${\kappa}=0.85$). Conclusion: These results suggest that the addition of montelukast in patients with persistent asthma that is suboptimally contolled by combination therapy of ICS and LABA might confer complementary effects on asthma control.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.4
• /
• pp.450-461
• /
• 2001

Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.6
• /
• pp.1252-1264
• /
• 1998

Background : Patients with established ARDS have a mortality rate that exceeds 50 percent despite of intensive care including artificial ventilation modality, Mortality has been associated with sepsis and organ failure preceding or following ARDS ; APACHE II score ; old age and predisposing factors. Revised ventilator strategy over last 10 years especially at ARDS appeared to improve the mortality of it. We retrospectively investigated 40 ARDS patients of respiratory-care unit to examine how these factors influence outcome. Methods : A retrospective investigation of 40 ARDS patients in respiratory-care unit with ventilator management over 46 months was performed. We investigated the clinical characteristics such as a risk factor, cause of death and mortality, and also parameters such as APACHE II score, number of organ dysfunction, and hypoxia score (HS, $PaO_2/FIO_2$) at day 1, 3, 7 of severe acute lung injury, and simultaneously the PEEP level and tidal volume. Results : Clinical conditions associated with ARDS were sepsis 50%, pneumonia 30%, aspiration pneumonia 20%, and mortality rate based on the etiology of ARDS was sepsis 50%, pneumonia 67%(p<0.01 vs sepsis), aspiration pneumonia 38%. Overall mortality rate was 60%. In 28 day-nonsurvivors, leading cause of death was severe sepsis(42.9%) followed by MOF(28.6%), respiratory failure(19.1 %), and others(9.5%). There were no differences in variables of age, sex, APACHE II score, HS, and numbers of organ dysfunction at day 1 of ARDS between 28-days survivor and nonsurvivors. In view of categorized variables of age(>70), APACHE II score(>26), HS(<150) at day 1 of ARDS, there were significant differences between 28-days survivor and nonsurvivors(p<0.05). After day 1 of ARDS, the survivors have improved their APACHE II score, HS, numbers of organ dysfunction over the first 3d to 7d, but nonsurvivors did not improve over a seven-day course. There were significant differences in APACHE II score and numbers of organ dysfunction of day 3, 7 of ARDS, and HS of day 7 of ARDS between survivors and nonsurvivors(p<0.05). Fatality rate of ARDS has been declined from 68% to less than 40% between 1995 and 1998. There were no differences in APACHE II score, HS, numbers of organ dysfunction, old age at presentation of ARDS. In last years, mean PEEP level was significantly higher and mean tidal volume was significantly lower than previous years during seven days of ARDS(p<0.01). Conclusions : Improvement of HS, APACHE II score, organ dysfunction over the first 3d to 7d is associated with increased survival Decline in ARDS fatality rates between 1995 and 1998 seems that this trend must be attributed to improved supportive therapy including at least high PEEP instead of conventional-least PEEP approach in ventilator management of acute respiratory distress syndrome.

• Tuberculosis and Respiratory Diseases
• /
• v.60 no.3
• /
• pp.330-336
• /
• 2006

Background : Aquaporins (AQPs) may play a role in the pathogenesis of pulmonary inflammation and edema. This study investigated the role ofAQPs in acute lung injury following bleomycin inhalation in rats. Methods : Sprague-Dawley rats were treated via inhalation with 10 U/kg bleomycin hydrochloride dissolved in 5 ml of normal saline. The control rats were treated with 5 ml normal saline. The animals (n = 6-8 rats per group) were sacrificed at 4, 7, and 14 d. The changes in AQP1, AQP4, and AQP5 expression levels over time were analyzed by Western blotting. The nitrate and nitrite concentrations in the bronchoalveolar lavage fluid (BALF) were measured using a modified Griess reaction. ELISA was used to check cytokines. Results : The respiration rates were significantly higher 4 and 7 days after the bleomycin treatment compared with those of the control rats. The tidal volume was lower in rats at 4 days after the bleomycin treatment, and the wet/dry weights of the lung were significantly higher than those of the control group. The nitrite and nitrate concentrations in the BALF from the rats at 4 days after exposure to bleomycin were greater than those from the saline-treated rats. Immunoblotting studies demonstrated that the AQP1 and AQP4 expression levels were lower in the rats at 4 days. However, the AQP4 expression level was higher at 7 days. The AQP5 expression level increased at 4, 7 and 14 days after the bleomycin treatment. Conclusion : This study demonstrates that AQPs are expressed differently in bleomycin-induced pulmonary edema.