Airway hyperresponsiveness and etiology in patients with chronic cough / 결핵

BACKGROUND:Chronic cough is commomly defined as a persistent or recurrent cough exceeding 3 week's duration. The prevalence of chroinc cough is reported to range from 14% to 23% for nonsmoking adults. The post nasal drip syndrome has been determined to be the most common cause of chronic cough, followed by asthma, chronic bronchitis, gastroesophageal reflux and bronchiectasis. Cough can be the only manifestation of asthma.. Bronchial provocation tests are useful in diagnosing cough variant asthma. We investigated the clinical or laboratory findings and the incidence of airway hyperresponsiveness and evaluated the etiology in patients with chronic cough. METHOD: We evaluated 46 patients with chronic cough. Methacholine challenge test were done. RESULTS: The results were as follows : 1) Thirty - five percent(16/46) of the chronic cough patients and 44% of the post nasal drip syndrom(7/16) showed the positive responses to methacholine challenge test. 2) The underlying causes of chronic cough were post nasal drip syndrome in 35%, bronchitis in 21.7%, cough-variant asthma in 17.4%, and unknown condition in 25.9%. 3) Airway hyperresponsiveness in chronic cough was not related to respiratory symptom, nasal symptom, post nasal drip, smoking, derangement of ventilatory function, atopy, or sinusitis. CONCLUSION: Airway hyperresponsivenss in patients with chronic cough increased in frequency when compaired with normal control, allergic rhinitis. Cough-variant asthma account for 17.4% of patients with chronic cough.

The Role of Protein Kinase C in Acute Lung Injury Induced by Endotoxin / 결핵

BACKGROUND: The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. METHODS: We studied the role of PKC in ETX-induced ALl using PKC inhibitor (staurosporine, 5Th) in the rat. Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg) pretreatment. STP was injected via tail vein 30mm before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3- or 6-hrs after IT of PMA or FTX respectively, to measure protein concentration, total and differential cell counts. RESULTS The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was 64.8 8.5 and 30.4 2.5% in the STP+PMA- and STP+ETX-group, respectively (p=0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p=0.003) and PMA group (p=0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p=0.22) and ETX-group (p=0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p<0.001). The differential cell counts was not different between the PMA and STP+PMA. On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. CONCLUSION: Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-in-duced ALI.

An Appreciation of Functional Role of Macrophage in the Acute Lung Injury in the Neutropenic Rat / 결핵

BACKGROUND: It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pufrnonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutiopenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. METHOD: The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cel]s was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. RESULTS: The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells In the ETX-group, the number of total cells (p<0.01) and of macrophage and neutrophll (p<0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC- group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and jt took part in less than 0.1% of total BAL cells (p<0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p<0.05 and <0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p<0.05 vs NC-group) , but the value was statistically not different from that of ETh-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p<0.05), but showed still a higher value compared to that of NC-group (p<0.05). A change of cytokine concentration in the BALF TNF-alpha and IL-6 were elevated in the ETX- and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p<0.0008 vs NC-group ), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveola r macrophages.

Diffuse Alveolar Damage Associated with Polymyositis / 결핵

Interstitial pneumonitis may be the presenting manifestation of polymyositis-dermatomyositis (PM-DM), or may occur later in the evolution of disease. The clinical picture is characterized by non-productive cough, dyspnea and hypoxemia. The chest radiograph demonstrates interstitial infiltrates with predilection for the lung bases, often with an alveolar pattern in addition. We experienced a case of polymyositis associated with diffuse alveolar damage(DAD) that was proven in open lung biopsy. The patient was a 52 year-old woman who was presented with 6 months' duration of generalized ache, edema on ankle and wrist, non-productive cough and mild dyspnea. She had typical symptoms and physical findings of interstitial pneuminitis, and elevated muscle enzyme levels in serum with characteristic histologic findings of myositis on muscle biopsy. She also had typical interstitial lung disease pattern on high resolution CT and restrictive pattern on pulmonary function tests. The findings of open lung biopsy was compatible with diffuse alveolar damage(DAD). She failed to respond to the therapeutic trials with corticosteroid and cyclophosphamide, and finally expired due to acute respiratory distress syndrome.