BACKGROUND: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4+ lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4+ lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-gamma. Th2 cells play a role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in BALF in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. METHODS : We measured the concentration of IL-12 in brochoalveolar lavage fluid(BALF) and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis (10 males, 16 females, mean age : 39.8 +/-2.1 years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. RESULTS: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients (49.3+/-9.2 pg/ml) than in normal control (2.5+/-0.4 pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis (70.3+/-14.8 pg/ml) than in inactive disease (24.8+/-3.1 pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte (p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1: in serum (p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM (p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 (206.2+/- 61.9 pg/ml) than those of control (68.3+/-43.7 pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. CONCLUSION: Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.
Culture Media, Conditioned ; Cytokines ; Female ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Immunity, Cellular ; Intercellular Adhesion Molecule-1 ; Interleukin-10 ; Interleukin-12* ; Interleukin-2 ; Interleukin-4 ; Interleukin-5 ; Lung ; Lymph Nodes ; Lymphocytes ; Macrophages, Alveolar ; Male ; Prognosis ; Remission, Spontaneous ; Sarcoidosis ; Sarcoidosis, Pulmonary* ; T-Lymphocytes ; Th1 Cells ; Th2 Cells ; Therapeutic Irrigation

BACKGROUND: Lung cancer is the second most frequent malignacy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1 (sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. SUBJECTS: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. RESULT: Clinically significant radiation pneumonitis deveoped in 7 patients. After RT, total cell count in BAL was significantly increased from (20.2+/-10.2)X106 cells/ml to (35.3+/-21.6)X106 cells/ml (p=0.0344) and % lymphocyte was also increased from 5.3 +/- 4.2% to 39.6 +/- 23.4% (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: 378 +/-148, 411 +/-150 ng/ml, BALF: 20.2 +/- 12.2, 45.1 +/-34.8 ng/ml,respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: 505 +/- 164 vs 345 +/- 102 ng/ml, p=0.0253, BALF: 67.9+/-36.3 vs 25.2+/-17.9ng/ml,p= 0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from 1.28 +/-0.479 to 1.63 +/-0.539, p=0.0605), but it was significantly high in patients with pneumonitis (2.10+/-0.390) compared to the patinets without pneumonitis (1.28+/-0.31,p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (beta2-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. CONCLUSION: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.
Carcinoma, Non-Small-Cell Lung ; Cell Count ; Cough ; Drug Therapy ; Dyspnea ; Fever ; Fibrosis* ; Humans ; Intention ; Intercellular Adhesion Molecule-1 ; Korea ; Lung Neoplasms* ; Lung* ; Lymphocytes ; Lymphocytosis ; Macrophages, Alveolar ; Pneumonia ; Pulmonary Fibrosis ; Radiation Pneumonitis* ; Radiotherapy* ; Thorax

BACKGROUND: Several national societies have published guidelines for empirical antimicrobial therapy in patients with severe community-acquired pneumonia (SCAP). This study investigated the etiologies of SCAP in the Asan Medical Center and assessed the relationship between the initial empirical antimicrobial regimen and 30 day mortality rate. METHOD: retrospective analysis was performed on patients with SCAP admitted to the ICU between March 2002 and February 2004 in the Asan Medical Center. The basic demographic data, bacteriologic study results and initial antimicrobial regimen were examined for all patients. The clinical outcomes including the ICU length of stay, the ICU mortality rate, and 30 days mortality rates were assessed by the initial antimicrobial regimen. RESULTS: One hundred sixteen consecutive patients were admitted to the ICU (mean age 66.5 years, 81.9 % male, 30 days mortality 28.4 %). The microbiologic diagnosis was established in 58 patients (50 %). The most common pathogens were S. pneumoniae (n=12), P. aeruginosae (n=9), K. pneumonia (n=9) and S. aureus (n=8). The initial empirical antimicrobial regimens were classified as: beta-lactam plus macrolide; beta-lactam plus fluoroquinolone; anti-Pseudomonal beta-lactam plus fluoroquinolone; Aminoglycoside combination regimen; beta-lactam plus clindamycin; and beta-lactam alone. There were no statistical significant differences in the 30-day mortality rate according to the initial antimicrobial regimen (p = 0.682). Multivariate analysis revealed that acute renal failure, acute respiratory distress syndrome and K. pneumonae were independent risk factors related to the 30 day mortality rate. CONCLUSION: S. pneumoniae, P. aeruginosae, K. pneumonia and S. aureus were the most common causative pathogens in patients with SCAP and K. pneumoniae was an independent risk factor for 30 day mortality. The initial antimicrobial regimen was not associated with the 30-day mortality.
Acute Kidney Injury ; Chungcheongnam-do ; Clindamycin ; Diagnosis ; Humans ; Length of Stay ; Male ; Mortality ; Multivariate Analysis ; Pneumonia* ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers*

BACKGROUND: Acinetobacter baumannii is an important nosocomial pathogen being reported with increasing frequency in outbreaks during the past decade. This prospective study was initiated to identify risk factors for the nosocomial acquisition of A. baumannii in patients admitted into a medical intensive care unit (MICU). METHODS: Nasal, rectal and skin swabs were obtained from patients within the 48 hours of admission to the MICU and weekly thereafter during the study period and the final swabs were taken at the time of discharge. If A. baumannii was isolated in the follow up surveillance or from clinical specimen, further culture was not done. Isolates were identified by using the morphology of the colonies in selective media, MicroScan and the ability to grow at 44degrees C. Risk factors of the patients with or without nosocomial acquisition of A. baumannii were compared. RESULTS: Sixty one of the 438 patients admitted to the MICU during the study periods were enrolled. Acquisition of A. baumannii was found in 28 (45.9%) of the 61 patients. The application (89.3% vs. 54.5%, P<0.01) and duration of mechanical ventilation (11.9+/-11.0 day vs. 7.9+/-11.0 day, P<0.05), and the useof nasogastric tubes (100% vs. 78.8%, P=0.01) were the significant risk factors associated with the acquisition of A. baumannii. The proportion of the patients whose APACHE III scores were more than 40 was higher in the acquired group compared to the non-acquired group (92.9% vs. 69.7%, P<0.05). The length of stay in MICU of the acquisition group was longer than those without acquisition (27.0+/-21.0 day vs. 18.7+/-17.0 day, P<0.05). Overall mortality of the patients with acquisition of A. baumannii was higher than in those without acquisition (53.6% vs. 27.3%, P<0.05). However, only the severity of illness evaluated by the APACHE III score (P<0.05) was retained as an independent risk factor for high mortality (odds ratio 1.05, 95% confidence interval 1.01~1.08). Most of A. baumannii showed multi-resistance to antimicrobial agents except imipenem. CONCLUSION: In our study, the risk of the nosocomial acquisition of A. baumannii was associated with the application of mechanical ventilation or nasogastric tube, the severity of illness, and prolonged MICU stay. Acquisition of A. baumannii was not associated with excess mortality, but the severity of illness evaluated by the APACHE III score was retained as an independent risk factor for high mortality.
Acinetobacter baumannii* ; Acinetobacter* ; Anti-Infective Agents ; APACHE ; Disease Outbreaks ; Follow-Up Studies ; Humans ; Imipenem ; Intensive Care Units* ; Critical Care* ; Length of Stay ; Mortality ; Prospective Studies* ; Respiration, Artificial ; Risk Factors ; Skin