Epidemiological analysis of critically ill adult patients with pandemic influenza A(H1N1) in South Korea.

A total of 245 patients with confirmed 2009 H1N1 influenza were admitted to the intensive-care units of 28 hospitals (South Korea). Their mean age was 55.3 years with 68.6% aged >50 years, and 54.7% male. Nine were obese and three were pregnant. One or more comorbidities were present in 83.7%, and nosocomial acquisition occurred in 14.3%. In total, 107 (43.7%) patients received corticosteroids and 66.1% required mechanical ventilation. Eighty (32.7%) patients died within 30 days after onset of symptoms and 99 (40.4%) within 90 days. Multivariate logistic regression analysis showed that the clinician's decision to prescribe corticosteroids, older age, Sequential Organ Failure Assessment score and nosocomial bacterial pneumonia were independent risk factors for 90-day mortality. In contrast with Western countries, critical illness in Korea in relation to 2009 H1N1 was most common in older patients with chronic comorbidities; nosocomial acquisition occurred occasionally but disease in obese or pregnant patients was uncommon.

Vitamin D-receptor polymorphisms and non-tuberculous mycobacterial lung disease in Korean patients.

This study investigated the potential role of vitamin D-receptor (VDR) gene polymorphisms in susceptibility to lung disease caused by non-tuberculous mycobacteria (NTM). TaqI and FokI polymorphisms were compared in 124 patients and 127 controls. The genotype, allele and haplotype frequencies did not differ between patients and controls. TaqI and FokI polymorphisms of the VDR gene do not appear to be responsible for host susceptibility to NTM lung disease, at least in this Korean population. An association cannot, however, be completely ruled out, as only two single nucleotide polymorphisms of the VDR gene were studied in this report.

Imaging of regional air distributions in porcine lungs using high-performance electrical impedance tomography system.

Electrical impedance tomography (EIT) allows functional imaging of regional lung ventilation for real-time bedside monitoring of mechanically ventilated patients. Images showing time-changes of regional air distributions in the lungs can provide valuable diagnostic information for lung protective mechanical ventilation. This paper reports in vivo porcine imaging experiments of regional lung ventilation using a 16-channel parallel EIT system. Real-time time-difference chest images of 10 animals were reconstructed during mechanical ventilations with a temporal resolution of 50 frame/s. Analyzing the images together with the airway volume-pressure information from the mechanical ventilator, we could successfully produce regional compliance images at PEEP (positive end expiratory pressure) titration. From in vivo animal experiments, we propose the method as a continuous monitoring means for LPV (lung protective ventilation).

Pulmonary TB and NTM lung disease: comparison of characteristics in patients with AFB smear-positive sputum.

OBJECTIVE: To compare the clinical and radiographic features of pulmonary tuberculosis (PTB) and non-tuberculous mycobacteria (NTM) lung disease in patients with acid-fast bacilli (AFB) positive sputum specimens. DESIGN: The initial clinical and radiographic features of 229 PTB patients were compared with those of 70 patients with NTM lung disease. The most commonly involved organisms in the NTM lung disease cases were Mycobacterium avium complex (n = 38, 54%) and M. abscessus (n = 26, 37%). RESULTS: Clinical and radiographic findings that were more common in patients with NTM lung disease than in PTB patients were: older age (P < 0.001), non-smoker (P < 0.001), history of previous TB treatment (P < 0.001), absence of pleural effusion (P = 0.017), involvement of middle and/or lower lung zones (P = 0.007), and bilateral disease (P = 0.005). Multivariate analysis showed that older age (> or = 40 years), non-smoker, previous TB treatment, absence of pleural effusion and involvement of middle and/or lower lung zones were significant independent predictors for NTM lung disease. CONCLUSIONS: There is considerable overlap in the clinical and radiographic appearances of PTB and NTM lung disease. The isolation and identification of causative organisms are mandatory for a correct diagnosis in patients with AFB-positive sputum specimens.

Recovery rate of NTM from AFB smear-positive sputum specimens at a medical centre in South Korea.

OBJECTIVE: To investigate the recovery rate of non-tuberculous mycobacteria (NTM) from acid-fast bacilli (AFB) smear-positive sputum specimens at a tertiary care medical centre in South Korea with a high pulmonary tuberculosis (PTB) burden. DESIGN: Retrospective analysis of data from AFB smear- and culture-positive sputum specimens collected between January 1998 and December 2001. RESULTS: Over 4 years, 1328 sputum specimens collected from 616 patients were AFB smear- and culture-positive. NTM were recovered from 9.1% (121/1328) of the smear-positive sputum specimens, and from 8.1% (50/616) of patients with smear-positive sputum. NTM were isolated at least twice in 94% (47/50) of the patients from whom NTM was recovered. The most common organism found was Mycobacterium avium complex, followed by M. abscessus. CONCLUSION: These results suggest that a substantial proportion of patients at a tertiary care medical centre in South Korea with AFB smear-positive sputum specimens may have NTM lung disease rather than PTB.

Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation.

PURPOSE: The purpose of this article is to evaluate the effect of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to investigate if lung damage associated with mechanical ventilation can be reduced by PLV. MATERIALS AND METHODS: Twenty-two New-Zealand white rabbits were ventilated in pressure-controlled mode maintaining constant tidal volume (10 mL/kg). Lung injury was induced by repeated saline lavage (PaO2 < 100 mm Hg). Two incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps were performed sequentially. The control group received the first IPSM in the supine position and were turned prone for the second IPSM. In the PLV group (n = 7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two IPSMs. The early prone group (n = 7) received both IPSMs in the prone position. Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology were examined. RESULTS: During the first IPSM, the PLV group showed a significant increase in PaO2 after instillation of perfluorodecalin (P < .05) and then showed a dose-dependent increase in PaO2 with PEER. The control and EP groups showed improvement in PaO2 only at higher PEEP, eventually showing no intergroup differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group retained its ability to increase PaO2 to the level obtained during the first IPSM (P < .05 compared with control and EP groups). During the first IPSM all three groups showed increasing trend in static compliance (Cst) with PEEP peaking at PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in static compliance with PEEP (P < .05 compared with other groups). Lung histology revealed significantly less hyaline membrane formation in the PLV group (P < .05). CONCLUSION: PLV shows dose-dependent increase in oxygenation with PEEP and may reduce lung damage associated with mechanical ventilation.

Toxocariasis as a cause of new pulmonary infiltrates.

SETTING: Patients with new pulmonary infiltrates on chest computed tomography (CT) scans at a tertiary centre in South Korea. OBJECTIVE: To demonstrate associations among radiological changes, blood eosinophilia (E) and Toxocara (T) seropositivity. DESIGN: We retrospectively reviewed blood eosinophilia, Toxocara seropositivity, history of raw meat intake and radiological features, and divided study patients into four groups according to blood eosinophilia and Toxocara seropositivity. RESULTS: Among 150 patients, 62 were E- and T-positive (E+T+), 45 were E-negative and T-positive (E-T+), 7 were E-positive and T-negative (E+T-), and 36 were E- and T-negative (E-T-). History of raw meat intake was found in 95 (63%) patients. The type and number of lesions on CT did not show any significant differences among the four groups. Among 119 patients who were not diagnosed with a specific disease, transient or migrating lesions were seen in 93% of E+T+, 93% of E-T+, 80% of E+T- and 52% of E-T- patients (P < 0.0001). Furthermore, the frequencies of migrating or new lesions and improvement were significantly higher in the Toxocara-positive group (88/95, 93%) than in the Toxocara-negative group (14/24, 58%; P = 0.002). CONCLUSION: Transient and migratory pulmonary infiltrates on chest CT scans were associated with blood eosinophilia and Toxocara seropositivity. Clinicians should consider asymptomatic toxocariasis as a cause of unexplained new pulmonary infiltrates in countries with dietary habits of raw meat intake.

Initial lactate level and mortality in septic shock patients with hepatic dysfunction.

An elevated serum lactate level is associated with morbidity and mortality in patients with severe sepsis and septic shock. In patients with hepatic dysfunction, however an elevated serum lactate level may be due to either impaired lactate clearance or excessive production. Thus, we evaluated whether the initial serum lactate level was also associated with mortality in septic shock patients with hepatic dysfunction. A retrospective observational study enrolled 307 patients with septic shock admitted to the intensive care unit (ICU) between May 2007 and July 2009. Hepatic dysfunction was defined as a serum total bilirubin > 34.2 micromol/l (2 mg/dl). Selected patients were divided into high (> or = 4 mmol/l) and low (< 4 mmol/l) lactate groups, according to the initial serum lactate level. Of 307 patients with septic shock, 118 (38%) patients with hepatic dysfunction were eligible for this study. The median lactate levels were 5.9 (interquartile range 4.7 to 9.0) and 2.6 (interquartile range 1.7 to 3.2) mmol/l for the high and low lactate groups respectively (P < 0.001). The initial serum lactate level was strongly associated with in hospital mortality in a univariate analysis (P < 0.001). After adjusting for potential confounding factors, the initial serum lactate level remained significantly associated with in-hospital mortality (odds ratio 1.281, 95% confidence interval 1.097 to 1.496, P = 0.002). In conclusion, the serum lactate level could be useful in predicting the outcome of patients with septic shock regardless of hepatic dysfunction.

Pulmonary paragonimiasis mimicking lung cancer in a tertiary referral centre in Korea.

OBJECTIVE AND DESIGN: To determine how pulmonary paragonimiasis may be confused with lung cancer, we retrospectively analysed the clinical and radiological characteristics of 47 patients (27 males, median age 55 years; interquartile range 49-61) with serologically or histopathologically confirmed pulmonary paragonimiasis seen between October 2004 and December 2009. RESULTS: Respiratory symptoms were present in 29 (62%) patients; the remaining 18 (38%) were asymptomatic. Chest radiography (CXR) revealed intrapulmonary parenchymal lesions (n = 35, 75%) more frequently than pleural lesions (n = 11, 23%). Of the 47 patients, 28 (60%) were referred for suspected lung cancer. The majority of these patients had no symptoms, and 22 (79%) patients with suspected lung cancer had nodular or mass lesions on CXR. As a result, additional diagnostic procedures were performed to make an accurate diagnosis in these patients, including bronchoscopy in 20, transthoracic lung biopsy in 11 and fluorodeoxyglucose positron emission tomography in seven. Surgical lung resection was performed unnecessarily in six patients. CONCLUSIONS: Pulmonary paragonimiasis presenting with nodular or mass lesions on CXR is common. Clinicians should therefore include pulmonary paragonimiasis in the differential diagnosis of asymptomatic nodular lesions in the lung in patients who have lived in or travelled to paragonimiasis-endemic areas.

Risk factors for post-pneumonectomy acute lung injury/acute respiratory distress syndrome in primary lung cancer patients.

Acute lung injury/acute respiratory distress syndrome (ALI / ARDS) is the most serious pulmonary complication after lung resection. This study investigated the incidence and outcome of patients with ALI / ARDS who required mechanical ventilation within one week of undergoing pneumonectomy for primary lung cancer and analysed the risk factors. We retrospectively reviewed the medical records of 146 patients who underwent pneumonectomy for primary lung cancer between May 2001 and April 2006. Preoperative, perioperative and postoperative clinical data were analysed. Post-pneumonectomy ALI / ARDS developed within the first postoperative week in 18 (12%) patients. Patients who developed ALI / ARDS had a longer hospital duration of stay (median [interquartile range], 26 [18 to 75] vs. 8 [7 to 11] days; P < 0.001) and higher in-hospital mortality (12 [67%] vs. 0 [0%]; P < 0.001). In an univariate analysis, post-pneumonectomy ALI / ARDS was associated with larger tidal volume (V(T)) and higher airway pressure (P(aw)) during one-lung ventilation (V(T) 8.2 [7.5 to 9.0] vs. 7.7 [6.9 to 8.2] ml/kg predicted body weight, P = 0.016; P(aw), 28.9 [27.6 to 30.0] vs. 27.2 [25.6 to 28.5] cmH2O, P = 0.001). V(T) during two-lung ventilation was also greater in patients who developed ALI / ARDS (P = 0.014) than in those who did not, but P(aw) during two-lung ventilation did not differ (P = 0.950). In a multiple logistic regression analysis, post-pneumonectomy ALI / ARDS was independently associated with a larger V(T) (OR 3.37 per 1 ml/kg predicted body weight increase; 95% confidence interval 1.65 to 6.86) and higher P(aw) (OR 2.32 per 1 cmH2O increase; 95% confidence interval 1.46 to 3.67) during the period of one-lung ventilation. In conclusion, a large V(T) and high P(aw) during one-lung ventilation were associated with an increased risk of post-pneumonectomy ALI / ARDS in primary lung cancer patients.

Safety and usefulness of bronchoscopy in ventilator-dependent patients with severe thrombocytopenia.

Flexible bronchoscopy is a useful diagnostic procedure in patients with respiratory failure due to unexplained pulmonary infiltrates, but its safety and usefulness in ventilator-dependent patients with severe thrombocytopenia have not been established. A retrospective review of the medical records of all patients who underwent bronchoscopy while receiving mechanical ventilation support at Samsung Medical Centre, Seoul, Korea between January 2002 and July 2006 was conducted. The medical records of 37 patients with severe thrombocytopenia (platelet count <50,000 /microl) at the time of bronchoscopy were analysed. Mean platelet count was 27,300+/-12,500 /microl. The most common underlying condition was haematologic malignancy, which occurred in 21(56.7%) patients, followed by severe sepsis in five (13.6%) and post-liver transplantation complications and autoimmune disease in four each (10.8%). The procedures performed were bronchoalveolar lavage in 33 patients, washing in three and transbronchial lung biopsy in five. Two patients died within 24 hours of completing the procedure. In patients surviving longer than 24 hours, there was no significant decline in oxygenation index (PaO2/FiO2), sequential organ failure assessment score or simplified acute physiological score II after the procedure. Lung compliance significantly decreased at two hours post-bronchoscopy but recovered to the pre-bronchoscopy level by 24 hours. Intensive care unit mortality was 51.4% (19 of 37 patients). Bronchoscopy was helpful in confirming the diagnosis in 17 patients (45.9%). Therapeutic modifications were made in 14 patients (37.8%) after bronchoscopy. Severe thrombocytopenia per se should not preclude bronchoscopy, even in patients receiving mechanical ventilation.

Impaired expression of Toll-like receptor 2 in nontuberculous mycobacterial lung disease.

The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such as Mycobacterium avium and lipoteichoic acid (LTA). Reverse transcriptase-PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-alpha. Expression of TLR2 mRNA by peripheral blood monocytes after stimulation with M. avium or LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-alpha mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreased M. avium- and LTA-induced IL-12 p40 and TNF-alpha production in healthy controls, but not in NTM patients. The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-alpha following Mycobacterium avium or lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.

Pulmonary tuberculosis presenting as acute respiratory failure: radiologic findings.

PURPOSE: The purpose of this work was to describe the radiologic findings of pulmonary tuberculosis in patients who presented with acute respiratory failure. METHODS: We included patients who had newly diagnosed active pulmonary tuberculosis and who presented with acute respiratory failure. Initial chest radiographic (n = 17) and high-resolution CT (n = 11) findings of each patient were analyzed retrospectively. RESULTS: Of 1,010 patients with active pulmonary tuberculosis, 17 patients (1.7%) presented with acute respiratory failure. Nine (53%) of the 17 patients died. The most common initial chest radiographic findings were small nodular lesions (16/17; 94%), consolidation (13/17; 76%), and ground-glass opacity (12/17; 70%). Eleven (69%) of 16 nodular lesions, 9 of 13 (69%) consolidations, and 10 of 12 (83%) ground-glass opacities were bilateral. On HRCT (n = 11), miliary micronodular lesions were seen in 6 patients (55%), whereas bronchogenic spread of tuberculosis with disseminated centrilobular nodules and tree-in-bud appearance was seen in 5 patients (45%). Diffuse areas of ground-glass attenuation were seen in all six patients with miliary nodules and four of five patients with bronchogenic spread of tuberculosis. CONCLUSION: Patients with pulmonary tuberculosis occasionally present with acute respiratory failure. In this condition, chest radiograph most commonly shows bilateral small nodular lesions mixed with consolidation or ground-glass opacity, whereas HRCT demonstrates findings of miliary or bronchogenic disseminated tuberculosis with diffuse areas of ground-glass attenuation.

Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation.

In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24 h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24 h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS (P < 0.05) or tubercle bacilli (P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1beta, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.

Partial liquid ventilation with perfluorocarbon improves gas exchange and decreases inflammatory response in oleic acid-induced lung injury in beagles.

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.

Predictors for benign solitary pulmonary nodule in tuberculosis-endemic area.

BACKGROUND: Solitary pulmonary nodule (SPN) may show different presentation in tuberculosis (TB)-endemic countries. The aim of this study was to identify clinical and radiological predictors favoring benign or malignant SPN in TB-endemic region. METHODS: Two hundred one SPNs in 201 consecutive Korean patients were included (< 3 cm in diameter, all confirmed by pathology or bacteriology, 93 benign and 108 malignant diseases). For clinical parameters, age, sex, smoking status and amount, and past history of pulmonary tuberculosis and diabetes mellitus were investigated retrospectively. For radiological parameters, size, location, margin characteristics, presence of calcification, pleural tag, surrounding satellite nodule, cavitation, internal low attenuation, open bronchus sign, surrounding ground-glass opacity, enhancement pattern of the SPNs and mediastinal lymph node (LN) enlargement were analyzed on chest CT scans. RESULTS: Patients with a older age (60.7 +/- 9.6 vs 56.2 +/- 13.1, p = 0.008) and more than 40-pack years smoking (27.8% vs 14.0%, p = 0.017) were more frequently related with malignant than benign SPN. On chest CT scans, spiculated margin, contrast enhancement more than 20 Hounsfield unit and presence of pleural tag and mediastinal LN enlargement were more frequently observed in malignant than benign SPNs. In contrast to previous studies, satellite lesions (21.5% vs 1.9%, p < 0.001) and cavitation (20.4% vs 5.6%, p = 0.001) were more frequently seen in benign than malignant SPN. Positive predictive values of benignity were 90.9% and 76.0%, respectively, when satellite lesions and cavitation were found in cases of SPN. CONCLUSION: Satellite lesions and cavitation on chest CT scan could be useful predictors for benign SPN in TB-endemic areas.

Small airway disease in rheumatoid arthritis.

Variety of pulmonary lesions are thought to be associated with rheumatoid arthritis (RA). These lesions traditionally have included pleurisy with or without effusion, Caplan's syndrome, pulmonary rheumatoid nodules, diffuse interstitial fibrosis, and pulmonary arteritis and hypertension. But little attention has been paid to the airways in RA. Recently, several reports have suggested an association between airflow limitation and RA, but its incidence is not known. Also whether there exists a parameter of disease activity of RA, suggesting the presence of small airway disease (SAD) is not clear. To answer these questions, the serologic parameters which reflect the disease activity of RA and pulmonary function tests which reflect small airway dysfunction were performed on 36 lifetime nonsmokers with RA who had normal chest x-ray findings. The prevalence of SAD and the relationships between the disease activity parameters of RA and pulmonary function were observed. The results were as follows. The percentages of patients with abnormal values for diffusing capacity, frequency dependence of compliance (C1.0/C0.0), forced expiratory flow 25-75%, Vmax50% and Vmax 75% were 45.5%, 62.5%, 40%, 22.8% and 11.4%, respectively. There was statistically significant negative correlation between C1.0/C0.0 and ESR. But consistent correlation between other pulmonary function tests and clinical and serologic parameters of RA, and differences in pulmonary function between patients who were serologically positive and negative for CRP and FANA, were not found. In conclusion, SAD, without the influence of smoking, is frequently associated with RA, but the presence of SAD cannot be predicted from any clinical and serologic parameters of RA currently in use.