Man Pyo Chung

Treatment Outcomes for HIV-Uninfected Patients with Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

BACKGROUND Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB, we assessed the treatment outcomes and prognostic factors for patients with MDR TB. METHODS This study included patients who received an individualized treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea, from January 1995 through December 2004. To identify the prognostic factors related to favorable treatment outcomes, univariate comparison and multiple logistic regression were performed. RESULTS Of 155 patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received treatment with first-line drugs, and 56 (36%) had received treatment with second-line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty-seven patients (17%) had extensively drug-resistant (XDR) TB at the start of treatment. Outcome assessment revealed that 102 patients (66%) were cured or completed therapy. The treatment success rates did not differ significantly between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%). Surgical resection was performed more frequently for patients with XDR TB than for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body mass index >/=18.5 (calculated as the weight in kilograms divided by the square of the height in meters), use of >4 effective drugs, and a negative sputum smear result were independent predictors of a favorable outcome. CONCLUSIONS Early aggressive treatment comprising at least 4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB.

Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases

OBJECTIVES Chronic necrotizing pulmonary aspergillosis (CNPA) is uncommon, and the optimal therapeutic regimen has not been established. In a retrospective cohort study, we investigated the clinical characteristics and treatment outcomes of patients with CNPA. METHODS We reviewed the medical records of all patients who had been diagnosed with CNPA at our institution over the last 10 years. RESULTS Forty-three patients were identified. Their median age was 60 years (interquartile range (IQR) 45-65 years), and 34 (79%) of the patients were men. The most common underlying lung disease was pulmonary tuberculosis (n=40, 93%). After CNPA was diagnosed, all patients were treated with antifungal drugs, including oral itraconazole (n=39, 91%) or intravenous amphotericin B (n=4, 9%). Seventeen (40%) patients discontinued therapy early (<3 months), 14 patients due to death and three to loss of follow-up. Twenty-six (60%) patients received oral itraconazole at a daily dose of 200-400mg for more than 3 months. The median treatment duration was 6 months (IQR 6-12 months). In these 26 patients, clinical improvement was observed in 15 (58%) and radiological improvement was observed in 11 (42%). Ten (38%) patients showed no improvement. Twenty-two (51%) patients died, including 18 (42%) CNPA-related deaths, during a median follow-up of 15 months (IQR 2.5-32 months). The median survival time was 62 months. CONCLUSIONS CNPA is difficult to treat and often has a poor outcome. Further studies with more patients are needed to identify the optimal therapy for patients with CNPA.

Prognostic Determinants among Clinical, Thin-Section CT, and Histopathologic Findings for Fibrotic Idiopathic Interstitial Pneumonias: Tertiary Hospital Study

PURPOSE To evaluate the utility of clinical, thin-section computed tomography (CT), and histopathologic findings in predicting the prognosis of patients with usual interstitial pneumonia (UIP) or fibrotic nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS The institutional review board approved this retrospective study, with waiver of informed consent. Included were 108 patients (71 men, 37 women; mean age, 61 years +/- 8 [standard deviation]) with UIP (n = 79; 60 men, 19 women; mean age, 63 years +/- 7.4) and fibrotic NSIP (n = 29; 11 men, 18 women; mean age, 57 years +/- 12.9). Patients underwent pulmonary function tests (PFTs), bronchoalveolar lavage (BAL) fluid analysis, and thin-section CT. Two chest radiologists independently assigned scores for the extent of lung abnormalities detected at CT twice at 3-month intervals. The effect of histopathologic diagnoses and clinical and thin-section CT features on survival was evaluated by using Cox regression analyses. RESULTS The 5-year survival rate (mean follow-up, 45 months) of patients with fibrotic NSIP was 76% in contrast to 46% for patients with UIP (P = .006). With multivariate analysis, a high fibrotic score (the extent of reticulation plus honeycombing) (hazard ratio = 1.200, P = .043) and an initial low diffusing capacity of lung for carbon monoxide (Dlco) level (hazard ratio = 0.973, P = .025) were identified as associated with increased death risk. CONCLUSION Patients with UIP or fibrotic NSIP who have a high fibrotic score determined at thin-section CT and a low Dlco level appear to have a high death risk.

Natural History of Pure Ground-Glass Opacity Lung Nodules Detected by Low-Dose CT Scan

BACKGROUND Although focal ground-glass opacity (GGO) lung nodules are generally reported to grow slowly, their natural course is unclear. The purpose of this study was to elucidate the natural course of screening-detected pure GGO lung nodules in patients with no history of malignancy. METHODS We retrospectively reviewed the database of subjects who had undergone screenings involving low-dose CT scans. We included patients with pure GGO lung nodules who were followed for > 2 years after the initial screening. RESULTS Between June 1997 and September 2006, 122 pure GGO nodules were found in 89 patients. The median nodule size was 5.5 mm (range, 3-20 mm) in the largest diameter on initial low-dose CT scan. The median follow-up period per patient was 59 months. On a per-person basis, the frequency of growth was 13.5% (12 of 89 patients). On a per-nodule basis, the frequency of growth was 9.8% (12 of 122 nodules). Nodule growth was significantly associated with initial size and new development of an internal solid portion. The median volume doubling time was 769 days for growing pure GGO nodules. A total of 11 growing nodules were surgically validated, and all lesions were confirmed as primary lung cancer. CONCLUSIONS About 90% of the screening-detected pure GGO lung nodules did not grow during long-term follow-up in subjects with no history of malignancy and most growing nodules had an indolent clinical course. A strategy of long-term follow-up and selective surgery for growing nodules should be considered for pure GGO lung nodules.

Amyloidosis and lymphoproliferative disease in Sjogren syndrome : thin-section computed tomography findings and histopathologic comparisons

Objective: To describe the thin-section computed tomography (CT) findings of Sjögren syndrome accompanying pulmonary amyloidosis and lymphoproliferative disease and to compare these with histopathologic findings. Subjects and Methods: The thin-section CT findings of 5 women (age range: 42-59 years, mean age = 50 years) with primary Sjögren syndrome accompanying pulmonary amyloidosis and lymphoproliferative disease were reviewed retrospectively by 2 chest radiologists, and decisions on findings were reached by consensus. The pathologic specimens of parenchymal lesions (nodules, dense consolidation, and cystic lesion at CT) obtained using video-assisted thoracoscopic surgery were studied to compare with the thin-section CT findings. Results: Nodules, observed in all 5 patients, were variable in size and ranged from 3 to 24 mm (mean = 9.9 mm) in diameter, with lobulated or irregular margins. Nodular calcifications were present in 3 patients. Cysts, which also were observed in all patients, ranged from 4 to 45 mm (mean = 18.6 mm) in diameter, with a thin (1-2 mm) or no visible wall. Multiple cysts were observed, especially in the distal portion of narrowed bronchioles. Nodules and cysts showed a random distribution. Mild bronchial wall thickening with bronchial dilatation was seen in all patients, ground-glass opacities were seen in 3, and consolidation was seen in 1. Nodules, consolidation, and bronchial wall thickening at CT were caused histopathologically by the interstitial and peribronchiolar deposition of mixed amyloid and lymphoproliferative cells. Cysts lined with respiratory epithelium contained amyloid deposition and lymphoproliferative cells in their walls. Conclusion: Sjögren syndrome accompanying pulmonary amyloidosis and lymphoproliferative disease manifests as multiple, large, thin-walled cysts; multiple nodules; parenchymal opacity; and bronchiectasis. These findings are caused by the interstitial or peribronchial infiltration of mixed amyloid and lymphoproliferative cells.

Thoracic involvement of systemic lupus erythematosus: clinical, pathologic, and radiologic findings.

Thoracic involvement occurs more frequently in systemic lupus erythematosus than in any other connective tissue diseases, and more than half of patients with the disease suffer from the involvement. Primary intrathoracic manifestations include pleural disease (effusions and/or thickening), acute lupus pneumonitis, subacute interstitial lung disease including bronchiolitis obliterans organizing pneumonia and non-specific interstitial pneumonia with fibrosis, chronic interstitial lung disease of usual interstitial pneumonia, pulmonary hemorrhage, pulmonary vascular disease, small airway disease of bronchiolitis obliterans, and pulmonary arterial hypertension. Secondary intrathoracic manifestations include atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, drug and oxygen toxicity, aspiration, and pleuropulmonary consequences of cardiac and renal failure.

Repeated derecruitments accentuate lung injury during mechanical ventilation.

OBJECTIVES The aim of our study was to assess whether repeated derecruitments induced by the repetitive withdrawal of high positive end-expiratory pressure could induce lung injury in a swine model. DESIGN Prospective, randomized, experimental animal study. SETTING University laboratory. SUBJECTS Specific pathogen-free pigs (Choong-Ang Laboratory Animals, Seoul, Korea) weighing around 30 kg. INTERVENTIONS After lung injury was induced by repeated saline lavage, pigs were ventilated in pressure-limited mode with the highest possible positive end-expiratory pressure with a tidal volume of 8 mL/kg and maximum inspiratory pressure of 30 cm H2O. With this initial ventilator setting, the control group (n = 5) received ventilation without derecruitments for 4 hours, and in the derecruitment group (n = 5), derecruitments were repeatedly induced by intentional disconnection of the ventilatory circuit for 30 seconds every 5 minutes for 4 hours. MEASUREMENTS AND MAIN RESULTS After the initial increase in positive end-expiratory pressure, the PaO2 increased to greater than 450 mm Hg in both groups. The PaO2 remained at greater than 450 mm Hg in the control group persistently, but in the derecruitment group, PaO2 significantly decreased to 427.7 mm Hg (adjusted p = 0.03) after 2 hours and remained significant for the rest of the study. PaCO2, oxygenation index, and alveolar-arterial oxygen gradient also significantly increased after 2 hours compared with the control group. However, the variables of respiratory mechanics except for minute volume at 2-hour point showed no difference between the two groups for the duration of the study. Histologically, significant bronchiolar injury was observed in the dependent portion of the derecruitment group compared with the controls (p = 0.03), but not in the nondependent area of the lung. CONCLUSIONS Repeated derecruitments exacerbated lung injury, particularly at the bronchiolar level in the dependent portion. Strategies to minimize this type of injury should be incorporated when designing optimal ventilator strategies in acute respiratory distress syndrome patients.Objectives:The aim of our study was to assess whether repeated derecruitments induced by the repetitive withdrawal of high positive end-expiratory pressure could induce lung injury in a swine model. Design:Prospective, randomized, experimental animal study. Setting:University laboratory. Subjects:Specific pathogen-free pigs (Choong–Ang Laboratory Animals, Seoul, Korea) weighing around 30 kg. Interventions:After lung injury was induced by repeated saline lavage, pigs were ventilated in pressure-limited mode with the highest possible positive end-expiratory pressure with a tidal volume of 8 mL/kg and maximum inspiratory pressure of 30 cm H2O. With this initial ventilator setting, the control group (n = 5) received ventilation without derecruitments for 4 hours, and in the derecruitment group (n = 5), derecruitments were repeatedly induced by intentional disconnection of the ventilatory circuit for 30 seconds every 5 minutes for 4 hours. Measurements and Main Results:After the initial increase in positive end-expiratory pressure, the PaO2 increased to greater than 450 mm Hg in both groups. The PaO2 remained at greater than 450 mm Hg in the control group persistently, but in the derecruitment group, PaO2 significantly decreased to 427.7 mm Hg (adjusted p = 0.03) after 2 hours and remained significant for the rest of the study. PaCO2, oxygenation index, and alveolar-arterial oxygen gradient also significantly increased after 2 hours compared with the control group. However, the variables of respiratory mechanics except for minute volume at 2-hour point showed no difference between the two groups for the duration of the study. Histologically, significant bronchiolar injury was observed in the dependent portion of the derecruitment group compared with the controls (p = 0.03), but not in the nondependent area of the lung. Conclusions:Repeated derecruitments exacerbated lung injury, particularly at the bronchiolar level in the dependent portion. Strategies to minimize this type of injury should be incorporated when designing optimal ventilator strategies in acute respiratory distress syndrome patients.

Inactive Hepatitis B Surface Antigen Carrier State and Hepatotoxicity During Antituberculosis Chemotherapy

STUDY OBJECTIVES To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide. DESIGN Retrospective case-control study. SETTING Tertiary university medical center. PATIENTS One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects. RESULTS The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects). CONCLUSIONS Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.

Imaging of Pulmonary Vasculitis

The presence of pulmonary vasculitis can be suggested by a clinical presentation that includes diffuse pulmonary hemorrhage, acute glomerulonephritis, chronic refractory sinusitis or rhinorrhea, imaging findings of nodules or cavities, mononeuritis multiplex, multisystemic disease, and palpable purpura. Serologic tests, including the use of cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and perinuclear ANCA, are performed for the differential diagnosis of the diseases. A positive cytoplasmic ANCA test result is specific enough to make a diagnosis of ANCA-associated granulomatous vasculitis if the clinical features are typical. Perinuclear ANCA positivity raises the possibility of Churg-Strauss syndrome or microscopic polyangiitis. Imaging findings of pulmonary vasculitis are diverse and often poorly specific. The use of a pattern-based approach to the imaging findings may help narrow the differential diagnosis of various pulmonary vasculitides. Integration of clinical, laboratory, and imaging findings is mandatory for making a reasonably specific diagnosis.

Pulmonary involvement in Churg-Strauss syndrome: an analysis of CT, clinical, and pathologic findings

We tried to assess retrospectively thin-section CT findings of Churg-Strauss syndrome (CSS) in 25 patients and to compare these findings with clinical and histopathologic findings. Of 25 patients, 19 (76%) had parenchymal abnormalities at CT; small nodules (n = 12; 63%), ground-glass opacity (n = 10; 53%), bronchial wall thickening (n = 10; 53%), and consolidation (n = 8; 42%). Parenchymal abnormalities (n = 19) were categorizable as an airway pattern in 11 and an airspace pattern in eight. Patients with an airway pattern (n = 5) had obstructive (n = 3) or combined (n = 2) PFT results, whereas those with an airspace pattern (n = 4) had restrictive (n = 3) or obstructive (n = 1) results. Parenchymal opacities at CT corresponded histologically to areas of eosinophilic pneumonia, necrotizing granulomas, and granulomatous vasculitis; small nodules to eosinophilic bronchiolitis and peribronchiolar vasculitis; and bronchial wall thickening to airway wall eosinophil and lymphocyte infiltration. Patients with airspace pattern responded more readily to treatment than those with airway pattern. CT shows lung parenchymal abnormalities in about three-quarters of CSS patients and these abnormalities can be categorized as airspace or airway patterns. This classification helps predict PFT data, underlying histopathology, and treatment response.