Yangjin Jegal

Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia

Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have primarily studied mortality. In order to clarify the detailed outcome and prognostic markers in idiopathic NSIP, the clinical course with initial radiological and clinical features was analysed. The clinical course of 83 patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27 males and 56 females; mean±sd age 54.4±10.1 yrs) was retrospectively analysed. In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a median (range) follow-up of 53 (0.3–181) months. Despite the favourable survival (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with recurrence rate of 36%. Reduced forced vital capacity at 12 months was a predictor of mortality. On follow-up, lung function was improved or stable in ∼80% of the patients. The extent of consolidation and ground-glass opacity on initial high-resolution computed tomography correlated significantly with serial changes of lung function, and the presence of honeycombing was a predictor of poor prognosis. During follow-up, eight (10%) patients developed collagen vascular disease. In conclusion, the overall prognosis of fibrotic nonspecific interstitial pneumonia was good; however, there were significant recurrences despite initial improvement and a subset of the patients did not respond to therapy. Some patients developed collagen vascular diseases at a later date.

Comparison between cryptogenic organizing pneumonia and connective tissue disease-related organizing pneumonia

OBJECTIVE Although the overall prognosis of CTD-related interstitial pneumonia is better than that of idiopathic interstitial pneumonia, the prognosis of CTD-related organizing pneumonia (CTD-OP) was suggested to be worse than that of cryptogenic organizing pneumonia (COP). The aim of this study was to compare the clinical features and outcome of the two conditions. METHODS A retrospective review of 100 patients diagnosed by lung biopsy as having organizing pneumonia patterns (CTD, 24; COP, 76) at three tertiary referral centres. RESULTS Underlying CTDs were mostly RA, SS and PM/DM. The median follow-up period was 43.6 months. There were no differences in initial symptoms, lung function or bronchoalveolar lavage fluid findings except significantly more females (83.3 vs. 59.2%, P = 0.048) in the CTD-OP than in the COP group. Over 80% of the patients in both the groups improved. However, complete recovery rate was lower in CTD-OP (20.8%) than in COP (46.1%; P = 0.028) with a tendency towards higher recurrence rate in CTD-OP (40.0 vs 20.3%; P = 0.072). There was no significant difference in the frequency of rapid progression or overall survival between the two groups. CONCLUSIONS The clinical features and prognosis of CTD-OP are similar to COP. However, lower complete recovery rate with a tendency towards higher recurrence rate in CTD-OP compared with COP suggest the need for closer follow-up in patients with CTD-OP.

γ-Herpes virus-68, but not Pseudomonas aeruginosa or influenza A (H1N1), exacerbates established murine lung fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) often do worse following infection, but the cause of the decline is not fully understood. We previously demonstrated that infection with a murine gamma herpes virus (γHV-68) could exacerbate established lung fibrosis following administration of fluorescein isothiocyanate (McMillan et al. Am J Respir Crit Care Med 177: 771-780, 2008). In the present study, we anesthetized mice and injected saline or bleomycin intratracheally on day 0. On day 14, mice were anesthetized again and infected with either a Gram-negative bacteria (Pseudomonas aeruginosa), or with H1N1 or γHV-68 viruses. Measurements were then made on days 15, 21, or 35. We demonstrate that infection with P. aeruginosa does not exacerbate extracellular matrix deposition post-bleomycin. Furthermore, fibrotic mice are effectively able to clear P. aeruginosa infection. In contrast, bleomycin-treated mice develop worse lung fibrosis when infected with γHV-68, but not when infected with H1N1. The differential ability of γHV-68 to cause increased collagen deposition could not be explained by differences in inflammatory cell recruitment or whole lung chemokine and cytokine responses. Alveolar epithelial cells from γHV-68-infected mice displayed increased expression of TGFβ receptor 1, increased SMAD3 phosphorylation, and evidence of apoptosis measured by cleaved poly-ADP ribose polymerase (PARP). The ability of γHV-68 to augment fibrosis required the ability of the virus to reactivate from latency. This property appears unique to γHV-68, as the β-herpes virus, cytomegalovirus, did not have the same effect.

The Clinical Efficacy of GOCA Scoring System in Patients with Acute Respiratory Distress Syndrome

To explore the following hypotheses: 1) Gas exchange, Organ failure, Cause, Associated disease (GOCA) score, which reflects both general health and the severity of lung injury, would be a better mortality predictor of acute respiratory distress syndrome (ARDS) than acute physiology and chronic health evaluation (APACHE II) or simplified acute physiology score (SAPS II), which are not specific to lung injury, and lung injury score (LIS) that focuses on the lung injury; 2) the performance of APACHE II and SAPS II will be improved when reinforced by LIS, we retrospectively analyzed ARDS patients (N=158) admitted to a medical intensive care unit for five years. The overall mortality of the ARDS patients was 53.2%. Calibrations for all models were good. The area under the curve of (AUC) of LIS (0.622) was significantly less than those of APACHE II (0.743) and SAPS II (0.753). The AUC of GOCA (0.703) was not better than those of APACHE II and SAPS II. The AUCs of APACHE II and SAPS II tended to further increase when reinforced by LIS. In conclusion, GOCA was not superior to APACHE II or SAPS II. The performance of the APACHE II or SAPS II tended to improve when combining a general scoring system with a scoring system that focused on the severity of lung injury.

Hypoxemia and Arrhythmia during Daily Activities and Six-minute Walk Test in Fibrotic Interstitial Lung Diseases

We performed 24-hr monitoring of pulse oximetric saturation (SpO2) with ECG and six-minute walk test (6MWT) in 19 patients with fibrotic interstitial lung diseases (ILD) to investigate; 1) The frequency and severity of hypoxemia and dysrhythmia during daily activities and 6MWT, 2) safety of 6MWT, and 3) the parameters of 6MWT which can replace 24-hr continuous monitoring of SpO2 to predict hypoxemia during daily activities. All patients experienced waking hour hypoxemia, and eight of nineteen patients spent > 10% of waking hours in hypoxemic state. Most patients experienced frequent arrhythmia, mostly atrial premature contractions (APCs) and ventricular premature contractions (VPCs). There were significant correlation between the variables of 6MWT and hypoxemia during daily activities. All of the patients who desaturated below 80% before 300 meters spent more than 10% of waking hour in hypoxemia (P = 0.018). In contrast to waking hour hypoxemia, SpO2 did not drop significantly during sleep except in the patients whose daytime resting SpO2 was already low. In conclusion, patients with fibrotic ILD showed significant period of hypoxemia during daily activities and frequent VPCs and APCs. Six-minute walk test is a useful surrogate marker of waking hour hypoxemia and seems to be safe without continuous monitoring of SpO2.

A Case of Atypical Skull Base Osteomyelitis with Septic Pulmonary Embolism

Skull base osteomyelitis (SBO) is difficult to diagnose when a patient presents with multiple cranial nerve palsies but no obvious infectious focus. There is no report about SBO with septic pulmonary embolism. A 51-yr-old man presented to our hospital with headache, hoarseness, dysphagia, frequent choking, fever, cough, and sputum production. He was diagnosed of having masked mastoiditis complicated by SBO with multiple cranial nerve palsies, sigmoid sinus thrombosis, and septic pulmonary embolism. We successfully treated him with antibiotics and anticoagulants alone, with no surgical intervention. His neurologic deficits were completely recovered. Decrease of pulmonary nodules and thrombus in the sinus was evident on the follow-up imaging one month later. In selected cases of intracranial complications of SBO and septic pulmonary embolism, secondary to mastoiditis with early response to antibiotic therapy, conservative treatment may be considered and surgical intervention may be withheld.

Regional differences of nontuberculous mycobacteria species in Ulsan, Korea

BACKGROUND In Korea recently, nontuberculous mycobacteria (NTM) have been more frequently isolated in respiratory specimens, while Mycobacterium tuberculosis (MTB) isolations have decreased. The major NTM lung disease species in Korea are M. intracellulare, M. avium, and M. abscessus, whereas M. kansasii is a rare species. This retrospective study was performed to determine if there are region-specific characteristics of lung disease-causing NTM species in Ulsan, a highly industrialized city in Korea. METHODS Between January 2010 and July 2013, the results of all acid-fast bacilli (AFB) cultures of respiratory specimens performed at Ulsan University Hospital (Ulsan, Korea) were collected. NTM were identified and regional differences of NTM species were compared. RESULTS AFB cultures were performed on 33,567 respiratory specimens, obtained from 10,208 patients, during the study period. Further, 10% of the specimens (3,287/33,567) were AFB culture-positive [MTB, 2,288/3,287 (70%); NTM 999/3,287 (30%)]. The proportion of NTM isolations gradually increased between 2010 and 2013, at 25% and 38%, respectively. The most common NTM species was M. intracellulare (356/999, 36%), followed by M. kansasii (295/999, 30%), M. avium (161/999, 16%), M. abscessus (117/999, 12%) and M. fortuitum (39/999, 4%). This trend was maintained throughout the study period. CONCLUSIONS In Ulsan, NTM isolation from respiratory specimens is increasing, consistent with previous studies performed in Korea. The distribution of respiratory NTM species, however, differed from previous studies that were performed in other regions of Korea: M. kansasii was the second most common NTM species in Ulsan. In Ulsan, there is a regional difference in the NTM species isolated.

The combination of real-time PCR and HPLC for the identification of non-tuberculous mycobacteria.

We used HPLC and AdvanSure real-time PCR (LG Life Sciences, Korea) to retrospectively analyze non-tuberculous mycobacteria (NTM) in 133 clinical specimens. The specimens were culture-positive for NTM and the HPLC method identified 130 strains of mycobacteria from the cultures (97.7%) at the species level. Among the isolates, 48 Mycobacterium. kansasii (36.1%), 39 M. intracellulare (29.3%), 17 M. avium (12.8%), 16 M. abscessus (12.0%), 6 M. fortuitum (4.5%), 2 M. szulgai (1.5%), 2 M. gordonae (1.5%), and 3 unclassified NTM strains (2.3%) were identified. The real-time PCR assay identified 60 NTM-positive specimens (45.1%), 65 negative specimens (48.9%), and 8 M. tuberculosis (TB)-positive specimens (6.0%). The real-time PCR assay is advantageous because of its rapid identification of NTM. However, in our study, the real-time PCR assay showed relatively low sensitivity (45.1%) when using direct specimens including sputum and bronchoalveolar lavage (BAL) fluid. HPLC is useful as it discriminates NTM at the species level, although it is time-consuming and requires specific equipment and technical expertise. A combination of both methods will be helpful for the rapid and accurate identification of mycobacteria in clinical laboratories.

Hemothorax caused by spontaneous rupture of a metastatic mediastinal lymph node in hepatocellular carcinoma: a case report.

To the Editor, The frequency of massive hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma (HCC) has been reported to be 10% to 18% because of the extensive vascular structure and relatively small amount of fibrous tissue in these tumors [1]. Hemothorax caused by rupture of a lung or pleural metastasis of HCC occurs less frequently. Although one case of cardiac tamponade caused by spontaneous rupture of a metastatic mediastinal lymph node (MLN) has been described [2], to our knowledge, no case of hemothorax due to spontaneous rupture of a metastatic MLN of HCC has been reported in the Korean- or English-language literature. We describe here a case of massive hemothorax due to spontaneous rupture of a metastatic MLN in HCC. A 60-year-old male Korean farmer was brought to the Department of Emergency, Ulsan University Hospital with dyspnea and left pleuritic chest pain within 6 hours after symptom onset. Six years earlier, he was diagnosed with chronic hepatitis B-related cirrhosis and 4 years earlier he had been diagnosed with HCC (Fig. 1A) and underwent a right hepatic lobectomy. Multiple metastatic pulmonary nodules were detected 3 months after the surgery and the patient received six cycles of a cisplatin-based chemotherapy regimen over 6 months. Contrast-enhanced computed tomography (CT) scanning showed complete disappearance of the multiple metastatic lung nodules after chemotherapy. At 8 months after finishing the chemotherapy, however, he was readmitted to our hospital due to a single metastatic nodule in the left lower lobe of the lung and underwent metastasectomy with video-assisted thoracoscopic surgery (VATS). Pathological examination of the lung nodule removed showed results consistent with metastatic HCC. Figure 1 Chest computed tomography scans showing (A) a 10-cm sized intrahepatic peripheral capsular enhanced mass, (B) a single enlarged lymph node (white arrow) in the left inferior pulmonary ligament, and (C) a 73 × 84-mm ruptured low-attenuated central ... At 1 year before admission, CT images of the chest showed a single enlarged lymph node (LN) in the left inferior pulmonary ligament, regarded as a metastatic MLN of HCC (Fig. 1B). Two weeks before this admission, follow-up CT images showed enlargement of the metastatic MLN, and the patient was scheduled for additional chemotherapy. On the day of admission, the patient experienced an abrupt onset of dyspnea and left pleuritic chest pain. Physical examination on admission revealed an acutely ill-looking man with body temperature of 36.5℃, pulse rate of 130 beats per minute, blood pressure of 100/70 mmHg, and a respiration rate of 32 breaths per minute. Laboratory test results included hemoglobin 12.3 g/dL, hematocrit 33.4%, white blood cell count 4.37 × 103/µL, platelet count 9.9 × 104/µL, aspartate aminotransferase 47 IU/L, alanine aminotransferase 60 IU/L, total bilirubin 2.0 mg/dL, albumin 3.2 mg/dL, and α-fetoprotein 819.2 ng/mL. Chest X-rays showed a massive left-sided pleural effusion, with the trachea deviated to the right side. Massive hemothorax was diagnosed by thoracentesis. CT images of the chest revealed a 73 × 84 mm-sized ruptured low-attenuated central necrotic mass with massive left side hemothorax (Fig. 1C). A chest tube was inserted and approximately 1,200 mL of bloody fluid was drained. Arteriography of the bronchial arteries revealed a massive ruptured LN in the left inferior pulmonary ligament, to which blood was supplied by an accessory bronchial artery originating 10 cm beneath the left bronchial artery. These findings indicated that the massive hemothorax was caused by a spontaneous rupture of a metastatic MLN of HCC into the intrapleural space. Transcatheter arterial embolization (TAE) of the left bronchial artery was performed successfully, injecting 13 mL of lipiodol ultraf luide (Guerbet, Aulnay-sous-Bois, France) and 30 mg of adriamycin (doxorubicin hydrochloride) with polyvinyl alcohol particles (contour emboli, Interventional Therapeutics Corp., Fremont, CA, USA) (Fig. 1D). No complication was observed and the pleural effusion gradually disappeared thereafter. The patients dyspnea improved, as did his physical condition. Following removal of the chest tube, he was discharged after 15 days in the hospital and was followed monthly as an outpatient at the department of oncology for 3 months. Serial chest X-rays revealed a decrease in the size of the MLN with lipiodol embolization. Four months later, however, the patient died at home. Due to its vascular structure and relatively small amount of fibrous tissue, spontaneous rupture of HCC is not uncommon [1]. Rupture of HCC is considered a medical emergency and is associated with high mortality. HCC frequently metastasizes, most often to the lungs, LNs, bones, and adrenal glands. Moreover, HCC metastases, like the primary tumors, may rupture spontaneously. Sohara et al. [3] reviewed 10 cases with HCC complicated by hemothorax, including four case reports in Japanese, describing patients with metastasis to the chest wall and rib, lung, pleura, diaphragm, and MLN [4]. Those reports included the first case of hemothorax from spontaneous rupture of a mediastinal metastasis [4]. Common clinical presentations are chest pain and dyspnea initially [3]. Other signs are palpitations and hypotension, consistent with hypovolemic shock. Reported rare signs included massive hemoptysis and respiratory failure. Our patient also developed hemothorax with sudden-onset chest pain, dyspnea, and tachycardia. Ruptured HCC can be treated surgically or by TAE, with the latter now used widely for HCC ruptured into the peritoneal cavity. Masumoto et al. [5] first reported hemothorax due to HCC rupture successfully controlled by TAE and our case was also successfully controlled using TAE. On the other hand, surgically treated and untreated failures have been reported and drainage-only cases do allow complete control [3]. Our patient had been diagnosed with HCC 4 years earlier and had undergone various treatments, including right hepatic lobectomy, six cycles of chemotherapy for multiple lung metastases, VATS metastasectomy for a single metastasis in the lung, and TAE for rupture of metastatic MLN causing massive hemothorax. TAE was effective, in that bleeding was successfully controlled and pleural effusion did not recur. Our findings suggest that patients with HCC should be closely monitored and suitably managed to improve survival. In conclusion, this is the first report of hemothorax secondary to spontaneous rupture of metastatic MLN of HCC in the Korean- or English-language literature. The hemothorax was successfully treated with TAE. The various manifestations observed in patients with HCC suggest the need for careful monitoring and suitable management.

A Case of Alveolar Soft Part Sarcoma of the Pleura

Alveolar soft part sarcoma (ASPS) is a rare malignant soft-tissue neoplasm of unknown histogenesis. The two main sites of occurrence are the lower extremities in adults and the head and neck in children. We report the first case of pleural ASPS occurring in a 58-yr-old man who presented with progressive dyspnea. A computed tomographic scan of the thorax revealed a large enhancing pleural mass with pleural effusion in the left hemithorax. Wide excision of the pleural mass was performed. Histologically, the tumor consisted of organoid nests of large polygonal cells, the cytoplasm of which had eosinophilic and D-PAS positive granules. Immunohistochemical staining showed that the tumor cell nuclei were positive for transcription factor 3 (TFE3). The pleural ASPS with multiple bone metastases recurred 1 yr after surgery and the patient died of acute pulmonary embolism 1.5 yr after diagnosis.