Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias.

BACKGROUND: Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP. METHODS: This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis. RESULTS: In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters. INTERPRETATION: These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

Analysis of drug treatment outcome in clarithromycin-resistant Mycobacterium avium complex lung disease.

BACKGROUND: Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease. METHODS: Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 µg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings. RESULTS: Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found. CONCLUSIONS: Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.

Thoracoscopic examination of empyema in a patient with sparganosis mansoni.

A 27-year-old man was admitted to our hospital with right pleural effusion. He had suffered from right chest and back pain and a high fever for one week prior to the admission. He had been treated with clarithromycin without improvement. Since thoracoscopy under local anesthesia revealed purulent effusion, synechiae and fibrous septa in the thoracic cavity, synechiotomy was performed and we started antibiotic treatment with the diagnosis of acute bacterial empyema. At the same time, we also suspected parasitic infection because of massive eosinophilic infiltration in pleural effusion and his dietary history of eating raw frogs. During the course of the disease, he had an infiltration in the right lower lobe and pneumothorax. Finally, we diagnosed him with sparganosis mansoni because his serum as well as pleural effusion was positive for the binding to sparganosis mansoni plerocercoid antigen, without any positive findings in bacteriology. His pleural effusion and lung infiltration were resolved after the administration of a high-dose praziquantel. We report this rare parasitic empyema with findings by thoracoscopic examination.

[CLINICAL EFFECTS OF INTRAVENOUSLY ADMINISTERED LEVOFLOXACIN IN PATIENTS WITH PULMONARY TUBERCULOSIS: A RETROSPECTIVE STUDY].

OBJECTIVES: Our aim was to investigate the clini- cal effects of levofloxacin (LVFX) administered intravenously to patients with pulmonary tuberculosis. METHODS: We studied 65 patients hospitalized at The National Hospital Organization Tokyo National Hospital between January 2010 and December 2012. The patients did not have human immunodeficiency virus (HIV) infection, and received anti-tuberculous drugs intravenously due to the inability to receive drugs orally. RESULTS: Twenty-seven patients were intravenously treated with isoniazid (INH), streptomycin (SM) and LVFX (HLS), and 38 patients were treated with INH and SM (HS). For both groups, mean age was very high (80.6±15.0 years, HLS group; 81.0± 12.1 years, HS group) and serum albumin levels were low (2.0 ± 0.62 mg/dl and 2.1 ± 0.42 mg/dl, respectively). Most patients were administered oxygen (81.5%, HLS; 78.9 %, HS). In radiological findings, most patients had bilateral (92.6%, HLS; 92.1%, HS) and widely spread (55.6%, HLS; 57.9%, HS) shadows. No significant differences were found between both groups in terms of the above data, except for sex. Almost 70% of all patients died; 51.9% of patients in the HLS group and 50.0% of those in the HS group died of tuberculosis, while 18.5% of patients in the HLS group and 18.4% of those in the HS group died of the other diseases. There were no significant differences in the causes of death and the survival rates of both groups. CONCLUSION: Patients with pulmonary tuberculosis who were administered intravenous drugs were elderly and in poor general health. As such, mortality of these patients was very high. In this study, no clinical effects were found in the patients administered intravenous LVFX with INH and SM compared with patients treated with INH and SM.

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy.

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy's effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25-8.8). Median survival time was 9.9 months (95% CI 9.2-10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889-9.328; 60 days, HR: 2.351, 95% CI 1.104-5.009; 90 days, HR: 2.416, 95% CI 1.232-4.739; and 120 days, HR: 2.521, 95% CI 1.357-4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.

Disseminated Mycobacterium avium complex infection in a patient carrying autoantibody to interferon-γ.

A 66-year-old man was admitted to our hospital on suspicion of lung cancer with bone metastasis. He suffered multiple joint and muscle pain. 18F-Fluorodeoxy glucose positron emission tomography (FDG-PET) showed multiple accumulations in the lung, bones including the vertebrae, and mediastinal lymph nodes. Anti-human immunodeficiency virus (HIV) antibody was negative. Because Mycobacterium avium complex (MAC) was isolated from bronchial lavage fluid, bronchial wall, peripheral blood, and muscle abscess, he was diagnosed as having disseminated MAC infection. Although multidrug chemotherapy was initiated, his condition rapidly deteriorated at first. After surgical curettage of the musculoskeletal abscess, his condition gradually improved. As for etiology, we suspected that neutralizing factors against interferon-gamma (IFN-γ) might be present in his serum because a whole blood IFN-γ release assay detected low IFN-γ level even with mitogen stimulation. By further investigation, autoantibodies to IFN-γ were detected, suggesting the cause of severe MAC infection. We should consider the presence of autoantibodies to IFN-γ when a patient with disseminated NTM infection does not indicate the presence of HIV infection or other immunosuppressive condition.

[A comparison of chest radiographs between patients with pulmonary Mycobacterium kansasii infection and those with Mycobacterium tuberculosis infection in the initial stage of disease].

OBJECTIVES: To elucidate the differences in affected lung segments between patients with pulmonary M. kansasii infection and those with M. tuberculosis infection in the initial stage of disease, we examined chest radiography images and CT scans. The initial stage of disease was defined as the period when less than one-sixth of the total lung area was affected by the infection, as visualized on chest radiography and CT. SUBJECTS AND METHODS: One hundred eighty-four patients were diagnosed with M.kansasii infection between 1996 and 2010 and 835 patients, with M.tuberculosis infection between 2008 and 2009 at our hospital. The diagnosis was made on the basis of the results of sputum culture and/or bronchial washing. After excluding the patients with underlying lung diseases such as chronic pulmonary emphysema, interstitial pneumonia, and old pulmonary tuberculosis as well as those in advanced stages, 24 patients with M. kansasii infection and 62 patients with M. tuberculosis infection were included in this study. The affected segments of the lungs and the rates of cavity development were determined by using CT scans. RESULTS: In patients with M.kansasii, 17 had an infected right lung, while 7 had an infected left lung. Additionally, in patients with M.tuberculosis, 58 had an infected right lung, 3 had an infected left lung, and 1 had a bilateral infection. In patients infected with M. kansasii, the upper lobes were affected in 22 cases and the lower lobes in 3 cases. In patients infected with M. tuberculosis, the upper, middle, and lower lobes and the lingular segment were affected in 41, 8, 24, and 1 cases, respectively. Upper lobe lesions were seen more frequently in patients with M. kansasii infection than in those with M. tuberculosis infection (p < 0.05). Cavity formation was identified more frequently in patients infected with M. kansasii (91.7%) than in those infected with M. tuberculosis (32.3%) (p < 0.001). Cavitary lesions were more frequently localized to the apical, posterior, and apico-posterior regions (S1, S2 or S1 +2) of the upper lobes in patients infected with M. kansasii (86.4%) than in those infected with M. tuberculosis (35%) (p < 0.001). A solitary lesion without endobronchial spread, which is characterized by centrilobular micronodules and tree-in-bud appearance, was more frequently demonstrated in patients infected with M.ka nsasii (45.8%) than in those infected with M. tuberculosis (6.5%) (p < 0.001). CONCLUSION: Our study revealed that the apical, posterior, and apico-posterior regions of the upper lobes are vulnerable to infection by not only M.tu berculosis, but also M.ka nsasii. It is likely that M.ka nsasii might gain access to these regions via the airways and that its weak virulence may lead to higher localization.

Doctor's delay in endobronchial tuberculosis.

OBJECTIVE: The aim of this study was to investigate the current status of doctor's delay in diagnosing endobronchial tuberculosis (EBTB) and to elucidate the risk factors contributing to the delay. METHODS: Retrospective clinicopathological analysis. PATIENTS: Sixty-two patients with EBTB were admitted at our hospital between 1999 and 2010. Their backgrounds, symptoms, diagnoses at initial consultation, delay in diagnosis, and clinical examination results were analyzed. RESULTS: Of the 62 patients, 59 had acid-fast, bacillipositive sputum smear test results at admission. Among the 40 patients with total diagnostic delay of more than 2 months, only 11 experienced long patient's delay exceeding 2 months. However, 22 patients experienced long doctor's delay of more than 2 months (28% vs. 55%, respectively, p < 0.05), suggesting that doctor's delay contributes more to total delay than patient's delay. Fever was less frequent in patients with long doctor's delays than in those without (0% vs. 18%, respectively), at the initial consultation. In addition, radiographs showed that patients with long doctor's delays more frequently presented with shadows in the lower lung field (50% vs. 23%, p < 0.05), and most of these patients had noncavitary shadows on admission. All 7 patients diagnosed with bronchial asthma at the initial consultation had long doctor's delays. CONCLUSION: These findings demonstrate that long doctor's delays in diagnosing EBTB remain an issue. The clinical features of EBTB with long doctor's delays were confirmed to be quite different from those of pulmonary tuberculosis.

Chemotherapy versus best supportive care in advanced lung cancer and idiopathic interstitial pneumonias: A retrospective multi-centre cohort study.

BACKGROUND: The clinical questions of whether chemotherapy as initial treatment, compared with best supportive care (BSC), improves overall survival (OS) and whether it increases the occurrence risk of acute exacerbation of idiopathic interstitial pneumonia (IIP) in patients with advanced-stage lung cancer and IIP remain inconclusive. This study addresses these issues, given that chemotherapy-related acute exacerbation of IIP may be a direct cause of mortality in these patients. METHODS: We enrolled 1003 patients from 110 Japanese institutions and collected clinical profiles from 707 and 296 patients in the chemotherapy (men: women, 645:62; mean age, 70.4 ± 6.9 years) and BSC (men: women, 261:35; mean age, 75.2 ± 7.8) groups, respectively. We used propensity score matching to create 222 matched pairs from both groups using patient demographic data (age, sex, smoking status, performance status, history of acute exacerbation of IIP, desaturation on exertion, clinical diagnosis of IIP, high-resolution computed tomography findings, serum fibrotic markers, pulmonary function status, and lung cancer histopathology). Logistic or Cox regression analyses were performed using matched data to assess the effects of chemotherapy on the risk of acute exacerbation of IIP or OS, respectively. RESULTS: In the well-matched cohort, chemotherapy improved OS (hazard ratio: 0.629, 95% confidence interval [CI]: 0.506-0.783, p < 0.0001); however, it involved significant acute exacerbation of IIP (odds ratio: 1.787, 95% CI: 1.026-3.113) compared to BSC. CONCLUSIONS: Compared with BSC, chemotherapy can improve OS in patients with advanced-stage lung cancer and IIP; however, it increases the risk of acute exacerbation of IIP.

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy.

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.

Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan.

OBJECTIVE: This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA). METHODS: We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab. RESULTS: Most cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients. CONCLUSION: CT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.

[A case of tuberculous pleurisy developing contralateral effusion during anti-tuberculosis chemotherapy].

A 55-year-old woman was admitted to our hospital because of chest pain, fever, and right pleural effusion that was exudative and lymphocyte-dominant with a high level of adenosine deaminase (ADA). Since her blood QuantiFERON-TB 3G test (QFT) was positive, she was diagnosed with tuberculous pleurisy. After initiation of anti-tuberculosis chemotherapy with isoniazid, rifampicin, ethambutol, and pyrazinamide, her symptoms improved. Later, liquid culture of the pleural effusion turned positive for Mycobacterium tuberculosis. On the 18th day of treatment, her chest X-ray and computed tomography exhibited pleural effusion in a moderate amount in the left thorax, with subsiding pleural effusion in the right thorax. Thoracocentesis demonstrated that the left thorax effusion was also exudative and lymphocyte-dominant, with elevated QFT response and high ADA concentration, suggesting tuberculous pleurisy. Mycobacterium tuberculosis was detected in the culture of a left pleural biopsy specimen obtained by thoracoscopy. We assumed that the left pleural effusion was due to paradoxical worsening because (1) on admission no effusion or lung parenchymal lesion was detected in the left hemithorax, (2) on the 14th day of treatment she was afebrile without pleural effusion on both sides, and (3) the bacilli were sensitive to the drugs she had been taking regularly. We performed drainage of the left effusion and continued the same anti-tuberculosis drugs, which led to the elimination of all her symptoms and of the pleural effusion on both sides. In conclusion, paradoxical worsening should be included in the differential diagnosis when contralateral pleural effusion is detected during the treatment of tuberculosis.

[Evaluation of tuberculosis treatment including levofloxacin (LVFX) in cases who could not continue standard regimen].

OBJECTIVE: The purpose of this study was to evaluate tuberculosis treatment including levofloxacin (LVFX) and to investigate the effectiveness of changing drug regimens at our hospital. SUBJECTS AND METHODS: A retrospective study was conducted on 331 patients with tuberculosis admitted to Tokyo National Hospital in 2005. Out of these 331 patients, LVFX was used in 48 (14.5%), 41 of which were initial-treatment cases. We studied why and how LVFX was used and compared bacteriological negative conversion rates between the initial-treatment cases in which the initial standard regimen was changed to regimens including LVFX, and those in which the initial standard regimen was either maintained throughout or modified with drugs other than LVFX. Sputum cultures were examined with Mycobacteria Growth Indicator Tube System (BACTEC MGIT 960). RESULTS: LVFX was used in 41 (13.6%) of 302 initial-treatment cases and in 7 (24.1%) of 29 retreatment cases. Out of the 269 initial-treatment cases starting with the standard regimen, LVFX was later used in 26 cases (9.7%). The reasons for using LVFX were adverse reaction to antituberculosis drugs in 23 cases (88.5%) and resistance to antituberculosis drugs in 3 cases (11.5%). We investigated the bacteriological conversion rate in 228 patients who could be followed up for more than five months. The conversion rates in 105 cases under the standard regimen including PZA (PZA+) were 92.4% in three months, 98.1% in four months, and 100% in five months. The rates in 56 cases under the standard regimen without PZA (PZA-) were 92.9 %, 98.2% and 100%,respectively. The rates of 22 cases under the initial regimen modified with LVFX (LVFX +) were 68.2 %, 95.5% and 100%, respectively. In 45 cases under the initial regimen modified with drugs other than LVFX (LVFX-), the rates were 80.0%, 97.8% and 100%, respectively. CONCLUSION: This study showed that LVFX was an effective drug in terms of the bacteriological conversion rate, without adverse reaction. LVFX is not approved as an antituberculosis drug in Japan, but it is often used in cases of MDR-TB or in situations in which the patients cannot continue treatment with the standard regimen. We hope that LVFX will be approved as an antituberculosis drug as soon as possible in Japan.

An autopsy case report of yellow nail syndrome coincided with primary biliary cholangitis.

Yellow nail syndrome (YNS) is a rare entity characterized by thickened yellowish nails, lymphedema and respiratory manifestations such as pleural effusion. Lymphatic dysfunction is considered as a cause of YNS. However, evidence of systemic dilatation/hyperplasia of lymphatics based on autopsy in YNS is not available. In this report, autopsy revealed dilatation and hyperplasia of lymphatic vessels in lungs, visceral and parietal pleurae, and intestines. We identified the direct opening of lymphatic vessels of the visceral pleura to the pleural cavity, which indicated the pathophysiology of uncontrollable pleural effusion in YNS. The current case was compromised with primary biliary cholangitis (PBC). The onset of PBC seemed to be related with the progression of YNS.

[A case of cold abscess of the chest wall due to thoracic drainage for tuberculous pleuritis].

A 56-year-old man underwent thoracic drainage for two weeks for tuberculous pleuritis. He was put on antituberculosis chemotherapy with INH (400 mg), RFP (450 mg), and EB (750 mg). Two months later, he developed an elastic hard subcutaneous mass in the area of the previous thoracic drainage. The mass was 10 cm in diameter, warm, reddish and painful. Chest computed tomography (CT) revealed localized and encapsulated empyema in the left thoracic space and a subcutaneous abscess with rim enhancement in the left lateral chest wall. Magnetic resonance imaging (MRI) demonstrated a dumbbell abscess in the subcutaneous tissue communicating with the empyema through the chest wall. A needle aspiration of the subcutaneous abscess had acid-fast bacilli smears of 2+ and tested positive by polymerase chain reaction (PCR) for Mycobacterium tuberculosis. Thus, he was diagnosed with a cold abscess of the chest, with the empyema in the thoracic space draining into the chest wall through the cut for artificial drainage. Continuation of the anti-tuberculosis treatment and the drainage of the empyema with repeated aspiration reduced the subcutaneous mass, and the clinical and radiological course was favorable. Both the smear and culture for acid-fast test became negative. After completion of chemotherapy, there has been no disease recurrence.

[Review of pulmonary Mycobacterium xenopi infection cases: 11 cases of our own and 18 other cases reported in Japan].

OBJECTIVE: To investigate clinical features of patients with pulmonary Mycobacterium xenopi infection treated at our hospital. SUBJECTS AND METHODS: We diagnosed 11 cases of M. xenopi infection at Tokyo National Hospital between 2000 and 2008 and recorded the drug susceptibility, patient characteristics, radiographic findings, treatments given and clinical courses. Eighteen other Japanese cases from the literature were discussed along with our findings. RESULTS AND METHODS: The cases of M. xenopi infection at our hospital consisted of 10 men and 1 woman with a mean age (+/- SD) of 55.1 +/- 19.4 years. Among the patients, 10 were smokers, 4 were heavy drinkers, and 6 had sequelae of pulmonary tuberculosis as an underlying disorder. Four patients had chronic obstructive pulmonary disease and 2 had diabetes mellitus, while there were 2 patients who had no underlying disease. All cases had radiographic opacities, predominantly found in the upper lung region, and cavernous lesions. These findings were demonstrated in both lungs in 5 patients, in the right lung only in 5 patients and in the left lung only in 1 patient. Concurrent aspergillosis was observed in 8 patients. The bacterial isolates from 7 cases were tested for drug sensitivity to levofloxacin (LVFX) and were found to be susceptible. M. xenopi disease was treated in 5 cases with INH+RFP+EB, in 2 cases with INH+RFP+Clarithromycin (CAM), and in 1 case with RFP+EB+CAM. Concurrent aspergillosis was treated with itraconazole in 2 cases. One patient underwent surgery for lung cancer. The duration of treatment was 16.4 +/- 12.8 months (range, 4-36 months). The radiographic findings were improved in 4 cases, deteriorated in 2 and unchanged in 5. M. xenopi was eradicated bacteriologically in 6 cases. The combination of radiographic and bacteriological findings indicated improvement in 3 cases, no change in 6 and deterioration in 2. DISCUSSION: The review of our cases disclosed that medical treatment alone was not sufficient in most cases for the control of clinical M. xenopi infection as reported overseas. Although we did not use LVFX for treatment, LVFX might be recommended for the treatment since all isolates tested proved to be susceptible to LVFX.

[Clinical investigation among elderly patients with tuberculosis].

OBJECTIVES: We discussed the factors which may confuse diagnosis and treatment of tuberculosis (TB) in elderly patients, in order to improve the situation. SUBJECTS AND METHODS: 414 patients who were hospitalized for active tuberculosis in Tokyo National Hospital were divided into three groups according to their ages (in years): less than 65, 65 to 74, and greater than 75. The three groups were compared in terms of performance status (PS), serum albumin level (whether over 3 g/dl or not), underlying diseases, symptoms at onset, sputum smear findings for acid-fast bacilli, presence or absence of cavitary lesion, regimen of treatment, adverse reaction to medications, and treatment outcome. RESULT: The older group had significantly poorer PS (3 or 4), lower albumin level, more complications, a larger proportion of non-respiratory to respiratory symptoms, less cavity formation, less likelihood of continuing to take drugs regularly and higher mortality. It is supposed that these characteristics are mostly due to the aging itself. CONCLUSION: Diagnosing and treating active tuberculosis among elderly people is difficult because of nonspecific and thus confusing findings due to other diseases or aging. Delay in diagnosis and start of treatment makes prognosis of their TB poorer. To improve this situation we should keep a high index to TB and make better use of novel diagnostic technologies. For satisfactory treatment that allows maintenance of a high level of activity of daily life, it is necessary to pay more attention to such aspects as nutrition and rehabilitation and to offer appropriate supports.

[Two cases of tuberculosis after treatment of rheumatoid arthritis with infliximab].

We report two cases of tuberculosis (TB) after treatment with infliximab (IFX) for rheumatoid arthritis (RA). The first case, a 69-year-old woman with RA, developed miliary TB with acute respiratory distress syndrome 21 months after initiation of IFX therapy. Sputum samples revealed smears and cultures positive for Mycobacterium tuberculosis and also positive polymerase chain reaction for TB (PCR-TB); in addition urine samples were smear-negative and culture-positive for TB. She was treated with corticosteroid pulse therapy and anti-tuberculosis drugs, and recovered. The second case, a 51-year-old man with RA, had had contact with a tuberculosis patient four years after initiation of IFX therapy. One year later, he developed pulmonary and pleural tuberculosis. Mycobacterium tuberculosis was detected in the bronchial lavage fluid and pleural effusion (smear-negative and culture- and PCR-TB positive). He clinically improved by treatment with anti-tuberculosis drugs. In both cases, the enzyme-linked immunosorbent spot (ELISPOT) tests revealed positive responses although the QuantiFERON TB-2G tests were not positive. We suggest that the ELISPOT test may be useful as a supportive diagnostic tool for tuberculosis in immunocompromised conditions including RA treated with a tumor necrosis factor-alpha (TNF-alpha) inhibitor.

[Rheumatoid arthritis diagnosis based on the detection of a pulmonary rheumatoid nodule in a patient with Hansen's disease].

A 77-year-old man with Hansen's disease was referred to our hospital because of a small nodular lesion detected adjacent to the pleura in the right lower lobe (S10) on chest CT. He had lost all ten fingers due to Hansen's disease and was using a prosthetic limb after amputation of the right lower leg. Although the patient had an 11-year history of shoulder and back pain and was suspected of having interstitial pneumonia 6 years previously, no detailed examination had been conducted. Bronchoscopy did not yield a definitive diagnosis, and a lung biopsy was performed under thoracoscopic guidance. Histological examination of the resected nodule with colliquative necrosis revealed palisading granulomas with multinucleated giant cells and plasma cell infiltration with formation of lymphoid follicles. Since serum levels of both anti-MMP3 and anti CCP antibodies were elevated, rheumatoid arthritis (RA) with rheumatoid lung was diagnosed. Therefore, the nodule was considered a rheumatoid nodule. Since diagnosis of rheumatoid arthritis is difficult when lacking characteristic joint manifestations, it is important to include rheumatoid nodules as a differential diagnosis and to measure RA specific autoantibodies, to make a comprehensive diagnosis for non-specific necrotizing granulomas.

[Nine cases of pulmonary sarcoidosis predominantly affecting the lower lung fields].

OBJECTIVES: Pulmonary sarcoidosis which predominantly affects the lower lung fields is relatively rare. We performed this study to clarify the clinical manifestations of this type of sarcoidosis. SUBJECTS AND METHODS: Over a period of 13 years, we diagnosed pulmonary sarcoidosis in 119 patients. Among these, we reviewed the clinical characteristics of 9 patients (3 men, 6 women, mean age 62 years) with pulmonary lesions predominantly affecting the lower lung fields. RESULTS: Four patients had a history of dust inhalation and 6 had symptoms of dyspnea. All patients had ocular lesions and 5 had cutaneous lesions. Serum KL-6 levels were elevated in all patients, whereas angiotensin-converting-enzyme (ACE) levels were elevated in 3. Pulmonary function tests revealed stenosis in 4 patients, and decreased diffusion capacity in 7. Chest CT findings in the lower lung fields revealed bronchovascular thickening, micronodular opacities in the vessels and chest wall, and interlobular septal thickening in 8 patients; ground-glass opacities in 5; curvilinear shadows in 4; and patchy shadows, traction bronchiectasis, and pleural effusion in 3. Histopathologic findings of lung biopsy specimens featured granulomas in all patients, and pulmonary interstitium fibrosis and small round-cell infiltration in the alveoli of most patients. CONCLUSION: Patients with sarcoidosis affecting the lower lung fields often had symptoms of dyspnea, extrapulmonary lesions in the eye and/or on the skin, and elevated serum KL-6 levels but not ACE. Chest CT showed findings typical of sarcoidosis, such as lymphatic distribution, but also showed unusual findings such as ground-glass opacities, curvilinear shadows, patchy shadows, traction bronchiectasis and pleural effusion. We speculated that 1 patient with ground-glass opacities and traction bronchiectasis without lymphatic distribution on CT, and fibroblastic foci with active alveolitis histopathologically, had complications of a different type of interstitial pneumonia.