Hard metal lung disease diagnosed on a transbronchial lung biopsy following recurrent contact dermatitis.

A 63-year-old man employed in a hard metal manufacturing company for 40 years presented with a chronic dry cough and exertional dyspnea 20 years after the onset of recurrent exanthemas. A chest radiograph revealed bilateral reticular shadows in the upper lung field. Pathological specimens in which tungsten was detected were obtained via a transbronchial lung biopsy. Patch tests were positive for cobalt and other metals. The patient was diagnosed with hard metal lung disease (HMLD) concurrent with contact dermatitis and treated with corticosteroids. This case suggests that allergies to metal may play a role in the onset of HMLD.

Anaplastic large cell lymphoma mimicking fibrosing mediastinitis.

Fibrosing mediastinitis is rare. One type of this disease is idiopathic fibrosing mediastinitis. It is necessary to rule out malignancy in order to accurately diagnose fibrosing mediastinitis. We herein report a case of anaplastic large cell lymphoma diagnosed three months after a preliminary diagnosis of fibrosing mediastinitis. Glucocorticoid therapy was not successful in controlling disease progression. Immediately after initiating chemotherapy for lymphoma, the patient's symptoms improved dramatically and the mediastinal lesion decreased in size. Although few similar cases have been reported, hidden malignancy may present as fibrosing mediastinitis. Therefore, physicians should consider the probability of malignancy in patients with fibrosing mediastinitis because treatments may vary accordingly.

[A clinical study of pulmonary Mycobacterium abscessus infection].

Pulmonary Mycobacterium abscessus infection is resistant to many antibiotics and is difficult to treat. We retrospectively analyzed the clinical characteristics of pulmonary infection due to M. abscessus. Eleven cases diagnosed as having pulmonary M. abscessus infection at Osaka Red Cross Hospital from January. 2008, to June, 2012 were enrolled in this study. The average age of the 11 cases was 63 years (all were females). Nine cases showed underlying diseases, comprising 5 cases with Mycobacterium avium complex lung infection, 3 with old pulmonary tuberculosis, and 3 with bronchiectasis. The radiological examination revealed that 10 cases showed the small nodular type, 7 showed the bronchiectatic type, 4 showed a cavity lesion and 4 showed infiltrative shadows. A microbiological definite diagnosis was made from sputum in 10 cases and bronchial lavage fluid in one. As treatment for M. abscessus pulmonary infection, combined multi-drug chemotherapy was carried out in 7 of the 11 cases. No patients were successfully treated with antibiotics alone, whereas 4 patients had no exacerbation of radiological findings without any treatment. One patient received antibiotics including clarithromycin, amikacin and levofloxacin for 2 to 12 months following surgical excision and her sputum cultures have been maintained as negative over the long-term. During the study, none of the 11 patients were known to have died. In this study, we found that M. abscessus pulmonary infection is more common among females, and is found frequently in patients with M. avium complex lung infection. We also found that the clinical course of M. abscessus pulmonary infection was different among patients. We think this is because M. abscessus was shown to comprise three closely related species. M. abscessus is extremely difficult to eradicate, and surgical resection of localized disease or the main lesion or cavity may be significantly effective in preventing the progression of disease.

[A case of nocardiosis with associated endobronchial excavated lesions].

A case of nocardiosis with associated endobronchial excavated lesions is reported. A 79-year-old woman was diagnosed as having dermatomyositis in March, 2010. She was started on prednisolone (50mg/day) and was then switched to betamethasone due to lower limb edema and tapered to a dose of 2.5mg/day. A periodic chest X-ray examination in July, 2010, incidentally revealed nodular densities and associated cavities in the upper right lung field. On thoracoabdominal computed tomography (CT), bilateral pulmonary nodular shadows with various-sized cavities and multiple, new, intrahepatic, low-density regions were also identified. On bronchoscopy, a white, excavated lesion resembling an ulcerous lesion was observed in the left upper lobe bronchus, and a small exophytic lesion was observed in the right B6 bronchus. Nocardia asteroides complex was isolated from cultures of bronchial lavage fluid and sputum. The patient was treated with 4 weeks of intravenous imipenem (1.5g/day), followed by oral minocycline therapy (200mg/day) for 6 months, after which lesion resolution was confirmed on CT and treatment was discontinued. No recurrence has been reported in the roughly 18 months of follow-up to date. Nocardiosis results from infection with bacteria of the zoonotic, aerobic, Actinomyces genus and presents with disseminated lesions. Reported cases of human infection are increasing due to greater numbers of immunocompromised patients and improved diagnostic techniques. However, nocardiosis involving endobronchial lesions is extremely rare, and, to the best of our knowledge, the present case is the first report of endobronchial excavated lesions caused by nocardiosis.

Clinical efficacy and safety of micafungin in Japanese patients with chronic pulmonary aspergillosis: a prospective observational study.

Aspergillosis has been the prevailing deep-seated mycosis in Japan since the 1990s. Although micafungin (MCFG) has been approved in Japan for the management of patients with such infections caused by Candida and Aspergillus species, there are relatively few reports on its use in patients with chronic pulmonary aspergillosis (CPA). Therefore, we conducted a prospective observational study to evaluate the efficacy and safety of the use of MCFG in Japanese patients with CPA. The efficacy of the antifungal was assessed on the basis of improvements in clinical symptoms and radiological findings. In addition, adverse events, including abnormal laboratory findings were determined. The overall clinical efficacy rate was 68.4% (26/38 patients), which is comparable to the results obtained in clinical trials for marketing approval conducted in Japan. Although adverse drug reactions were observed in six patients (15.8%), they were not serious. The most common of these reactions was abnormal liver functions. No relationship between the incidence of adverse drug reactions and age of the patients, MCFG dose, or duration of treatment was observed. Consequently, MCFG has favorable efficacy and safety profiles in Japanese CPA patients with various backgrounds.

Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: a multicenter trial in Japan.

Chronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory pulmonary syndrome due to Aspergillus spp. The evidence regarding CPA treatment is limited. We conducted a randomized, multicenter, open-label trial comparing intravenous micafungin (MCFG) of 150-300 mg once daily with intravenous voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily for the treatment of 107 in patients with CPA to compare the efficacy and safety of both drugs as initial treatment in Japan. Treatment effectiveness was defined by clinical, mycological, radiological and serological responses 2 weeks after the initial administration and at the end of therapy. The total of 50 and 47 patients were assigned to the MCFG and VRCZ groups, respectively. The difference in efficacy rates between MCFG and VRCZ was not significant, either after 2 weeks [68.0% vs. 58.7%; the absolute difference, 9.3% with a 95% confidence interval (CI), -9.97 to 28.58, P = 0.344] or at the end of therapy (60.0% vs. 53.2%; the absolute difference, 6.8% with a 95% CI, -12.92 to 26.54, P = 0.499). In the safety evaluation, fewer adverse events occurred in the MCFG than VRCZ group (26.4% vs. 61.1%, P = 0.0004). MCFG was as effective as VRCZ and significantly safer than as an initial treatment of CPA. (UMIN Clinical Trials Registry number, UMIN000001786.).

[Seven cases of gemcitabine-induced lung injury during treatment for pancreatic or biliary tract cancers].

Gemcitabine is an anti-cancer drug known to be safe and effective for pancreatic or biliary tract cancers, but lung injury is also known to be a rare side effect that sometimes becomes severe. Here we report seven cases of lung injury during gemcitabine treatment. Drug-induced lung injury was suspected in all cases. The male: female ratio was 5:2, and the average patient age was 71. Four had pancreatic cancers and three had biliary tract cancers. Gemcitabine had been administered an average 5.9 times at a dose of 1,141 mg. Patients showed a diffuse or patchy shadow mainly in the lower lung on computed tomography examination. Grades of adverse events were greater than 3 in all cases. Three patients died of the lung injury. Five cases had pulmonary emphysema, 2 had metastatic lung tumor as underlying pulmonary lesions, and these were assumed to have been important risk factors for drug-induced interstitial lung injury during gemcitabine treatment.

Specific IgE response to trichophyton and asthma severity.

BACKGROUND: Sensitization to Trichophyton, a major dermatophyte, has been associated with asthma. Whether such sensitization is generally associated with the severity of asthma, like other molds such as Alternaria, is unknown. METHODS: We compared 258 patients with asthma, which was classified by severity as mild (n = 123), moderate (101), or severe (34), and 114 healthy control subjects, with regard to specific IgE titers against Trichophyton rubrum and other common allergens such as mixed molds, house-dust mite, cat dander, dog dander, Japanese cedar pollen, mixed Graminea pollens and mixed weed pollens. RESULTS: Positive rate of Trichophyton-specific IgE was higher in the patients with moderate asthma (15.8%) than in the control subjects (7.0%, p = 0.04) and patients with mild asthma (4.9%, p < 0.006), and it was also higher in the patients with severe asthma (32.4%) than in control subjects (p = 0.0001), and patients with mild asthma (p < 0.0001) and moderate asthma (p = 0.04), but it did not differ between the control subjects and patients with mild asthma. The positive rates of mixed molds, cat dander, and dog dander were almost invariably higher in patients in all asthma subgroups than in the control subjects but did not differ among patients in the three asthma subgroups. The positive rates of other allergens were not different in all groups. Reanalysis of positive rate of Trichophyton-specific IgE after excluding 52 subjects with positive results for mixed molds showed a similar statistical trend to that of the original cohort. This may negate the potential effect of cross-reactivity to these molds. Multivariate analysis of asthma subgroups identified positive IgE results for Trichophyton as an independent determinant of asthma severity. CONCLUSIONS: Specific IgE response to Trichophyton may be associated with more severe asthma.

Primary choriocarcinoma of the lung manifesting as diffuse alveolar hemorrhage.

An autopsy case of primary pulmonary choriocarcinoma that manifested as diffuse alveolar hemorrhage is reported. A 44-year-old nurse presented with fever, dry cough, hemoptysis, and progressive dyspnea, and died after a downhill course of 2 weeks. Chest radiographs showed diffuse parenchymal shadows throughout the entire lung and a nodular lesion in the right lower lobe. Findings suggestive of acute renal failure were not seen. The autopsy revealed primary pure choriocarcinoma of the right lower lobe and diffuse alveolar hemorrhage throughout the entire lung. Findings of small vessel vasculitis ("pulmonary alveolar capillaritis") were not observed, and extensive neoplastic involvement of the pulmonary vasculature was considered the cause of the diffuse alveolar hemorrhage. Small metastatic foci were found in the liver, adrenal glands, pancreas, and ovaries. This case shows that primary pulmonary neoplasms, on rare occasions, can produce the clinical and pathologic features of diffuse alveolar hemorrhage, probably through elevated pulmonary venous pressure caused by extensive destruction of the vasculature.

Effect of short-term treatment with inhaled corticosteroid on airway wall thickening in asthma.

PURPOSE: Computed tomography studies demonstrate thickening of the asthmatic airway wall and its relation to disease severity. We evaluated the effect of inhaled corticosteroid on this phenomenon. METHODS: Cross-sectional images of the right upper lobe apical segmental bronchus were obtained by helical computed tomography in 45 corticosteroid-naïve patients with persistent asthma and 28 healthy controls. Airway wall thickness was measured as airway wall area normalized to body surface area. Computed tomography, pulmonary function, and serum levels of eosinophil cationic protein were examined before and after treatment with beclomethasone (800 microg/d for 12 weeks). RESULTS: Before treatment, airway wall thickness was greater in asthma patients than in controls (P <0.0001). After treatment, it decreased by 11% (P <0.001) but remained high (P <0.0001 vs. control); the serum level of eosinophil cationic protein decreased, and airflow obstruction was reduced, but not to the level in controls. The decrease in wall thickness was associated with a decrease in the serum level of eosinophil cationic protein (r = 0.39, P = 0.009) and an increase in the forced expiratory volume in 1 second (r = 0.45, P = 0.003) and was inversely related to disease duration at entry (r = -0.38, P = 0.009). Post-treatment wall thickness was related to disease duration (r = 0.45, P = 0.003) and remaining airflow obstruction. CONCLUSION: Wall thickening of asthmatic central airways responds partially to inhaled corticosteroid therapy and may reflect an overall reduction in airway inflammation. "Unresponsive components," possibly involving structural changes, may increase in the absence of inhaled corticosteroid treatment, potentially leading to chronic airflow obstruction.

Chronic eosinophilic pneumonia: treatment with inhaled corticosteroids.

BACKGROUND: Chronic eosinophilic pneumonia (CEP) is highly sensitive to systemic corticosteroids, but frequently relapses if the dose is tapered or treatment discontinued. Long-term usage of systemic corticosteroids may cause side effects. Alternative treatments are therefore desired. OBJECTIVES: We evaluated the response of CEP to monotherapy with inhaled corticosteroids (ICS). METHODS: Four patients who had CEP without spontaneous resolution were studied. Patients received inhaled beclomethasone dipropionate (BDP) at a dose of 0.8 mg/day in 1 patient and 1.6 mg/day in 3 patients for 2 weeks. Treatment was continued if a patient showed improvement in at least 1 of the following indices: radiological findings, symptoms, and blood eosinophilia. RESULTS: After the initial 2 weeks of treatment with BDP, the blood eosinophil count increased in 2 patients and decreased in 2. Symptoms worsened in 2 and improved in 2. Infiltrates on chest radiography increased in 3 and showed little change in 1. In the 2 patients with worsening of all 3 outcome indices, oral prednisolone was started; the indices improved. In the remaining 2 patients, BDP alone was continued. One patient had worsening of CEP after 2 months of treatment, and another had relapse of CEP at 3.5 years while receiving 1.6 mg/day of BDP. All patients thus finally had worsening or relapse of CEP during treatment with BDP. CONCLUSIONS: ICS may not be effective when given as monotherapy in patients with CEP.

Successful treatment with faropenem and clarithromycin of pulmonary Mycobacterium abscessus infection.

Mycobacterium abscessus accounts for 80% of rapidly growing mycobacterial pulmonary infections and can be lethal. Treatment is difficult because of the paucity of effective drugs. We describe a patient with pulmonary M. abscessus infection who was treated with a regimen that included faropenem, a novel oral penem, and clarithromycin. He showed favorable responses to the treatment for more than 12 months. In vitro, faropenem had considerable inhibitory activities against 56 strains of rapidly growing mycobacteria, including M. peregrinum, M. chelonae, M. fortuitum, and M. abscessus (stated in order of increasing minimal inhibitory concentrations). Thus, faropenem has the potential to be used as an adjunctive drug with clarithromycin for the treatment of infection with rapidly growing mycobacteria, including M. abscessus.