A case of diffuse panbronchiolitis, associated with severe pulmonary hypertension, managed with bilateral lung transplantation from a brain-dead donor.

Diffuse panbronchiolitis (DPB) is a chronic respiratory disease that mainly involves the respiratory bronchioles, and has historically been associated with a very poor prognosis. The development of long-term low dose macrolide therapy in the 1980s has dramatically improved the prognosis of DPB. Nevertheless, some cases are resistant to macrolide therapy, and ultimately develop severe respiratory failure and pulmonary hypertension; in such cases lung transplantation is a viable treatment option. Here we report the case of a 40-year-old patient with a 20-year history of DPB, who underwent bilateral lung transplantation due to severe respiratory failure with pulmonary hypertension.

Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis.

A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone.

Familial interstitial pneumonia complicated by lung cancer in 2 sisters.

A 29-year-old woman was referred to our hospital because of progressive dyspnea on exertion, and her 36-year-old sister was also referred for the evaluation of an abnormal chest radiograph. Radiologic and pathologic findings of the 2 sisters resembled each other closely. In both cases, computed tomography revealed diffuse reticulation, micronodules, diffusely distributed interlobular septal thickening, and an ill-defined nodule in the left lower lobe. Radiologic-pathologic correlation revealed that the reticulation and micronodules corresponded to centrilobular and perilobular fibrosis without architectural lung distortion and that the nodules represented pulmonary adenocarcinoma. To our knowledge, this is the first report of familial interstitial pneumonia complicated by lung cancer in 2 family members, suggesting a possible etiologic association between familial interstitial pneumonia and lung cancer.

Consolidation with a twisted appearance along the airways: a report of five cases of interstitial pneumonia.

High-resolution CT showed areas of airspace consolidation with a twisted appearance of the airways, along with areas of peribronchial ground-glass attenuation and traction bronchiectasis, in five patients with interstitial pneumonia. These areas of airspace consolidation were termed "twisted consolidation" (TwC). The five patients included two patients receiving treatment for rheumatoid arthritis (RA), one patient with newly diagnosed RA, and one patient who subsequently showed RA. Three patients showed improvement after steroid administration. An association of TwC with RA is suspected, but further studies are necessary.

Nationwide epidemiological survey of chronic hypersensitivity pneumonitis in Japan.

BACKGROUND: In 1999, a Japanese epidemiological survey of chronic hypersensitivity pneumonitis (HP) showed that summer-type HP was the most prevalent variant of the disease. The number of reported cases of chronic HP has recently been increasing, and the clinical features of the disease seem to have changed. We conducted another nationwide epidemiological survey of chronic HP in Japan to determine better estimates of the frequency and clinical features of the disease. METHODS: A questionnaire was sent to qualified hospitals throughout Japan, and data on cases of chronic HP diagnosed between 2000 and 2009 were collected. RESULTS: In total, 222 cases of chronic HP from 22 hospitals were studied. Disease subtypes included bird-related HP (n=134), summer-type HP (n=33), home-related HP (n=25), farmer's lung (n=4), isocyanate-induced HP (n=3), and other types (n=23). The median proportion of lymphocytes in bronchoalveolar lavage fluid was high (24.5%). The primary findings of computed tomography of the chest were ground-glass attenuation and interlobular septal thickening. Centrilobular fibrosis was the major pathological finding on examination of surgical lung biopsy specimens from 93 patients. The median survival time was 83 months. CONCLUSIONS: The proportion of bird-related HP was higher than that in the previous epidemiological survey, and the proportions of isocyanate-induced HP and farmer's lung were lower. A crucial step in diagnosing chronic HP is to thoroughly explore the possibility of antigen exposure.

[Study on pulmonary lesions in which nontuberculous mycobacteria were detected by percutaneous aspiration--a proposal to add "culture positivity of percutaneous aspiration material" to the bacteriological diagnostic criteria of pulmonary nontuberculous mycobacterial diseases].

OBJECTIVES: Culture positivity of percutaneous aspiration material" is not included in the current bacteriological criteria for diagnosis of pulmonary nontuberculous mycobacterial (NTM) diseases, which were published by the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) in 2007 or those released by the Japanese Society for Tuberculosis in 2008. However, percutaneous aspiration is a reliable technique for the detection of causative microorganisms isolated from the focus of infection. We discuss the benefits of including positive culture of percutaneous aspiration material in the bacteriological diagnostic criteria of pulmonary NTM diseases. METHODS: We reviewed the radiological images and clinical courses of pulmonary diseases in which NTM cultures were obtained from percutaneously aspirated materials at our hospital from 1991 to 2011. Aspiration was carried out under local anesthesia, usually with fluoroscopic guidance. After percutaneous insertion of a 22-gauge needle attached to a 20-mL syringe containing about 3 mL of saline, the lesion specimen was withdrawn together with the saline. After the needle was pulled out, the aspirated material and saline were transferred to test tubes for cytological and microbiological examinations. In patients with thin-walled cavitary lesions, saline was injected into the cavity and then aspirated. RESULTS: Percutaneous aspiration was performed in 2,742 patients and NTM disease was detected in 51 patients. Of these 51 patients, 12 had solitary nodular lesions, and in many of these patients, no NTM bacilli could be detected in the sputa or bronchial washing specimens. Mycobacterium avium was identified in 10 of the 12 cases. Four of these 10 patients were followed up after their diagnosis without any treatment: 3 showed spontaneous reduction in lesion size, while 1 patient's condition remained unchanged. Four of the remaining 6 cases were treated with anti-NTM medications, and lesion size reduced in 2 cases, while no change or deterioration was seen in the other 2. Aspiration from solitary small cavitary lesions showed a relatively high number of NTM colonies. Pneumothorax was the only complication of the aspiration procedure. DISCUSSION: If the diagnostic criteria for pulmonary NTM diseases include positive culture in percutaneous aspiration material, the diagnosis of solitary nodular NTM lesions would become easier; at present, these lesions are often diagnosed only upon surgical resection. Further, clinical studies on the possibility of spontaneous shrinkage of the solitary lesion and the value of its medical treatment would be promoted. Aspiration can easily differentiate NTM disease from pulmonary abscess or fungal infection in patients with a solitary lesion or small cavity.

[A case of pleural tuberculoma with intra-pulmonary invasion during anti-tuberculosis therapy].

A 27-year-old woman who had been treated for pulmonary tuberculosis with anti-tuberculosis drugs for three months was admitted to our hospital because of pain in the chest and back. Chest CT showed improvement in the pulmonary tuberculosis lesions in the right middle lobe and S8, but there was a large pleural mass in the right lower lung field. Histopathological findings of the percutaneous biopsy showed epithelioid cell granulomas that were negative for acid-fast bacilli. We diagnosed the mass as pleural tuberculoma with intrapulmonary invasion. The pleural tuberculoma improved without any additional therapy.

[A case of respiratory bronchiolitis-associated interstitial lung disease].

A 37-year-old man was referred to our hospital with a cough. His blood test result and chest radiography findings were normal. High resolution chest computed tomography (HRCT) showed diffuse ground glass attenuation (GGA) with centrilobular distribution in the bilateral upper lung fields. As diagnosis could not be made using transbronchial lung biopsy and bronchoalveolar lavage, video-assisted lung biopsy was performed. The histological findings were a thickening of the alveolar walls with infiltration of lymphocyte-dominant inflammatory cells, and exudation of pigmented macrophages in the air spaces of the respiratory bronchioles and alveolis. We diagnosed his illness as respiratory bronchiolitis-associated interstitial lung disease. Six months after stopping smoking, his symptoms, and the GGA on chest HRCT improved.

[Seven cases of diffuse alveolar hemorrhage with acute respiratory failure treated by plasma exchange].

We conducted a retrospective analysis of 7 cases of diffuse alveolar hemorrhage at our hospital, diagnosis of which was made on the presence of bloody bronchoalveolar lavage fluid. There were 3 men and 4 women, with a mean age of 68 years. A rapidly progressiving diffuse infiltrative shadow on chest X-ray film and failing to respond to antibiotic therapy were the major signs of the condition in these cases. Respiratory failure was seen in all cases. In addition to high-dose steroid therapy and mechanical ventilation, we immediately performed plasma exchange. All of the 3 MPO-ANCA-positive patients survived, but 3 of the 4 MPO-ANCA-negative patients died. Diffuse alveolar hemorrhage secondary to ANCA-associated vasculitis usually advances rapidly and its prognosis tends to be poor. However, early initiation of plasma exchange can be expected to improve the survival rate of patients with this disease.

[Hypersensitivity pneumonitis caused by isocyanate exposure during recreational painting].

A 36-year-old man began painting his car as a hobby every weekend in early February 2007 using a paint containing isocyanate. In March, 2007, he developed a dry cough, dyspnea and fever of 40 degrees C. These symptoms appeared repeatedly several hours after engaging in painting activity. His chest X-ray film showed diffuse small granular and reticular shadows in bilateral lung fields. His computed tomogram showed ground glass images in bilateral lung fields. Pulmonary function tests showed significantly decreased DLco. Histological findings of transbronchial lung biopsy revealed cellular interstitial pneumonia. These symptoms improved after cessation of painting and administration of prednisolone. Based on these results, we diagnosed this patient's illness as hypersensitivity pneumonitis due to isocyanate exposure.

[Long-term follow up study of four cases of pulmonary Langerhans' cell histiocytosis].

We reported the clinical features of 4 cases with pulmonary Langerhans' cell histiocytosis. All of them were men who had a history of smoking. They ranged in age from 23 to 46 years. Cases 1 and 3 did not stop smoking, while Cases 2 and 4 did stop smoking. All of the chest CTs revealed small nodules and cysts, and during the follow-up period of 8 to 13 years, the numbers of nodules decreased and the walls of the cysts became thin in all of the cases. Their pulmonary function tests revealed restrictive impairment in 3 cases and reduced diffusion capacity in 2 cases, but none showed obstructive impairment. FEV1% and DL(CO) deteriorated during the follow-up period. Case 1 died of respiratory failure after 8 years. Cases 2 and 4 were both alive with home oxygen therapy after 11 and 12 years, respectively. Case 3 was alive but complained of dyspnea on exertion after 13 years. In conclusion, all of the 4 cases showed deterioration of pulmonary function, and one of them died due to respiratory failure. The prognosis of patients with pulmonary Langerhans' cell histiocytosis appears to be poor.

[Case of pulmonary tuberculosis with miliary granules, mediastinal lymph node enlargement and elevation of soluble interleukin-2 receptor].

An 80-year-old woman suffered from fever and loss of appetite. Her chest X-ray showed mediastinal tumors and diffuse granular shadows in the bilateral lung fields. Elevations of sIL-2r and M-protein were present. HRCT showed numerous small granules in both lungs and mediastinal lymph node enlargement. Tuberculosis DNA was detected by PCR in her sputum. Later, Mycobacterium tuberculosis was cultured from her sputum. After she started anti-tuberculosis therapy, her general fatigue and elevation of sIL-2r improved gradually. Her chest X-ray revealed a decrease in the size of mediastinal lymph nodes and small granules.

[A case of nonspecific interstitial pneumonia with reversed halo sign on chest HRCT].

A 39-year-old man was referred to our hospital with anterior chest discomfort, dry cough and shortness of breath. His blood test revealed mild inflammatory change and high serum KL-6 levels. Chest radiograph and computed tomography (CT) showed ground glass attenuation with volume loss in both lower lung fields, and in particular a reversed halo sign was shown on high-resolution CT (HRCT). As transbronchial lung biopsy and bronchoalveolar lavage did not enable a diagnosis, video-assisted thoracic surgery was performed. The histological findings of the resected specimen showed cellular nonspecific interstitial pneumonia. This suggested the possibility of collagen vascular disorder (CVD) associated with interstitial pneumonitis, but no criteria of CVD were fulfilled. Although the reversed halo sign is relatively specific for cryptogenic organizing pneumonia, we report a case of cellular nonspecific interstitial pneumonia showing this sign on chest HRCT.

[A case of primary pulmonary cryptococcosis showing lobar pneumonia on chest X-ray].

A 36-year-old male who had been in good health visited our hospital because of fever, productive cough and lobar pneumonia of the right lower lobe. Bronchoscopic examination revealed pulmonary cryptococcosis. After the initiation of fluconazole the pneumonia started to improve, however, it was aggravated after the discontinuation of fluconazole because of liver dysfunction induced by it. The pulmonary cryptococcosis improved by lobectomy of the right lower lobe. There have been few reports of lobar pneumonia caused by primary pulmonary cryptococcosis. We report this case with fourteen other cases of primary pulmonary cryptococcosis which have been experienced in our hospital.

Mental state as a possible independent prognostic variable for survival in patients with advanced lung carcinoma.

BACKGROUND: Although psychologic factors have been reported to influence the progression of cancer, this theory remains controversial. A prospective study of patients with advanced lung carcinoma was performed to explore the influence of the patient's mental state on survival. METHODS: The patient's mental state was assessed with the Tokyo University Egogram. In a preliminary study, the egograms of long-term survivors (survival > 3 years) with TNM Stage IIIB or Stage IV lung carcinoma were compared with the egograms of consecutive, newly diagnosed lung carcinoma patients (controls). Next, in a prospective study, 123 patients with nonsmall cell lung carcinoma and 56 patients with small cell lung carcinoma (Stage IIIB or Stage IV; Eastern Cooperative Oncology Group performance status of 0 or 1) completed the egogram. Based on the results of the preliminary study, the subjects in the prospective study were divided into Group A (Free Child [FC] >or= 50th percentile and Adapted Child [AC] < 50th percentile) and Group B (FC < 50 percentile or AC >or= 50 percentile). The survival of the two groups was compared. The Cox proportional hazards model was used to determine the joint effect of the patient's mental state and other prognostic factors. RESULTS: In the preliminary study, the FC score of the long-term survivors was significantly higher and the AC score was significantly lower than those of the controls. In the prospective study, the survival of Group A was significantly longer than that of Group B both in the nonsmall cell lung carcinoma and small cell lung carcinoma patients (P = 0.002 and P = 0.005, respectively, by the log-rank test). Multivariate analysis demonstrated that after adjustment for clinical factors, being in Group A was a significant predictor of survival both in the nonsmall cell and small cell lung carcinoma patients. CONCLUSIONS: The results of the current study demonstrate that the mental state of the patient as assessed by the egogram may have prognostic significance in patients with advanced lung carcinoma.

[Chronic eosinophilic pneumonia--a follow-up study of 12 cases].

In this study, twelve cases of CEP were followed for a mean period of 10.9 years (range 9.3-12.9 years) at National Himeji Hospital. Of the five women and seven men examined, two patients possessed preexisting asthma and one developed asthma during the course of CEP disease. None of the patients exhibited any symptoms of allergic rhinitis. All had dramatic responses to corticosteroid therapy without developing extrathoracic manifestations. During the course of CEP, one patient died from acute myocardial infarction. Relapses, which occurred in six patients, responded as well to the treatment as in the original episode. One patient continued long-term oral corticosteroids (5 mg/day) and steroid inhalants (800 micrograms/day) as treatment for asthma. Another was administered steroid inhalants (800 micrograms/day) to treat both asthma and relapsing CEP; two additional patients received 800-600 micrograms/day to prevent relapse. These data indicate that, with proper treatment, the long-term prognosis for patients with CEP is excellent.