Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder for which there are currently no specific or effective medical treatments. A multicentre, prospective, randomized, controlled clinical trial was conducted to assess the efficacy of inhaled N-acetylcysteine (NAC) monotherapy in Japanese patients with early stage IPF. METHODS: Eligible patients had well-defined IPF of mild-to-moderate severity, with no desaturation on exercise. Of 100 patients screened, 76 were randomly assigned to an NAC treatment group (group A; n = 38) that received 352.4 mg of NAC by inhalation twice daily or to a control group (group B; n = 38) that received no therapy. The primary endpoint was the change from baseline in forced vital capacity (FVC) at 48 weeks. RESULTS: There were no significant overall differences in the change in FVC between groups A and B. Post hoc exploratory analyses showed that NAC therapy was associated with stability of FVC in (i) a subset of patients with initial FVC <95% of predicted (n = 49; difference in FVC decline 0.12 L; P = 0.02) and (ii) in patients with initial diffusing capacity of carbon monoxide <55% of predicted (n = 21; difference in FVC decline 0.17 L; P = 0.009). CONCLUSIONS: These findings indicate that NAC monotherapy may have some beneficial effect in patients with early stage IPF. Further trials in more select IPF populations with progressive disease are required to prove the efficacy of inhaled NAC.

The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trial.

BACKGROUND: Our phase III clinical trial of pirfenidone for patients with idiopathic pulmonary fibrosis (IPF) revealed the efficacy in reducing the decline of vital capacity (VC) and increasing the progression-free survival (PFS) time by pirfenidone. Recently, marginal decline in forced VC (FVC) has been reported to be associated with poor outcome in IPF. We sought to evaluate the efficacy of pirfenidone from the aspects of 5% change in VC. METHODS: Improvement ratings based on 5% change in absolute VC, i.e., "improved (VC ≥ 5% increase)", "stable (VC < 5% change)", and "worsened (VC ≥ 5% decrease)" at month 3, 6, 9 and 12 were compared between high-dose pirfenidone (1800 mg/day; n = 108) and placebo (n = 104) groups, and (high-dose and low-dose (1200 mg/day; n = 55)) pirfenidone (n = 163) and placebo groups. PFS times with defining the disease progression as death or a ≥ 5% decline in VC were also compared between high-dose pirfenidone and placebo groups, and low-dose pirfenidone and placebo groups. Furthermore, considering "worsened" and "non-worsened (improved and stable)" of the ratings at months 3 and 12 as "positive" and "negative", respectively, and the positive and negative predictive values of the ratings were calculated in each group. RESULTS: In the comparison of the improvement ratings, the statistically significant differences were clearly revealed at months 3, 6, 9, and 12 between pirfenidone and placebo groups. Risk reductions by pirfenidone to placebo were approximately 35% over the study period. In the comparison of the PFS times, statistically significant difference was also observed between pirfenidone and placebo groups. The positive/negative predictive values in placebo and pirfenidone groups were 86.1%/50.8% and 87.1%/71.7%, respectively. Further, the baseline characteristics of patients worsened at month 3 had generally severe impairment, and their clinical outcomes including mortality were also significantly worsened after 1 year. CONCLUSIONS: The efficacy of pirfenidone in Japanese phase III trial was supported by the rating of 5% decline in VC, and the VC changes at month 3 may be used as a prognostic factor of IPF. TRIAL REGISTRATION: This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (REGISTRATION NUMBER: JAPICCTI-050121).

Exploratory analysis of a phase III trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment.

BACKGROUND: A phase III trial in Japan showed that pirfenidone is effective for idiopathic pulmonary fibrosis (IPF). To find out which patients specifically benefit from pirfenidone, we analyzed in an exploratory manner the data from the phase III trial. METHODS: The patients in the phase III trial were stratified by baseline percentage predicted vital capacity (%VC), arterial oxygen partial pressure (PaO(2)), and the lowest oxygen saturation by pulse oximetry (SpO(2)) during the 6-minute steady-state exercise test (6MET). In the subpopulations, changes in VC and subjective symptoms (cough and dyspnea on the Fletcher, Hugh-Jones [F, H-J] Classification scale) were evaluated in patients treated with high-dose (1800 mg/day) pirfenidone, low-dose (1200 mg/day) pirfenidone, and placebo at week 52. RESULTS: Significant efficacy of pirfenidone in reducing the decline in VC could be seen in a subpopulation having %VC ≥ 70% and SpO(2) < 90% at baseline. This favorable effect was accompanied by categorical change in VC and progression-free survival time. In the subpopulation, pirfenidone significantly suppressed cough and dyspnea. CONCLUSIONS: IPF patients having %VC ≥ 70% and SpO(2) < 90% at baseline will most likely benefit from pirfenidone when evaluated using changes in VC (and %VC), and cough and dyspnea symptoms. This subpopulation could expect to benefit most from pirfenidone treatment. TRIAL REGISTRATION: This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (REGISTRATION NUMBER: JAPICCTI-050121).

[Case of lung edema occurring as a result of inhalation of fumes from a Teflon-coated flying pan overheated for 4 hours].

The patient was a 59-year-old man who had been treated with continuous positive airway pressure for a diagnosis of obstructive sleep apnea syndrome. While cooking buckwheat noodles, the patient fell asleep with a frying pan on the fire. After four hours, he was awakened by the smell of burning as well as pharyngalgia, and visited this hospital. He was found to have hypoxia, and diagnostic imaging showed diffuse concentration increase with peripheral clear zones in bilateral lung fields, a typical finding of pulmonary edema. In view of the peculiar temporal course of his disease and inhalation of Teflon fumes immediately before its occurrence, he was considered to have polymer fume fever with non-cardiogenic pulmonary edema. After admission, he was treated with oxygen inhalation and diuretics, and experienced a rapid improvement of his general condition and findings on diagnostic imaging. In European countries and the United States, cases with a history of inhalation of Teflon fumes have been given a diagnosis of polymer fume fever. This case is of interest as it is apparently the first such disease reported in Japan.

[A case of cryptogenic organizing pneumonia after postoperative irradiation for breast cancer].

The patient was a 69-year-old woman who had undergone breast-conserving surgery of the right breast, followed by tangential irradiation of 50 Gy to the remaining breast. Her subsequent progress was monitored by endocrine therapy with toremifene. Symptoms consisting of cough and slight fever developed 5 months after completion of radiation therapy. A chest X-ray image revealed an infiltrating shadow in the right middle and lower pulmonary fields, and the patient visited our hospital. BOOP was diagnosed by thoracoscopic biopsy. Spontaneous remission was observed during monitoring of the patient's progress. A shadow subsequently reappeared, for which a steroid was administered. Improvement was rapid. This case suggests that when tangential irradiation with or without endocrine therapy is provided, subsequent to breast-conserving treatment, patients should be monitored for the occurrence of BOOP.

[An autopsy case of obliterative bronchiolitis associated with Stevens-Johnson syndrome].

We reviewed an autopsied 27-year-old female with obliterative bronchiolitis associated with Stevens-Johnson syndrome. She had a history of Stevens-Johnson syndrome at age 10 years old and was treated with corticosteroids. Two months after the onset of dermatitis, the patient complained of dyspnea on exertion. The chest radiograph showed hyperinflation, and pulmonary function tests revealed obstructive impairment. The respiratory failure progressed due to respiratory tract infection and pneumothorax. She underwent thoracoscopic cyst surgery for right pneumothorax. Although the patient was clinically diagnosed as having obliterative bronchiolitis and received corticosteroids therapy and mechanical ventilation, she died of progressive respiratory failure 17 years after the onset of Stevens-Johnson syndrome. On autopsy, the macroscopic appearance of both lungs showed multiple white nodules in the centrilobular lesion corresponding to the obliteration of the small bronchioli. The microscopic appearance revealed constrictive bronchiolitis in the membranous bronchioli of both lungs associated with secondary bronchiectasis caused by superimposed infection.

[A case of pleural sarcoidosis in which vats lung biopsy, obtained pleural and pulmonary lesions].

Here we report a case that was diagnosed as sarcoidosis but required differential diagnosis from pneumoconiosis. A 51-year-old asymptomatic man, who showed signs of bilateral hilar lymphadenopathy (BHL) on a chest X-ray taken during a medical check, was given a diagnosis of sarcoidosis, based on the results of mediastinoscopic mediastinal lymph node biopsy. Because of the presence of large and small nodular lesions adjacent to the pleura extending from the bilateral upper lobes into the lung field, and continuous bead-like, small nodular lesions in the right interlobar pleura, pleural sarcoidosis was suspected and thoracoscopy was performed. Macroscopically, multiple grayish-white nodules with distinct margins, up to 1cm in diameter surrounded by a proliferation of capillaries were found in the pleura, particularly in the upper lobes. Lesions were also scattered over the interlobar pleura and diaphragmatic surface. Histopathologically, several non-caseous epithelioid cell granulomas and silicotic nodule-like lesions of hyaline degeneration were found; therefore, pneumoconiosis, or more specifically chronic berylliosis, was suspected. Despite these symptoms, the patient did not have a history of exposure, and the results of the lymphocyte stimulation test using beryllium were negative in blood and bronchoalveolar lavage fluid. The patient was given a diagnosis of pleural sarcoidosis and has been observed without treatment.

[A case of pulmonary abscess in which Haemophilus parainfluenzae and Streptococcus intermedius were isolated by percutaneous needle aspiration].

Some microbes, including the Bacteroides species, Staphylococcus aureus and Streptococcus milleri groups, can cause pulmonary abscess. Haemophilus parainfluenzae is usually categorized as one of the normal flora which colonizes in the ears and the nasopharynx, and it has been long considered that H. parainfluenzae has little pathogenicity in the lower respiratory tract and lung parenchymal. In this report, we present a case of pulmonary abscess caused by both H. parainfluenzae and Streptococcus intermedius. The patient was a 75-year-old man who had had total esophageo-gastrectomy because of esophageal cancer. He presented with purulent sputum, and chest X-ray film showed a dense consolidation in the right upper lung field. CT-guided transcutaneous fine needle aspiration was performed as a diagnostic procedure. Since both H. parainfluenzae and S. intermedius had been isolated from the lesion, pulmonary abscess caused by these two pathogens was diagnosed. The patient was treated with panipenem/betamipron, and his symptoms and pulmonary infiltrates on the chest X-ray film improved thereafter. So far, very few cases have been reported in which H. parainfluenzae caused lower respiratory tract infection. Although S. intermedius is known as one of the pathogens of pulmonary abscess, it is possible that H. parainfluenzae could also be pathogenic in infectious diseases of the lung.

Surgically curable peripheral lung carcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival.

STUDY OBJECTIVES: To define characteristics of surgically curable, early cancers of the lung, we retrospectively studied relationships between thin-section CT (TS-CT) scans, pathologic features, and outcome data in 287 patients with resected small-diameter (< 20 mm) peripheral lung carcinoma. Cases included 260 adenocarcinomas, 16 squamous cell carcinomas, 6 small cell carcinomas, 3 large cell carcinomas, and 2 others. MEASUREMENTS AND RESULTS: All tumors were classified by tumor shadow disappearance rate (TDR) on TS-CT as having either an "air-containing" or "solid-density" pattern. Adenocarcinomas are typically classified into these patterns. Air-containing patterns (n = 136) showed 1% pleural involvement and 2% vascular invasion, with no lymphatic permeation by pathology. Solid-density patterns (n = 124) showed 34% pleural involvement, 42% vascular invasion, and 29% lymphatic permeation. No cases of relapse or death were observed in cases with the air-containing pattern, in contrast to the high relapse and death rate in solid-density cases (p < 0.0001). All non-adenocarcinoma cases (n = 25) had a solid-density pattern, with 4% pleural involvement, 52% vascular invasion, and 44% lymphatic permeation. The overall 5-year survival rate for non-adenocarcinoma was 60%, similar to that for solid-density adenocarcinoma. CONCLUSIONS: When peripheral lung cancers < 20 mm in diameter show air-containing patterns on TS-CT images, surgical outcomes may be favorable with curable disease.

Risk factors for acute exacerbation of idiopathic pulmonary fibrosis--Extended analysis of pirfenidone trial in Japan.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a lifethreatening event and one of the important endpoints in clinical trials involving IPF. Despite this, there has been little evaluation of the potential risk factors for AE-IPF in clinical trials. We evaluated the risk factors for AE-IPF in a phase III clinical trial of pirfenidone in Japanese IPF patients. METHODS: The study population comprised 267 patients. The effects of various baseline characteristics as possible risk factors for AE-IPF during the study, as well as those of a ≥10% decline in percent vital capacity (%VC) within 6 months, were evaluated using Cox׳s proportional hazard model. The ≥10% decline in %VC was calculated in two ways: (1) an absolute decline (e.g. from 60% predicted to 50%); and (2) a relative decline (e.g. from 60% predicted to 54%). RESULTS: Over 52 weeks, 14 patients experienced AE-IPF. Univariate analysis using Cox׳s proportional hazards model showed that both relative and absolute ≥10% decline in %VC within 6 months were significant risk factors for AE-IPF. Stepwise multivariate analysis demonstrated that absolute or relative decline in both %VC and alveolar to arterial oxygen pressure difference (AaDO2) were significant risk factors for AE. The model using absolute decline [Hazard Ration (HR)=7.405, p=0.0007] and baseline AaDO2 (HR=1.063, p=0.0266) had a better fit than the model using relative decline and baseline AaDO2. CONCLUSIONS: Rapid %VC decline (≥10% within 6 months), and high baseline AaDO2, may be risk factors for AE-IPF.

Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan.

BACKGROUND: A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population. METHODS: Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations. RESULTS: Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF. CONCLUSION: This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results.

Small lung tumors with the size of 1cm or less in diameter: clinical, radiological, and histopathological characteristics.

BACKGROUND: The detection rate of small nodules in the peripheral lung area is increasing due to the widespread use of CT scanning. However, the radiological and pathological characteristics of very small tumors have not been fully investigated. METHODS: We evaluated 44 lung tumors with the size of 1cm or less in diameter resected from 38 patients (19 men and 19 women, with an average of 62 years) from 1997 through 2001. The clinical records, the findings of high-resolution CT (HRCT) and histopathological features of resected specimens were analyzed. Adenocarcinoma was histologically further subclassified into types A to F according to the Noguchi's classification. RESULTS: Lobectomy was performed in 20 patients, wedge resection in 15 and segmentectomy in 3, respectively. Thirty-two tumors were adenocarcinomas, 4 were squamous cell carcinomas, and eight were atypical adenomatous hyperplasia (AAH), respectively. All carcinoma cases were proved to be stage IA. In adenocarcinoma, type A was detected in 12 tumors, type B in 13, type C in 1, type D in 2, type E in 1, and type F in 3, respectively. Most of AAH and type A showed pure ground-glass attenuation on HRCT scan, whereas types B to F as well as squamous cell carcinoma frequently had malignant CT signs such as lobulation and convergence of peripheral vessels. Lymphatic or vascular invasion was observed in two adenocarcinomas (types D and F) and two squamous cell carcinomas, and HRCT scan of these four tumors showed soft-tissue attenuation occupying more than two-thirds of each nodule. All patients are currently alive without signs of recurrence after a mean follow-up period of 35.5 months. CONCLUSION: Types A and B of adenocarcinoma were the most common histologic types among lung tumors with the size of 1cm or less in diameter. Limited lung resection appears to be an adequate for such small lung tumors in which soft-tissue attenuation consists of less than two-thirds of the nodule on HRCT.

Multiple atypical adenomatous hyperplasia with synchronous multiple primary bronchioloalveolar carcinomas.

We report a case of multiple atypical adenomatous hyperplasia (AAH) associated with synchronous multiple primary bronchioloalveolar carcinomas (BACs). A 58-year-old man was visited for bronchial asthma. A chest computed tomography (CT) scan revealed small, multiple nodules with ground glass attenuation (GGA) throughout both lungs, predominantly in the upper lobes. A high resolution CT (HRCT) scan disclosed well-defined nodules with uniform GGA. Thoracoscopic wedge lung biopsy confirmed the diagnosis. The patient was treated with chemotherapy and had stable disease for two years. It is important to recognize that multiple AAH associated with multiple BACs can present as diffuse, well-defined nodules with uniform GGA on HRCT.

[A clinical study of cryptococcal meningitis--sequential changes of cryptococcal antigen titers].

We reviewed the clinical manifestations, sequential changes in cryptococcal antigen titers in serum and cerebrospinal fluid (CSF), and the antifungal drug susceptibility of Cryptococcus neoformans in three patients with cryptococcal meningitis between 1996 and 2000. Cryptococcal antigen titers were measured using the latex agglutination method with Pastrex Cryptococcus (Fuji Mebio, Tokyo) and Serodirect Cryptococcus (Eiken Chemical, Tokyo). The underlying systemic diseases in the three patients were liver cirrhosis, non-Hodgkin's lymphoma associated with miliary tuberculosis, and malignant thymoma associated with systemic lupus erythymatosus. The CSF samples showed positive indian ink staining in two of the three patients and C. neoformans was cultured from all three. The cryptococcal antigen titers in serum were higher than those in the CSF. The serum and CSF cryptococcal antigen titers measured by Serodirect Cryptococcus were higher than those measured by Pastrex Cryptococcus. The maximum titers of antigen in serum and CSF measured by Serodirect Cryptococcus were greater than 1,024 in all three patients. The treatment regimens used for the three patients were amphotericin-B (AMPH-B) and flucytosine (5-FC), fluconazole (FLCZ) and intrathecal AMPH-B, FLCZ and 5-FC, and intrathecal AMPH-B, respectively. The antigen titers in serum and CSF decreased after treatment in all three patients. The antigen titers decreased slowly over 7.3 months in the most seriously ill patient who had non-Hodgkin's lymphoma associated with miliary tuberculosis. The time between the beginning of treatment and CSF cryptococal antigen titers falling to less than 8 was 1.7 to 7.3 months in the three patients, but the serum titers did not decrease to less than 8 during this period. The minimum inhibitory concentration was 0.06-0.25 microgram/ml for AMPH-B, 4-8 micrograms/ml for 5-FC, 2-8 micrograms/ml for FLCZ, 0.125-0.5 microgram/ml for miconazole and 0.03-0.125 microgram/ml for itraconazole. The measurement of sequential changes in cryptococcal antigen titers in serum and CSF was useful for evaluating the response to treatment.

[A case of pulmonary coccidioidomycosis presented with bilateral infiltrative opacities and eosinophilia].

A 53-year-old male was admitted to our hospital complaining of high fever with chillness, cough and dyspnea after traveling to Arizona in the United States. The chest X-ray films taken on admission showed consolidation in the right middle lung field and bilateral nodular shadows. The laboratory data revealed an increase in white blood cell counts with eosinophilia, and a rise in erythrocyte sediment rate and serum C-reactive protein. The biopsied lung specimen by video-assisted thoracoscopic surgery showed granulomatous inflammation consisting of eosinophils and giant cells. In addition, typical spherules filled with endopores were detected in the specimen. The diagnosis of primary pulmonary coccidioidomycosis was made. After the treatment of a three months' regimen with itraconazole at the daily dosage of 200 mg, the patient's symptoms, laboratory data and radiological findings markedly improved.

[Adverse effects and adherence to nasal continuous positive airway pressure in patients with obstructive sleep apnea hypopnea syndrome].

The adverse effects of and adherence of a treatment with nasal continuous positive airway pressure (nCPAP) for obstructive sleep apnea and hypopnea syndrome (OSAHS) were examined. The subjects comprised 321 patients with OSAHS. An all-night polysomnography was performed for all subjects. Titration of CPAP was performed manually. Regarding the adverse effects of nCPAP therapy, the subjects most frequently complained of nasal symptoms, air-leaks and any trouble with the mask. Complaints heard less frequently were sleep disturbances, dry pharyngeal and oral cavities, noises, and pronounced pressure sensations due to CPAP. No adverse effects were noted in 13% of the subjects. The adherence was as high as 73.0% in 122 patients in whom time spent for nCPAP treatment could be analyzed. The mean treatment time was 4.7 +/- 1.8 hours. We found no significant correlation between mean treatment time and age, BMI, ESS, CPAP, AHI, Ar-I, ODI, lowest SpO 2, or %TST with SpO 2 < 90%. Multivariate analysis revealed no factor significantly correlated with treatment time. These results showed that detailed instructions for the prevention of adverse effects may improve the adherence of CPAP.

[Fatal acute exacerbation of idiopathic pulmonary fibrosis/usual interstitial pneumonia initially in the right lung after surgery lobectomy for left lung cancer].

A tumor was found in the left S10 in a chest CT scan of a 72-year-old male patient with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). He underwent left lower lobectomy and resection of the hilar and mediastinal lymph nodes under video-assisted thoracoscopic surgery. The histopathological evaluation disclosed a well-differentiated squamous cell carcinoma (T1N0M0; stage IA) associated with UIP. On the sixth postoperative day, a severe hypoxemia (PaO2 48 mmHg) developed, and the chest CT showed diffuse ground glass opacity (GGO) in the right lung. A diagnosis of acute exacerbation of IPF/UIP was made, and steroid pulse therapy with cyclosporin A was started. However, despite this therapy, the diffuse GGO extended to both lung fields, and the patient died of respiratory failure 82 days later. The histopathology at autopsy demonstrated diffuse alveolar damage due to UIP that was consistent with acute exacerbation of IPF/UIP. It is suggested that the acute exacerbation of IPF/UIP could have been triggered by a high concentration of oxygen or mechanical lung injury during the patient's surgery.

[A suspected case of negative PR 3-ANCA Wegener's granulomatosis associated with marked endobronchial lesion and systemic angitis].

A 72-year-old woman had been diagnosed as having organizing pneumonia at another hospital. She was treated with antibiotics, bronchodilators and prednisolone, but her cough, fever and inflammatory signs were not resolved completely. She was admitted to our hospital for further evaluation of the lung lesion. The chest CT scan revealed narrowing of the segmental bronchus and the serum samples showed elevated MPO-ANCA but negative PR 3-ANCA levels. Physical examination also revealed marked bilateral episcleritis and eyeground angitis. Fiberoptic bronchoscopy showed bilateral marked stenotic segmental bronchi associated with mucosal erosions and small nodular lesions. Bronchial and renal biopsy specimens demonstrated marked angitis in the bronchial arteries and glomeruli. A generalized form of Wegener's granulomatosis (WG) was diagnosed and was treated with 60 mg/day of prednisolone, 50 mg/day of cyclophosphamide and 4 g/day of sulfamethoxazole-trimethoprim, which resulted in a marked improvement of the clinical symptoms and endobronchial lesions. In WG, the incidence of endobronchial involvement is 16 to 55% and that of positive serum MPO-ANCA alone is only 14.3%. The present case of WG was considered a rare case with WG which because of the MPO-ANCA-positive but PR 3-ANCA-negative findings associated with marked endobronchial lesions and systemic angitis.

[High efficacy of pleurodesis using OK-432 for controlling intractable pneumothorax associated with pulmonary lymphangioleiomyomatosis].

We evaluated the efficacy of pleurodesis using OK-432 (Picibanil) for the treatment of pneumothorax associated with pulmonary lymphangioleiomyomatosis (LAM). Seven episodes of pneumothorax in five patients with LAM were treated with pleurodesis using OK-432. First, all patients underwent tube thoracostomy drainage. After drainage, 5 or 10 KE of OK-432 was administered via the tube. If incomplete lung expansion or a continuous air leak occurred, an additional 5 KE of OK-432 was administered. Of the five patients, two developed pneumothorax for the first time and three had a history of previous pneumothorax. The mean total dose of OK-432 administered was 13.6 KE, and the mean period of tube drainage was 11 days. The only recurrence of ipsilateral pneumothorax after OK-432 pleurodesis was observed seven years and eight months later in association with chronic respiratory failure in one patient. This patient was successfully treated with repeated pleurodesis using OK-432 during mechanical ventilation, and no recurrence has developed in the eight years since then. The main side effects of the procedure with OK-432 were fever and chest pain, which were well controlled by non-steroidal anti-inflammatory drugs. The study concluded that pleurodesis with OK-432 was an effective and safe treatment for intractable and recurrent pneumothorax associated with LAM.

[Pulmonary cryptococcosis combined with pulmonary tuberculosis].

We report a rare combination of pulmonary cryptococcosis and pulmonary tuberculosis in a diabetic patient. A 63-year-old man was admitted to our hospital in January 2002 for evaluation of an abnormal chest radiograph. In 1999, the abnormality had first been detected by mass screening radiography. In 2000, an abnormality in a chest radiograph was again detected in a mass screening, and he visited another hospital. A chest CT scan revealed a cavitating lesion and several nodules in the left lower lobe. Fiberoptic bronchoscopy was performed, but was not diagnostic. The patient was referred to our hospital. He had a history of diabetes mellitus starting in 1984. The chest CT scan revealed solid nodules in the left lower lobe and several micronodules in both upper lobes. Video-assisted thoracoscopic surgery was performed and specimens were obtained from the left S8 and left S1 + 2. Histologically, cryptococci were detected in the resected left S8. In addition, mycobacterium tuberculosis was cultured from the resected left S1 + 2. A diagnosis of combined pulmonary cryptococcal and tuberculous infections was made and treatment with itraconazole, isoniazid sodium methansulfonate, rifampicin, and ethambutol hydrochloride was given.