A clinical study of idiopathic eosinophilic pneumonia.

To better characterize idiopathic eosinophilic pneumonia (IEP), we studied the clinical and laboratory features of 27 patients. Patients with IEP could be divided into those with chronic eosinophilic pneumonia (CEP) (n = 14) and acute eosinophilic pneumonia (AEP) (n = 13). CEP was characterized by (1) multiple and dense areas of consolidation on chest radiographs and computed tomographic (CT) scans, (2) persistent symptoms, (3) a requirement for steroid therapy, and (4) possible relapses. On the other hand, AEP was characterized by (1) diffuse ground-glass and micronodular infiltrates on radiographs and CT scans (in mild cases, the lesions were sparse or localized), (2) acute onset with high fever, (3) spontaneous improvement, and (4) no relapse. In addition, peripheral blood eosinophil count was significantly higher in patients with CEP than in patients with AEP at the first examination. However, the eosinophil fraction also became markedly elevated during the subsequent courses of AEP. Analysis of bronchoalveolar lavage fluid revealed that the percentage of eosinophils was higher in patients with CEP than that in patients with AEP, whereas the percentage of lymphocytes was significantly greater in patients with AEP than patients with CEP. It was also noted that 75 percent of patients with CEP and 82 percent of patients with AEP had allergic diathesis, suggesting that both conditions are likely to occur in atopic individuals.

Wegener's granulomatosis responding to antituberculous drugs.

We present a case of Wegener's granulomatosis (WG) that responded to antituberculous drugs. A 44-year-old woman with multiple nodules on chest radiograph received a diagnosis of pulmonary tuberculosis because open-lung biopsy specimens showed caseous granulomas. Her chest shadows underwent repeated resolution after the start of antituberculous treatment, and relapse after the cessation of the drugs. Antineutrophil cytoplasmic antibody was positive (14 enzyme-linked immunosorbent assay units), and the second lung biopsy specimens showed necrotizing granulomas and vasculitis without pathogenic organisms. Thus, the patient received a diagnosis of WG and was successfully treated with trimethoprim/sulfamethoxazole 10 years after her initial evaluation. Antituberculous drugs were effective in this case of WG.

Development of bronchus-associated lymphoid tissue in chronic hypersensitivity pneumonitis.

STUDY OBJECTIVES: Bronchus-associated lymphoid tissue (BALT) is well defined in animals. In humans, however, BALT has been reported to be inducible under pathologic conditions, such as chronic respiratory infection, although it is not present in healthy adults. Thus, induced BALT is considered to be involved in the mucosal immunity of the human lung under these conditions. However, there have been few studies to investigate BALT development in hypersensitivity pneumonitis. The aim of this study was to examine the presence of BALT in hypersensitivity pneumonitis, especially in its chronic form. METHODS: The subjects included five patients with chronic hypersensitivity pneumonitis (CHP) diagnosed from clinical and histologic findings. We investigated histologically the development of BALT in these patients. Further, the cellular distribution of BALT was also examined by immunohistochemistry. RESULTS: BALT was present in three of five patients with CHP. Immunohistochemical examination revealed the follicular area of BALT to be composed mainly of B cells, while the parafollicular area comprised predominantly T cells. Centroblasts located in the germinal center of BALT expressed Ki-67 antigen, a marker of cell proliferation, suggesting that these cells were actively proliferating after antigenic stimulation. Cells expressing bcl-2, which is present primarily on memory B cells, were confined to the follicular area, devoid of any germinal centers. S-100-positive, CD1a-negative interdigitating dendritic cells were observed in the dome area of BALT. CONCLUSIONS: These observations suggest that chronic antigenic stimulation and/or inflammation in CHP may cause BALT development, which, in turn, is likely to play an important role in the mucosal immune response of this disease.

Lack of evidence for a role of Epstein-Barr virus in the increase of lung cancer in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is known as an independent risk factor for lung cancer. Because Epstein-Barr virus (EBV) may be involved in the genesis of IPF as well as certain malignancies, we investigated whether EBV contributes to the increased incidence of lung cancer in IPF The formalin-fixed and paraffin-embedded lung sections were prepared from 22 lung cancer patients with IPF and 22 lung cancer patients without IPF All ofthe IPF patients pathologically showed usual interstitial pneumonia. In situ hybridization for EBV-encoded small non-polyadenylated RNAs failed to show positive signals in the cancer tissues of either IPF or non-IPF patients. This study did not provide evidence for an etiologic role of EBV in the development of lung cancer in IPF.

Diffuse panbronchiolitis and rheumatoid arthritis-associated bronchiolar disease: similarities and differences.

There is a considerable overlap between diffuse panbronchiolitis (DPB) and bronchiolar disease associated with rheumatoid arthritis. The present study assessed how these conditions could be differentiated. The subjects included 25 DPB patients and 15 RA patients with bronchiolar disease (RA-BD). Patients with either condition had chronic cough, purulent sputum, dyspnea and coarse crackles. Most patients with either DPB or RA-BD had a history of sinusitis as well as elevated cold hemagglutin titers and decreased levels in partial pressure of oxygen (PaO2), forced expiratory volume in one second (FEV1.0) and V 25/Ht. On histological examination, both conditions also shared various histological patterns although panbronchiolitis lesions were more common in DPB than RA-BD (68% vs 20%) and bronchiolar obliteration appeared to occur at more proximal sites in RA-BD than DPB. However, there were important differences: long-term treatment with erythromycin had less effect in RA-BD than DPB, and the frequency of HLA B54 tended to be higher in DPB than RA-BD (50.0% vs 22.2%), suggesting that they are distinct conditions.

A clinical study of minocycline-induced pneumonitis.

We studied the clinical features of minocycline-induced pneumonitis in seven patients. Acute symptoms included fever, dry cough and dyspnea, indicating acute respiratory failure. Diffuse ground glass shadows with Kerley's B lines, bronchial wall thickening, swelling of vascular bundles and pleural effusion were visible on radiography. Bronchoalveolar lavage or transbronchial lung biopsy confirmed pulmonary eosinophilia. Cessation of minocycline led to rapid remission with no treatment or only short-term steroid therapy. The lymphocyte stimulation test for minocycline with peripheral blood lymphocytes was not found to be useful for diagnosis.

Partial anomalous pulmonary venous return showing anomalous venous return to the azygos vein.

Partial anomalous pulmonary venous return (PAPVR) is a congenital heart disease with a reported incidence of autopsied case. The location of the anomalous pulmonary venous return is usually the right atrium, superior vena cava (SVC), and sometimes the brachiocephalic vein, inferior vena cava (IVC) or coronary venous sinus. Recently we experienced a rare case of PAPVR showing anomalous right total pulmonary venous return to the azygos vein. Furthermore, downward translocation of the right upper lobe bronchus was evident. This rare case is reported along with a review of the related literature.

Dyskeratosis congenita showing usual interstitial pneumonia.

A 46-year-old man was admitted to our hospital with cough and dyspnea on exertion. A chest X-ray film showed diffuse interstitial shadows. He had hyperpigmentation forming a network pattern around his neck and dystrophy of the fingernails and toenails, and was diagnosed as having dyskeratosis congenita. Histological examination of the lung specimen obtained from the left S4b by open lung biopsy revealed usual interstitial pneumonia pattern with neither asbestos bodies nor silicotic nodules. Taken together with previously published findings, pulmonary involvement is considered to be an important complication of dyskeratosis congenita.

Weekly low-dose methotrexate therapy for sarcoidosis.

Low-dose methotrexate therapy has been used to treat a variety of chronic inflammatory diseases; a few studies have discussed the efficacy of this therapy for sarcoidosis. We present a patient with symptomatic sarcoidosis who was successfully treated with low-dose methotrexate after being refractory to steroids. This patient showed significant clinical improvement without development of any severe side effects. These findings suggest that low-dose methotrexate therapy may be a useful alternative treatment for sarcoidosis.

Varicella pneumonia in a healthy adult presenting with severe respiratory failure.

We describe a case of varicella pneumonia in a 24-year-old healthy man presenting with severe respiratory failure. A chest radiograph showed diffuse, bilateral airspace consolidation; additional complications included liver dysfunction and thrombocytopenia. However, treatment with intravenous acyclovir and gamma-globulin improved his clinical symptoms and signs. A greater than four-fold change in paired titers of the varicella-zoster virus antibody was observed. Bronchoalveolar lavage performed during the recovery phase revealed increased total cell and lymphocyte counts and a decreased CD4:CD8 ratio of T lymphocytes. Transbronchial lung biopsy findings were compatible with a diagnosis of interstitial pneumonia.

[Aspergillosis with non-cavitary lung cancer].

Growth of Aspergillus was observed in the necrotic tissue of non-cavitary lung cancer. Case 1 was a 60-year-old male complaining of cough and fever and was found to have left lower lobe atelectasis on chest X-ray. Bronchoscopic examination showed the yellow soft lesion occluding the left upper and lower lobe bronchus. Specimen from the lesion demonstrated adenocarcinoma and hyphae of Aspergillus in the necrotic tumor. Case 2 was a 53-year-old male who was found to have a left upper lobe mass by chest X-ray screening. Bronchoscopic examination showed the yellow polypoid lesion occluding the left upper division bronchus. Pneumonectomy was done and resected specimen of the lesion demonstrated adenocarcinoma and the hyphae of Aspergillus growing in both necrotic tissue and cancer tissue. As both patients had hyphae of Aspergillus in the necrotic tumor, it is considered that the presence of necrosis may cause the growth of Aspergillus.

[Usefulness of percutaneous instillation of antifungal agents for pulmonary aspergilloma].

We studied the usefulness of percutaneous instillation of antifungal agents for treatment of pulmonary aspergilloma. The subjects were six patients, four males and two females, with a mean age of 69 years (range, 45 to 90 years). In all cases, radiography revealed a fungus ball or thickened cavity wall in residual tuberculous cavities. The patients had clinical symptoms including hemoptysis, fever, cough and sputum, and most of them showed severe emaciation, anemia, hypoalbuminemia and hypoxia. Miconazole or fluconazole was instilled through an indwelling catheter inserted percutaneously into the cavity from the anterior chest wall or parascapular region under fluoroscopic observation. After treatment with a total dose of 610 to 2070 mg over a period of 6 to 18 weeks, clinical symptoms were diminished in all patients and radiographic findings were improved in five. Furthermore, Aspergillus fumigatus, which had been isolated from sputum samples of three patients, was eradicated. According to evaluation of the overall therapeutic effects, this therapy was considered to be effective in five patients, giving an efficacy rate of 83%. No recurrence has been detected in six patients during a mean follow-up of 13 months after treatment. Since percutaneous instillation involves less pain and stress than other kinds of

[A case of streptomycin-induced lupus].

A case of streptomycin-induced lupus occurring in a 48-year-old female is presented. She was admitted to our hospital in July 1990, complaining of productive cough and general fatigue. A chest roentgenogram showed cavitary lesions and infiltrative shadows in the bilateral upper and middle lung fields and a sputum smear tested positive for acid-fast bacilli. She was diagnosed as lung tuberculosis and antituberculous therapy with isoniazid, rifampicin and streptomycin was started. Ten days after starting the treatment, she began to complain of high fever and erythema on her face and forearms. Blood cell count revealed leucopenia. The antinuclear antibody and antihistone antibody were positive. The improvement of clinical findings and the lowering of antinuclear antibody titer seen after stopping streptomycin confirmed the diagnosis as streptomycin-induced lupus. Streptomycin-induced lupus is very rare.

[A case of asthma relieved by aspirin--the first case in Japan and investigation of its mechanism].

We report a case of asthma that was relieved by aspirin and other cyclooxygenase inhibitors. The patient, a 51-year-old man, was admitted to our hospital because of an asthmatic attack. Onset of asthma had occurred at the age of 40 years, after a flu-like infection, and was preceded for several years by perennial rhinitis and loss of the sense of smell. The course was perennial, and unrelated to the seasons. These clinical features resembled those of aspirin-induced asthma (AIA). Therefore, suspecting AIA, we performed a aspirin-DL-lysine iv challenge test. After aspirin-DL-lysine injection, FEV1 was increased by about 30% and nasal obstruction was improved. Other cyclooxygenase inhibitors (indomethacin, mefenamic acid, ketoprofen) also improved FEV1 by more than 30%. Hydrocortisone sodium succinate (HCs) improved FEV1 about 20%. Lipoxygenase inhibitor (AA861) produced an evident attack, but continued administration did not result in complete tolerance. On the other hand, seven other AIA patients showed no reaction to AA861. DSCG had an acute bronchodilative effect similar to that of AIA. Paraben and chloramphenicol sodium succinate (CMs) produced an asthmatic attack. The present patient showed a marked improvement in response to cyclooxygenase inhibitors and HCs, in contrast to the situation in AIA, and developed an evident asthmatic attack in response to lipoxygenase inhibitor. He showed marked improvement in the response to DSCG and developed an asthmatic attack in response to paraben and CMs, as in AIA. Our results suggest an abnormality of Arachidonic acid metabolism not only in AIA but also in asthma relieved by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sodium cromoglycate nebulized solution has an acute bronchodilative effect in patients with aspirin-intolerant asthma (AIA)].

Sodium cromoglycate (SCG) (Intal) is a well-known anti-allergic agent which protects against allergen- and exercise-induced bronchospasms. The effect has been recognized non-acute, unlike that of bronchodilators. However, we have found that some patients with aspirin-intolerant asthma (AIA) show significant improvement soon after a single inhalation of SCG nebulized solution. In this study, we investigated the acute bronchodilator effect of SCG given by nebulizer in adult asthmatics, especially compairing AIA with non-AIA (aspirin-tolerant asthma) patients. Twenty patients with AIA and 11 with non-AIA participated in the study. After performing spirometry on remission, they inhaled either SCG via a nebulizer or 4 ml of placebo in a randomized double-blind fashion. After inhalation, spirometry was performed every ten minutes for one hour. The placebo used was a saline solution of the same osmolarity as that of the SCG nebulized solution. Placebo inhalation provoked asthmatic attacks in five of the patients with AIA and one with non-AIA, but SCG did not. In the AIA group, twelve out of the twenty patients also had improved nasal symptoms soon after inhalation of SCG. Forced expiratory volume in one second (FEV1) was significantly improved 10 minutes after inhalation of SCG. Fifty minutes after SCG inhalation, the percent degree of FEV1 improvement was approximately 17%. However, FEV1 was significantly decreased by approximately 14% after inhalation of placebo. In the non-AIA group, FEV1 was not increased after inhalation of SCG. V25 was not changed after inhalation of SCG in AIA and non-AIA groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Testicular sarcoidosis].

We report a rare case of testicular sarcoidosis. A 68-year-old man was admitted for detailed examination of uveitis and swelling of the testes. A chest X-ray film and computed tomographic scans disclosed ground-glass shadows in the lower fields of both lungs with mediastinal lymphadenopathy. Ga scintigram showed pronounced accumulations in the testes, hilum, and mediastinum. Transbronchial lung and testicular biopsy specimens demonstrated noncaseating epithelioid granulomas, thus confirming the diagnosis of sarcoidosis with testicular involvement. The patient was followed up without systemic steroids. A review of the world literature found only 12 reported cases of clinically evident testicular sarcoidosis.

[A case of tracheobronchomegaly].

We report a rare case of tracheobronchomegaly with crescent-type tracheobronchomalacia. A 77-year-old man with a chronic cough was referred to our hospital because of fever and dyspnea. Radiographic examination showed enlargement of the trachea and main bronchi. On chest radiography, the transverse diameter of the trachea was 31 mm, and consolidation shadows were seen in both upper lung fields. Tracheobronchomegaly with pneumonia was diagnosed. The pneumonia was improved by administration of PAPM/BP. On bronchoscopic examination, the trachea and main bronchi were extremely dilated on inspiration, and were collapsed on expiration. The biopsy specimen from the bronchial mucosa showed non-specific chronic inflammation.

[Compensatory growth of residual lung after pneumonectomy in childhood].

Though pneumonectomy proved to be a potent stimulus to compensatory growth in the animal model, the literature on this subject in human patients is sparse. We report a rare case of compensatory growth after pneumonectomy in childhood. A 17-year-old man was admitted to our hospital because of chest pain. He had been capable of normal exercise despite a history of pneumonectomy at the age of 4. Chest radiography showed pneumothorax and a displaced heart. In a chest CT scan, both pleural spaces were filled with the enlarged left lung. Since thoracoscopic examination showed a bulla at the surface of S3, bullectomy was performed. The specimen resected from the lung showed slight dilatation of the alveoli. It is considered that the enlargement of the residual lung had occurred as a result of alveolar multiplication rather than by dilatation of the existing alveoli. This case demonstrates lung regeneration in childhood.

[Lung cancer obscured by aspergillus hyphae].

A 66-year-old man was referred to our hospital because of cough. Chest X-ray films showed complete atelectasis of the left lung. Serum CYFRA was elevated. Bronchoscopic examination disclosed a white polypoid lesion occluding the left main bronchus. A biopsy specimen from the lesion revealed numerous aspergillus hyphae. Oral itraconazole (100 mg) and weekly endobronchial instillation of fluconazole were administered. Three months later, on the 12th bronchoscopic examination, the tumor occluding the left main bronchus was detected after the removal of aspergillus, and the biopsy findings yielded a diagnosis of squamous cell carcinoma. Aspergillosis complicated by lung cancer without cavity formation is very rare, and compounded the difficulty of diagnosing lung cancer in this case.