Detection of nocturnal wheezing in bronchial asthma using intermittent sleep tracheal sounds recording.

Common clinical features of bronchial asthma include bronchoconstriction during the night, particularly while asleep. Although bronchoconstriction reduces the quality of life and can cause life-threatening events, a clinical technique for evaluating bronchoconstriction during sleep has not been widely applied. In this study, we measured nocturnal wheezing by intermittent sleep tracheal sounds recording (ISTSR) to detect bronchoconstriction during the hours of sleep. Using ISTSR, we studied the number and duration of nocturnal wheezing episodes in 27 adult patients with bronchial asthma. Nocturnal wheezing was detected in 36 of 39 recordings. Although the pattern of hourly nocturnal wheezing count (hourly NWC pattern) varied among subjects, there appeared to be a reproducible pattern within individuals. When wheezing alternated between long and short duration, bronchoconstriction tended to be more severe. The NWC in 1 h (NWC/H) was positively correlated with subjective symptoms and inversely correlated with the morning per cent peak expiratory flow. The hourly NWC was significantly greater at 05:00 than that at midnight. Intermittent sleep tracheal sounds recording has potential to be a non-invasive clinical tool for detecting nocturnal bronchoconstriction during hours of sleep in patients with asthma.

[Diffuse panbronchiolitis with myeloperoxidase-specific antineutrophil cytoplasmic antibody-related vasculitis].

A 46-year-old woman was referred to our department in July 1996 with complaints of fever and myalgia in her calves. She had a 20-year history of purulent sputum; diffuse panbronchiolitis had been diagnosed in 1983. Physical examination revealed low-pithed rhonchi over the lung fieldis and hypesthesia of the right leg. She had a white blood cell count of 16,100/mm3, including 4% eosinophils, and a platelet count of 80.0 x 10(4)/mm3. The serum IgE level was 2,200 U/ml, and the cold hemagglutinin titer was high. Pulmonary-function tests showed mixed ventilatory dysfunction, and arterial blood gas analysis revealed a PaO2 of 55.8 Torr on room air. Pseudomonas aeruginosa was cultured from her sputum. A chest X-ray film and CT scan showed diffuse nodular shadows and bronchiectatic changes with mild hyperinflation. An infiltrative lesion in right S6 area could also be seen. Administration of broad-spectrum antibiotics did not alleviate her symptoms. The level of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) in serum was 245 EU/ml, and 67Ga scintigraphy showed marked accumulation in the abdomen. Abdominal angiography demonstrated a bead-like appearance and irregularities in the peripheral branches of the hapatic artery, the splenic artery, the cystic artery, and the superior mesenteric artery. Because of the high MPO-ANCA level and the angiographic abnormalities, MPO-ANCA-related vasculitis was diagnosed. She was treated with 1 g of methylprednisolone daily for 3 days, followed by 60 mg of prednisolone and 50 mg of cyclophosphamide daily. Her condition improved dramatically, and the MPO-ANCA level became almost normal. During treatment, her blood pressure rose markedly with a normal serum creatinine level and normal urinalysis. Plasma renin activity was 13.3 ng/ml/hr. Renal angiography showed stenoses and irregularities in the peripheral branches of renal arteries bilaterally. These findings led to a diagnosis of renovascular hypertension due to vasculitis. Her blood pressure was controlled with an angiotensin-converting enzyme inhibitor and a calcium antagonist. Vasculitis associated with chronic supportive lung disease has occasionally been reported, which suggests a casual relation between chronic respiratory infection and ANCA-related vasculitis. Systemic vasculitis should be taken into account as a potential complication of chronic suppurative lung disease.

Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia.

A 31-year-old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon-alpha since February 1995. After 16 months, he complained of low-grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X-ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.

Alpha-fetoprotein producing pulmonary blastoma in a patient with systemic sclerosis: pathogenetic analysis.

We describe a rare case of pulmonary blastoma complicated with systemic sclerosis. The serum alpha-fetoprotein level was elevated at presentation and the biopsied tumour stained positively against anti-alpha-fetoprotein antibody. The alpha-fetoprotein produced autonomously by tumour cells was of yolk-sac origin. Although the pathogenesis of pulmonary blastoma has not been clarified, we suggest that this pulmonary blastoma is a type of yolk-sac tumour.

Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis.

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.

Multiple pulmonary nodules in association with pyoderma gangrenosum.

This report describes a patient with extensive pyoderma gangrenosum in whom there were co-existent lung abnormalities. The patient's X-ray showed peripherally sited multiple pulmonary lesions bilaterally. A lung biopsy showed chronic non-specific inflammatory changes with neutrophil and lymphocyte infiltration which were similar to the skin lesions. This case was diagnosed as multiple aseptic nodules in pyoderma gangrenosum. The pulmonary infiltrative shadows were controlled only with prednisolone treatment. Steroid therapy is considered to be the first choice to control pulmonary lesions of this disease.

Diffuse alveolar hemorrhage associated with proteinase 3-specific anti-neutrophil cytoplasmic antibodies.

A 31-year-old man was referred to our hospital for the management of progressive diffuse alveolar hemorrhage associated with renal dysfunction. Leukocytoclastic vasculitis was shown by skin biopsy and crescentic glomerulonephritis was also detected, in addition to positivity for proteinase 3-specific anti-neutrophil cytoplasmic antibodies (PR3-ANCA). The patient was diagnosed as a rare case of PR3-ANCA-positive pulmonary-renal vasculitic syndrome without granulomatous lesions. There was a good response to combination therapy with steroids and cyclophosphamide.

[Successful treatment of chronic eosinophilic pneumonia with suplatast tosilate].

The patient was a 59-year-old woman who complained of coughing, sputum production, and dyspnea. Abnormal moving shadows were found by chest radiography. There was prolonged eosinophilia in blood. Eosinophilia was also found in bronchoalveolar lavage fluid, and examination of a specimen obtained by transbronchial lung biopsy revealed eosinophil infiltration in alveolar septal walls, which led to a diagnosis of chronic eosinophilic pneumonia. Because of an attack of bronchial asthma and a high level of IL-5 in serum on admission, the patient was given suplatast tosilate. Symptoms were relieved, eosinophil counts in blood and in bronchoalveolar lavage fluid decreased, and the radiographic abnormality disappeared. The patient was not treated with steroids, and there has been no reccurrence to date, one year after discharge.

Protein kinase inhibitor attenuates an increase in endothelial monolayer permeability induced by tumour necrosis factor-alpha.

We questioned the mechanism of the increase in pulmonary endothelial permeability induced by tumour necrosis factor-alpha (TNF-alpha), a cytokine implicated in the pathogenesis of adult respiratory distress syndrome. As a measure of permeability, we determined the albumin transferred across cultured pulmonary endothelial monolayers prepared on a porous filter. The agents evaluated included protein kinase inhibitors H-7 and H-8, a calmodulin antagonist W-7, and protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and SC-9. H-7, more potent in inhibiting PKC than H-8, failed to attenuate the increase in permeability induced by TNF-alpha. Neither PMA nor SC-9 increased permeability. However, H-8, which is a potent inhibitor of cyclic nucleotide-dependent protein kinases, prevented the increase in permeability induced by TNF-alpha. These results suggest that protein kinase other than PKC are involved in the signal transduction in endothelial permeability increase induced by TNF-alpha. Calmodulin pathway may not be implicated in the increase in permeability induced by TNF-alpha.

Clinical evaluation of serum type IV collagen 7S in idiopathic pulmonary fibrosis.

Type IV collagen is one of the major components of the basement membrane (BM). 7S domain (7S collagen) of type IV collagen is an N-terminal peptide which is stable against protease and heat. We investigated serum concentration of 7S collagen in patients with idiopathic pulmonary fibrosis (IPF) and other pulmonary diseases. The aim of this study was to evaluate whether changes in the serum concentration of 7S collagen reflect the fibrotic process of IPF. We measured the concentration of serum 7S collagen with radioimmunoassay in patients with IPF, chronic pulmonary emphysema (CPE), sarcoidosis, infectious pulmonary diseases (IPD) and normal healthy controls. We also monitored 7S collagen during the clinical course in some patients with IPF and investigated the correlation between the serum 7S collagen, and lactate dehydrogenase (LDH) and erthrocyte sedimentation rate (ESR) in patients with IPF. Patients with IPF showed significantly higher serum concentration of 7S collagen than other pulmonary diseases and healthy controls. The serum concentration of 7S collagen significantly decreased in IPF patients who showed roentgenographic improvement after corticosteroid treatment. There was a correlation between the serum 7S collagen and LDH, and ESR. In conclusion, serum concentrations of 7S collagen increase in patients with IPF. The measurement of 7S collagen is useful for the evaluation of fibrotic change in the lung.

Superoxide release and NADPH oxidase components in mature human phagocytes: correlation between functional capacity and amount of functional proteins.

We evaluated the interrelationship between the respiratory activity and amount of proteins responsible for this function in normal and subnormal human phagocytes, neutrophils, eosinophils, monocytes, and macrophages. The superoxide-producing capacity was eosinophils > neutrophils > monocytes = macrophages when the cells were stimulated with chemotactic peptide or phorbol ester. Consonant with this finding, the protein content of three essential components of phagocyte oxidase (p22-phox, p67-phox, and p47-phox) was also eosinophils > neutrophils > monocytes = macrophages. On the other hand, the amount of another essential component, gp91-phox, was macrophage > neutrophils > eosinophils > monocytes. These findings together indicate an overall positive interrelationship between protein content and its responsible function, though only gp91-phox was not associated with the functional capacity and low amounts of this component supported the increased respiratory burst activity of eosinophils.

[Subsets of lymphocytes in bronchoalveolar-lavage fluid from patients with idiopathic bronchiolitis obliterans organizing pneumonia].

Lymphocyte activation may be involved in interstitial inflammatory processes in the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from 5 patients with idiopathic bronchiolitis obliterans organizing pneumonia and from 7 control subjects. Lymphocytes were analyzed by two-flow cytometry. Differential cell counts showed that the percentage and the number of lymphocytes was higher in the patients (32.9 +/- 21.9%, 12.8 +/- 8.32 x 10(4) cells/ml) than in the controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4) cells/ml, p < 0.05). In particular, the patients had many more CD8+ S6F1+ lymphocytes (which are considered to be activated cytotoxic T lymphocytes; 32.2 +/- 11.8%, 42.0 +/- 26.5 x 10(3) cells/ml) than did the controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3) cells/ml, p < 0.01). These data indicate that activated cytotoxic T lymphocytes may be important in the pathogenesis of bronchiolitis obliterans organizing preumonia.

[Lymphocyte subsets in bronchoalveolar lavage fluid from patients with idiopathic interstitial pneumonia].

Lymphocyte activation may be involved in interstitial inflammatory processes in the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from 15 patients with idiopathic interstitial pneumonia (IIP) and from 7 controls. Clinical criterial were used to divide the patients with IIP into two groups: acute (n = 5) and chronic (n = 10). Lymphocytes in the bronchoalveolar lavage fluid were analyzed with a flow-cytometric two-color system. Differential cell counts showed that percentages and numbers of lymphocytes were significantly higher in patients with acute IIP (44.2 +/- 25.2%, 12.3 +/- 8.18 x 10(4)/ml) than in controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4)/ml, p < 0.05) and in patients with chronic IIP (8.44 +/- 6.11%, 1.58 +/- 1.08 x 10(4)/ml, p < 0.05). In particular, percentages and numbers of CD8+ S6F1+ lymphocytes, which are regarded as activated cytotoxic T lymphocytes were markedly higher in patients with acute IIP (32.3 +/- 16.0%, 39.6 +/- 37.1 x 10(3)/ml), than in controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3)/ml, p < 0.05) and in patients with chronic IIP (10.6 +/- 6.16%, 1.88 +/- 1.42 x 10(3)/ml, p < 0.05). These data suggest that patients with acute IIP differ from those with chronic IIP in the percentage and the number of lymphocytes in bronchoalveolar lavage fluid, and that activated cytotoxic T lymphocytes may play an important role in the pathogenesis of acute IIP.

[Frequency analysis of crackles recorded with a stethoscope-equipped recorder].

Crackles were recorded with one of two systems in a total of 58 cases and compared. In one system a stethoscope was attached to a microphone; in the other system no stethoscope was used (see reference 9). Coarse crackles were recorded with the stethoscope system in 11 patients, and with the microphone-only system in 12 patients. Most patients with coarse crackles had bronchiectasis. Fine crackles were recorded with the stethoscope system in 13 patients, and with the microphone-only system in 22 patients. Most patients with fine crackles had idiopathic pulmonary fibrosis. Each record was examined visually, and all crackles recorded during one inspiration were selected. Power spectra were estimated with the maximum entropy method and peak frequencies were determined with the damped least-squares method. Type-I crackles were defined as those with all peak frequencies below 800 Hz; these low-pitched sounds may correspond to coarse crackles. Type-II crackles were defined as those with peak frequencies over 800 Hz regardless of the existence of peaks below 800 Hz; these high-pitched sound may correspond to fine crackles. The "%Type II" was defined as the percentage of the total crackles that were Type-II crackles. The %Type II value among coarse crackles was 10 +/- 16% with the stethoscope and 3 +/- 7% with the microphone. Among fine crackles, the values were 65 +/- 22% with the stethoscope and 79 +/- 23% with the microphone. For both kinds of equipment, the %Type II differed significantly between coarse and fine crackles (p < 0.01). The stethoscope-transmitted sound had components that could be used to differentiate fine crackles from coarse crackles. For clinical purposes, crackles recorded with a stethoscope are as useful as those recorded with a microphone only.

[Chronic respiratory failure--survival for nine years with home mechanical ventilation].

We report the case of a woman, now 58 years old, with chronic respiratory failure due to spinal progressive muscular atrophy. She first noticed gradual progressive muscular weakness in her extremities in 1973. She started to complain of dyspnea on exertion in 1978. Chronic respiratory failure due to spinal progressive muscle atrophy was diagnosed in 1983. Home oxygen therapy was begun, but CO2 narcosis and exacerbation of chronic respiratory failure occurred at the end of that year. A tracheotomy was done and mechanical ventilation was begun. As her general condition improved and she could breathe without the ventilator for a few hours each day, home mechanical ventilation was begun. Seven years later, her general condition is still good and she can live without any life-threatening distress. There are few reports of patients in Japan who have survived for long periods of time with home mechanical ventilation. We believe that improvement in her respiratory care and in her social situation contributed to her long standing clinical course.

Fat embolism syndrome caused by vegetable oil injection.

We present a case of fat embolism syndrome following vegetable oil injection for augmentation mammaplasty. Although vegetable oil is a stable neutral fat under usual storage conditions, it caused fat embolism and pulmonary injury in this patient. We investigated this mechanism by compound analysis of the injected oil, transbronchial lung biopsy and special staining of alveolar macrophages. This is the first description of the human response to vegetable oil injection. These data should aid in the investigation of the side effects of many types of lipids which may be applied to humans for various purposes in the future.

[Diagnosis of B-cell lymphoma of lung by kappa-lambda imaging in broncho-alveolar lavage fluid lymphocytes].

We attempted to verify the clonality of proliferating cells in broncho-alveolar lavage fluid (BALF) by using a sophisticated technique known as kappa-lambda imaging. We applied this method to BALF lymphocytes from 3 cases suspected of having primary pulmonary B-cell lymphoma, by transbronchial lung biopsy, and from 2 cases with B-cell lymphoma revealing abnormal shadows. (One was diagnosed as small cell carcinoma, the other mycotic infection). B-cell monoclonality was found in the former 3 cases, but not in the latter 2 cases. We conclude that kappa-lambda imaging in BALF lymphocytes is useful for diagnosing B-cell lymphoma of the lung.

[An autopsy case of lymphoepithelioma-like carcinoma of the mediastinum].

A case of lymphoepithelioma-like carcinoma of the mediastinum is reported. A 67-year-old male was admitted to Tokyo Medical College Hospital, in February of 1992, for evaluation of an abnormal mediastinal shadow on chest X-ray. The mediastinal tumor was biopsied using mediastinoscopy. Histological diagnosis was undifferentiated carcinoma and radiation therapy was performed. Six months after treatment, he complained of dyspnea. Combination chemotherapy was performed. Although the tumor size decreased, he died of pneumonia. Histological findings at autopsy included nesting of large carcinoma cells with vacuolar nuclei and large nucleoli, interstitial lymphocytic infiltration similar to that of lymphoepithelioma of the epipharynx, and lymphoepithelioma-like carcinoma in the thymus. The epipharynx and thymus were, however, intact at autopsy. We found no other origins of this tumor, including the trachea and lung. This case was therefore diagnosed as lymphoepithelioma-like carcinoma of the mediastinum.

[A case of pulmonary fibrosis associated with CMV inclusion body].

A 71-year-old woman admitted to our hospital with complaints of progressive dyspnea on exertion and weight loss. Roentgenological examination demonstrated peripheral pulmonary fibrosis and a mediastinal tumor suggesting thymoma. The pathological findings of transbronchial lung biopsy (TBLB) confirmed pulmonary fibrosis. Moreover, cytomegalic inclusion bodies in TBLB and a high titer of serum CMV IgG antibody suggested pulmonary CMV infection. It is considered that pulmonary fibrosis and CMV infection were coexistent in this patient.