Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis.

BACKGROUND: Human beta-defensin (HBD)-1 and -2 are antimicrobial peptides present in the respiratory tract. Recent reports have indicated reduced activity of beta-defensins in cystic fibrosis, suggesting that beta-defensins may play an important role in the pathological process of chronic respiratory tract infection. Diffuse panbronchiolitis (DPB) is a progressive disease characterised by frequent episodes of superimposed infection, typically caused by Pseudomonas aeruginosa. The aim of this study was to elucidate the role of these antimicrobial peptides in this disease. METHODS: The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB. RESULTS: High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid (total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1beta. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against P aeruginosa. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles. CONCLUSIONS: These results indicate that beta-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.

Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Neutrophils are thought to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Human neutrophils contain antimicrobial and cytotoxic peptides in the azurophil granules which belong to a family of mammalian neutrophil peptides named alpha-defensins. A study was undertaken to investigate the role of alpha-defensins in the pathogenesis of IPF. METHODS: The concentrations of alpha-defensins (human neutrophil peptides (HNPs) 1, 2, and 3) in plasma and bronchoalveolar lavage (BAL) fluid of 30 patients with IPF and 15 healthy subjects were measured by radioimmunoassay. RESULTS: The concentrations of alpha-defensins in plasma, but not in BAL fluid, were significantly higher in IPF patients than in controls. BAL fluid concentrations of interleukin (IL)-8 in patients with IPF, which were significantly higher than in controls, correlated with those of alpha-defensins. An inverse relationship was seen between plasma alpha-defensin levels and the arterial oxygen tension (PaO(2)) and pulmonary function (vital capacity (%VC), forced expiratory volume in 1 second (FEV(1)), and carbon monoxide transfer factor (%TLCO)) in patients with IPF. Plasma levels of alpha-defensins also correlated with the clinical course in IPF patients with an acute exacerbation. Immunohistochemically, positive staining was observed inside and outside neutrophils in the alveolar septa, especially in dense fibrotic areas. CONCLUSION: These findings suggest that alpha-defensins play an important role in the pathogenesis of IPF, and that the plasma alpha-defensin level may be a useful marker of disease severity and activity.

Clinicoradiologic features of pleuropulmonary Paragonimus westermani on Kyusyu Island, Japan.

STUDY OBJECTIVE: Recently, the number of new cases of Paragonimus westermani in humans has gradually increased, and paragonimiasis is a re-emerging public health issue in Kyusyu, Japan. We review our recent experience with pleuropulmonary Paragonimus westermani. PATIENTS: Pulmonary paragonimiasis was diagnosed in 13 patients at the Third Department of Internal Medicine, Miyazaki Medical College between 1993 and 1999. RESULTS: Both sputum and bronchoscopic examinations revealed ova in four of nine patients; bronchoscopy yielded ova in two additional patients. Twelve patients (92%) had respiratory symptoms, including cough (92%), sputum and/or hemoptysis (92%), and chest pain (46%). Chest radiography and CT showed pleural lesions (62%) and parenchymal lesions (92%). Of note was the high frequency of solitary nodular lesions (62%), mimicking lung cancer, tuberculosis, or fungal diseases. Immunodiagnosis and bronchoscopic examination were also useful for diagnosis. Praziquantel treatment was very effective and had minimal side effects. One patient required surgical decortication for empyema in spite of treatment with praziquantel. Eosinophilia was noted in peripheral blood and body fluids, which was probably due to increased levels of interleukin-5. CONCLUSIONS: Our findings indicate that our patients with Paragonimus westermani presented with a wide variety of radiographic findings, which were different from the classic presentations reported earlier. Bronchoscopic examination and serologic tests are very useful for accurate diagnosis. As dietary habits change and international transportation increases, it appears likely that paragonimiasis will also increase in frequency in various parts of the world.

[Clinical features in twenty-three patients with paragonimiasis westermani].

We assessed the clinical features in twenty-three cases diagnosed as paragonimiasis westermani from April 1988 to May 2000 in our clinic at Miyazaki Medical College Hospital. Twenty-one patients had eaten wild boar or crab meat. Their symptoms included productive cough, chest pain and hemosputum. The findings of radiography and computed tomography (CT) were nodules, masses, infiltrative shadows and pleural effusion. The percentages of eosinophils in the peripheral blood were elevated in 16 of 23 patients, and the serum IgE values were elevated in 12 of 18 patients. Serologic tests, which are very helpful for diagnostic purposes were performed on the blood sera of all patients, and on the pleural effusions of five patients. It is often difficult to diagnose paragonimiasis westermani in patients in whom eosinophilia or increased serum IgE is not present. However, paragonimiasis westermani should also be considered as a possible diagnosis when abnormal shadows are found in chest radiographs and chest CT.

[Pulmonary dirofilariasis with cavity formation and pleural effusion].

A 61-year-old man visited a community hospital because of hemosputum. A solitary nodule in the left lower lung field was pointed out on a chest roentgenogram. The patient was treated with antibiotics, but the solitary nodule increased in size. He was referred to our hospital because of high fever and observations of cavity formation and pleural effusion on a chest roentgenogram. The pleural effusion showed no cytologic evidence of malignancy, and cultures were also negative for bacteria. An increased percentage of lymphocytes was detected in the pleural effusion, but slight eosinophilia was found in blood samples. Dot enzyme-linked immunosorbent assay and Ouchterlony's double-diffusion test yielded a diagnosis of pulmonary dirofilariasis. After drainage of the pleural effusion by thoracentesis, spontaneous regression was observed. Cavity formation, pleural effusion, and spontaneous regression are in general rare in patients with pulmonary dirofilariasis.

[Bronchial atresia with atelectasis of the left upper lobe].

A 69-year-old woman visited her physician on October 1 complain of dry cough. However, the chest radiograph revealed no abnormalities. She was later admitted to our hospital because a radiograph taken by another physician on November 26 revealed a massive lesion in the right upper mediastinum. Computed tomographic findings showed a massive lesion containing a branching structure with a few calcifications, suggesting a case of atelectasis of the left upper lobe with mucus plug. Bronchoscopic examination revealed complete obstruction of the orifice of the left upper lobe bronchus, and so a diagnosis of bronchial atresia was made. However, since the patient had a history of tuberculous peritonitis and the mass lesion was somewhat calcified, the possibility that this was an acquired case could not be ruled out. After treatment with oral antibiotics, the size of the atelectasis was decreased. Therefore, we considered that the expansion of the atelectasis could have been due to superimposed bacterial infection.

[A case of severe Legionnaires' disease complicated by rhabdomyolysis, acute renal failure, liver dysfunction and encephalopathy].

A 67-year-old male was admitted to our hospital due to a high fever with abnormal shadows on chest X-ray films. On admission, his laboratory data showed hyponatremia, rhabdomyolysis and liver dysfunction. Encephalopathy, acute renal failure and respiratory failure developed, despite fluid management and antimicrobial therapy. His condition worsened rapidly in a few days enough to require mechanical ventilation. Legionnaires' disease was suspected, because pneumonia was found to be associated with multiple organ dysfunction. Intravenous erythromycin and methylprednisolone were administered. The patient's condition was rapidly improved, although he needed hemodialysis for 30 days. Later, indirect fluorescent antibody testing of the patient's serum against Legionella pneumophila was definitely positive (1:1024). We reported the first case of severe Legionnaires' disease in Miyazaki Prefecture, Japan.