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.

Elevated IL-5 levels in pleural fluid of patients with paragonimiasis westermani.

To investigate the pathogenic mechanisms of eosinophilic pleural effusion in patients with paragonimiasis, we measured the levels of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) in pleural effusions. Samples were obtained from 11 patients with Paragonimus westermani infection. In addition, samples from 12 patients with pleural transudates, 16 with tuberculous pleurisy, seven with empyema and 20 with lung cancer were also examined. Eosinophilia was remarkable in peripheral blood (range 4-34%, median 23.4%) and pleural fluid (range 0-95%, median 71%) of paragonimiasis patients. IL-5 concentrations in pleural effusions of paragonimiasis were markedly higher than those in other groups. Although marked elevation of GM-CSF and IFN-gamma levels was observed in pleural effusion of empyema and tuberculosis patients, it was marginal in the pleural effusion of paragonimiasis patients. In paragonimiasis patients, IL-5 levels in the pleural effusion correlated well with the percentage of eosinophils in peripheral blood and pleural fluid. Such a correlation was not observed between GM-CSF levels in pleural effusion and percentages of eosinophils in pleural fluid or peripheral blood. Our findings suggest that in paragonimiasis IL-5 in the local inflammatory site is particularly important in mediating eosinophilia in peripheral blood and pleural effusion.

[A case of bird fanciers' disease caused by parrot droppings].

A 50-year-old woman who had been treated for Parkinson's disease was admitted to our hospital because of exertional dyspnea and weight loss. Her chest computed tomography showed diffuse ground glass opacities in both lung fields. Bronchofiberscopy was performed, and the bronchoalveolar lavage fluid showed an elevated lymphocyte count. The serum Ouchterlony test yielded positive results for parrot droppings as well as for pigeon serum and droppings. She had had a parrot for several years, but no pigeon, and so we diagnosed bird fanciers' disease associated with parrot droppings. This responded well to steroid therapy. This case of bird fanciers' disease was caused by the droppings of only one parrot.

[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.

[A case of paragonimiasis westermani with a high level of interleukin 5 in bronchoalveolar lavage fluid].

A 49-year-old man was admitted to our hospital with a productive cough and bloody sputum. Peripheral blood eosinophil counts and serum IgE values were elevated. Chest radiography and chest computed tomography revealed a solitary nodule with cavitation and satellite lesions in the right middle lobe, in contact with the pleura. The diagnosis of paragonimiasis westermani was confirmed by detection of ova in the sputum and bronchoalveolar lavage fluid (BALF) samples, and by immunoserological examination. The patient was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg. After treatment, his clinical symptoms and radiological abnormalities disappeared. The IL-5 level was high in BALF, but it was undetectable in the plasma, suggesting that IL-5 in inflammatory lesions may be particularly important in mediating eosinophilia in the blood and BALF in paragonimiasis westermani.