Risk factors for disease-related deterioration following diagnostic bronchoalveolar lavage procedures in diffuse lung disease: a case-control study

Background Although the risk factors for diagnostic bronchoalveolar lavage (BAL)-induced acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF) have been previously reported, no study has assessed these in patients with non-IPF. We aimed to identify the risk factors for BAL-induced disease deterioration (BAL-DD) in all types of diffuse lung disease. Methods Patients with diffuse lung disease who underwent BAL at our hospital from April 2012 to November 2017 were retrospectively analyzed. The patient information, laboratory data, radiological findings, and BAL fluid analysis results in patients who developed BAL-DDs were compared with those in patients who did not. Results BAL-DDs occurred in 14 (3.3%) of the 429 patients included the study. The BAL-DD group had a significantly poorer performance status, higher C-reactive protein level, lower partial pressure of oxygen in the arterial blood at rest, greater proportion of desaturation on exertion and cases having followed a progressive clinical course before BAL, and more extensive consolidation and ground-glass opacity on chest high-resolution computed tomography (HRCT) than the non-BAL-DD group. A high total cell concentration and an increased number of eosinophils in the BAL fluid were more frequently found in patients with BAL-DD than in those without. Conclusions Patients with decreased physical activity level, increased level of inflammatory markers, low oxygenation status, and extensive lung involvements on chest HRCT and following a progressive clinical course before BAL may be warned of the BAL-DD risk. Elevated eosinophil counts in the BAL fluid could be associated with the triggering of BAL-DDs

悪性黒色腫におけるカテプシンＤの過剰発現

Cathepsin D is an aspartic lysosomal endopeptidase present in most mammalian cells. Overexpression of cathepsin D is associated with the progression of several human cancers including melanoma. We examined the expression levels of cathepsin D in 20 primary malignant melanomas, 20 metastatic malignant melanomas, 20 benign nevus pigmentosus and 10 normal skin samples in Japanese. In normal skin, granular or dotted pattern of positive staining was observed along the granular layer of epidermis and hair follicle with apparent moderate to strong staining in sebaceous and eccrine glands. The percent positivity and staining intensity of cathepsin D in primary and metastatic malignant melanomas were significantly higher than that of nevus pigmentosus. Moreover, the expression levels of cathepsin D in metastatic malignant melanomas were significantly higher than those of primary malignant melanomas. Data from our and previous reports strongly supports a notion that the upregulation of cathepsin D may be critically involved in the malignant transformation and progression of melanocytic tumors.カテプシンDはリソゾーム内に存在するエンドペプチダーゼであるが, 胃癌, 乳癌, 卵巣癌などでは周辺正常組織に比べ, 過剰発現していることが知られている. 悪性黒色腫においても, その過剰発現が2編の文献報告で知られているが, 日本人を対象とした検討は行われていない. 我々は, 20例の原発性悪性黒色腫, 20例の転移性悪性黒色腫, 20例の良性色素細胞母班, 10例の健常皮膚を用いて, カテプシンD の発現を免疫組織学的に検討した. 正常皮膚では, カテプシンDは表皮および毛囊の上層・顆粒層に顆粒状に発現しており, 脂腺やエクリン汗腺では強い発現を認めた. 原発性悪性黒色腫や転移性悪性黒色腫のカテプシンDの発現は, 良性色素細胞母班のそれよりも有意に上昇していた. また転移性悪性黒色腫では, 原発性悪性黒色腫よりも有意に高い発現が認められた. これらの結果から, カテプシンDの発現は色素細胞の悪性化と腫瘍進展に関与していると考えられた