Respiratory Bronchiolitis-associated Interstitial Lung Disease with Unusual Histopathological Findings

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a mild inflammatory reaction commonly seen in asymptomatic young male cigarette smokers. This report describes unusual pathological findings in a 63-yearold Japanese female with RB-ILD. She had a 40 pack-year smoking history. Chest computed tomography showed multiple patchy shadows, especially in the right lower lobe. Diagnosis could not be established by bronchoalveolar lavage and transbronchial lung biopsy. Thoracoscopic lung biopsy was performed from right S5 and S9, which demonstrated the typical pathological findings of RB-ILD, including the presence of pigmented macrophages within respiratory bronchioles, thickening of alveolar septa by fibrosis, accumulation of intrapulmonary blue bodies and lack of granulomatous changes. Our patient had atypical RB-ILD based on old age at presentation (commonly -40 years of age), marked fibrosis and presence of numerous blue bodies

Significance of subepithelial deposits in patients diagnosed with IgA nephropathy

Subepithelial deposits are observed in rare adult IgA nephropathy (IgAN) cases and are a key diagnostic finding in IgA-dominant infection-related glomerulonephritis (IgA-IRGN). Sometimes, it is difficult to distinguish IgA-IRGN from IgAN without a precise clinical history. We hypothesized that some IgA-IRGN cases might be diagnosed as IgAN with subepithelial deposits (IgAN-SD) and aimed to clarify the significance of subepithelial deposits in patients diagnosed with IgAN. We examined 464 patients diagnosed with IgAN at Nagasaki University Hospital and affiliated hospitals between 1996 and 2013. The differences in clinicopathological findings between IgAN-SD and IgAN with no subepithelial deposits (IgAN-NSD) were investigated.In addition to clinical data and typical IgAN pathological features, we analyzed complement levels, immunoglobulin localization, light chain staining patterns, and intramembranous deposits. There were 214 men and 250 women with a mean age of 38.8 ± 18.3 years. Subepithelial deposition was observed in 51 patients (11%). Compared to patients with IgAN-NSD, those with IgAN-SD had significantly lower mean serum protein (6.4 g/dL vs. 6.7 g/dL; p = 0.02), albumin (3.7 g/dL vs. 3.9 g/dL; p = 0.02), and complement (C3) (94 mg/dL vs. 103 mg/dL; p = 0.02) levels.Diffuse mesangial hypercellularity (M) (65% vs. 45%; p<0.01), endocapillary hypercellularity: (E) (43% vs. 28%; p = 0.03),and IgA staining in the glomerular capillary wall (22% vs. 8%; p<0.01) were more common in patients with IgAN-SD. The incidence of light chain lambda predominance was lower in patients with IgAN-SD (47% vs. 63%; p = 0.03). Hump-shaped subepithelial deposits and intramembranous deposits were observed in nine and 17 patients with IgAN-SD, respectively. Patients with IgAN-SD tended to have the characteristics of IgA-IRGN rather than IgAN-NSD.Since the therapeutic strategies for IgA-IRGN differ from those for IgAN, we should review the clinical history and pay careful attention to the clinical course in cases with atypical findings, such as subepithelial deposits

Bronchiolitis Obliterans Organizing Pneumonia Induced by Minocycline

We report a case of bronchiolitis obliterans organizing pneumonia (BOOP) caused by minocycline (MINO). A 59- year-old man visited to our hospital because of flu-like symptoms. He had been treated with MINO for a few weeks for the skin eruption. The chest radiograph showed consolidations in both lung fields. He was admitted to our hospital for further examination. An elevation of lymphocyte percentage was seen in his bronchoalveolar lavage and a diagnosis of BOOP was confirmed by video-assisted thoracoscopic lung biopsy. The symptoms, laboratory and radiological findings gradually improved without steroid therapy. Although the lymphocyte stimulation test (LST) of peripheral blood for MINO was negative, a positive oral provocation test confirmed the role of MINO in the induction of BOOP

Peak power estimated from 6-minute walk distance in Asian patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

ABSTRACT Background and objective: Pulmonary rehabilitation guidelines recommend cycle ergometry training at an intensity that exceeds 60% of peak power (P(peak)) with the aim of achieving a physiologic response. However, many clinicians do not have access to an incremental cycle ergometry test (ICET) to allow prescription of training intensity. No studies have investigated whether the 6MWT can be used to estimate the P(peak) achieved during an ICET in subjects with IPF or in Asian subjects with COPD. Methods: A total of 90 Japanese subjects (IPF n = 45, COPD n = 45) undertook a 6MWT and a symptom-limited ICET in random order. Anthropometry, quadriceps strength and lung function were measured. Results: Exercise tests were prematurely terminated in 10 subjects with IPF due to profound oxygen desaturation (SpO(2) < 80%). The ICET elicited higher peak heart rates, dyspnea and leg fatigue in both subject cohorts (all P < 0.01). The magnitude of oxygen desaturation was greater during the 6MWT (P < 0.01). 6MWD was strongly associated with P(peak) (r = 0.80, P < 0.01) in both subject cohorts. In subjects with IPF, the predictive equation that accounted for the greatest proportion of variance in P(peak) included 6MWD and FVC %pred (R(2) = 0.70). In the COPD subjects, 6MWD alone accounted for 64% of the variance in P(peak) and the inclusion of other variables did not increase R(2). Conclusions: P(peak) can be estimated from the 6MWT in Japanese subjects with IPF and COPD. This may allow individualized prescription of the intensity for cycle-based training based on the 6MWT

Respiratory Bronchiolitis-associated Interstitial Lung Disease

We report a case of respiratory bronchiolitis-associated interstitial lung disease (RB-ILD). A 57-year-old man with a 74-pack-year smoking history, had cough, stridor, yellow purulent sputum and general fatigue for several days. The symptoms almost improved after treatment. However, chest computed tomography (CT) showed diffuse centrilobular ground glass opacities although the chest X-ray film showed no obvious opacities. Examination of bronchoalveolar lavage fluid showed relative lymphocytosis. Examination of lung biopsy obtained by video-assisted thoracoscopy allowed the diagnosis of RBILD. The opacities on the CT scan were improved spontaneously without any treatment after cessation of smoking

Juvenile Idiopathic Nonspecific Interstitial Pneumonia. and Review of Literature

We describe a case of juvenile idiopathic nonspecific interstitial pneumonia (NSIP). This is the first report of a Japanese patient with idiopathic NSIP aged 27 years. A computed tomographic scan of the chest showed groundglass opacities and reticular opacities in subpleural distribution. Bronchoalveolar lavage fluid revealed no specific finding except for decreased CD4/CD8 ratio of lymphocyte subset. Histopathological features on examination of thoracoscopic lung biopsy specimens were consistent with those of NSIP group III. The patient was treated with corticosteroids and immunosuppressants, but no clinical improvement was noted and the general condition has gradually worsened. Although the prognosis is generally considered to be good in patients with NSIP, some patients die as a result of progression of the disease. The prediction of prognosis based on histopathological, radiologic, and bronchoalveolar lavage cell findings in NSIP seems to be difficult at present

Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis.

Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role in the processing and/or secretion of procollagen. However, the knowledge on which cells are actually synthesizing HSP47 in the lung parenchyma in pulmonary fibrosis was only limited. The aim of the present study was to investigate the localization of HSP47 messenger ribonucleic acid (mRNA) in normal lung and in the lungs of mice in bleomycin-induced pulmonary fibrosis, using in situ hybridization. For the purpose, ICR mice were intravenously injected with 10 mg/kg per day of bleomycin for five consecutive days. The lung cells expressing HSP47 mRNA were identified in control (saline alone) and bleomycin-treated mice by in situ hybridization. The signal for HSP47 mRNA was markedly increased in bleomycin-treated lungs compared with that of controls. HSP47 mRNA was localized in alpha-smooth-muscle-actin-positive myofibroblasts, surfactant-protein-A-positive type II pneumocytes, and F4/80-positive macrophages in the active fibrotic areas. These results suggest that these cells may synthesize procollagen in the fibrotic process of bleomycin-treated lungs through upregulation of HSP47 mRNA and play an important role in fibrogenesis

Efficacy of clarithromycin in patients with mild COVID-19 pneumonia not receiving oxygen administration: protocol for an exploratory, multicentre, open-label, randomised controlled trial (CAME COVID-19 study)

Introduction: The COVID-19 pandemic has emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, very few treatment strategy has been established for patients with mild COVID-19 who do not require oxygen administration. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza. In this study, we aim to evaluate the efficacy of clarithromycin in patients with mild COVID-19.Methods and analysis: This is an exploratory, multicentre, open-label, randomised controlled trial. This study was initiated in May 2021 and will end in July 2022. Patients with mild COVID-19 pneumonia who do not require oxygen administration will be enrolled and randomly assigned in a 1:1:1 ratio to group A (administration of clarithromycin 800 mg/day), group B (administration of clarithromycin 400 mg/day) or group C (standard treatment without clarithromycin). The planned number of enrolled patients is 60 (20 patients × three groups). The primary endpoint is the number of days required to improve the clinical symptoms as measured by the severity score. Secondary endpoints include days for recovery of the body temperature, proportion of patients with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers and pneumonia infiltrations.Ethics and dissemination: The study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act and other current legal regulations in Japan. Written informed consent will be obtained from all the participants. The results of this study will be reported as journal publications.Trial registration number: jRCTs071210011

Interstitial Pneumonia Associated with Linear Immunoglobulin A/Immunoglobulin G Bullous Dermatosis

A 76-year-old man with interstitial lung disease was admitted to our institution after developing persistent dyspnea upon effort. He also had a relapse of bullous eruptions on the skin of the trunk and extremities, previously diagnosed as vesicular pemphigoid. Direct immunofluorescence of a skin biopsy specimen using fluorescence microscopy showed the linear deposition of immunglobulin A (IgA), IgG and C3 along the basement membrane. These findings indicated a definitive diagnosis of linear IgA/IgG bullous dermatosis. Chest computed tomography, bronchoalveolar lavage and transbronchial lung biopsy findings suggested nonspecific interstitial pneumonia. Direct immunofluorescence of the lung biopsy specimens using fluorescence microscopy also showed a deposition of IgA, IgG and C3 along the epithelial cell membranes and basement membranes of the bronchioles and alveoli. Lung disorders associated with linear IgA/IgG bullous dermatosis are extremely rare and, to our knowledge, this is the first report of such a case of interstitial pneumonia.著者版でのFigure 1は非公開。出版社版はDOIリンクを参照のこと