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

Acute exacerbation of airspace enlargement with fibrosis

AbstractIn 2008, Kawabata et al. described a lesion which they termed “airspace enlargement with fibrosis” that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of another type. An 82-year-old man was referred to our department for worsening dyspnea and new alveolar opacities on chest radiograph following left pulmonary segmentectomy (S6) for cancer. A diagnosis of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of other types was made, based on pathological evidence of airspace enlargement with fibrosis and organizing diffuse alveolar damage. Treatment with high-dose methylprednisolone followed by tapered oral prednisolone resulted in gradual improvement of the clinical condition and chest radiographic findings. Clinicians should be aware that patients with airspace enlargement with fibrosis may experience acute exacerbation

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

Characteristics and disease severity of healthcare-associated pneumonia among patients in a hospital in Kitakyushu, Japan.

Healthcare-associated pneumonia (HCAP) is a newly identified condition, and epidemiologic studies in Japan are still limited. We retrospectively observed patients with HCAP and community-acquired pneumonia (CAP) who were hospitalized between December 2004 and March 2005, and compared their disease characteristics. A total of 34 patients (14 with HCAP and 20 with CAP) were evaluated. Of the patients with HCAP, seven (50%) were hospitalized for at least 2 days in the preceding 90 days and five (35.7%) resided in a nursing home or extended care facility. Compared with patients with CAP, patients with HCAP were older, had more complications, including central nerve diseases, had greater disease severity, but lower serum albumin level. More methicillin-resistant Staphylococcus aureus, Pseudomonas spp., and anaerobes were isolated from patients with HCAP than from those with CAP. Conversely, more Streptococcus pneumoniae was detected and more penicillin was used in patients with CAP. This study provides additional evidence that HCAP should be distinguished from CAP and suggests the pathogenesis and therapeutic strategy for HCAP may be similar to those for hospital-acquired pneumonia

Acute exacerbation of airspace enlargement with fibrosis

In 2008, Kawabata etal. described a lesion which they termed "airspace enlargement with fibrosis" that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of another type. An 82-year-old man was referred to our department for worsening dyspnea and new alveolar opacities on chest radiograph following left pulmonary segmentectomy (S6) for cancer. A diagnosis of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of other types was made, based on pathological evidence of airspace enlargement with fibrosis and organizing diffuse alveolar damage. Treatment with high-dose methylprednisolone followed by tapered oral prednisolone resulted in gradual improvement of the clinical condition and chest radiographic findings. Clinicians should be aware that patients with airspace enlargement with fibrosis may experience acute exacerbation

Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts.

Pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and patients with idiopathic pulmonary fibrosis (IPF). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen and plays an important role in the pathogenesis of IPF. The present study evaluated the in vitro effects of pirfenidone on expression of HSP47 and collagen type I in cultured normal human lung fibroblasts (NHLF). Expression levels of HSP47 and collagen type I in NHLF stimulated by transforming growth factor (TGF)-beta1 were evaluated genetically, immunologically and immunocytochemically. Treatment with TGF-beta1 stimulated both mRNA and protein expressions of both HSP47 and collagen type I in NHLF, and pirfenidone significantly inhibited this TGF-beta1-enhanced expression in a dose-dependent manner. We concluded that the anti-fibrotic effect of pirfenidone may be mediated not only through direct inhibition of collagen type I expression but also at least partly through inhibition of HSP47 expression in lung fibroblasts, with a resultant reduction of collagen synthesis in lung fibrosis

Serum heat shock protein 47 levels are elevated in acute interstitial pneumonia

Background: Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. We hypothesized that HSP47 could be a useful marker for fibrotic lung disease. The aim of this study was to evaluate serum levels of HSP47 in patients with various idiopathic interstitial pneumonias (IIPs).Methods: Subjects comprised 9 patients with acute interstitial pneumonia (AIP), 12 with cryptogenic organizing pneumonia (COP), 16 with nonspecific interstitial pneumonia (NSIP), 19 with idiopathic pulmonary fibrosis (IPF), and 19 healthy adult volunteers.Results: Patients with AIP had serum HSP47 levels that were significantly higher than those of COP, NSIP or IPF patients and those of healthy volunteers. In contrast, serum levels of HSP47 among patients with COP, NSIP, IPF, and healthy volunteers did not differ significantly. Receiver operating characteristic curves revealed that the cut-off level for HSP47 that resulted in the highest diagnostic accuracy for discriminating between AIP and COP, NSIP, IPF, and healthy controls was 859.3 pg/mL. The sensitivity, specificity, and diagnostic accuracy were 100.0%, 98.5%, and 98.7%, respectively.Conclusion: The present results demonstrate that, among patients with various IIPs, serum levels of HSP47 were elevated specifically in patients with AIP

Differential effects of human neutrophil peptide-1 on growth factor and interleukin-8 production by human lung fibroblasts and epithelial cells.

alpha-Defensins, antimicrobial peptides produced mainly by neutrophils, have been reported to be associated with a wide variety of lung diseases, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and diffuse panbronchiolitis (DPB). In each disease, alpha-defensins are located in different areas, such as around the alveolar septa in IPF and around the airways in CF and DPB, suggesting that alpha-defensins play different roles. Meanwhile, growth factors are known to contribute to IPF, CF, and DPB. alpha-Defensins are known to induce interleukin (IL)-8 in airway epithelial cells, but the effects of alpha-defensins on the release of growth factors from various components in the lung have not been sufficiently investigated. In the present study, the in vitro effects of human neutrophil peptide (HNP)-1 (a subtype of alpha-defensin) on the expressions of IL-8 and growth factors in lung fibroblasts, bronchial epithelial cells, and alveolar epithelial cells were examined. HNP-1 mainly enhanced the expression of IL-8 in epithelial cells, whereas it enhanced transforming growth factor-beta and vascular endothelial growth factor expressions in lung fibroblasts. These results suggest that alpha-defensins play different roles in the pathogenesis of IPF, CF, and DPB according to the location in the lung where the alpha-defensins are mainly produced

HSP47 in lung fibroblasts is a predictor of survival in fibrotic nonspecific interstitial pneumonia.

BACKGROUND: The histopathologic pattern is currently the most important prognostic marker for idiopathic interstitial pneumonia (IIP). However, more highly sensitive markers are now required. Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and it has been demonstrated that HSP47 expression is significantly higher in the lung specimens of idiopathic UIP than in UIP associated with collagen vascular diseases (CVD). However, its expression in nonspecific interstitial pneumonia (NSIP), the other common pathological pattern of IIP, has not been well investigated. Therefore, the association between lung fibroblast HSP47 expression and prognosis in fibrotic NSIP was evaluated. METHODS: Surgical lung biopsy specimens of 63 patients [idiopathic fibrotic NSIP=19, fibrotic NSIP associated with CVD=9, idiopathic UIP=26, and UIP associated with CVD=9] were reviewed, and a score for lung fibroblast HSP47 expression was assigned. These patients\u27 clinical features and survival were also analyzed. RESULTS: There was no significant difference in HSP47 expression between idiopathic fibrotic NSIP and fibrotic NSIP associated with CVD. The idiopathic fibrotic NSIP patients with higher HSP47 expression levels in their lung specimens had a poorer prognosis than patients with lower HSP47 expression levels. CONCLUSIONS: The present results suggest that lung fibroblast HSP47 expression may be a useful new prognostic marker for idiopathic fibrotic nonspecific interstitial pneumonia