[Show abstract][Hide abstract] ABSTRACT: To assess clinical, laboratory and radiographic findings associated with outcomes and to clarify more practical ways to predict hospital mortality in patients with acute exacerbation (AE) of chronic fibrosing interstitial pneumonia (CFIP).
Single-centre retrospective cohort study.
University Hospital in Japan.
We identified 51 consecutive patients with AE of idiopathic CFIP through multidisciplinary discussion. Patients who had connective tissue disease, drug-induced lung disease, pneumoconiosis, hypersensitivity pneumonitis, sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis and eosinophilic pneumonia were excluded.
There were no interventions.
The main outcome was determination of in-hospital mortality predictors. Other outcomes included clinical, laboratory and radiographic differences between non-survivors and survivors in patients with AE of CFIP.
The mean age of the patients with AE of CFIP was 71 years. Compared with survivors, non-survivors had a significantly shorter duration of symptoms before admission, lower prevalence of peripheral distribution of ground-glass opacity and centrilobular emphysema (CLE) on thin-section CT, lower peripheral lymphocyte count, higher brain natriuretic peptide titre, lower Pao2:Fio2 (P:F) ratio, higher prevalence of systemic inflammatory response syndrome (SIRS) and higher SIRS score on admission (p=0.0069, 0.0032, 0.015, 0.040, 0.0098, 0.012, 9.9×10(-7) and 5.4×10(-6), respectively). Multivariate analysis revealed SIRS (HR=6.2810, p=0.015), CLE (HR=0.0606, p=3.6×10(-5)) and serum procalcitonin level (HR=2.7110, p=0.022) to be independent predictors of in-hospital mortality. A Kaplan-Meier estimate on the basis of stratification according to the presence or absence of SIRS and CLE demonstrated a distinct survival curve for each subset of patients.
Distinct survival curves documented by stratification according to the presence or absence of SIRS and CLE may provide basic information for a rational management strategy for patients with AE of CFIP on admission.
BMJ Open 07/2013; 3(7). DOI:10.1136/bmjopen-2013-002971 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and objective: Immunoglobulin G4 (IgG4)-related disease is a multi-organ disorder that can include the lungs. IgG4-related lung disease can present in various forms; the clinical, radiological and pathological features of patients with this disease have been assessed. Methods: Forty-eight patients suspected of having IgG4-related lung disease, with a high serum concentration of IgG4 and abundant IgG4-positive plasma cell infiltration into the intrathoracic organs, were retrospectively evaluated. Their clinical features, chest imaging findings and pathological findings were examined, with final diagnoses made by an open panel conference. Results: Of the 48 patients, 18 with extrathoracic manifestations were diagnosed as having IgG4-related lung disease. Most of these patients were middle-aged to elderly men. IgG4-related lung disease was characterized by high serum concentrations of IgG and IgG4, normal white blood cell count and serum C-reactive protein concentration and a good response to corticosteroids. Common radiological findings included mediastinal lymphadenopathy and thickening of the perilymphatic interstitium, with or without subpleural and/or peribronchovascular consolidation. Pathological examination showed massive lymphoplasmacytic infiltration with fibrosis in and around the lymphatic routes, with distribution well correlated with radiological manifestations. Conclusions: The findings suggest that the intrathoracic manifestations of IgG4-related lung disease develop through lymphatic routes of the lungs and show various clinical characteristics. Because some lymphoproliferative disorders show similar findings, the correlation of clinicoradiological and pathological characteristics is crucial for the diagnosis of IgG4-related lung disease.
[Show abstract][Hide abstract] ABSTRACT: Based on clinical and radiological findings, Cottin defined combined pulmonary fibrosis and emphysema (CPFE) as pulmonary emphysema in the upper lungs and interstitial pneumonia in the lower lungs with various radiological patterns. Pathologic findings of CPFE probably corresponded with diffuse interstitial pneumonia with pulmonary emphysema, emphysema with fibrosis, and the combination of both. We described reported radiological findings of CPFE.
[Show abstract][Hide abstract] ABSTRACT: Ehlers-Danlos syndrome type IV (EDS type IV), vascular type, an autosomal dominant disorder caused by a mutation of the type III procollagen gene (COL3A1) is the most severe form of EDS and often presents with aortic hemorrhage or organ perforation. This report discusses a male patient with EDS type IV with dyspnea due to hemopneumothorax. He had thin skin and hypermobile joints and was clinically confirmed as having EDS type IV. The diagnosis was genetically confirmed by a mutation c.2528 G>A (p.Gly843Glu) in the COL3A1 gene. The position of the mutation has never been reported.
Internal Medicine 01/2010; 49(16):1797-800. DOI:10.2169/internalmedicine.49.3435 · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic hypersensitivity pneumonitis (HP) eventually ensues to extensive lung fibrosis when exposure to the causative antigen continues. Differential diagnosis from idiopathic interstitial pneumonias is sometimes difficult especially in the advanced stage.
To describe the clinical course of chronic summer-type HP, which is the most prevalent type of HP in Japan, in terms of early diagnosis and similarity to idiopathic pulmonary fibrosis (IPF).
14 patients with chronic summer-type HP diagnosed between 2000 and 2005 were reviewed retrospectively.
KL-6, a mucin-like glycoprotein, and surfactant protein-D (SP-D) were elevated in most cases. Specific antibodies against Trichosporon asahii (T. asahii) and T. mucoides in sera and BAL fluids were positive in 12 of 14 cases. A lymphocyte proliferation test induced by Trichosporon related antigen was positive in all examined cases (n=5). On high-resolution CT, traction bronchiectasis and honeycombing were observed in more than 70% of cases. By video-assisted thoracoscopic surgery (VATS) and autopsy specimens, honeycombing, fibroblastic foci, centrilobular fibrosis, and bridging fibrosis between bronchiolar and subpleural areas were observed. Antigen avoidance by improving domestic environments kept patients stable without decline in vital capacity (VC). However, 3 of the 4 patients who did not remedy their houses died of respiratory failure after progression of this disease.
Correct diagnosis in the early stage is crucial, since chronic summer-type HP can result in a fatal outcome after continuous exposure to the causative antigen.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 10/2007; 24(2):141-7. · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 49-year-old woman was admitted with cough, general fatigue, and dyspnea on effort. Her hobby was the Japanese traditional handicraft of lacquer-carving. She sometimes used smut spores of Ustilago esculenta, pronounced as "Makomozumi"on lacquer ware. The chest radiographs showed diffuse ground-glass opacities and small centrilobular nodules. Bronchoalveolar lavage yielded a marked number of lymphocytes as well as total cell counts and a low CD4 +/CD8 + ratio. The transbronchial lung biopsy specimen revealed lymphocytic alveolitis and non-necrotizing epithelioid cell granulomas. The results of provocation test by Makomozumi were positive. Serum tests of the specific antibody against extracted soluble antigens of smut spores were positive. The peripheral lymphocyte proliferation test, performed with Mokomozumi antigens was also positive. The final diagnosis was hypersensitivity pneumonitis induced by smut spores of fungus Ustilago esculenta.
[Show abstract][Hide abstract] ABSTRACT: We studied the effect of cigarette smoke extract (CSE) on a three-dimensional (3-D) co-culture model with epithelial cells and mesenchymal cells to clarify how epithelial cells protect lung tissue from cigarette smoke in-vivo. Two types of gels were prepared. The one was the co-culture of human fetal lung fibroblasts (HFL-I) embedded in type-I collagen gel, with alveolar epithelial cells (A549) cultured covering the top of the gel. The other was HFL-I cells alone. After 48 hours from CSE exposure, gel contraction, levels of fibronectin, transforming growth factor (TGF)-beta and GSH were assessed. CSE inhibited fibroblast-mediated gel contraction and this inhibition was lessened in co-culture associated with higher GSH concentration and TGF-beta1 level as compared to the level in HFL-I cells alone. CSE lowered fibronectin level to a lesser extent in co-culture as compared to the level in HFL-I cells alone. Exogenous TGF-beta1 restored the inhibition of gel contraction by CSE independent of GSH level. Cigarette smoke may interfere with 3-D co-culture gel contraction by diminishing GSH, fibronectin and TGF-beta1 action in the epithelial-mesenchymal interaction.
Journal of medical and dental sciences 03/2007; 54(1):109-16.
[Show abstract][Hide abstract] ABSTRACT: People have the opportunity to inhale inorganic dusts under various environments. Inorganic dust exposures as a result of occupational exposure may induce or modulate pulmonary fibrosis. We analyzed the deposition of elements in lung tissues of patients with idiopathic pulmonary fibrosis (IPF) and compared element deposition with chronic hypersensitivity pneumonitis (chronic HP) and collagen vascular diseases (CVD). Thirty-five patients (18 men and 17 women with the mean age of 64.3) were studied, including 15 IPF, 8 chronic HP, 6 CVD, and 6 control patients. Four IPF patients have occupational dust exposures. Inorganic particles were counted by polarizing light microscopy and scanning electron microscopy. Energy dispersive X-ray spectroscopy was performed to analyze an elemental deposition. The number of birefringent particles was greater in IPF, even in IPF without occupational exposure, than in controls. The silicon (Si)/sulfur (S) ratio and aluminium (AI)/S ratio were increased in IPF independent of occupational exposure. A point elemental analysis showed that the major compound of the particles was aluminium-silicate in IPF. These results suggest that unrecognized dust exposures are relatively common in some IPF patients and aluminium-silicate could be associated with the disease process of IPF.
Journal of medical and dental sciences 03/2007; 54(1):9-16.
[Show abstract][Hide abstract] ABSTRACT: Hypersensitivity pneumonitis (HP) is an immunologically-mediated lung disease caused by repeated inhalation of dispersed antigen. Various cytokines have been reported to be involved in the immunopathogenesis of HP Recently, some reports suggested an association between the genetic control of cytokine production and disease susceptibility. To evaluate whether cytokine gene polymorphisms are associated with HP, we performed a case-control association study involving 61 patients with HP, consisting of summer-type HP (SHP) and bird fancier's lung (BFL, also named bird fancier's disease), as well as 101 healthy controls. Polymorphisms of the genes for tumor necrosis factor (TNF)-alpha (-308G/A, -857C/T, -863C/A, -1031T/C), interleukin (IL)-10 (-592C/A, -819C/T, -1082G/A), transforming growth factor (TGF)-beta1 (-509C/T, +869T/C), and IL-6 (-634C/G) were examined by restriction fragment length polymorphism analysis. There were no significant differences in allele frequency and genotype distribution among control, SHP, and BFL group. When HP group was divided into acute or chronic, no significant differences were detected between any groups. LPS-stimulated IL-6 secretion by whole blood cells was similar between subjects with GG genotype and non-GG genotype in IL-6 -634C/G polymorphism. In conclusion, the association between HP susceptibility and cytokine polymorphisms studied was not demonstrated.
Journal of medical and dental sciences 04/2006; 53(1):75-83.
[Show abstract][Hide abstract] ABSTRACT: Bird fancier's lung (BFL) is a type of hypersensitivity pneumonitis induced by the inhalation of bird-related antigens. The BFL induced by feathers is difficult to diagnose because feathers are generally unrecognized as a causative antigen.
To determine the clinical features of BFL presumably induced by feather duvets (feather duvet lung) to provide clues for diagnosis.
We performed a retrospective review of the medical records of patients with feather duvet lung evaluated between April 1, 2000, and June 30, 2003, at the Tokyo Medical and Dental University Hospital in Japan.
Seven patients with feather duvet lung were included in this study; 4 patients had acute disease and 3 had chronic BFL. Duration of contact with feather duvets was 1 month to 10 years. Serum KL-6 and surfactant protein D levels were elevated in all the patients. Specific antibodies against avian antigens were positive in acute BFL but negative in chronic BFL. Antigen-induced lymphocyte proliferation in peripheral blood or bronchoalveolar lavage cells was positive in all the patients. The diagnosis was confirmed by an environmental or inhalation provocation test.
Feather duvets can induce acute and chronic BFL. Physicians should be aware of feather duvets as a cause of BFL because feather duvets are becoming more prevalent.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2006; 96(1):98-104. DOI:10.1016/S1081-1206(10)61047-2 · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Factors predicting gefitinib sensitivity and adverse events in non-small cell lung cancer (NSCLC) remain controversial.
Correlations among clinicopathological characteristics, gefitinib sensitivity and adverse events were studied in 154 patients with NSCLC, whereas epidermal growth factor receptor (EGFR) mutations were analyzed in 44 patients.
Female, non-smoker, adenocarcinoma of stage I-II, and gefitinib effectiveness correlated with longer time to progression (TTP) and overall survival (OS), while the rate of interstitial lung disease in patients undergoing thoracic radiotherapy and stomatitis in females or those who never smoked were significantly higher. EGFR mutations were identified in 18 cases, and among 34 gefitinib-treated patients, 16 patients harboring mutations tended to do better, both in terms of TTP and OS. The results of the mutation analysis from surgical and non-surgical specimens were identical.
Certain clinicopathological characteristics and EGFR mutations can be either predictive of gefitinib sensitivity or adverse events.
Anticancer research 01/2006; 26(6B):4519-25. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic bird fancier's lung (BFL) has often been misdiagnosed as one of the idiopathic interstitial pneumonias (IIPs).
To define the clinical and pathological characteristics of chronic BFL, 26 patients with chronic BFL from whom a surgical lung biopsy specimen was taken between October 1992 and June 2001 were evaluated. The histopathological characteristics of the surgical lung biopsy specimens were examined and correlations between the histopathology and clinical characteristics were analysed. The quality of chronic inflammatory and fibrotic changes was expressed according to the 2002 ATS/ERS consensus classification of IIPs.
Two patients were diagnosed as having bronchiolitis obliterans organising pneumonia (BOOP)-like lesions, five as having cellular non-specific interstitial pneumonia (NSIP)-like lesions, and eight as having fibrotic NSIP-like lesions. The other 11 patients were considered to have usual interstitial pneumonia (UIP)-like lesions because of the temporal heterogeneous appearances of the fibrotic changes. However, fibrosis in these patients had developed in centrilobular as well as perilobular areas, suggestive of hypersensitivity pneumonitis. Nineteen patients (73.1%) had multinucleated giant cells, often with cholesterol clefts, while only five patients (19.2%) had granulomas. Patients with BOOP-like or cellular NSIP-like lesions tended to have recurrent acute episodes, whereas patients with UIP-like lesions had an insidious onset. Patients with BOOP-like or cellular NSIP-like lesions had a more favourable outcome than those with fibrotic NSIP-like and UIP-like lesions.
The qualities of chronic inflammatory and fibrotic lesions vary significantly among patients with chronic BFL but correlate with clinical features and prognosis.
[Show abstract][Hide abstract] ABSTRACT: A 67-year-old man was admitted due to fever and exertional dyspnea. He used to raise budgerigars and hill mynahs from 1980 to 1988. He was diagnosed as having chronic bird fancier's lung (BFL) based on a positive peripheral lymphocyte proliferation to pigeon serum in 1994. His disease was stable until 2000. Three months before admission he became a daily user of a feather duvet. A chest CT showed newly-developed peribronchial ground-glass opacities and preexisting honeycombing. Inhalation provocation test was positive. Administration of steroids improved his condition. He has been well after refraining from the use of the feather duvet.
Internal Medicine 10/2004; 43(9):835-7. DOI:10.2169/internalmedicine.43.835 · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 74-year-old man was admitted to our hospital because of exertional dyspnea in January 2003. He had first noticed slight exertional dypnea in 1997, which had since gradually progressed. He has been a dentist since the age of 23. Chest radiography demonstrated bilateral reticular shadows, infiltrates, and thickened pleural adhesion, which had progressed for one year and five months. Chest CT scans disclosed irregular peribronchial opacities, centrilobular nodules, and interlobular septal lines. Bronchoalveolar lavage fluid showed an increase in total cells and lymphocytosis with an increased CD 4/CD 8 ratio. Transbronchial lung biopsy demonstrated fibrosis around bronchioles, involving adjacent alveolar structures and scattered birefringent particles under polarized light. Energy-dispersive X-ray analysis (EDXA) of the small particles around the bronchioles using electron microscopy showed high peaks for silicon (Si) and aluminium (Al). Pneumoconiosis, possibly induced by some of the mechanical and technical procedures of dentistry, was diagnosed.
[Show abstract][Hide abstract] ABSTRACT: A 77-year-old man was admitted to our hospital. He had first noticed a cough, sputum production, and low-grade fever during the summer of 1988. He was diagnosed as having summer-type hypersensitivity pneumonitis (HP) in 1989 on the basis of positive findings of anti-Trichosporon antibodies in the serum and bronchoalveolar lavage (BAL) fluid and and in environmental provocation tests. Thereafter, he presented with re-exacerbation of his disease in summer every year. In 1995, he retired from his work at a moldy hotel and moved to another house to avoid the causative antigen completely. There was no recurrence for the following 5 years. He suffered from cough, sputum production, and dyspnea 4 months after returning to his previous moldy house in October, 2000. A chest CT scan showed peribronchial and subpleural honeycombing, ground glass opacities, and traction bronchiectasis. BAL demonstrated that the lymphocyte count had changed from 78.9% to 42.9% and the CD4/CD8 ratio from 0.39 to 4.07 in 12 years. Antigen avoidance and steroid therapy have improved his condition. However, he stayed repeatedly in his moldy house, and finally died from acute exacerbation in March, 2002. Postmortem examination demonstrated diffuse alveolar damage (DAD) superimposed on honeycombing in the lungs.
[Show abstract][Hide abstract] ABSTRACT: A 57-year-old woman was admitted to our hospital because of cough and low-grade fever for 2 months and shortness of breath for 2 weeks. She had raised two budgerigars for the last 15 years and had been using a feather duvet for one year. A chest radiograph showed diffuse ground-glass opacities in both lung fields, and a chest CT scan showed centrilobular micronodules and ground-glass opacities. Bronchoalveolar lavage (BAL) revealed a marked increase in lymphocytes, and a transbronchial lung biopsy (TBLB) specimen showed alveolitis due to the infiltration of mononuclear cells. Since she had specific antibodies against pigeon and budgerigar dropping extracts and her peripheral blood lymphocytes proliferated on addition of pigeon serum, she was diagnosed as having bird fancier's lung (BFL). She was treated with steroids, which brought about a marked improvement. After she visited her husband who had been hospitalized where a feather duvet was provided for each patient, both subjective and objective findings deteriorated. This deterioration was preventable when she wore a protective mask for micro-dust while visiting her husband. The feather duvets seemed to induce acute BFL in this case, though raising budgerigars may well be related to her sensitization with bird-related antigens.
[Show abstract][Hide abstract] ABSTRACT: The most common form of hypersensitivity pneumonitis in Japan is summer-type hypersensitivity pneumonitis (SHP), which is caused by the inhalation of Trichosporon asahii or Trichosporon mucoides. To seek protein antigens relevant to the immunopathogenesis of SHP, we constructed a cDNA expression library of T. asahii, a major causative yeast species of SHP. Using the immunoscreening method, we identified and cloned a novel gene encoding a 19-kD protein, named TA-19, which proved to be specifically recognized in the bronchoalveolar lavage (BAL) fluids and sera of patients with SHP. IgG, IgA, and IgM antibodies to the recombinant TA-19 protein were significantly elevated in the sera as well as in the BAL fluids from SHP patients compared with those from non-SHP groups. This protein also induced SHP-specific proliferation of the mononuclear cells from both the peripheral blood and BAL. These results reveal that TA-19 derived from T. asahii may play a relevant role in specific cellular and humoral immune responses in patients with SHP.
American Journal of Respiratory and Critical Care Medicine 05/2003; 167(7):991-8. DOI:10.1164/rccm.200206-589OC · 11.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We encountered a fatal case of mediastinal fibromatosis in a 67-year-old female in whom there was aggressive infiltration into the large vessels, nerves and pericardium. She presented with the superior vena cava syndrome, Horner's syndrome, paralysis of bilateral vocal cords and diaphragm and heart failure. Mediastinoscopical examination revealed an extremely firm tumor adhering to the sternum, trachea and brachiocephalic artery. She died of severe heart failure due to the disturbed dilatation of the heart and ventilatory insufficiency. Although mediastinal fibromatosis is very uncommon and sometimes difficult to diagnose at an early stage, physicians should be aware of this disease for the differential diagnosis of mediastinal tumors.