Yujiro Takai

Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma.

BACKGROUND Bronchial asthma is characterized by airway wall remodeling. Matrix metalloproteinases (MMPs) are members of a family of proteolytic enzymes that degrade the extracellular matrix and that restrain the effects of their tissue inhibitors (TIMPs). Treatment with inhaled corticosteroids may prevent airway remodeling in asthma. However, the effects of corticosteroid treatment on MMPs and TIMPs in asthma are unknown. OBJECTIVE We examined the effects of inhaled beclomethasone dipropionate (BDP) on the expression of MMP-9 and TIMP-1 and subepithelial collagen deposition in bronchial biopsy specimens from 30 subjects with asthma. METHODS Inhaled BDP, 800 microg daily, or placebo was administered for 6 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined for extent of collagen type III in the subepithelial basement membrane by means of immunohistochemistry, and expression of both epithelial and submucosal MMP-9 and TIMP-1 was quantitated. Numbers of inflammatory cells were also determined. RESULTS We observed significant decreases in collagen type III deposition (P <.01) and the expression of submucosal MMP-9 (P <.01) and a significant increase in the expression of submucosal TIMP-1 (P <.05) in the BDP group. Significant correlations were found between the subepithelial collagen type III deposition and epithelial (r (s ) = 0.37, P <.05) and submucosal expression of MMP-9 (r (s ) = 0.47, P <.01). Additionally, the number of many inflammatory cells and myofibroblasts in airway mucosa were significantly decreased in the BDP group. CONCLUSION Our findings suggest that corticosteroid treatment of asthma can reduce subepithelial collagen deposition by downregulation of MMP-9 expression and upregulation of TIMP-1 expression.

Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma.

Background Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied.

Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti‐cancer therapy

Background and objective:  To clarify the clinical characteristics and risk factors for acute respiratory deterioration following anti‐cancer therapy in patients with pulmonary fibrosis (PF) and lung cancer.

Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone

The results of studies examining the outcome and the factors predicting prognosis in combined pulmonary fibrosis and emphysema (CPFE) have so far been contradictory. Our objective was to determine prognosis and the prognostic factors for CPFE.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

Background: Germline alterations in the proapoptotic protein Bcl-2–like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non–small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. Methods: We studied 70 patients with EGFR mutation-positive non–small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. Results: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864–8.547; p < 0.001). Conclusions: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study.

Treatment with pirfenidone may slow the decline in vital capacity and increase progression‐free survival (PFS) in idiopathic pulmonary fibrosis (IPF). The effects of combination therapy with inhaled N‐acetylcysteine (NAC) and pirfenidone are unclear. We assessed the effects of this combination therapy in patients with advanced IPF.

Cephalometric assessment of craniofacial morphology in Japanese male patients with obstructive sleep apnea–hypopnea syndrome

Craniofacial morphological anomalies can be divided into two principal categories: skeletal anomalies and soft tissue anomalies. This study examined the hypothesis that the assessment of indices representing both skeletal and soft tissue can be used to appropriately identify the risk factor of obstructive sleep apnea-hypopnea syndrome (OSAHS). 232 suspected OSAHS male patients were examined with polysomnography and divided into two groups (202 males with OSAHS and 30 male controls without OSAHS). Cephalometric analysis was performed on all patients to evaluate craniofa-cial morphological anomalies. The measurement sites were as follows: skeletal morphology; soft tissue morphology; mixed morphology including mandibular plane to hyoid bone (MP-H); and jaw soft tissue (JS) ratio; a novel ratio we defined, between the area of jaw and area of tongue with soft palate. JS ratio increased with AHI as well as MP-H. MP-H and JS ratio showed significant but weak correlation with apnea-hypopnea index. JS ratio was significantly associated with an increased risk for severe OSAHS, even after adjusting age and BMI, its odds ratio was the greatest among these variables. These results showed that mixed craniofacial, skeletal and soft tissue morphology are correlated with AHI, and JS ratio may be a useful parameters to explain the characteristics of OSAHS in male patients.

Pathological response and prognosis of stage III non-small cell lung cancer patients treated with induction chemoradiation.

Aim:  The aim of this study was to clarify the relationship between pathological effects and the prognosis of patients with stage III non‐small cell lung cancer (NSCLC) treated with induction chemoradiation.

Usefulness of fluoro-2-deoxyglucose positron emission tomography for investigating unexplained rising carcinoembryonic antigen levels that occur during the postoperative surveillance of lung cancer patients

BackgroundPositron emission tomography with 18-fluorodeoxyglucose (FDG-PET) has been useful for the detection of recurrent lung cancer. However, such technology is expensive and is not always widely available. In this study, we evaluated the selected use of FDG-PET for lung cancer patients with re-elevated levels of serum carcinoembryonic antigen (CEA) after curative surgery.MethodsAmong 327 patients who underwent curative resection for primary lung cancer from May 2002 through March 2007, 199 had adenocarcinoma, of whom 78 (39%) had elevated levels of serum CEA before treatment. After surgery, the level was monitored every 1 to 3 months. Re-elevation of CEA was recognized in 39 (50%) patients, 22 of whom underwent FDG-PET and were included in this study. FDG-PET images were visually inspected, and abnormally increased FDG uptake was interpreted as recurrence. The sensitivity, specificity, positive predictive value, and negative predictive value of PET in detecting recurrent lung cancer were determined.ResultsFDG-PET correctly identified 14 out of 15 relapses and gave true negative results in six out of seven remissions, i.e., one false-negative and one false-positive were observed. The sensitivity, specificity, positive predictive value, and negative predictive value were 93%, 86%, 93%, and 86%, respectively.ConclusionIn 64% of the patients with unexplained increased CEA levels, FDG-PET provided decisive diagnostic clues guiding further diagnostic and therapeutic interventions. The selected use of FDG-PET for patients with re-elevated serum CEA levels after surgery can be a practical and effective mode of surveillance for detecting recurrent lung cancer.

Primary Antiphospholipid Syndrome Associated with Diffuse Alveolar Hemorrhage and Pulmonary Thromboembolism

Antiphospholipid syndrome (APS) is clinically characterized by arterial or venous thrombosis; however, non-thromboembolic lung manifestations, such as diffuse alveolar hemorrhage (DAH), have also been previously reported. DAH is relatively common in APS patients with systemic lupus erythematosus, although it is rare in primary APS. We encountered a 78-year-old man who presented with hemoptysis and dyspnea. Chest CT showed diffuse ground-glass opacity with pulmonary thromboembolism. He was successfully treated with corticosteroids and heparin; however, DAH recurred after the corticosteroid treatment was stopped. The treatment was intricate due to the concurrent bleeding and thrombotic manifestations.