Tatsuya Hosono

Risk of Acute Exacerbation After Video-assisted Thoracoscopic Lung Biopsy for Interstitial Lung Disease.

Biopsy by video-assisted thoracoscopic surgery (VATS) for interstitial pneumonia allows collection of samples sufficient for accurate histologic diagnosis. Although VATS is relatively safe, several reports have suggested that surgical lung biopsy may be a risk factor for acute exacerbation of idiopathic pulmonary fibrosis (IPF). We retrospectively reviewed data on the 113 cases that underwent biopsy by VATS to diagnose diffuse parenchymal lung disease in our department between 1994 and 2006, and analyzed its complications, in particular, risk of acute exacerbation of IPF. As the final diagnosis, idiopathic interstitial pneumonia was most frequent, involving 52 cases, of which IPF was most frequently found followed by nonspecific interstitial pneumonia and cryptogenic organizing pneumonia, in that order. Among our cases, there were 2 deaths after VATS (mortality rate, 1.8%), and both were IPF cases with acute exacerbation. When examining clinical markers in the 2 fatal IPF cases with acute exacerbation, we found that the percentage of predicted forced vital capacity was 55 or lower, percentage of predicted carbon monoxide diffusing capacity was 40 or lower, serum interstitial pneumonia markers KL-6 and SP-D were elevated, intraoperative inhalation of 100% O2 was 80 minutes or longer, and postoperative thoracic drainage was required for 10 days or longer. Although acute exacerbations of IPF seem to occur at any time during the course of disease, it is important to be aware of the possibility of acute exacerbation of IPF after VATS.

Torque teno virus DNA titre elevated in idiopathic pulmonary fibrosis with primary lung cancer

Background and objective:  IPF is an independent risk factor for lung cancer, but the mechanism of this association has not fully been elucidated. The role of Torque teno virus (TTV) in respiratory disease is poorly understood, although it has been shown that infection with TTV is associated with the activity and prognosis of IPF. This study aimed to investigate the prevalence and titre of TTV DNA among patients with IPF and lung cancer.

Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice

Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg·kg−1 of BLM. Edaravone (300 mg·kg−1) was administered by intraperitoneal administration 1 h before BLM challenge. Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E2 concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E2 production in the present experimental murine system.

Effect of hochuekkito on alveolar macrophage inflammatory responses in hyperglycemic mice.

Diabetes mellitus reduces immunological activity and increases susceptibility to various infections. Hochuekkito (TJ-41) has been reported to improve the weakened physical condition of various chronic diseases. BALB/c mice were divided into three groups; groups A and B were fed a standard diet, and group C, a TJ-41 diet. Two weeks after starting these diets, hyperglycemia was induced in groups B and C by injection with streptozotocin. Two weeks later, bronchoalveolar lavage was performed. Toll-like receptor (TLR) ligands (TLR2: peptidoglycan, PGN; TLR4: lipopolysaccharide, LPS; TLR5: flagellin, FLG) were used to stimulate alveolar macrophages (AMs), and TNF-α production was measured. Under hyperglycemic conditions and PGN or FLG stimulation, TNF-α production from AMs was significantly reduced in group B compared with group A. However, treatment with TJ-41 (group C) significantly improved the impaired production of TNF-α. These results suggest that, under hyperglycemic conditions, TJ-41 can improve the inflammatory responses of AMs with stimulation of TLR ligands.

Serum Torque Teno Virus DNA Titer in Idiopathic Pulmonary Fibrosis Patients with Acute Respiratory Worsening

OBJECTIVE Acute respiratory worsening is defined as the unexpected rapid deterioration of idiopathic pulmonary fibrosis (IPF), and idiopathic acute respiratory worsening is known as an acute exacerbation of IPF. Torque teno virus (TTV) is a circular single-stranded DNA virus whose pathological significance remains unclear. The aim of the present study was to investigate the prevalence and titer of TTV DNA in IPF patients with acute respiratory worsening. METHODS The serum TTV DNA titer was measured using real-time PCR in nine IPF patients (two treated with steroids and immunosuppressants; seven treated without steroids or immunosuppressants) who developed acute worsening, including five patients with acute exacerbation. The serum TTV DNA titer was also measured in eight stable IPF cases and four IPF cases of lung cancer. In addition, in order to examine time course changes in the TTV DNA titer, the titer was measured more than once, with an interval of four weeks or longer, in eight patients. RESULTS Among the nine IPF patients with acute worsening, the TTV DNA titer was above 1×10(6) copies/mL in two subjects without acute exacerbation who had been continuously treated with steroids and immunosuppressants. Meanwhile, the mean TTV DNA titer was 2.4±2.6 (×10(4) copies/mL) in the five patients with acute exacerbation and 3.1±3.4 (×10(4) copies/mL) in the eight patients with stable IPF. Moreover, the TTV DNA titers were increased in all three IPF patients who started treatment with steroids and immunosuppressants. CONCLUSION Our results suggest that it is unlikely that TTV is directly involved in the onset of acute exacerbation of IPF and that the serum TTV DNA titer potentially reflects the immunosuppressive state of the host due to treatment.