There was a correlation between irAE and efficacy in NSCLC patients treated with nivolumab.

No abstract

No abstract

Virus infections are a major cause of chronic obstructive pulmonary disease (COPD) exacerbations. Recently, Toll-like receptor 3 (TLR3) has been demonstrated to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether oxidative stress, which is involved in the pathogenesis of COPD, enhances the responses of TLR3 in airway epithelial cells. The effect of hydrogen peroxide (H 2 O 2 ) on the release of IL-8 from BEAS-2B cells and primary human bronchial epithelial cells after stimulation with polyinosinepolycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and a ligand for TLR3, and the signal transduction were examined. One hundred to 150 mM H 2 O 2 significantly potentiated the release of IL-8 from the epithelial cells after stimulation with 10 mg/ml poly(I:C). The H 2 O 2 -augmented IL-8 release was inhibited by treatment with N-acetylcysteine. One hundred micromoles of H 2 O 2 enhanced the translocation of nuclear factor (NF)-kB p65, but not that of interferon regulatory factor-3 (IRF-3), into the nucleus and the NF-kB DNA binding activity after poly(I:C) stimulation, which effect was inhibited not by the silencing of IRF-3 but by MG132, a proteasome inhibitor, or dexamethasone. One hundred micromoles of H 2 O 2 potentiated the TLR3 expression on the airway epithelial cells treated with poly(I:C). These data suggest that oxidative stress augments the response of TLR3 in airway epithelial cells via NF-kB and that this effect might be partly mediated by the enhancement of TLR3 expression. Modulation of this pathway may be a therapeutic target for viral-induced exacerbations of COPD.

Background: The DynaPort Activity Monitor (DAM) has been reported to be useful to evaluate the activity in healthy subjects and patients with chronic obstructive pulmonary disease (COPD). However, it is difficult to estimate the activity of COPD patients using DAM, because its battery works only for several hours and sensors should be worn at two parts of the body. A newly developed compact, single-position triaxial accelerometer (Actimarker) can measure the activity for >1 month, but has not been validated for COPD patients. Objectives: The validity of the Actimarker was evaluated in COPD patients. Methods: In study 1, the validity of the device was tested in 14 stable COPD patients by comparing it with DAM. In study 2, the influence of the weather on activity was examined. In study 3, the number of measurement days required to ensure repeatability was determined. Results: The durations of activity measured by the Actimarker and DAM were significantly correlated at intensity values ≧2.0, ≧2.5 and ≧3.0 METs. The duration of activity on rainy days was significantly shorter than that on non-rainy days. The values of intraclass correlation coefficients were >0.8 in 3-, 4- or 5-day measurements, and there was no systematic bias at any number of days or intensities with Bland-Altman plots. Conclusions: The validity of the Actimarker was confirmed, and repeatability was obtained when the data from at least 3 non-rainy weekdays were analyzed. Actimarker appears to be useful as a simplified method to evaluate the physical activity of COPD patients.