The pneumotachometer is currently the most accepted device to measure tidal breathing, however, it requires the use of a mouthpiece and thus alteration of spontaneous ventilation is implied. Respiratory inductive plethysmography (RIP), which includes two belts, one thoracic and one abdominal, is able to determine spontaneous tidal breathing without the use of a facemask or mouthpiece, however, there are a number of as yet unresolved issues. In this study we aimed to describe and validate a new RIP method, relying on a combination of thoracic RIP and nasal pressure signals taking into account that exercise-induced body movements can easily contaminate RIP thoracic signals by generating tissue motion artifacts. A custom-made time domain algorithm that relies on the elimination of low amplitude artifacts was applied to the raw thoracic RIP signal. Determining this tidal ventilation allowed comparisons between the RIP signal and simultaneously-recorded airflow signals from a calibrated pneumotachometer (PT). We assessed 206 comparisons from 30 volunteers who were asked to breathe spontaneously at rest and during walking on the spot. Comparisons between RIP signals processed by our algorithm and PT showed highly significant correlations for tidal volume (Vt), inspiratory (Ti) and expiratory times (Te). Moreover, bias calculated using the Bland and Altman method were reasonably low for Vt and Ti (0.04 L and 0.02 s, respectively), and acceptable for Te (<0.1 s) and the intercept from regression relationships (0.01 L, 0.06 s, 0.17 s respectively). The Ti/Ttot and Vt/Ti ratios obtained with the two methods were also statistically correlated. We conclude that our methodology (filtering by our algorithm and calibrating with our calibration procedure) for thoracic RIP renders this technique sufficiently accurate to evaluate tidal ventilation variation at rest and during mild to moderate physical activity.

Mycobacterium abscessus (Mabs), a non-tuberculous mycobacterium, is an emerging and rapidly growing opportunistic pathogen that is frequently found in patients with cystic fibrosis and in immunosuppressed patients. Its high tolerance to antibiotics is of great concern for public health. In this study, our results showed that human THP-1-derived macrophages infected with M. abscessus presented an increase in ROS production and cell necrosis. In addition, M. abscessus infection triggered activation of the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway, and the induction of HO-1 and NQO1 expression levels. Interestingly, pretreatment of macrophages with sulforaphane (SFN), an activator of the antioxidant key regulator Nrf2, followed by M. abscessus infection significantly decreased mycobacterial burden. We demonstrated that this reduction in mycobacterial growth was due to an activation in cell apoptosis in SFN-pretreated and M. abscessus-infected macrophages. Pretreatment with specific MAPK inhibitors, PD98059, SP600125, and SB203580 to ERK, JNK, and p38 respectively, failed to inhibit induction of Nrf2 expression, suggesting that Nrf2 signaling pathway was upstream of MAPK signaling. Activation of cell apoptosis was caspase 3/7 independent but p38 MAPK dependent. Moreover, p38 MAPK induction was abolished in macrophages transfected with Nrf2 siRNA. In addition, p38 inhibitor abolished Nrf2-dependent apoptosis in infected macrophages. Taken together, our results indicate that modulation of the Nrf2 signaling using Nrf2 activators may help potentiate the actual drug therapies used to treat mycobacterial infection.