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Background: Pursed-lips breathing (PLB) is a technique to attenuate small airway collapse by regulating the expiratory flow. During mandatory ventilation, flow-controlled expiration (FLEX), which mimics the expiratory flow course of PLB utilizing a digital system for measurement and control, was shown to exert lung protective effects. However, PLB requires a patient's participation and coordinated muscular effort and FLEX requires a complex technical setup. Here, we present an adjustable flow regulator to mimic PLB and FLEX, respectively, without the need of a patient's participation, or a complex technical device., Methods: Our study consisted of two parts: First, in a lung model which was ventilated with standard settings (tidal volume 500 ml, respiratory rate 12 min -1 , positive end-expiratory pressure (PEEP) 5 cmH 2 O), the possible reduction of the maximal expiratory flow by utilizing the flow regulator was assessed. Second, with spontaneously breathing healthy volunteers, the short-term effects of medium and strong expiratory flow reduction on airway pressure, the change of end-expiratory lung volume (EELV), and breathing discomfort was investigated., Results: In the lung model experiments, expiratory flow could be reduced from - 899 ± 9 ml·s -1 down to - 328 ± 25 ml·s -1 . Thereby, inspiratory variables and PEEP were unaffected. In the volunteers, the maximal expiratory flow of - 574 ± 131 ml·s -1 under baseline conditions was reduced to - 395 ± 71 ml·s -1 for medium flow regulation and to - 266 ± 58 ml·s -1 for strong flow regulation, respectively (p < 0.001). Accordingly, mean airway pressure increased from 0.6 ± 0.1 cmH 2 O to 2.9 ± 0.4 cmH 2 O with medium flow regulation and to 5.4 ± 2.4 cmH 2 O with strong flow regulation, respectively (p < 0.001). The EELV increased from baseline by 31 ± 458 ml for medium flow regulation and 320 ± 681 ml for strong flow regulation (p = 0.033). The participants rated breathing with the flow regulator as moderately uncomfortable, but none rated breathing with the flow regulator as intolerable., Conclusions: The flow regulator represents an adjustable device for application of a self-regulated expiratory resistive load, representing an alternative for PLB and FLEX. Future applications in spontaneously breathing patients and patients with mandatory ventilation alike may reveal potential benefits., Trial Registration: DRKS00015296, registered on 20th August, 2018; URL: https://www.drks.de/drks&#95;web/setLocale&#95;EN.do ., (© 2021. The Author(s).)

Members of the transient receptor potential (TRP) superfamily are broadly expressed in our body and contribute to multiple cellular functions. Most interestingly, the fourth member of the vanilloid family of TRP channels (TRPV4) serves different partially antagonistic functions in the respiratory system. This review highlights the role of TRPV4 channels in lung fibroblasts, the lung endothelium, as well as the alveolar and bronchial epithelium, during physiological and pathophysiological mechanisms. Data available from animal models and human tissues confirm the importance of this ion channel in cellular signal transduction complexes with Ca 2+ ions as a second messenger. Moreover, TRPV4 is an excellent therapeutic target with numerous specific compounds regulating its activity in diseases, like asthma, lung fibrosis, edema, and infections.

Background: Flow-controlled ventilation (FCV) is a new ventilation mode that provides constant inspiratory and expiratory flow. FCV was shown to improve gas exchange and lung recruitment in porcine models of healthy and injured ventilated lungs. The primary aim of our study was to verify the influences of FCV on gas exchange, respiratory mechanics and haemodynamic variables in mechanically ventilated lung-healthy patients., Methods: After obtaining ethical approval and informed consent, we measured arterial blood gases, respiratory and haemodynamic variables during volume-controlled ventilation (VCV) and FCV in 20 consecutive patients before they underwent abdominal surgery. After baseline (BL) ventilation, patients were randomly assigned to either BL-VCV-FCV or BL-FCV-VCV. Thereby, BL ventilation settings were kept, except for the ventilation mode-related differences (FCV is supposed to be used with an I:E ratio of 1:1)., Results: Compared to BL and VCV, PaO 2 was higher [PaO 2 : FCV: 38.2 (7.1), BL ventilation: 35.0 (5.8), VCV: 35.2 (7.0) kPa, P < .001] and PaCO 2 lower [PaCO 2 : FCV: 4.8 (0.5), BL ventilation: 5.1 (0.5), VCV: 5.1 (0.5) kPa, P < .001] during FCV. With comparable plateau pressure [BL: 14.9 (1.9), VCV: 15.3 (1.6), FCV: 15.2 (1.5) cm H 2 O), P = .185], tracheal mean pressure was higher during FCV [BL: 10.2 (1.1), VCV: 10.4 (0.7), FCV: 11.5 (1.0) cm H 2 O, P < .001]. Haemodynamic variables did not differ between ventilation phases., Conclusion: Flow-controlled ventilation improves oxygenation and carbon dioxide elimination within a short time, compared to VCV with identical tidal volume, inspiratory plateau pressure and end-expiratory pressure., (© 2019 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: The application of positive end-expiratory pressure (PEEP) may reduce dynamic strain during mechanical ventilation. Although numerous approaches for PEEP titration have been proposed, there is no accepted strategy for titrating optimal PEEP. By analyzing intratidal compliance profiles, PEEP may be individually titrated for patients., Methods: After obtaining informed consent, 60 consecutive patients undergoing general anesthesia were randomly allocated to mechanical ventilation with PEEP 5 cmH 2 O (control group) or PEEP individually titrated, guided by an analysis of the intratidal compliance profile (intervention group). The primary endpoint was the frequency of each nonlinear intratidal compliance (C RS ) profile of the respiratory system (horizontal, increasing, decreasing, and mixed). The secondary endpoints measured were respiratory mechanics, hemodynamic variables, and regional ventilation, which was assessed via electrical impedance tomography., Results: The frequencies of the C RS profiles were comparable between the groups. Besides PEEP [control: 5.0 (0.0), intervention: 5.8 (1.1) cmH 2 O, p < 0.001], the respiratory and hemodynamic variables were comparable between the two groups. The compliance profile analysis showed no significant differences between the two groups. The loss of ventral and dorsal regional ventilation was higher in the control [ventral: 41.0 (16.3)%; dorsal: 25.9 (13.8)%] than in the intervention group [ventral: 29.3 (17.6)%; dorsal: 16.4 (12.7)%; p (ventral) = 0.039, p (dorsal) = 0.028]., Conclusions: Unfavorable compliance profiles indicating tidal derecruitment were found less often than in earlier studies. Individualized PEEP titration resulted in slightly higher PEEP. A slight global increase in aeration associated with this was indicated by regional gain and loss analysis. Differences in dorsal to ventral ventilation distribution were not found., Trial Registration: This clinical trial was registered at the German Register for Clinical Trials (DRKS00008924) on August 10, 2015.

Background: In obese patients, high closing capacity and low functional residual capacity increase the risk for expiratory alveolar collapse. Constant expiratory flow, as provided by the new flow-controlled ventilation (FCV) mode, was shown to improve lung recruitment. We hypothesized that lung aeration and respiratory mechanics improve in obese patients during FCV., Methods: We compared FCV and volume-controlled (VCV) ventilation in 23 obese patients in a randomized crossover setting. Starting with baseline measurements, ventilation settings were kept identical except for the ventilation mode related differences (VCV: inspiration to expiration ratio 1:2 with passive expiration, FCV: inspiration to expiration ratio 1:1 with active, linearized expiration). Primary endpoint of the study was the change of end-expiratory lung volume compared to baseline ventilation. Secondary endpoints were the change of mean lung volume, respiratory mechanics and hemodynamic variables., Results: The loss of end-expiratory lung volume and mean lung volume compared to baseline was lower during FCV compared to VCV (end-expiratory lung volume: FCV, - 126 ± 207 ml; VCV, - 316 ± 254 ml; p < 0.001, mean lung volume: FCV, - 108.2 ± 198.6 ml; VCV, - 315.8 ± 252.1 ml; p < 0.001) and at comparable plateau pressure (baseline, 19.6 ± 3.7; VCV, 20.2 ± 3.4; FCV, 20.2 ± 3.8 cmH 2 O; p = 0.441), mean tracheal pressure was higher (baseline, 13.1 ± 1.1; VCV, 12.9 ± 1.2; FCV, 14.8 ± 2.2 cmH 2 O; p < 0.001). All other respiratory and hemodynamic variables were comparable between the ventilation modes., Conclusions: This study demonstrates that, compared to VCV, FCV improves regional ventilation distribution of the lung at comparable PEEP, tidal volume, P Plat and ventilation frequency. The increase in end-expiratory lung volume during FCV was probably caused by the increased mean tracheal pressure which can be attributed to the linearized expiratory pressure decline., Trial Registration: German Clinical Trials Register: DRKS00014925. Registered 12 July 2018.

Pulmonary fibrosis (PF) is a chronic progressive lung disease without effective medical treatment options leading to respiratory failure and death within 3-5years of diagnosis. The pathological process of PF is driven by aberrant wound-healing involving fibroblasts and myofibroblasts differentiated by secreted profibrotic transforming growth factor β (TGF-β1). Classical transient receptor potential 6 (TRPC6), a Na + - and Ca 2+ -permeable cation channel, is able to promote myofibroblast conversion of primary rat cardiac and human dermal fibroblasts and TRPC6-deficiency impaired wound healing after injury. To study a potential role of TRPC6 in the development of PF we analyzed lung function, gene and protein expression in wild-type (WT) and TRPC6-deficient (TRPC6-/-) lungs utilizing a bleomycin-induced PF-model. Fibrotic WT-mice showed a significant higher death rate while bleomycin-treated TRPC6-deficient mice were partly protected from fibrosis as a consequence of a lower production of collagen and an almost normal function of the respiratory system (reduced resistance and elastance compared to fibrotic WT-mice). On a molecular level TGF-β1 induced TRPC6 up-regulation, increased Ca 2+ influx and nuclear NFAT localization in WT primary murine lung fibroblasts (PMLFs) resulting in higher stress fiber formation and accelerated contraction rates as compared to treated TRPC6-deficient fibroblasts. Therefore, we conclude that TRPC6 is an important determinant for TGF-β1-induced myofibroblast differentiation during fibrosis and specific channel inhibitors might be beneficial in a future treatment of PF., (Copyright © 2016 Elsevier B.V. All rights reserved.)