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New Findings: What is the central question in this study?How reliable is the combined measurement of the pulmonary diffusing capacity to carbon monoxide and nitric oxide (DLCO/NO) during exercise and in the resting supine position, respectively?What is the main finding and its importance?The DLCO/NO technique is reliable with a very low day‐to‐day variability both during exercise and in the resting supine position, and may thus provide a useful physiological outcome that reflects the alveolar–capillary reserve in humans. DLCO/NO, the combined single‐breath measurement of the diffusing capacity to carbon monoxide (DLCO) and nitric oxide (DLNO) measured either during exercise or in the resting supine position may be a useful physiological measure of alveolar–capillary reserve. In the present study, we investigated the between‐day test–retest reliability of DLCO/NO‐based metrics. Twenty healthy volunteers (10 males, 10 females; mean age 25 (SD 2) years) were randomized to repeated DLCO/NO measurements during upright rest followed by either exercise (n = 11) or resting in the supine position (n = 9). The measurements were repeated within 7 days. The smallest real difference (SRD), defined as the 95% confidence limit of the standard error of measurement (SEM), the coefficient of variance (CV), and intraclass correlation coefficients were used to assess test–retest reliability. SRD for DLNO was higher during upright rest (5.4 (95% CI: 4.1, 7.5) mmol/(min kPa)) than during exercise (2.7 (95% CI: 2.0, 3.9) mmol/(min kPa)) and in the supine position (3.0 (95% CI: 2.1, 4.8) mmol/(min kPa)). SRD for DLCOc was similar between conditions. CV values for DLNO were slightly lower than for DLCOc both during exercise (1.5 (95% CI: 1.2, 1.7) vs. 3.8 (95% CI: 3.2, 4.3)%) and in the supine position (2.2 (95% CI: 1.8, 2.5) vs. 4.8 (95% CI: 3.8, 5.4)%). DLNO increased by 12.3 (95% CI: 11.1, 13.4) and DLCOc by 3.3 (95% CI: 2.9, 3.7) mmol/(min kPa) from upright rest to exercise. The DLCO/NO technique provides reliable indices of alveolar–capillary reserve, both during exercise and in the supine position. [ABSTRACT FROM AUTHOR]

In chronic obstructive pulmonary disease (COPD), the progressive loss of lung tissue is widely considered irreversible. Thus, various treatment and rehabilitation schemes, including exercise-based pulmonary rehabilitation (PR) are thought to slow down but not reverse or halt the disease. Nonetheless, the adult lung conceals the intrinsic capacity for de novo lung tissue formation in the form of abundant progenitor/stem cell populations. In COPD, these maintain their differentiation potential but appear to be halted by a state of cellular senescence in the mesenchyme, which normally functions to support and coordinate their function. We propose that notably high-intensity interval training may improve pulmonary gas exchange during exercise in patients with COPD by interrupting mesenchymal senescence, thus reestablishing adaptive angiogenesis. By means of this, the downward spiral of dyspnea, poor quality of life, physical inactivity, and early death often observed in COPD may be interrupted. If this is the case, the perception of the regenerative capacity of the lungs will be fundamentally changed, which will warrant future clinical trials on various exercise schemes and other treatments targeting the formation of new lung tissue in COPD. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?The use of proning for improving pulmonary gas exchange in critically ill patients.What advances does it highlight?Proning places the lung in its 'natural' posture, and thus optimises the ventilation‐perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life‐threatening hypoxaemia in COVID‐19 and other types of critical illness with respiratory failure. The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID‐19‐associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation‐perfusion (V̇A--Q̇${\dot V_{\rm{A}}}\hbox{--}\dot Q$) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral‐to‐dorsal) V̇A/Q̇${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V̇A/Q̇${\dot V_{\rm{A}}}/\dot Q$ ratio gradient is present in both postures, but with better V̇A--Q̇${\dot V_{\rm{A}}}\hbox{--}\dot Q$ matching in the prone position. In ARDS and CARDS, the vertical V̇A/Q̇${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life‐threatening hypoxaemia in patients with ARDS and CARDS. [ABSTRACT FROM AUTHOR]