In everyday life during terrestrial locomotion our body interacts with two media opposing the forward movement of the body: the ground and the air. Whereas the work done to overcome the ground reaction force has been extensively studied, the work done to overcome still air resistance has been only indirectly estimated by means of theoretical studies and by measurements of the force exerted on puppets simulating the geometry of the human body. In this study, we directly measured the force exerted by still air resistance on eight male subjects during walking and running on an instrumented treadmill with a belt moving at the same speed of a flow of laminar air facing the subject. Overall, the coefficient of proportionality between drag and velocity squared (Aeff) was smaller during running than walking. During running Aeff decreased progressively with increasing average velocity up to an apparently constant, velocity independent value, similar to that predicted in the literature using indirect methods. A predictive equation to estimate drag as a function of the speed and the height of the running subject is provided.
Recent studies in healthy mice and rats have reported that positive pressure ventilation delivered with physiological tidal volumes at normal end-expiratory volume worsens lung mechanics and induces cytokine release, thus suggesting that detrimental effects are due to positive pressure ventilation per se. The aim of this study in healthy animals is to assess whether these adverse outcomes depend on the mode of mechanical ventilation.Rats were subjected to 4 h of spontaneous, positive pressure, and whole-body or thorax-only negative pressure ventilation (N = 8 per group). In all instances the ventilatory pattern was that of spontaneous breathing. Lung mechanics, cytokines concentration in serum and broncho-alveolar lavage fluid, lung wet-to-dry ratio, and histology were assessed. Values from eight animals euthanized shortly after anesthesia served as control.No evidence of mechanical ventilation-dependent lung injury was found in terms of lung mechanics, histology, or wet-to-dry ratio. Relative to control, cytokine levels and recruitment of polymorphonuclear leucocytes increased slightly, and to the same extent with spontaneous, positive pressure, and whole-body negative pressure ventilation. Thorax-only negative pressure ventilation caused marked chest and lung distortion, reversible increase of lung elastance, and higher polymorphonuclear leucocyte count and cytokine levels.Both positive and negative pressure ventilation performed with tidal volumes and timing of spontaneous, quiet breathing neither elicit an inflammatory response nor cause morpho-functional alterations in normal animals, thus supporting the notion of the presence of a critical volume threshold above which acute lung injury ensues. Distortion of lung parenchyma can induce an inflammatory response, even in the absence of volotrauma.
Background: to date, a reliable functional predictor of acute bronchodilator response in terms of forced expiratory volume in 1 second (FEV1) in patients with COPD does not exist. We hypothesized that ventilation inhomogeneity may have a role in the distribution of inhaled drugs. Aim: to explore which physiological parameter is predictive of FEv1 response in patients with COPD Methods: an interventional, randomized, double blind, double dummy study was conducted in the Pulmonary Rehabilitation Unit of S. Maugeri, Milan, Italy. The acute effects of tiotropium 18 µg (TIO) and indacaterol 150 µg (IND) on closing volume (CV) and ventilation inhomogeneity were investigated in patients with moderate to very severe COPD. Patients underwent body plethysmography, arterial blood gas analysis, dyspnea assessment, and simultaneous recording of single-breath N2 test and transpulmonary pressure-volume curve (PLV), before and 1 h after drug administration. Results: 50 stable COPD patients, 25 per arm, (mean±SD age 70±7 yr, 82% men) were enrolled. Pre-bronchodilator and post-bronchodilator parameters did not differ between groups (ΔFEV1 90±110 vs. 60±110 mL, for IND and TIO;P=0.296), therefore results were pooled. ΔFEV1 significantly correlated with baseline vital capacity (Pearson coefficient, VC, 0.283; P=0.047), total lung capacity (TLC, 0.295; P=0.038) and closing volume to VC ratio (CV/VC, 0.483;P=0.023). In a multivariate regression model, only CV/VC significantly predicted the FEV1 response to bronchodilators (Beta -0.010; 95%CI: -0.017,-0.002; P=0.013). Conclusion: the amount of closed airways during drug inhalation affects the response to bronchodilators in terms of airflow obstruction.
Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (aged 70 ± 7 yr, mean ± SD; 82% men) with moderate to very severe COPD. Patients underwent body plethysmography, arterial blood gas analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single-breath N2 test and transpulmonary pressure-volume curve (PL-V), before and 1 h after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) scale and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (-5 ± 4 and -2.5 ± 2.1%, respectively, both P < 0.001), with an increase in both slope and height of phase IV and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3 ± 3 mmHg and 2 ± 2%, respectively, both P < 0.001); their changes negatively correlated with those of phase III slope (r = -0.659 and r = -0.454, respectively, both P < 0.01). The vital capacity (VC) increased substantially, but the PL-V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small-airway damage and positively affect gas exchange.NEW & NOTEWORTHY This is the first study investigating in stable chronic obstructive pulmonary disease patients the acute effects of two long-acting bronchodilators, a β-agonist and a muscarinic antagonist, on peripheral airways using simultaneous lung pressure-volume curve and single-breath N2 test. By lessening airway mechanical property heterogeneity, both drugs similarly reduced ventilation inhomogeneity and extent of small-airway closure, as indicated by the decrease of phase III slope, increased oxygen saturation, and fall of closing volume, often below expiratory reserve volume.
The airway epithelium stretches and relaxes during the normal respiratory cycle, and hyperventilation exaggerates this effect, resulting in changes in lung physiology. In fact, stretching of the airways influences lung function and the secretion of airway mediators, which in turn may cause a potentially injurious inflammatory response. This aim of the present narrative review was to illustrate the current evidence on the importance of mechanical stress in the pathophysiology of lung diseases with a particular focus on chronic obstructive pulmonary disease (COPD) and to discuss how this may influence pharmacological treatment strategies. Overall, treatment selection should be tailored to counterpart the effects of mechanical stress, which influences inflammation both in asthma and COPD. The most suitable treatment approach between a long-acting β 2-agonists/long-acting antimuscarinic-agonist (LABA/LAMA) alone or with the addition of inhaled corticosteroids should be determined based on the underlying mechanism of inflammation. Noteworthy, the anti-inflammatory effects of the glycopyrronium/indacaterol combination on hyperinflation and mucociliary clearance may decrease the rate of COPD exacerbations, and it may synergistically improve bronchodilation with a double action on both the cyclic adenosine monophosphate (cAMP) and the acetylcholine pathways.
