Still air resistance during walking and running.

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.

Acute dyspnea in the emergency department: a clinical review.

Acute dyspnea represents one of the most frequent symptoms leading to emergency room evaluation. Its significant prognostic value warrants a careful evaluation. The differential diagnosis of dyspnea is complex due to the lack of specificity and the loose association between its intensity and the severity of the underlying pathological condition. The initial assessment of dyspnea calls for prompt diagnostic evaluation and identification of optimal monitoring strategy and provides information useful to allocate the patient to the most appropriate setting of care. In recent years, accumulating evidence indicated that lung ultrasound, along with echocardiography, represents the first rapid and non-invasive line of assessment that accurately differentiates heart, lung or extra-pulmonary involvement in patients with dyspnea. Moreover, non-invasive respiratory support modalities such as high-flow nasal oxygen and continuous positive airway pressure have aroused major clinical interest, in light of their efficacy and practicality to treat patients with dyspnea requiring ventilatory support, without using invasive mechanical ventilation. This clinical review is focused on the pathophysiology of acute dyspnea, on its clinical presentation and evaluation, including ultrasound-based diagnostic workup, and on available non-invasive modalities of respiratory support that may be required in patients with acute dyspnea secondary or associated with respiratory failure.

Plethysmographic assessment of tidal expiratory flow limitation.

Chronic obstructive pulmonary disease (COPD) patients often experience tidal expiratory flow-limitation (tEFL), a condition causing respiratory and cardiovascular detrimental effects. As the appearance of tEFL should increase expiratory (Rexp) relative to inspiratory (Rins) resistance, we hypothesized that Rexp/Rins can be used to detect tEFL. Rexp/Rins was measured with a commercial plethysmograph in 109 healthy subjects and, before and after bronchodilation (BD), in 64 COPD patients, 36 with and 28 without tEFL according to the NEP technique. Before BD, the median (interquartile range) of Rexp/Rins was significantly greater (P < 0.001) in COPD patients with tEFL (2.47(3.06;7.07)) than in COPD patients without tEFL (1.63(1.44;1.82)) and in healthy subjects (1.52(1.35;1.62)). In COPD patients Rexp/Rins above 1.98 predicted the presence of tEFL with 96 % specificity and 92 % sensitivity, Rexp2/Rins performing even better. After BD the predictive ability of Rexp/Rins slightly declined, but remained elevated. The non-invasive measurement of Rexp/Rins is an easy, inexpensive, routinely usable method to detect tEFL in spontaneously breathing COPD subjects.

The funny current: Even funnier than 40 years ago. Uncanonical expression and roles of HCN/f channels all over the body.

Discovered some 40 years ago, the If current has since been known as the "pacemaker" current due to its role in the initiation and modulation of the heartbeat and of neuronal excitability. But this is not all, the funny current keeps entertaining the researchers; indeed, several data discovering novel and uncanonical roles of f/HCN channel are quickly accumulating. In the present review, we provide an overview of the expression and cellular functions of HCN/f channels in a variety of systems/organs, and particularly in sour taste transduction, hormones secretion, activation of astrocytes and microglia, inhibition of osteoclastogenesis, renal ammonium excretion, and peristalsis in the gastrointestinal and urine systems. We also analyzed the role of HCN channels in sustaining cellular respiration in mitochondria and their participation to mitophagy under specific conditions. The relevance of HCN currents in undifferentiated cells, and specifically in the control of stem cell cycle and in bioelectrical signals driving left/right asymmetry during zygote development, is also considered. Finally, we present novel data concerning the expression of HCN mRNA in human leukocytes. We can thus conclude that the emerging evidence presented in this review clearly points to an increasing interest and importance of the "funny" current that goes beyond its role in cardiac sinoatrial and neuronal excitability regulation.

Diagnostic Insights from Plethysmographic Alveolar Pressure Assessed during Spontaneous Breathing in COPD Patients.

Since its introduction in the clinical practice, body plethysmography has assisted pneumologists in the diagnosis of respiratory diseases and patients' follow-up, by providing easy assessment of absolute lung volumes and airway resistance. In the last decade, emerging evidence suggested that estimation of alveolar pressure by electronically-compensated plethysmographs may contain information concerning the mechanics of the respiratory system which goes beyond those provided by the simple value of airway resistance or conductance. Indeed, the systematic study of expiratory alveolar pressure-flow loops produced during spontaneous breathing at rest has shown that the marked expansion of expiratory loops in chronic obstructive pulmonary disease patients mainly reflects the presence of tidal expiratory flow-limitation. The presence of this phenomenon can be accurately predicted on the basis of loop-derived parameters. Finally, we present results suggesting that plethysmographic alveolar pressure may be used to estimate non-invasively intrinsic positive end-expiratory pressure (PEEPi) in spontaneously breathing patients, a task which previously could be only accomplished by introducing a balloon-tipped catheter in the esophagus.

Cardiovascular Responses During Sepsis.

Sepsis is the life-threatening organ dysfunction arising from a dysregulated host response to infection. Although the specific mechanisms leading to organ dysfunction are still debated, impaired tissue oxygenation appears to play a major role, and concomitant hemodynamic alterations are invariably present. The hemodynamic phenotype of affected individuals is highly variable for reasons that have been partially elucidated. Indeed, each patient's circulatory condition is shaped by the complex interplay between the medical history, the volemic status, the interval from disease onset, the pathogen, the site of infection, and the attempted resuscitation. Moreover, the same hemodynamic pattern can be generated by different combinations of various pathophysiological processes, so the presence of a given hemodynamic pattern cannot be directly related to a unique cluster of alterations. Research based on endotoxin administration to healthy volunteers and animal models compensate, to an extent, for the scarcity of clinical studies on the evolution of sepsis hemodynamics. Their results, however, cannot be directly extrapolated to the clinical setting, due to fundamental differences between the septic patient, the healthy volunteer, and the experimental model. Numerous microcirculatory derangements might exist in the septic host, even in the presence of a preserved macrocirculation. This dissociation between the macro- and the microcirculation might account for the limited success of therapeutic interventions targeting typical hemodynamic parameters, such as arterial and cardiac filling pressures, and cardiac output. Finally, physiological studies point to an early contribution of cardiac dysfunction to the septic phenotype, however, our defective diagnostic tools preclude its clinical recognition. © 2021 American Physiological Society. Compr Physiol 11:1605-1652, 2021.

Heliox administration in anesthetized rabbits with spontaneous inspiratory flow limitation.

We investigated the effects of heliox administration (80% helium in O2) on tidal inspiratory flow limitation (tIFL) occurring in supine anesthetized spontaneously breathing rabbits, regarded as an animal model of obstructive apnea-hypopnea syndrome. 22 rabbits were instrumented to record oro-nasal mask flow, airway opening, tracheal and esophageal pressures, and diaphragm and genioglossus electromyographic activities while breathing either room air or heliox, and, in 12 rabbits, also during the application of continuous positive airway pressure (CPAP; 6 cmH2O). For the group, heliox increased peak inspiratory flow, ventilation (18 ± 11%), peak inspiratory tracheal and dynamic transpulmonary pressures, but in no animal eliminated tIFL, as instead CPAP did in all. Muscle activities were unaffected by heliox. In the presence of IFL the increase in flow with heliox (ΔV̇ifl) varied markedly among rabbits (2 to 49%), allowing the distinction between responders and non-responders. None of the baseline variables discriminated responders and non-responders. However, fitting the Rohrer equation (R = K1 + K2V̇) to the tracheal pressure-flow relationship over the first 0.1 s of inspiration while breathing air allowed such discrimination on the basis of larger K2 in responders (0.005 ± 0.002 versus 0.002 ± 0.001 cmH2O·s2·ml-2; P < 0.001), suggesting a corresponding difference in the relative contribution of laminar and turbulent flow. The differences in ΔV̇ifl between responders and non-responders were simulated by modeling the collapsible segment of the upper airways as a non-linear resistor and varying its pressure-volume curve, length, and diameter, thus showing the importance of mechanical and geometrical factors in determining the response to heliox in the presence of tIFL.NEW & NOTEWORTHY In an obstructive sleep apnea rabbit model, heliox never abolishes tidal inspiratory flow limitation (IFL), but increases inspiratory flow and tidal volume, substantially in some and nearly nil in other animals. Positive response to heliox cannot be predicted on the basis of breathing pattern characteristics or upper airway resistance that preceded IFL onset, but is related to the mechanical and geometrical features of upper airway collapsible segment, as indicated by model simulation.

Tidal expiratory flow limitation induces expiratory looping of the alveolar pressure-flow relation in COPD patients.

During spontaneous breathing at rest, the alveolar pressure (Palv)-flow (V̇) relation exhibits a prominent expiratory loop in many chronic obstructive pulmonary disease (COPD) patients. Among the possible determinants of the loop, tidal expiratory flow limitation (tEFL) may be the main responsible. To compare the characteristics of the expiratory loop in COPD patients with flow limitation (FL) and without flow limitation (NFL), tEFL was assessed with the negative expiratory pressure technique in stable mild to very severe COPD patients undergoing body plethysmography before and after bronchodilation (BD), an intervention that is able to reduce mechanical heterogeneity, recruitment/derecruitment, and gas trapping but rarely abolishes tEFL. The magnitude of the expiratory loop was indexed by the integral of Palv on V̇ during expiration (Aexp). Before BD, Aexp was 360% greater in FL (n = 35) than in NFL (n = 25) patients (P < 0.001). After BD, Aexp was unchanged in NFL patients (ΔAexp 0%, P = 0.882) and slightly decreased in FL patients who remained FL (n = 32, ΔAexp -17%, P = 0.064). Three FL patients became NFL after BD, and their Aexp decreased markedly (ΔAexp -61%), reaching values similar to those observed in NFL patients at baseline. In conclusion, the greater Aexp measured in FL relative to NFL COPD patients, its relative invariance after BD when flow limitation persists, and its fall when flow limitation is abolished indicate that tEFL is a major determinant of the magnitude of the expiratory loop. Furthermore, Aexp can be used as a predictor of the presence of tEFL.NEW & NOTEWORTHY In stable chronic obstructive pulmonary disease (COPD) patients spontaneously breathing at rest, tidal expiratory flow limitation is the major determinant of the occurrence of expiratory looping in the plethysmographic flow-alveolar pressure diagram. In these patients the magnitude and the characteristics of the loop can be used as predictors of the presence of tidal expiratory flow limitation.

The Relevance of Targeting Treatment to Small Airways in Asthma and COPD.

COPD and asthma have different risk factors and pathogenesis, but they share a pathophysiologic hallmark characterized by small airways disease. Although difficult to explore and measure, modifications of distal airways' pathophysiology and biology represent an early sign of obstructive disease and should be researched and assessed in everyday clinical practice. In the last 15 years, computed microtomography scans have shed light on the anatomy and physiology of the so-called silent zone, and research devoted to investigate the effect of inhaled treatments on small airway pathophysiology has been increasing. This narrative review offers a historical summary of researchers and landmark studies that reported, defined, and advanced the research on small airways. We then discuss the latest findings on the role and characteristics of the small airways' inflammatory and cellular structure, and we describe the assessment tools available to detect small airways dysfunction in COPD and asthma and the effect of bronchodilators and inhaled steroids on functional and biological biomarkers. Finally, we analyze the newest technological therapeutic advances aimed at small airways treatment in terms of inhalation devices and small particle size molecules.

The development of various forms of lung injury with increasing tidal volume in normal rats.

Sixty-three, open-chest normal rats were subjected to mechanical ventilation (MV) with tidal volumes (VT) ranging from 7.5-39.5ml kg-1 and PEEP 2.3 cmH2O. Arterial blood gasses and pressure, and lung mechanics were measured during baseline ventilation (VT = 7.5ml kg-1) before and after test ventilation, when cytokine, von Willebrand factor (vWF), and albumin concentration in serum and broncho-alveolar lavage fluid (BALF), wet-to-dry weight ratio (W/D), and histologic injury scores were assessed. Elevation of W/D and serum vWF and cytokine concentration occurred with VT > 25ml kg-1. With VT > 30ml kg-1 cytokine and albumin concentration increased also in BALF, arterial oxygen tension decreased, lung mechanics and histology deteriorated, while W/D and vWF and cytokine concentration increased further. Hence, the initial manifestation of injurious MV consists of damage of extra-alveolar vessels leading to interstitial edema, as shown by elevated vWF and cytokine levels in serum but not in BALF. Failure of the endothelial-epithelial barrier occurs at higher stress-strain levels, with alveolar edema, small airway injury, and mechanical alterations.

Lung Microbiome in Asthma: Current Perspectives.

A growing body of evidence implicates the human microbiome as a potentially influential player actively engaged in shaping the pathogenetic processes underlying the endotypes and phenotypes of chronic respiratory diseases, particularly of the airways. In this article, we specifically review current evidence on the characteristics of lung microbiome, and specifically the bacteriome, the modes of interaction between lung microbiota and host immune system, the role of the "lung-gut axis", and the functional effects thereof on asthma pathogenesis. We also attempt to explore the possibilities of therapeutic manipulation of the microbiome, aiming at the establishment of asthma prevention strategies and the optimization of asthma treatment.

The Airways' Mechanical Stress in Lung Disease: Implications for COPD Pathophysiology and Treatment Evaluation.

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 ß2-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.

Expiratory flow-limitation in mechanically ventilated patients: A risk for ventilator-induced lung injury?

Expiratory flow limitation (EFL), that is the inability of expiratory flow to increase in spite of an increase of the driving pressure, is a common and unrecognized occurrence during mechanical ventilation in a variety of intensive care unit conditions. Recent evidence suggests that the presence of EFL is associated with an increase in mortality, at least in acute respiratory distress syndrome (ARDS) patients, and in pulmonary complications in patients undergoing surgery. EFL is a major cause of intrinsic positive end-expiratory pressure (PEEPi), which in ARDS patients is heterogeneously distributed, with a consequent increase of ventilation/perfusion mismatch and reduction of arterial oxygenation. Airway collapse is frequently concomitant to the presence of EFL. When airways close and reopen during tidal ventilation, abnormally high stresses are generated that can damage the bronchiolar epithelium and uncouple small airways from the alveolar septa, possibly generating the small airways abnormalities detected at autopsy in ARDS. Finally, the high stresses and airway distortion generated downstream the choke points may contribute to parenchymal injury, but this possibility is still unproven. PEEP application can abolish EFL, decrease PEEPi heterogeneity, and limit recruitment/derecruitment. Whether increasing PEEP up to EFL disappearance is a useful criterion for PEEP titration can only be determined by future studies.

Standard and viscoelastic mechanical properties of respiratory system compartments in dogs: Effect of volume, posture, and shape.

In 9 anesthetized, paralyzed dogs lung and chest-wall standard (viscous resistance, Rint, and quasi-static elastance, Est) and viscoelastic parameters (resistance, Rvel, and time constant, τvel) were measured in the supine posture before and after rib-cage block, after application of an expiratory threshold load, and after 75° head-up tilting before and after wide chest opening. Lung and chest-wall τvel were the same under all conditions. Rvel was independent of volume and posture, and greater for the lung. Chest-wall Rint was independent of flow, volume, and posture. Lung Rint decreased with increasing volume. Chest-wall Rint, Est and Rvel increased with rib-cage block, allowing the assessment of both abdominal-wall and rib-cage characteristics. When chest opening did not elicit bronchoconstriction, the decrease of Rvel was ∼6%. Main conclusions: lung and chest-wall exhibit linear tissue viscoelasticity within the range studied; rib-cage and abdomen characteristics are similar, and asynchronous motion is not expected at physiological respiratory rates; in normal lungs, heterogeneity of parallel time constants plays a marginal role.

Plethysmographic Loops: A Window on the Lung Pathophysiology of COPD Patients.

Plethysmographic alveolar pressure-flow (Palv-F) loops contain potentially relevant information about the pathophysiology of chronic obstructive pulmonary disease (COPD), but no quantitative analysis of these loops during spontaneous breathing has ever been performed. The area of the loop's inspiratory (Ains) and expiratory portion (Aexp), and the difference between the end-expiratory and end-inspiratory alveolar pressure (ΔPalv) were measured in 20 young, 20 elderly healthy subjects, and 130 stable COPD patients. Ains and ΔPalv increased by 55 and 78% from young to elderly subjects, and by 107 and 122% from elderly subjects to COPD patients, reflecting changes in mechanical heterogeneity, lung-units recruitment/derecruitment, and possibly air trapping occurring with aging and/or obstructive disease. Aexp increased by 38% from young to elderly subjects, and by 198% from elderly subjects to COPD patients, consistent with the additional contribution of tidal expiratory flow-limitation, which occurs only in COPD patients and affects Aexp only. In COPD patients, Aexp and ΔPalv showed a significant negative correlation with VC, FEV1, IC, and a significant positive correlation with RV/TLC. The results suggest that the analysis of plethysmographic Palv-F loops provides an insight of the pathophysiological factors, especially tidal expiratory flow-limitation, that affect lung function in COPD patients.

Limiting Factors in Walking Performance of Subjects With COPD.

INTRODUCTION: Exercise intolerance is the most predominant symptom in patients with COPD. Nevertheless, it is unclear whether walking economy and gait variability are altered in these patients. Thus, our main objective was to compare the cost of transport and gait variability as a function of speed, including the self-selected walking speed, in subjects with COPD relative to healthy subjects. METHODS: 22 subjects, 11 with COPD (FEV1 = 45 ± 17% of predicted) and 11 age- and sex-matched healthy subjects undertook an evaluation that involved walking on a treadmill at 6 speeds (at 3.2 km/h, at a self-selected walking speed, and at 2 speeds below and 2 speeds above the self-selected walking speed) and measuring the cost of transport (the oxygen consumption normalized by mass and distance), gait variability, perceived dyspnea, and leg fatigue. RESULTS: In subjects with COPD, the cost of transport decreased with increasing walking speed, contrary to healthy subjects, who presented a minimum at the self-selected walking speed. No difference was found in cost of transport between the experimental groups at the same absolute velocity (P = .62). In subjects with COPD, dyspnea sensation rose above the self-selected walking speed, doubling at the maximal walking velocity (P = .03), and gait variability was higher at low speeds. CONCLUSION: Subjects with COPD choose their walking speed so as to keep the dyspnea sensation tolerable and to keep gait variability and cost of transport at an acceptable level. These outcomes suggest that interventions acting on dyspnea and gait pattern may increase patients' self-selected walking speed and improve their quality of life.

Acute effects of long-acting bronchodilators on small airways detected in COPD patients by single-breath N2 test and lung P-V curve.

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 ß-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.

Improvements in Lung Diffusion Capacity following Pulmonary Rehabilitation in COPD with and without Ventilation Inhomogeneity.

BACKGROUND: Lung diffusing capacity (DLCO) and lung volume distribution predict exercise performance and are altered in COPD patients. If pulmonary rehabilitation (PR) can modify DLCO parameters is unknown. OBJECTIVES: To investigate changes in DLCO and ventilation inhomogeneity following a PR program and their relation with functional outcomes in patients with COPD. METHODS: This was a prospective, observational, multicentric study. Patients were evaluated before and after a standardized 3-week PR program. Functional assessment included body plethysmography, DLCO, transfer factor (KCO) and alveolar volume (VA), gas exchange, the 6-min walking test (6MWT) and exercise-related dyspnea. Patients were categorized according to the severity of airflow limitation and presence of ventilation inhomogeneity, identified by a VA/TLC <0.8. RESULTS: Two hundred and fifty patients completed the study. Baseline forced expiratory volume in 1 s (FEV1) % predicted (mean ± SD) was 50.5 ± 20.1 (76% males); 137 patients had a severe disease. General study population showed improvements in 6MWT (38 ± 55 m; p < 0.01), DLCO (0.12 ± 0.63 mmol × min-1 kPa-1; p < 0.01), lung function and dyspnea. Comparable improvements in DLCO were observed regardless of the severity of disease and the presence of ventilation inhomogeneity. While patients with VA/TLC <0.8 improved the DLCO increasing their VA (177 ± 69 ml; p < 0.01), patients with VA/TLC >0.8 improved their KCO (8.1 ± 2.8%; p = 0.019). The latter had also better baseline lung function and higher improvements in 6MWT (14.6 ± 6.7 vs. 9.0 ± 1.8%; p = 0.015). Lower DLCO at baseline was associated with lower improvements in 6MWT, the greatest difference being between subjects with very severe and mild DLCO impairment (2.7 ± 7.4 vs. 14 ± 2%; p = 0.049). CONCLUSIONS: In COPD patients undergoing a PR program, different pathophysiological mechanisms may drive improvements in DLCO, while ventilation inhomogeneity may limit improvements in exercise tolerance.

Airway occlusion assessed by single breath N2 test and lung P-V curve in healthy subjects and COPD patients.

PURPOSE: To determine whether the analysis of the slow expiratory transpulmonary pressure-volume (PL-V) curve provides an alternative to the single-breath nitrogen test (SBN) for the assessment of the closing volume (CV). METHODS: SBN test and slow deflation PL-V curve were simultaneously recorded in 40 healthy subjects and 43 COPD patients. Onset of phase IV identified CV in SBN test (CVSBN), whereas in the PL-V curve CV was identified by: a) deviation from the exponential fit (CVexp), and b) inflection point of the interpolating sigmoid function (CVsig). RESULTS: In the absence of phase IV, COPD patients exhibited a clearly discernible inflection in the PL-V curve. In the presence of phase IV, CVSBN and CVexp coincided (CVSBN/CVexp=1.04±0.04 SD), whereas CVsig was systematically larger (CVsig/CVexp=2.1±0.86). CONCLUSION: The coincidence between CVSBN and CVexp, and the presence of the inflection in the absence of phase IV indicate that the deviation of the PL-V curve from the exponential fit reliably assesses CV.