Search

Spontaneous pneumomediastinum (SPM), pneumothorax (PNX) and subcutaneous emphysema are rare complications of COVID-19 pneumonia. In this paper we describe 3 cases of COVID-19 pneumonia complicated by SPM with or without PNX. Patient 1 was a 56-year-old woman whose medical history was significant for chronic leukemia. She presented with typical clinical signs of COVID-19 pneumonia and after 2 weeks of hospitalization she developed SPM and subcutaneous emphysema. The management of pneumomediastinum (PNM) was conservative and follow-up computed tomography showed resolution of PNM. Patient 2 was a 67-year-old man presenting with fever, cough and dyspnea. Computed tomography pulmonary angiography was performed after 2 weeks of hospitalization and showed bilateral peripheral consolidations together with massive PNM and right-sided PNX. Thoracic drainage catheter was inserted in his right chest. Despite all supportive care, the patient succumbed to illness. Patient 3 was a 74-year-old man who was admitted to our hospital with COVID-19 pneumonia and spontaneous right-sided PNX. A thoracic drainage catheter was inserted immediately and then removed after ten days which has led to progression of subcutaneous emphysema, PNX and newly diagnosed PNM. Patient was carefully monitored for the next 2 weeks. Follow-up chest x-ray showed regression of PNM and PNX. SPM, PNX and subcutaneous emphysema are rare complications of COVID-19 pneumonia. Increased alveolar pressure and diffuse alveolar injury in severe COVID-19 pneumonia may make the alveoli more prone to rupturing which leads to gas dissemination along the peribronchovascular sheath to the mediastinum. Most cases of SPM and PNX resolve with conservative management.

Pulmonary atelectasis is common in the perioperative period. Physiologically, it is produced when collapsing forces derived from positive pleural pressure and surface tension overcome expanding forces from alveolar pressure and parenchymal tethering. Atelectasis impairs blood oxygenation and reduces lung compliance. It is increasingly recognized that it can also induce local tissue biologic responses, such as inflammation, local immune dysfunction, and damage of the alveolar–capillary barrier, with potential loss of lung fluid clearance, increased lung protein permeability, and susceptibility to infection, factors that can initiate or exaggerate lung injury. Mechanical ventilation of a heterogeneously aerated lung (e.g., in the presence of atelectatic lung tissue) involves biomechanical processes that may precipitate further lung damage: concentration of mechanical forces, propagation of gas–liquid interfaces, and remote overdistension. Knowledge of such pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should guide optimal clinical management.

Mean airway pressure (Pmean) is a common pressure monitoring parameter of mechanical ventilators that is closely correlated with mean alveolar pressure and represents stresses applied to the lung parenchyma during ventilation. Pmean is determined by the peak inspiratory pressure, positive end-expiratory pressure (PEEP), and inspiratory-to-expiratory time ratio with dynamic and real-time characteristics, which represents mechanical power affected by the ventilator mode. Additionally, Pmean is an important parameter that affects hemodynamics. Tidal forces and PEEP increase pulmonary vascular resistance (PVR) in direct proportion to their effects on Pmean. Therefore, Pmean is increasingly considered to be related to the prognosis of patients on mechanical ventilation. We propose a 3P strategy (Pmean, central venous pressure [CVP], and perfusion index [PI]) which is indicated to achieve circulation protection mechanical ventilation with flow priority. Titrating the appropriate CVP and meeting PI to ensure tissue perfusion with a lower Pmean are the core purposes. Pmean links the circulatory and respiratory systems and is expected to become a potential parameter for intelligent ventilation.

Background Complete airway closure during expiration may underestimate alveolar pressure. It has been reported in cases of acute respiratory distress syndrome (ARDS), as well as in morbidly obese patients with healthy lungs. The authors hypothesized that complete airway closure was highly prevalent in obese ARDS and influenced the calculation of respiratory mechanics. Methods In a post hoc pooled analysis of two cohorts, ARDS patients were classified according to body mass index (BMI) terciles. Low-flow inflation pressure-volume curve and partitioned respiratory mechanics using esophageal manometry were recorded. The authors' primary aim was to compare the prevalence of complete airway closure according to BMI terciles. Secondary aims were to compare (1) respiratory system mechanics considering or not considering complete airway closure in their calculation, and (2) and partitioned respiratory mechanics according to BMI. Results Among the 51 patients analyzed, BMI was less than 30 kg/m in 18, from 30 to less than 40 in 16, and greater than or equal to 40 in 17. Prevalence of complete airway closure was 41% overall (95% CI, 28 to 55; 21 of 51 patients), and was lower in the lowest (22% [3 to 41]; 4 of 18 patients) than in the highest BMI tercile (65% [42 to 87]; 11 of 17 patients). Driving pressure and elastances of the respiratory system and of the lung were higher when complete airway closure was not taken into account in their calculation. End-expiratory esophageal pressure (ρ = 0.69 [95% CI, 0.48 to 0.82]; P Conclusions Prevalence of complete airway closure was high in ARDS and should be taken into account when calculating respiratory mechanics, especially in the most morbidly obese patients. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Plateau and driving pressures have been shown to correlate with mortality in adult respiratory distress syndrome (ARDS). However, these static airway pressures may not always accurately reflect alveolar pressure.It has recently been recognized that in ARDS, airway closure may occur while some alveoli are still inflated. This may result in a biased estimate of mean alveolar pressure.Complete airway closure can only be measured by the inflection point on the initial portion of a low-flow inflation pressure-volume or pressure-time curve with the absence of cardiac oscillations and very low compliance, most likely in the terminal bronchioles.In 25 to 33% of patients with ARDS, airway opening pressure (the inflection point value) is greater than the total positive end-expiratory pressure measured by an end-expiratory maneuver. What this article tells us that is new In a post hoc analysis of two cohort studies of respiratory mechanics in ARDS, the authors compared the prevalence of complete airway closure stratified by body mass index and its effects on respiratory mechanics.Complete airway closure was present in 41% of patients, increasing with body mass index tercile (65% in the highest).Driving pressure and respiratory system elastances (lung, chest wall) were higher when complete airway closure was not adjusted for.

During spontaneous breathing at rest, the alveolar pressure (Palv)-flow (V) 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 V 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.

Inflation of hollow elastic structures can become unstable and exhibit a runaway phenomenon if the tension in their walls does not rise rapidly enough with increasing volume. Biological systems avoid such inflation instability for reasons that remain poorly understood. This is best exemplified by the lung, which inflates over its functional volume range without instability. The goal of this study was to determine how the constituents of lung parenchyma determine tissue stresses that protect alveoli from instability-related overdistension during inflation. We present an analytical model of a thick-walled alveolus composed of wavy elastic fibres, and investigate its pressure–volume behaviour under large deformations. Using second-harmonic generation imaging, we found that collagen waviness follows a beta distribution. Using this distribution to fit human pressure–volume curves, we estimated collagen and elastin effective stiffnesses to be 1247 kPa and 18.3 kPa, respectively. Furthermore, we demonstrate that linearly elastic but wavy collagen fibres are sufficient to achieve inflation stability within the physiological pressure range if the alveolar thickness-to-radius ratio is greater than 0.05. Our model thus identifies the constraints on alveolar geometry and collagen waviness required for inflation stability and provides a multiscale link between alveolar pressure and stresses on fibres in healthy and diseased lungs.

Often, in supporting patients suffering from severe respiratory diseases with mechanical ventilation, obstacles are encountered due to pulmonary and/or thoracic alterations, reductions in the ventilable lung parenchyma, increases in airway resistance, alterations in thoraco-pulmonary compliance, advanced age of the subjects. All this involves difficulties in finding the right ventilation parameters and an adequate driving pressure to guarantee sufficient ventilation. Therefrom, new mechanical ventilation techniques were sought that could help overcome the aforementioned obstacles. A new mode of mechanical ventilation is being presented, i.e., a Positive + Negative Synchronized Ventilation (PNSV), characterized by the association and integration of two pulmonary ventilators; one acting inside the chest with positive pressures and one externally with negative pressure. The peculiarity of this combination is the complete synchronization, which takes place with specific electronic modifications. The PNSV can be applied both in a completely non-invasive and invasive way and, therefore, be used both in acute care wards and in ICU. The most relevant effect found, due to the compensation of opposing pressures acting on the chest, is that, during the entire inspiratory act created by the ventilators, the pressure at the alveolar level is equal to zero even if adding together the two ventilators’ pressures; thus, the transpulmonary pressure is doubled. The application of this pressure for 1 hour on elderly patients suffering from severe acute respiratory failure, resulted in a significant improvement in blood gas analytical and clinical parameters without any side effects. An increased pulmonary recruitment, including posterior lung areas, and a reduction in spontaneous ventilatory rate have also been demonstrated with PNSV. This also paves the way to the search for the best ventilatory treatment in critically ill or ARDS patients. The compensation of intrathoracic pressures should also lead, although not yet proven, to an improvement in venous return, systolic and cardiac output. In the analysis of the study in which this method was applied, the total transpulmonary pressure delivered was the sum of the individual pressures applied by the two ventilators. However, this does not exclude the possibility of reducing the pressures of the two machines to modulate a lower but balanced total transpulmonary pressure within the chest.

During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30–50 mL × cmH2O−1) and resistances (5–20 cmH2O × L−1 × s−1) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmH2O, inspiratory pressure 10 cmH2O, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmH2O−1 decreased the tidal volume (VT) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmH2O × L−1 × s−1 decreased VT by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, p &lt, 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmH2O. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient’s needs and has a high risk of cross-interference.

In the review we have discussed the mechanisms of the changes of the venous return and pulmonary hemodynamics which take place in clinical cases of the mechanical lung ventilation with positive end-expiratory pressure. In these conditions the elevating of right atrial pressure does not cause the decreasing of the venous return, because the mean circulatory filling pressure also increases. Thus, the gradient for venous return remains relatively constant. In case of the mechanical lung ventilation with positive end-expiratory pressure the decreasing of the venous return is the result of the elevation of the venous resistance as consequence of the direct increasing of the intrathoracic and transdiaphragmatic pressures and activation of the reflectory neurogenic mechanisms. In the conditions, indicated above, the increased alveolar pressure leads to the improvement of the diffused lung capacity for oxygen, which decreases the manifestations of the hypoxic pulmonary vasoconstriction and thus diminishes pulmonary vascular resistance. The character of changes of the last one is determined by the reactions of the two types (alveolar and extraalveolar) intraparenchimal pulmonary vessels. This leads to the changes of the resistive and capacitive functions of the pulmonary vessels. In case of the high levels of the positive end-expiratory pressure (more than 30 cm of water column) the value of alveolar pressure is comparable or even more excessive than pulmonary artery pressure (1216 mm Hg), which can be the reason of the decreasing of the right ventricular contractility and the venous return. The increasing of the capillary filtration coefficient of pulmonary vessels in the conditions of the mechanical lung ventilation with positive end-expiratory pressure can be the result of the activation of the mechanosensitive transient receptor potential vanilloid-4 (TRPV4) channels and the increasing endothelial calcium entry.

Background Recent analyses of patient data in acute respiratory distress syndrome (ARDS) showed that a lower ventilator driving pressure was associated with reduced relative risk of mortality. These findings await full validation in prospective clinical trials. Methods To investigate the association between driving pressures and ventilator induced lung injury (VILI), we calibrated a high fidelity computational simulator of cardiopulmonary pathophysiology against a clinical dataset, capturing the responses to changes in mechanical ventilation of 25 adult ARDS patients. Each of these in silico patients was subjected to the same range of values of driving pressure and positive end expiratory pressure (PEEP) used in the previous analyses of clinical trial data. The resulting effects on several physiological variables and proposed indices of VILI were computed and compared with data relating ventilator settings with relative risk of death. Results Three VILI indices: dynamic strain, mechanical power and tidal recruitment, showed a strong correlation with the reported relative risk of death across all ranges of driving pressures and PEEP. Other variables, such as alveolar pressure, oxygen delivery and lung compliance, correlated poorly with the data on relative risk of death. Conclusions Our results suggest a credible mechanistic explanation for the proposed association between driving pressure and relative risk of death. While dynamic strain and tidal recruitment are difficult to measure routinely in patients, the easily computed VILI indicator known as mechanical power also showed a strong correlation with mortality risk, highlighting its potential usefulness in designing more protective ventilation strategies for this patient group. Electronic supplementary material The online version of this article (10.1186/s12931-019-0990-5) contains supplementary material, which is available to authorized users.

Made available in DSpace on 2021-06-26T06:17:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 BACKGROUND: In mechanically ventilated subjects, intra-tracheal secretions can be aspirated with either open suction systems (OSS) or closed suction systems (CSS). In contrast to CSS, conventional OSS require temporarily disconnecting the patient from the ventilator, which briefly diminishes PEEP and oxygen supply. On the other hand, CSS are more expensive and less effective at aspirating secretions. Thus, it was hypothesized that the 2 procedures differentially affect pulmonary and cardiovascular parameters after suction. METHODS: Subjects in the ICU (N = 66) were quasi-randomized for initial treatment with OSS or CSS in a crossover design. To compare the potential for these suction systems to compromise cardiorespiratory stability, changes in cardiopulmonary physiology were assessed from before to just after use of each suction system (three 10-s aspirations). RESULTS: For most pulmonary and cardiovascular parameters (ie, peak inspiratory pressure, airway resistance, pressure plateau, heart rate, and arterial pressures), the effects of aspiration inversely correlated with baseline values for that parameter, with a similar regression slope between suction systems. However, when controlling for baseline values, OSS caused significantly greater increases in airway resistance and peak inspiratory pressure (P < .001 and < .01 vs CSS, respectively). CONCLUSIONS: Elevated airway resistance prior to endotracheal suction may justify use of a CSS and contraindicate a conventional OSS in mechanically ventilated subjects. Adoption of this approach into clinical guidelines may prevent suction-induced pulmonary injury in subjects, especially for those with underlying diseases involving increased airway resistance or increased alveolar pressure. Fac Med ABC, Lab Delineamento Estudos & Escrita Cient, Santo Andre, SP, Brazil Univ Fed Espirito Santo UFES, Dept Educ Integrada Saude, Vitoria, ES, Brazil Harvard Sch Publ Hlth, Dept Environm Hlth, 677 Huntington Ave, Boston, MA 02115 USA Univ Fed Sao Paulo, Dept Cardiol, Sao Paulo, SP, Brazil Univ Cidade Sao Paulo, Fac Med, Sao Paulo, Brazil Univ Estadual Paulista, Dept Escudos Sistema Nervoso Auton, Fac Ciencias & Tecnol, Presidente Prudente, SP, Brazil Univ Louisville, Diabet & Obes Ctr, Christina Lee Brown Envirome Inst, Sch Med, Louisville, KY USA Univ Louisville, Dept Physiol, Sch Med, Louisville, KY USA Univ Estadual Paulista, Dept Escudos Sistema Nervoso Auton, Fac Ciencias & Tecnol, Presidente Prudente, SP, Brazil

The focus of this chapter is on understanding the complexity associated with the resistance to flow through the pulmonary circulation. Pulmonary vascular resistance (PVR) is a variable that reflects the physical size (diameter and length) of the vascular tree at any moment in time. If PVR is increased, then it will take more energy for the right ventricle to pump the venous return through the lungs. One obvious complexity with the magnitude of the PVR is that the pulmonary resistance changes with lung inflation. There may also be resistance changes in response to various stimuli, as well as in different lung pathologies, and it can play an important role in the impact of heart–lung interactions. Although it is easy to define pulmonary resistance analogous to Ohm’s law, the underlying basis of pathophysiologic changes in this resistance is neither simple nor always intuitive, and it is important to understand the limitations of this measurement. A fundamental issue in the interpretation (or even definition) of PVR involves uncertainty about what downstream pressure to use (and how to measure it in vivo). A ubiquitous understanding of the pulmonary vasculature today revolves around the three zones of the lung as defined by West et al. In an upright human, a certain fraction of the lung would be in a zone 2 condition, where alveolar pressure becomes the effective downstream pressure. However, at any given time, there will always be a mixture of zones in the pulmonary circulation, so how can one define or measure the PVR? In addition to this puzzle, there are changes in PVR related to the effect of lung inflation on different serial regions of the pulmonary vasculature, as well as effects of the nonlinear distensibility of the elastic vessels. In what follows, we deal with these issues in an effort to define when and where it might be appropriate to measure the PVR, and more importantly how it might be useful in physiologic research and clinical settings.

Intrapleural pressure during a forced vital capacity (VC) maneuver is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression [TGC]), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across the “effort‐dependent” region of VC in healthy young men (n = 11) and women (n = 12). Subjects performed VC maneuvers at varying efforts while airflow, volume, and esophageal pressure (POES) were measured. Quasistatic expiratory deflation curves were used to obtain lung recoil (PLUNG) and alveolar pressures (i.e., PALV = POES–PLUNG). The raw maximal expiratory flow–volume (MEFVraw) curve was obtained from the “maximum effort” VC maneuver. The TGC‐corrected curve was obtained by constructing a “maximal perimeter” curve from all VC efforts (MEFVcorr). TGC was examined via differences between curves in FEFs (∆FEF), area under the expiratory curves (∆AEX), and estimated compressed gas volume (∆VGC) across the VC range. Men displayed greater total ∆AEX (5.4 ± 2.0 vs. 2.0 ± 1.5 L2·s−1; p, We sought to examine whether sex influences the degree to which thoracic gas compression (TGC) underestimates forced expiratory flows at a given lung volume during forced expiration. Men displayed greater TGC than women, particularly at 25% of the forced expired volume. This greater TGC was likely due to greater expiratory pressures generated by men throughout the maneuver. Failure to appropriately account for TGC results in a greater underestimation of expiratory airflow in men, primarily during the early phase of forced expiration.

During thoracic operations, surgical staplers resect cancerous tumors and seal the spared lung. However, post-operative air leaks are undesirable clinical consequences: staple legs wound lung tissue. Subsequent to this trauma, air leaks from lung tissue into the pleural space. This affects the lung’s physiology and patients’ recovery.The objective is to biomechanically and visually characterize porcine lung tissue with and without staples in order to gain knowledge on air leakage following pulmonary resection. Therefore, a syringe pump filled with air inflates and deflates eleven porcine lungs cyclically without exceeding 10 cmH2O of pressure. Cameras capture stereo-images of the deformed lung surface at regular intervals while a microcontroller simultaneously records the alveolar pressure and the volume of air pumped. The raw images are then used to compute tri-dimensional displacements and strains with the Digital Image Correlation method (DIC).Air bubbles originated at staple holes of inner row from exposed porcine lung tissue due to torn pleural on costal surface. Compared during inflation, left upper or lower lobe resections have similar compliance (slope of the pressure vs volume curve), which are 9% lower than healthy lung compliance. However, lower lobes statistically burst at lower pressures than upper lobes (p-valueex vivo conditions confirming previous clinical in vivo studies. In parallel, the lung deformed mostly in the vicinity of staple holes and presented maximum shear strain near the observed leak location. To conclude, a novel technique DIC provided concrete evidence of the post-operative air leaks biomechanics. Further studies could investigate causal relationships between the mechanical parameters and the development of an air leak.

The relationship between regional variabilities in airflow (ventilation) and blood flow (perfusion) is a critical determinant of gas exchange efficiency in the lungs. Hypoxic pulmonary vasoconstriction is understood to be the primary active regulator of ventilation-perfusion matching, where upstream arterioles constrict to direct blood flow away from areas that have low oxygen supply. However, it is not understood how the integrated action of hypoxic pulmonary vasoconstriction affects oxygen transport at the system level. In this study we develop, and make functional predictions with a multi-scale multi-physics model of ventilation-perfusion matching governed by the mechanism of hypoxic pulmonary vasoconstriction. Our model consists of (a) morphometrically realistic 2D pulmonary vascular networks to the level of large arterioles and venules; (b) a tileable lumped-parameter model of vascular fluid and wall mechanics that accounts for the influence of alveolar pressure; (c) oxygen transport accounting for oxygen bound to hemoglobin and dissolved in plasma; and (d) a novel empirical model of hypoxic pulmonary vasoconstriction. Our model simulations predict that under the artificial test condition of a uniform ventilation distribution (1) hypoxic pulmonary vasoconstriction matches perfusion to ventilation; (2) hypoxic pulmonary vasoconstriction homogenizes regional alveolar-capillary oxygen flux; and (3) hypoxic pulmonary vasoconstriction increases whole-lobe oxygen uptake by improving ventilation-perfusion matching., Author summary The relationship between regional ventilation (airflow) and perfusion (blood flow) is a major determinant of gas exchange efficiency. Atelactasis and pulmonary vascular occlusive diseases, such as acute pulmonary embolism, are characterized by ventilation-perfusion mismatching and decreased oxygen in the bloodstream. Despite the physiological and medical importance of ventilation-perfusion matching, there are gaps in our knowledge of the regulatory mechanisms that maintain adequate gas exchange under pathological and normal conditions. Hypoxic pulmonary vasoconstriction is understood to be the primary regulator of ventilation-perfusion matching, where upstream arterioles constrict to direct blood flow away from areas that have low oxygen supply, yet it is not understood how this mechanism affects oxygen transport at the system level. In this study we present a computational model of the ventilation-perfusion matching and hypoxic pulmonary vasoconstriction to better understand how physiological regulation at the regional level scales to affect oxygen transport at the system level. Our model simulations predict that this regulatory mechanism improves the spatial overlap of airflow and blood flow, which serves to increase the uptake of oxygen into the bloodstream. This improved understanding of ventilation-perfusion matching may offer insights into the etiology of, and therapeutic interventions for diseases characterized by ventilation-perfusion mismatching.

Objective. During launch and atmospheric re-entry in suborbital space flights, astronauts are exposed to high G-acceleration. These acceleration levels influence gas exchange inside the lung and can potentially lead to hypoxaemia. The distribution of air inside the lung can be monitored by Electrical Impedance Tomography (EIT). This imaging technique might reveal how high gravitational forces affect the dynamic behavior of ventilation and impair gas exchange resulting in hypoxaemia. Approach. We performed a trial in a long-arm centrifuge with ten participants lying supine while being exposed to +2, +4 and +6\,Gx (chest-to-back acceleration) to study the magnitude of accelerations experienced during suborbital spaceflight. Main results. First, the tomographic images revealed that the dorsal region of the lung emptied faster than the ventral region. Second, the ventilated area shifted from dorsal to ventral. Consequently, alveolar pressure in the dorsal area reached the pressure of the upper airways before the ventral area emptied completely. Finally, the upper airways collapsed and the end-expiratory volume increased. This resulted in ventral gas trapping with restricted gas exchange. Significance. At +4x changes in ventilation distribution varied considerably between subjects potentially due to variation in individual physical conditions. However, at +6\,Gx all participants were affected similarly and the influence of high gravitational conditions was pronounced.

Objectives Respirophasic variation of inferior vena cava (IVC) size is affected by large variability with spontaneous breathing. This study aims at characterizing the dependence of IVC size on controlled changes in intrathoracic pressure. Methods Ten healthy subjects, in supine position, performed controlled isovolumetric respiratory efforts at functional residual capacity, attaining positive (5, 10, and 15 mmHg) and negative (−5, −10, and −15 mmHg) alveolar pressure levels. The isovolumetric constraint implies that equivalent changes are exhibited by alveolar and intrathoracic pressures during respiratory tasks. Results The IVC cross-sectional area equal to 2.88 ± 0.43 cm2 at baseline (alveolar pressure = 0 mmHg) was progressively decreased by both expiratory and inspiratory efforts of increasing strength, with diaphragmatic efforts producing larger effects than thoracic ones: −55 ± 15% decrease, at +15 mmHg of alveolar pressure (P

Respiratory acidosis, or primary hypercapnia, occurs when carbon dioxide production exceeds elimination via the lung and is mainly owing to alveolar hypoventilation. Concurrent increases in Paco2, decreases in pH and compensatory increases in blood HCO3- concentration are associated with respiratory acidosis. Respiratory acidosis can be acute or chronic, with initial metabolic compensation to increase HCO3- concentrations by intracellular buffering. Chronic respiratory acidosis results in longer lasting increases in renal reabsorption of HCO3-. Alveolar hypoventilation and resulting respiratory acidosis may also be associated with hypoxemia, especially evident when patients are inspiring room air (20.9% O2).

The airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy. The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall. Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance. The model could be used in the study of the interaction between respiratory and cardiovascular systems in pathophysiological conditions., Highlights • Detailed description of normal breathing in both healthy and pathological conditions. • Equations of some constitutive functions reported in literature have been corrected. • Some mathematical details not reported in the literature have been highlighted. • Changing constitutive functions parameters pathological conditions are simulated. • Different pathological respiratory conditions have been analysed.

Alveolar stresses are fundamental to enable the respiration process in mammalians and have recently gained increasing attention due to their mechanobiological role in the pathogenesis and development of respiratory diseases. Despite the fundamental physiological role of stresses in the alveolar wall, the determination of alveolar stresses remains challenging, and our current knowledge is largely drawn from 2D studies that idealize the alveolar septal wall as a spring or a planar continuum. Here we study the 3D stress distribution in alveolar walls of normal lungs by combining ex-vivo micro-computed tomography and 3D finite-element analysis. Our results show that alveolar walls are subject to a fully 3D state of stresses rather than to a pure axial stress state. To understand the contributions of the different components and deformation modes, we decompose the stress tensor field into hydrostatic and deviatoric components, which are associated with isotropic and distortional stresses, respectively. Stress concentrations arise in localized regions of the alveolar microstructure, with magnitudes that can be up to 27 times the applied alveolar pressure. Interestingly, we show that the stress amplification factor strongly depends on the level of alveolar pressure, i.e, stresses do not scale proportional to the applied alveolar pressure. In addition, we show that 2D techniques to assess alveolar stresses consistently overestimate the stress magnitude in alveolar walls, particularly for lungs under high transpulmonary pressure. These findings take particular relevance in the study of stress-induced remodeling of the emphysematous lung and in ventilator-induced lung injury, where the relation between transpulmonary pressure and alveolar wall stress is key to understand mechanotransduction processes in pneumocytes.

Total liquid ventilation (TLV) is an innovative experimental method of mechanical ventilation in which lungs are totally filled with a breathable perfluorochemical liquid (PFC). The main objective is to develop a method to estimate the alveolar pressure from a pressure mouth measurement during pause in liquid ventilation. Experimental results show that the measured mouth pressure is disturbed by disturbances (damped oscillations due to fluid-structure tube resonances and cardiogenic oscillation). Numerical analysis of \(P_Y\) allow to obtain a fractional-order model of \(\alpha =0.7\) for the alveolar pressure.

Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical WLAM application, the transport and deposition of asthma drugs from a commercial dry-powder inhaler is discussed in Part II. A validated whole-lung-airway model is presented which can predict segmental and total particle-depositions in the human lung.It represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration plus an exponentially expanding 1-D conduit.It is a time-and-resources efficient tool to analyze toxicological effects as well as the pharmacological impact of drugs (see Part II).

The aim of the study was to determine in human patients the effect of lung resection on lung compliance and on pleuro-pulmonary fluid balance. Pre and post-operative values of compliance were measured in anesthetized patients undergoing resection for lung cancer (N=11) through double-lumen bronchial intubation. Lung compliance was measured for 10-12 cm H2O increase in alveolar pressure from 5 cm H2O PEEP in control and repeated after resection. No air leak was assessed and pleural fluid was collected during hospital stay. A significant negative correlation (r(2)=0.68) was found between compliance at 10 min and resected mass. Based on the pre-operative estimated lung weight, the decrease in compliance following lung resection exceeded by 10-15% that expected from resected mass. Significant negative relationships were found by relating pleural fluid drainage flow to the remaining lung mass and to post-operative lung compliance. Following lung re-expansion, data suggest a causative relationship between the decrease in compliance and the perturbation in pleuro-pulmonary fluid balance.

Supplemental Digital Content is available in the text., Objectives: Elucidate how the degree of ventilator-induced lung injury due to atelectrauma that is produced in the injured lung during mechanical ventilation is determined by both the timing and magnitude of the airway pressure profile. Design: A computational model of the injured lung provides a platform for exploring how mechanical ventilation parameters potentially modulate atelectrauma and volutrauma. This model incorporates the time dependence of lung recruitment and derecruitment, and the time-constant of lung emptying during expiration as determined by overall compliance and resistance of the respiratory system. Setting: Computational model. Subjects: Simulated scenarios representing patients with both normal and acutely injured lungs. Measurements and Main Results: Protective low-tidal volume ventilation (Low-Vt) of the simulated injured lung avoided atelectrauma through the elevation of positive end-expiratory pressure while maintaining fixed tidal volume and driving pressure. In contrast, airway pressure release ventilation avoided atelectrauma by incorporating a very brief expiratory duration () that both prevents enough time for derecruitment and limits the minimum alveolar pressure prior to inspiration. Model simulations demonstrated that has an effective threshold value below which airway pressure release ventilation is safe from atelectrauma while maintaining a tidal volume and driving pressure comparable with those of Low-Vt. This threshold is strongly influenced by the time-constant of lung-emptying. Conclusions: Low-Vt and airway pressure release ventilation represent markedly different strategies for the avoidance of ventilator-induced lung injury, primarily involving the manipulation of positive end-expiratory pressure and , respectively. can be based on exhalation flow values, which may provide a patient-specific approach to protective ventilation.

The equal pressure point (EPP) states that expiratory flow limitation occurs at the precise location along the tracheobronchial tree where intraluminal and peribronchial pressures are equal (i.e., where the local transmural pressure is 0 cmH2O). The EPP may be determined numerically via the expiratory isovolume pressure flow (IVPF) curve. For instance, using data from a given isovolume curve, the EPP is determined as the point along the x‐axis at which pressure‐flow data fails to conform to Rohrer’s equation: driving pressure = k1(flow) + k2(flow2). The probability of incurring expiratory flow‐limitation can be greatly determined by the EPP such that a lower EPP at a given lung volume requires only minimal pressure development to create a flow‐limiting segment during expiration. The EPP is affected by two principal factors: lung elastic recoil (PLUNG) & airway geometry. Given recent evidence suggesting that airway geometry is different between men & women, we sought to determine whether the EPP is likewise affected by sex in healthy adults. Purpose Determine whether or not there is an effect of sex on the magnitude of the EPP. Methods To address this question, 11 men (23.1 ± 4.8 years) and 12 women (21.2 ± 1.0 years) completed a study requiring two visits to the laboratory. On the initial visit, we obtained written informed consent and conducted spirometry to ensure subjects met the inclusion criteria of normal (>85% of predicted) lung function. During the second visit, a balloon catheter was passed intranasally to the lower one‐third of the esophagus and remained there for the duration of the visit to measure esophageal pressure (PES). Subjects then performed a minimum of 10–15 graded vital capacity maneuvers from 100‐5% of maximal effort. Data were imported into Matlab and, using custom‐written code, multiple calculations were performed. First, the lowest effort vital capacity efforts were taken as quasi‐static expiratory deflations of the lung and the negative sign of PES was taken to equal PLUNG. Second, alveolar pressure (PALV) was taken to equal PES + PLUNG. Finally, the EPP was determined by iteratively fitting Rohrer’s equation to pressure‐flow data at a given iso‐volume. The pressure at which Rohrer’s equation no longer adequately fit the data (>5% error) was termed the EPP. To test for an effect of sex and lung volume, a two‐way ANOVA was computed. Pairwise comparisons were adjusted for multiple comparisons using the Tukey‐Sidak post hoc test. Results There was no effect of sex on PLUNG, but PALV was greater in men than women throughout the entire VC range. EPP was significantly greater in men than women during the initial half of VC (95‐55% of VC) (p 0.05). Conclusion Because PLUNG did not differ between men and women, the differing location of EPP was the result of a greater PES in men. This suggests that the larger airways present in men are more resistant to compression than those of women.

Airway transmural pressure in healthy homogeneous lungs with dilated airways is approximately equal to the difference between intraluminal and pleural pressure. However, bronchoconstriction causes airway narrowing, parenchymal distortion, dynamic hyperinflation, and the emergence of ventilation defects (VDefs) affecting transmural pressure. This study aimed to investigate the changes in transmural pressure caused by bronchoconstriction in a bronchial tree. Transmural pressures before and during bronchoconstriction were estimated using an integrative computational model of bronchoconstriction. Briefly, this model incorporates a 12-generation symmetric bronchial tree, and the Anafi and Wilson model for the individual airways of the tree. Bronchoconstriction lead to the emergence of VDefs and a relative increase in peak transmural pressures of up to 84% compared to baseline. The highest increase in peak transmural pressure occurred in a central airway outside of VDefs, and the lowest increase was 27% in an airway within VDefs illustrating the heterogeneity in peak transmural pressures within a bronchial tree. Mechanisms contributing to the increase in peak transmural pressures include increased regional ventilation and dynamic hyperinflation both leading to increased alveolar pressures compared to baseline. Pressure differences between intraluminal and alveolar pressure increased driven by the increased airway resistance and its contribution to total transmural pressure reached up to 24%. In conclusion, peak transmural pressure in lungs with VDefs during bronchoconstriction can be substantially increased compared to dilated airways in healthy homogeneous lungs and is highly heterogeneous. Further insights will depend on the experimental studies taking these conditions into account.

Dynamic hyperinflation occurs when mean alveolar pressure exceeds the mean airway pressure measured in the airway opening. The dynamic hyperinflation develops as a consequence of insufficiently long expiration terminated by the subsequent inspiration. Two main principles are supposed to create the dynamic hyperinflation during high frequency oscillatory ventilation (HFOV): expiratory flow limitation and different inspiratory and expiratory airway resistances (Re > Ri). The aim of the study is to design and test a physical model of the respiratory system comprising both the mechanisms causing dynamic hyperinflation and to characterize their effect upon dynamic hyperinflation or hypoinflation development during HFOV. The models were created using a rigid volume and passive pneumatic components mimicking the required characteristics of the airway resistance. The models were connected to a HFOV ventilator and different ventilator settings were applied in order to investigate the parameters having the most significant effect on dynamic hyperinflation development. The main result of the study is that the expiratory flow limitation corresponds better with the observed and published properties of the respiratory system during HFOV. The magnitude of dynamic hyperinflation depends on ventilator setting. The acquired results are supported by recently published studies using mathematical-physical modeling and correspond with results of the published clinical trials.

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.

Fick's principle, “the speed of disappearing solute from the region is net flux,” has been applied to measure cardiac output and cerebral blood flow. The equation of Fick's first law of diffusion can be mathematically transformed into the equation of Fick's second law of diffusion. The concentration gradient of gases or small nonpolar lipid soluble molecules in the membrane was calculated using a model and solving the equation of Fick's second law of diffusion. It was evaluated to be linear when the concentrations of the both sides of membrane are maintained at different constant values. Pressure difference between the atmospheric pressure and alveoli per air flow through trachea gives the airway resistance. The pressure changes in the air-tight body plethysmograph with a patient sitting in give the alveolar pressure change in the lungs after correlation, which makes the measurement of the airway resistance possible without a cannulation into the patient.

BackgroundDespite the theoretical benefits of high-frequency oscillatory ventilation (HFOV) in preterm infants, systematic reviews of randomized clinical trials do not confirm improved outcomes. The authors hypothesized that oscillating a premature lung with multiple frequencies simultaneously would improve gas exchange compared with traditional single-frequency oscillatory ventilation (SFOV). The goal of this study was to develop a novel method for HFOV, termed “multifrequency oscillatory ventilation” (MFOV), which relies on a broadband flow waveform more suitable for the heterogeneous mechanics of the immature lung.MethodsThirteen intubated preterm lambs were randomly assigned to either SFOV or MFOV for 1 h, followed by crossover to the alternative regimen for 1 h. The SFOV waveform consisted of a pure sinusoidal flow at 5 Hz, whereas the customized MFOV waveform consisted of a 5-Hz fundamental with additional energy at 10 and 15 Hz. Per standardized protocol, mean pressure at airway opening () and inspired oxygen fraction were adjusted as needed, and root mean square of the delivered oscillatory volume waveform (Vrms) was adjusted at 15-min intervals. A ventilatory cost function for SFOV and MFOV was defined as , where Wt denotes body weight.ResultsAveraged over all time points, MFOV resulted in significantly lower VC (246.9 ± 6.0 vs. 363.5 ± 15.9 ml2 mmHg kg−1) and (12.8 ± 0.3 vs. 14.1 ± 0.5 cm H2O) compared with SFOV, suggesting more efficient gas exchange and enhanced lung recruitment at lower mean airway pressures.ConclusionOscillation with simultaneous multiple frequencies may be a more efficient ventilator modality in premature lungs compared with traditional single-frequency HFOV.

The research goal was to formulate and substantiate the hypothesis explaining support for an expiratory air flow in case of pulmonary emphysema. The research method consisted in comparing the mechanical properties of lungs in practically healthy individuals (37 individuals, mean age – (30.4 ± 1.7) y.o.) and COPD patients with pronounced lung emphysema (30 patients, mean age – (52.1 ± 2.3) y.o.) as well as those of isolated normal lungs (n = 14) and isolated lungs of patients who died of COPD (n = 5). Pulmo-nary mechanics was studied via the simultaneous measurement of transpulmonary pressure and lung ven-tilation volume. General lung hysteresis and elastic lung hysteresis were calculated. The mechanical properties of isolated lungs were studied using passive ventilation under the Donders bell. The air flow was interrupted in order to measure alveolar pressure and develop an elastic lung hysteresis curve. Pres-sure in the Donders bell was changed by means of a special pump in automatic and manual modes. The research has not revealed any fundamental differences between the mechanical properties of the normal and emphysematous lungs. A minimum increase in the pressure inside the Donders bell over atmospheric pressure used to stop air ejection in both normal and the emphysematous lungs as the result of flap-valve bronchial obstruction. In living beings, air is ejected from lungs with an increase in pressure under the conditions of forced expiration. Pressure increases up to (38.6 ± 2.71) cm H2O in healthy individuals and up to (20.5 ± 1.86) cm H2O in COPD patients. Probably, an expiratory air flow is supported by active expiratory bronchial dilatation that counteracts flap-valve bronchial obstruction. The hypothesis is based on the confirmed ability of the lungs to perform inspiratory actions (in addition to the action of respiratory muscles) and the theory of mechanical lung activity.

Background: Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. Methods: Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. Results: Respiratory acidosis induced a significant decrease in maximum shortening velocity (−33%, P < 0.001), active isometric force (−36%, P < 0.001), and peak power output (−59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (−35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction–relaxation coupling under isotonic (−26%, P < 0.001) or isometric (−44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction–relaxation coupling were observed in the metabolic acidosis group. Conclusions: In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

Two functional levels of mechanical energy intrapulmonary source have been viewed in this article for the first time. The first level is located into the perialveolar space. This level provides inspiratory and expiratory activity of the lungs together with respiratory muscles. Due to this, the inspiratory alveolar pressure is lower than the intrapleural pressure and the expiratory alveolar pressure is higher than the intrapleural pressure. This is deter mined by work of breathing measured as negative elastic hysteresis area and allows overcoming some nonelastic resistance of the lungs. The lung activity on overcoming the elastic resistance is estimated by multiplying the total work of breathing by a functional coefficient of lung elasticity (FCLE). The latter is calculated by dividing the total lung compliance by the dynamic lung compliance and reflects change in the elastic lung tension from spontaneous breathing level to the total lung compliance level. FCLE approximates 1 in healthy subjects and in patients with normal lung elastic recoil (LER). LER is lower and the total lung capacity is higher in lung obstructive diseases. Consequently, the total lung compliance could increase and FCLE could grow up to 10 in such cases (for instance, in severe emphysema). This leads to increasing lung activity on overcoming the elastic resistance up to 10 kgf × m / min or higher. Actually, this huge work of breathing is not performed due to the 2nd level of lung mechanical activity that is an active dilation of the large airways on expiration; this mechanism prevents valvular bronchial obstruction.

Background: A non-invasive means of measuring pulmonary blood flow (PBF) would have numerous benefits in medicine. Tradition ally, respiratory-based methods require breathing maneuvers, partial rebreathing, or foreign gas mixing because exhaled CO2 volume on a per-breath basis does not accurately represent alveolar exchange of CO2. We hypothesized that if the dilutional effect of the functional residual capacity was accounted for, the relationship between the calculated volume of CO2 removed per breath and the alveolar partial pressure of CO2 would be reversely linear. Methods: A computer model was developed that uses variable tidal breathing to calculate CO2 removal per breath at the level of the alveoli. We iterated estimates for functional residual capacity to create the best linear fit of alveolar CO 2 pressure and CO2 elimination for 10 minutes of breathing and incorporated the volume of CO2 elimination into the Fick equation to calculate PBF. Results: The relationship between alveolar pressure of CO2 and CO2 elimination produced an R 2 = 0.83. The optimal functional residual capacity differed from the “actual” capacity by 0.25 L (8.3%). The repeatability coefficient leveled at 0.09 at 10 breaths and the difference between the PBF calculated by the model and the preset blood flow was 0.62 ± 0.53 L/minute. Conclusions: With variations in tidal breathing, a linear relationship exists between alveolar CO2 pressure and CO2 elimination. Existing technology may be used to calculate CO2 elimination during quiet breathing and might therefore be used to accurately calculate PBF in humans with healthy lungs.

In six male anesthetized, tracheotomized, and mechanically ventilated rabbits we derived indications on alveolar mechanics from in vivo imaging, using a “pleural window” technique (pleural space intact) that allows unrestrained movement of the same subpleural alveoli ( N = 60) on increasing alveolar pressure from 4 to 8 cmH 2 O. Absolute compliance ( C abs , ratio of change in alveolar surface area to the change in alveolar pressure) was significantly lower in smaller compared to larger alveoli. Specific compliance, C sp , obtained by normalizing C abs to alveolar surface area, was essentially independent of alveolar size. Both C abs and C sp were affected by large variability likely reflecting the complex matching between elastic and surface forces. We hypothesize that the relative constancy of C sp might contribute to reduce interregional differences in parenchymal and surface forces in the lung tissue by contributing to assure a uniform stretching in a model of mechanically inter-dependent alveoli.

BACKGROUND: Percutaneous dilational tracheostomy is normally a bronchoscope-guided procedure. The insertion of a bronchoscope into an endotracheal tube (ETT) affects resistance, flow, and alveolar pressure. To improve airway management and ventilation during percutaneous tracheostomy, we developed a double lumen endotracheal tube (DLET). The aim of this in vitro study was to compare the linear constant of the Rohrer equation (K1), the nonlinear constant of the Rohrer equation (K2), the inspiratory and expiratory airway resistance, and ventilatory and airway pressures using the DLET with different standard sized ETTs. METHODS: A trachea and lung model was used to compare the DLET to ETTs with 7, 7.5, and 8 mm inner diameters with and without a bronchoscope (4.5 mm external diameter), and 4 and 5 mm inner diameter ventilation tubes (F4, F5) of a translaryngeal tracheostomy. For each device, the pressure drop across the device and the Rohrer equation linear constant (K1) and nonlinear constant (K2) were calculated during a continuous flow of 10–90 L/min, the inspiratory and expiratory airway resistance values were calculated during volume controlled mechanical ventilation, and respiratory airway pressure values were calculated during volume and pressure controlled mechanical ventilation. RESULTS: DLET had lower K2, pressure drop, and inspiratory and expiratory airway resistance compared with conventional ETTs plus fiberoptic bronchoscope. Furthermore, during mechanical ventilation, DLET had a lower value of peak pressure, mean pressure, and intrinsic PEEP than the other ETTs plus fiberoptic bronchoscope. CONCLUSIONS: Use of the DLET during percutaneous dilational tracheostomy allows fiberoptic bronchoscopy without imposing excessive airway resistance. Reduced tube resistance during this procedure may confer additional safety in what is well known to be a hazardous procedure.

Background and objective During forced expiration, alveolar pressure (PALV) increases and intrathoracic gas is compressed. Thus, 1-s forced expiratory volume measured by spirometry (FEV1-sp) is smaller than 1-s forced expiratory volume measured by plethysmography (FEV1-pl). Thoracic gas compression volume (TGCV) depends on the amount of gas within the lung when expiratory flow limitation occurs in the airways. We therefore tested the hypothesis that bronchoconstrictor and bronchodilator responses using FEV1-sp are biased by height and gender, which are major determinants of lung volume. Methods We studied 54 asthmatics during methacholine challenge and 55 subjects with airway obstruction (FEV1-sp increase >200 mL and >12% after salbutamol) measuring at the same time FEV1-sp or FEV1-pl. Results During methacholine challenge, TGCV increased more in males than females, correlated with PALV, total lung capacity (TLC) and height, and the provocative dose was lower using FEV1-sp than FEV1-pl. With salbutamol, FEV1-pl increased

Recent literature suggests that optimization of tidal driving pressure (ΔP) would be a better variable to target for lung protection at the bedside than tidal volume (VThis was a retrospective, observational study in a university-affiliated and house staff-aided institution with respiratory care protocols based on extant lung-protective guidelines for VThe mean ΔP was significantly higher at Time 1 (mean 16.1, range 7.0-31.0 cm HSuggested safety thresholds for ΔP are often violated by a strategy that focuses on only V

Spirometry is the gold standard to detect airflow limitation, but it does not measure airway resistance, which is one of the physiological factors behind airflow limitation. In this study, we describe the dynamics of forced expiration in spirometry using a deflating balloon and using this model. We propose a methodology to estimate &zeta, (zeta), a dimensionless and effort-independent parameter quantifying airway resistance. In N = 462 (65 &plusmn, 8 years), we showed that &zeta, is significantly (p &lt, 0.0001) greater in COPD (2.59 &plusmn, 0.99) than healthy smokers (1.64 &plusmn, 0.18), it increased significantly (p &lt, 0.0001) with the severity of airflow limitation and it correlated significantly (p &lt, 0.0001) with airway resistance (r = 0.55) and specific conductance (r = &minus, 0.60) obtained from body-plethysmography. &zeta, also showed significant associations (p &lt, 0.001) with diffusion capacity (r = &minus, 0.64), air-trapping (r = 0.68), and CT densitometry of emphysema (r = 0.40 against % below &minus, 950 HU and r = &minus, 0.34 against 15th percentile HU). Moreover, simulation studies demonstrated that an increase in &zeta, resulted in lower airflows from baseline. Therefore, we conclude that &zeta, quantifies airway resistance from forced expiration in spirometry&mdash, a method that is more abundantly available in primary care than traditional but expensive methods of measuring airway resistance such as body-plethysmography and forced oscillation technique.

Volume and protein concentration of pleural liquid in anesthetized rabbits after 1 or 3 h of mechanical ventilation, with alveolar pressure equal to atmospheric at end expiration, were compared to those occurring after spontaneous breathing. Moreover, coefficient of kinetic friction between samples of visceral and parietal pleura, obtained after spontaneous or mechanical ventilation, sliding in vitro at physiological velocity under physiological load, was determined. Volume of pleural liquid after mechanical ventilation was similar to that previously found during spontaneous ventilation. This finding is contrary to expectation of Moriondo et al. (2005) , based on measurement of lymphatic and interstitial pressure. Protein concentration of pleural liquid after mechanical ventilation was also similar to that occurring after spontaneous ventilation. Coefficient of kinetic friction after mechanical ventilation was 0.023 ± 0.001, similar to that obtained after spontaneous breathing.

Registered spirogram and transpulmonary pressure in spontaneous breathing in 10 healthy volunteers and in 10 patients with community-acquired pneumonia. For the first time the work inside the lung-a source of mechanical energy (RVI) was measured by the method of interruption of the air on 0.2 with inhalation and exhalation in the middle of the respiratory cycle. Alveolar pressure exceeding the total nonelastic pressure on the inhale and exhale through self-mechanical activity of the lungs. RVI was determined by the area of a triangle, where one cathetus were breathing capacity and the amount of excess air pressure. The total work of breathing (TWB) was measured by the square of the chart pressure-volume. Total breathing (Рt) was determined by adding TWB and RVI. RVI average was 29.6 (25.0–43.3)% to Рt in healthy individuals and to 19.4 (0–55.1) % of patients with community-acquired pneumonia. In 2 patients, RVI has not been determined, and 2 were increased significantly. The nature of variations RVI in healthy people and change its degree of severity of community-acquired pneumonia remain unknown.

Submersion and increased pressure (depth) characterize the diving environment and may independently increase demand on the respiratory system. To quantify changes in respiratory mechanics, this study employed a unique protocol and techniques to measure, in a hyperbaric chamber, inspiratory and expiratory alveolar pressures (interrupter technique), inspiratory and expiratory resistance in the airways (RawI and RawE, esophageal balloon technique), nitric oxide elimination (thought to correlate with Raw), inspiratory and expiratory mechanical power of breathing, and the total energy cost of ventilation. Eight healthy adult men underwent experiments at 1, 2.7, and 4.6 atmospheres absolute (ATA) in dry and fully submersed conditions. Subjects rested, cycled on an ergometer at 100 W, and rested while voluntarily matching their ventilation to their own exercise hyperpnea (isocapnic simulated exercise ventilation). During isocapnic simulated exercise ventilation, increased O2 uptake (above rest values) resulted from increased expired ventilation. RawI decreased with submersion (mean 43% during rest and 20% during exercise) but increased from 1 to 4.6 ATA (19% during rest and 75% during exercise), as did RawE (53% decrease with submersion during rest and 10% during exercise; 9% increase from 1 to 4.6 ATA during rest and 66% during exercise). Nitric oxide elimination did not correlate with Raw. Depth increased inspiratory mechanical power of breathing during rest (40%) and exercise (20%). Expiratory mechanical power of breathing was largely unchanged. These results suggest that the diving environment affects ventilatory mechanics primarily by increasing Raw, secondary to increased gas density. This necessitates increased alveolar pressure and increases the work and energy cost of breathing as the diver descends. These findings can inform physician assessment of diver fitness and the pulmonary risks of hyperbaric O2 therapy.

Exercise-induced pulmonary haemorrhage is a major cause of poor performance in the equine athlete. It is an important cause of exercise intolerance and results from strenuous exercise and pathophysiological changes in the equine lung and possibly in the airways. Endoscopic surveys of the respiratory tracts of horses after competitive events have shown that many horses experience exercise-induced pulmonary haemorrhage. The reported incidence of exercise-induced pulmonary haemorrhage in different breeds varies between 40–85%. The cause of bleeding in exercising horses has fostered considerable debate over the past three centuries, but currently, the most accepted hypothesis is that the source of haemorrhage is disruption of the pulmonary capillaries during exercise. Furosemide is the medication used most widely for the treatment and prevention of exercise-induced pulmonary haemorrhage. This review provides an update on the aetiology, clinical signs, physiopathology, diagnosis and treatment of exercise-induced pulmonary haemorrhage. EIPH, pulmonary pressure, equine The clinical signs of pulmonary bleeding after exercise in horses were first described by Markham (1688). Robertson (1913) reported the existence of epistaxis in racehorses, attributing it to a hyperaemic condition of the pulmonary vessels. Later, the epistaxis was attributed to an inherited condition in thoroughbred racehorses. Despite the time that has passed since the conditions of disease were first described, the cause of the disease and the optimal approach to treatment has not been established yet. According to Hinchcliff (2000), this phenomenon should not be considered a disease as such, but rather a common condition in sport horses. Other authors noted that bleeding after exercise is a physiological phenomenon related to extreme exercise, as the horse is genetically prepared for prolonged physical effort but with submaximal speed (West and Mathieu-Costello 1995). As stated by Derksen et al. (1992), the term that best describes this bleeding after athletic stress in horses is Exercise-Induced Pulmonary Haemorrhage (EIPH). This condition is defined as the presence of blood in the tracheobronchal circulation derived from the alveolar capillaries (Sweeney 1991). Its importance lies in the high incidence of this condition in sport horses; according to some authors, between 42 to 85% of horses that perform at high speeds suffer from it (Hillidge and Whitlock 1986; Birks et al. 2002, Newton and Wood 2002; Moran et al. 2003; Araya et al. 2007). Currently, the most accepted hypothesis regarding the origin and mechanism of EIPH involves the rupture of pulmonary capillaries during exercise (Poole et al. 2007). Predisposing factors for exercise-induced pulmonary haemorrhage Exercise-induced pulmonary haemorrhage does not have a single aetiologic factor such as race, sport, age, sex, environment or horse management, but it is supported by the coexistence of multiple predisposing factors (Art and Lekeux 1994). Many authors agree that the occurrence of EIPH is caused by effort, training or career (West et al. 1993). Horses subjected to high-speed sprinting that induces a heart rate of 240/min will suffer EIPH during the race or after it (Harkins et al. 1997). It is thought that the rate ACTA VET. BRNO 2013, 82: 309–316; doi:10.2754/avb201382030309 Address for correspondence: Gabriel Moran Department of Pharmacology, Faculty of Veterinary Science Universidad Austral de Chile, Valdivia, Chile Phone: +56-63-221936 Fax: +56-63-221444 E-mail: gmoran@uach.cl http://actavet.vfu.cz/ of acceleration of 17 m/s, which develops at the start of the race, causes an increase in pulmonary intravascular pressure and leads to EIPH (Erickson 1992). It has been found that pulmonary arterial pressure and venous pressure can reach 100 mmHg and 80 mmHg during peak exercise, respectively. Because pulmonary capillary pressure is in between the pulmonary arterial and venous pressure values, it has been estimated that pulmonary capillary pressure approaches 90–95 mmHg during intense exercise (Langsetmo et al. 2000). These changes in pressure, accompanied by a negative pleural pressure and largevolume ventilation during maximal exercise may induce transmural capillary pressure that breaks the endothelial cell junctions in the alveolar epithelium, which ruptures the pulmonary capillaries (Manohar et al. 1993; West and Mathieu-Costello, 1994, 1995; Deksen et al. 2001). It has been shown that there is insufficient gas exchange due to the disruption of pulmonary capillaries, which suffer from arterial hypoxaemia and hypercapnia, which leads to increased anaerobic metabolism (Manohar et al. 2001; Caillaud et al. 2002). The fact that EIPH occurs after high-intensity exercise and prolonged low-intensity exercise suggests that this problem is due to extreme mechanical stresses on the tissue and pulmonary vessels during exercise (Art and Lekeux 1994). However, West et al. (1993) observed episodes of EIPH in horses just after walking and trotting. There is a trend related to age, where older horses have shown increased susceptibility to episodes of EIPH (Lapointe et al. 1994). Derksen (2009) suggested that increased prevalence of EIPH in older horses is due to progressive lung damage from repeated episodes of bleeding and the development of diseases of the upper airways. On the other hand, Oikawa (1999) showed that the equine lung is vulnerable to post-stress bleeding in individuals aged between 18 and 22 months. In addition, this part is vulnerable to trauma during exercise especially by the scapulo-humeral joint, where the forces are transmitted actively through the chest wall to reach the lung parenchyma (Newton et al. 2005). This may be because the scapula acts as a hinge to the spine, so that a portion of its surface moves toward the ribs plus some surrounding muscles may move medially (Schroter et al. 1998). Some authors have mentioned that the risk of developing EIPH cannot be readily determined from a combination of age, environment, race speed, race distance, track hardness or air quality (Hinchcliff et al. 2010). Possible causes of exercise-induced pulmonary haemorrhage The real causes of EIPH are still unknown. Numerous causes and pathophysiological mechanisms for the development of this disease have been proposed. These include infectious pulmonary diseases, which facilitate the development of fundamental EIPH by weakening the alveolar capillary walls and thus facilitating their rupture (McKane and Slocombe 2002), diseases of the lower airways, higher airway obstruction (Cook et al. 1988), blood hyperviscosity induced by exercise (Fedde and Wood 1993; Weiss and Smith 1998), mechanical stress associated with breathing and locomotion (Schroter et al. 1999), redistribution of blood flow in the lungs (Bernard et al. 1996, Erickson et al. 1999) and fluctuations in alveolar pressure and pulmonary hypertension (Pascoe 1997). Several of these factors can exert severe stress on the pulmonary system to the point that the capillaries fail. Obstruction of the upper and lower airways, which decreases pulmonary ventilatory capacity, would be one of the factors considered as important in the presentation of the disease (Cook et al. 1988). In this regard, Cook (2002) proposed that the dorsal displacement of the soft palate (DDSP) interrupts the flow of air into the lungs and therefore represents a major predisposing cause of EIPH. In an equine disease that manifests as DDSP upon exercise, the horse may appear normal when examined at rest. When exercise is initiated, displacement occurs suddenly, resulting in a reduction of speed or sudden arrest of the horse’s movement. Some animals may even fall due to choking episodes, while others may experience fatal pulmonary bleeding. Moreover, trauma to the 310

This paper presents an algorithm for noninvasive estimation of alveolar pressure in mechanically ventilated patients who are spontaneously breathing. Continual monitoring of alveolar pressure is desirable to prevent ventilator-induced lung injury and to assess the intrinsic positive end-expiratory pressure (PEEPi), which is a parameter of clinical relevance in respiratory care and difficult to measure noninvasively. The algorithm is based on a physiological model of the respiratory system and, as such, it also provides insight into the respiratory mechanics of the patient under mechanical ventilation. In particular, the algorithm allows one to correctly estimate other clinical parameters of interest such as the patient's respiratory resistance and elastance, even in the presence of PEEPi.

We examined whether or not coherence between chest wall intercostal and oblique muscles changed as a function of lung volume excursion, alveolar pressure, and muscular demand. We also assessed the effects of acute expiratory threshold loading (ETL) on chest wall muscular control. A total of 15 healthy adults (7 males; average age = 28 years) completed maximum performance and ETL tasks. Chest wall surface electromyographic and kinematic recordings were made. Participants also performed a session of acute ETL. We showed that corticomuscular control of the chest wall varied as a function of lung volume excursion and muscular effort. Acute ETL had some effect on respiratory kinematics but not coherence.

Partial extracorporeal CO2 removal allows a decreasing tidal volume without respiratory acidosis in patients with acute respiratory distress syndrome. This, however, may be associated with worsening hypoxemia, due to several mechanisms, such as gravitational and reabsorption atelectasis, due to a decrease in mean airway pressure and a critically low ventilation-perfusion ratio, respectively. In addition, an imbalance between alveolar and artificial lung partial pressures of nitrogen may accelerate the process. Finally, the decrease in the respiratory quotient, leading to unrecognized alveolar hypoxia and monotonous low plateau pressures preventing critical opening, may contribute to hypoxemia. peerReviewed

Weibel’s symmetrical bifurcation model of the bronchial tree provides the basis for analyzing respiratory flows. Flow is turbulent in the central airways and laminar in the peripheral airways, and for quiet breathing, most of the pressure drop occurs in the central airways. For higher frequency forced oscillatory flow, lung impedance is frequency-dependent if lung elastance or resistance is non-uniform. For higher frequencies, resonances occur. Expiratory flow is limited by the wave-speed condition at higher lung volumes and by viscous flow limitation at lower lung volumes. Maximum expiratory flow is a strong function of lung volume, and the maximum expiratory flow-volume curve changes with disease. During inspiration, inspired gas is carried to the periphery by convection in the larger airways and diffusion in the periphery, and a stationary front with a large gradient in oxygen concentration is established at the boundary between the two regions. Regional ventilation of the parenchyma is markedly non-uniform.

Mechanical ventilation using low tidal volumes has become universally accepted to prevent ventilator-induced lung injury. High-frequency oscillatory ventilation (HFOV) allows pulmonary gas exchange using very small tidal volume (1-2 mL/kg) with concomitant decreased risk of atelectrauma. However, its use in pediatric critical care varies between only 3% and 30% of all ventilated children. This might be explained by the fact that the beneficial effect of HFOV on patient outcome has not been ascertained. Alternatively, in contrast with present recommendations, one can ask if HFOV has been employed in its most optimal fashion related especially to the indications for and timing of HFOV, as well as to using the best oscillator settings. The first was addressed in one small randomized study showing that early use of HFOV, instead of rescue use, was associated with improved survival. From a physiologic perspective, the oscillator settings could be refined. Lung volume is the main determinant of oxygenation in diffuse alveolar disease, suggesting using an open-lung strategy by recruitment maneuvers, although this is in practice not custom. Using such an approach, the patient can be oscillated on the deflation limb of the pressure-volume (P-V) curve, allowing less pressure required to maintain a certain amount of lung volume. Gas exchange is determined by the frequency and the oscillatory power setting, controlling the magnitude of the membrane displacement. Experimental work as well as preliminary human data have shown that it is possible to achieve the smallest tidal volume with concomitant adequate gas exchange when oscillating at high frequency and high fixed power setting. Future studies are needed to validate these novel approaches and to evaluate their effect on patient outcome.