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1.
The mechanical properties of the lung periphery are vital to the overall function of the whole organ, and play a key role in the symptomatology of many lung diseases. We first review the experimental methodologies that have been used to investigate peripheral lung mechanics, including the retrograde catheter, the alveolar capsule, the alveolar capsule oscillator, and the forced oscillation technique. We then discuss the interpretation of the data provided by these techniques in terms of inverse mathematical models of the lung, including the constant-phase model. Finally, we describe efforts to construct anatomically accurate forward models of the lung based on data from imaging modalities such as computed tomography and magnetic resonance imaging. Together, these various approaches have provided a great deal of information about the relative importance of the lung periphery in mechanical function in animal models of lung disease and in human patients. An increasing body of evidence indicates that constriction in this part of the lung is a crucial determinant of the severity of asthma. 相似文献
2.
Heterogeneity of regional lung mechanics is an important determinant of the work of breathing and may be a risk factor for
ventilator associated lung injury. The ability to accurately assess heterogeneity may have important implications for monitoring
disease progression and optimizing ventilator settings. Inverse modeling approaches, when applied to dynamic pulmonary impedance
data (Z
L), are thought to be sensitive to the detection of mechanical heterogeneity with the ability to characterize global lung function
using a minimal number of free parameters. However, the reliability and bias associated with such model-based estimates of
heterogeneity are unknown. We simulated Z
L spectra from healthy, emphysematous, and acutely injured lungs using a computer-generated anatomic canine structure with
asymmetric Horsfield branching and various predefined distributions of stochastic lung tissue heterogeneity. Various inverse
models with distinct topologies incorporating linear resistive and inertial airways with parallel tissue viscoelasticity were
then fitted to these Z
L spectra and evaluated in terms of their quality of fit as well as the accuracy and reliability of their respective model
parameters. While all model topologies detected appropriate changes in tissue heterogeneity, only a topology consisting of
lumped airway properties with distributed tissue properties yielded accurate estimates of both mean lung tissue stiffness
and the spread of regional elastances. These data demonstrate that inverse modeling approaches applied to noninvasive measures
of Z
L may provide reliable and accurate assessments of lung tissue heterogeneity as well as insight into distributed lung mechanical
properties.
Address correspondence to David W. Kaczka, Division of Obstetric and Regional Anesthesia, Department of Anesthesiology and
Critical Care Medicine, The Johns Hopkins Hospital, 600 North Wolfe Street, Meyer 299C, Baltimore, MD 21287, USA. Electronic
mail: dkaczka1@jhmi.edu
An erratum to this article can be found at 相似文献
3.
Tavana H Zamankhan P Christensen PJ Grotberg JB Takayama S 《Biomedical microdevices》2011,13(4):731-742
Airways of the peripheral lung are prone to closure at low lung volumes. Deficiency or dysfunction of pulmonary surfactant
during various lung diseases compounds this event by destabilizing the liquid lining of small airways and giving rise to occluding
liquid plugs in airways. Propagation of liquid plugs in airways during inflation of the lung exerts large mechanical forces
on airway cells. We describe a microfluidic model of small airways of the lung that mimics airway architecture, recreates
physiologic levels of pulmonary pressures, and allows studying cellular response to repeated liquid plug propagation events.
Substantial cellular injury happens due to the propagation of liquid plugs devoid of surfactant. We show that addition of
a physiologic concentration of a clinical surfactant, Survanta, to propagating liquid plugs protects the epithelium and significantly
reduces cell death. Although the protective role of surfactants has been demonstrated in models of a propagating air finger
in liquid-filled airways, this is the first time to study the protective role of surfactants in liquid plugs where fluid mechanical
stresses are expected to be higher than in air fingers. Our parallel computational simulations revealed a significant decrease
in mechanical forces in the presence of surfactant, confirming the experimental observations. The results support the practice
of providing exogenous surfactant to patients in certain clinical settings as a protective mechanism against pathologic flows.
More importantly, this platform provides a useful model to investigate various surface tension-mediated lung diseases at the
cellular level. 相似文献
4.
The mechanical properties of the respiratory system are paramount in converting neural output into ventilation. The highly compliant chest wall of the newborn results in chest distortion and volume loss during inspiration and, as the chest is also unable to resist the inward recoil of the lung, there is a reduction in lung volume at end expiration (functional residual capacity) and a tendency for alveoli to collapse. Vagal innervation of the lungs and airways is responsible for eliciting various reflexes that result in the dynamic modification of respiratory mechanics and an improvement in ventilation. From the first breath, the newborn increases the frequency of augmented breaths to improve lung compliance and prolongs the expiratory time constant in order to increase the amount of air remaining in the lung at end expiration and help prevent lung collapse. This review examines the respiratory mechanics of the mammalian neonate at birth and during early development together with the vagal reflexes that are responsible for the dynamic modification of respiratory mechanics in order to ensure that effective gas exchange occurs from birth. 相似文献
5.
A new approach to mechanical simulation of lung behaviour: Pressure-controlled and time-related piston movement 总被引:1,自引:0,他引:1
Verbraak AF Rijnbeek PR Beneken JE Bogaard JM Versprille A 《Medical & biological engineering & computing》2001,39(1):82-89
A mechanical lung simulator is described (an extension of a previous mechanical simulator) which simulates normal breathing
and artificial ventilation in patients. The extended integration of hardware and software offers many new possibilities and
advantages over the former simulator. The properties of components which simulate elastance and airway resistance of the lung
are defined in software rather than by the mechanical properties of the components alone. Therefore, a more flexible simulation
of non-linear behaviour and the cross-over effects of lung properties is obtained. Furthermore, the range of lung compliance
is extended to simulate patients with emphysema. The dependency of airway resistance on lung recoil pressure and transmural
pressure of the airways can also be simulated. The new approach enables one to incorporate time-related mechanics such as
the influence of lung viscosity or cardiac oscillation. The different relations defined in the software can be changed from
breath to breath.
Three simulations are presented: (1) computer-controlled expiration in the artificially ventilated lung; (2) simulation of
normal breathing; and (3) simulation of viscoelastance and cardiac influences during artificial ventilation. The mechanical
simulator provides a reproducible and flexible environment for testing new software and equipment in the lung function laboratory
and in intensive care, and can be used for instruction and training. 相似文献
6.
Benjamin L. Schwartz Ron C. Anafi Minara Aliyeva John A. Thompson-Figueroa Gilman B. Allen Lennart K. A. Lundblad Jason H. T. Bates 《Annals of biomedical engineering》2011,39(1):497-507
The mechanical properties of the lung are embodied in its mechanical input impedance, which it is interpreted in physiological
terms by being fit with a mathematical model. The normal lung is extremely well described by a model consisting of a single
uniformly ventilated compartment comprised of tissue having a constant-phase impedance, but to describe the abnormal lung
it frequently becomes necessary to invoke additional compartments. To date, all evidence of regional mechanical heterogeneity
in the mouse lung has been assumed to be of the parallel variety. We therefore investigated the use of a serial heterogeneity
model, relative to parallel heterogeneity and homogeneous models, for describing impedance spectra in mice subjected to a
variety of interventions designed to make their lungs heterogeneous. We found that functional evidence of the finite stiffness
of the airway wall in mice with airways obstruction can sometimes be apparent in lung impedance below 20 Hz. The model estimates
of airway stiffness were smaller than direct estimates obtained from micro-CT images of the lung in vivo, suggesting that the conducting airways alone are likely not the precise anatomical correlate of proximal functional stiffness
in the lung. Nevertheless, we conclude that central airway shunting in mice can sometimes be an important physiological phenomenon. 相似文献
7.
《Journal of medical engineering & technology》2013,37(7):338-343
Airway disease such as tumours and asthma lead to lung injuries. Therefore, a better understanding of airway mechanics parameters is very important to avoid lung injuries in patients undergoing mechanical ventilation for treatment of respiratory problems in intensive-care medicine as well as pulmonary medicine. The objective of this study was to investigate the role of airway diseases such as asthma and tumours on airway mechanics parameters using coupled fluid–solid computational analysis. The results obtained indicate that both tumours and asthma greatly affect the airway mechanics parameters (airflow velocity increased by about 15% and the strains increased by about 40%). Strain results of this study highlight significant changes in levels of airway parameters, which may translate into higher health risk associated with airway tumours and the asthmatic airways. These results combined with optimization suggest that it is possible to develop mechanical ventilation protocols to avoid lung injuries in patients. 相似文献
8.
Airway disease such as tumours and asthma lead to lung injuries. Therefore, a better understanding of airway mechanics parameters is very important to avoid lung injuries in patients undergoing mechanical ventilation for treatment of respiratory problems in intensive-care medicine as well as pulmonary medicine. The objective of this study was to investigate the role of airway diseases such as asthma and tumours on airway mechanics parameters using coupled fluid-solid computational analysis. The results obtained indicate that both tumours and asthma greatly affect the airway mechanics parameters (airflow velocity increased by about 15% and the strains increased by about 40%). Strain results of this study highlight significant changes in levels of airway parameters, which may translate into higher health risk associated with airway tumours and the asthmatic airways. These results combined with optimization suggest that it is possible to develop mechanical ventilation protocols to avoid lung injuries in patients. 相似文献
9.
Ueda T Niimi A Matsumoto H Takemura M Hirai T Yamaguchi M Matsuoka H Jinnai M Muro S Chin K Mishima M 《The Journal of allergy and clinical immunology》2006,118(5):1019-1025
BACKGROUND: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. OBJECTIVE: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. METHODS: Both lungs were scanned at full-inspiratory and full-expiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. RESULTS: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV(1)/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV(1)/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV(1) and FEV(1)/FVC) and peripheral airflow obstruction. CONCLUSION: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. CLINICAL IMPLICATIONS: Small airways are an important therapeutic target in asthma. 相似文献
10.
Verbanck S Schuermans D Paiva M Vincken W 《The Journal of allergy and clinical immunology》2006,118(2):340-346
BACKGROUND: The target of anti-inflammatory therapy in asthma is thought to be situated, at least partly, in the lung periphery, and inhaled steroid aerosols are being engineered to reach it. However, the potential effect of such aerosols cannot be fully evaluated by conventional lung function tests because these are insensitive to peripheral lung structure. OBJECTIVE: A prospective cohort study was conducted to investigate whether ultrafine steroid aerosols can elicit a response in the lung periphery, using a validated multibreath washout technique that can distinguish acinar from conductive lung zone function. METHODS: In 30 stable patients with asthma with a wide range of disease severity (FEV(1) 27% to 108% predicted), we assessed conductive and acinar airway function abnormality at baseline, with patients on a standard dry powder steroid aerosol and after switching them to an ultrafine steroid aerosol. RESULTS: Only in those patients with abnormal acinar airway function at baseline (n = 16) did acinar heterogeneity show a consistent improvement after switching to an ultrafine steroid aerosol; the improvement was also correlated with baseline acinar heterogeneity (r = -0.67; P = .007). Although all patients with asthma also presented conductive airway abnormality at baseline, no changes were observed in this lung zone with the switch to the ultrafine aerosol (P > .1). CONCLUSION: Among stable patients with asthma, those with acinar lung zone abnormality at baseline have the potential to receive functional benefit from an ultrafine steroid aerosol. Clinical studies comparing the efficacy of steroid aerosols targeted to the deep lung should at least include a measurement of peripheral lung zone function. CLINICAL IMPLICATIONS: A new noninvasive measure of small airways function reveals why, and for which particular patients with asthma, small steroid aerosol particles can be of therapeutic use. 相似文献
11.
Monfraix S Bayat S Porra L Berruyer G Nemoz C Thomlinson W Suortti P Sovijärvi AR 《Physics in medicine and biology》2005,50(1):1-11
The aim of this study was to assess the feasibility of a novel respiration-gated spiral synchrotron radiation computed tomography (SRCT) technique for direct quantification of absolute regional lung volumes, using stable xenon (Xe) gas as an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic x-ray beams was used to visualize and directly quantify inhaled Xe concentrations and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume measurements were validated using a hollow Xe-filled phantom. Spiral images spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20% O2 gas mixture, in two anaesthetized and mechanically ventilated rabbits at baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung sections were obtained at functional residual capacity (FRC) and at end-inspiration. 3D images showed large patchy filling defects in peripheral airways and alveoli following histamine provocation. Local specific lung compliance was calculated based on FRC/end-inspiration images in normal lung. This study demonstrates spiral SRCT as a new technique for direct determination of regional lung volume, offering possibilities for non-invasive investigation of regional lung function and mechanics, with a uniquely high spatial resolution. An example of non-uniform volume distribution in rabbit lung following histamine inhalation is presented. 相似文献
12.
This review discusses the history and current state of the art of the forced oscillation technique (FOT) to measure respiratory impedance. We focus on how the FOT and its interaction with models have emerged as a powerful method to extract out not only clinically relevant information, but also to advance insight on the mechanisms and structures responsible for human lung diseases, especially asthma. We will first provide a short history of FOT for basic clinical assessment either directly from the data or in concert with lumped element models to extract out specific effective properties. We then spend several sections on the more exciting recent advances of FOT to probe the relative importance of tissue versus airway changes in disease, the impact of the disease on heterogeneous lung function, and the relative importance of small airways via synthesis of FOT with imaging. Most recently, the FOT approach has been able to directly probe airway caliber in humans and the distinct airway properties of asthmatics that seem to be required for airway hyperresponsiveness. We introduce and discuss the mechanism and clinical implications of this approach, which may be substantial for treatment assessment. Finally, we highlight important future directions for the FOT, particularly its use to probe specific lung components (e.g., isolated airways, isolated airway smooth muscle, etc.) and relate such data to the whole lung. The intent is to substantially advance an integrated understanding of structure–function relationships in the lung. 相似文献
13.
The definition of asthma has evolved from that of an episodic disease characterized by reversible airways constriction to a chronic inflammatory disease of the airways, with at least partially reversible airway constriction. Increasing evidence supports the notion that small and large airways play a central role in asthma pathophysiology with regard to inflammation, remodeling and symptoms. The contribution of the distal airways to the asthma phenotype carries implications for the delivery of inhaled medications to the appropriate areas of the lung and for the monitoring of the response to asthma treatment. Asthma control is evaluated on the basis of symptoms, lung function and exacerbations. However, evidence suggests that dissociation between lung function and respiratory symptoms, quality of life and airway inflammation exists. In this study, common spirometric parameters offer limited information with regard to the peripheral airways, and it is therefore necessary to move beyond FEV1 . Several functional parameters and inflammatory markers, which are discussed in the present study, can be employed to evaluate distal lung function. In this study, extrafine formulations deliver inhaled drugs throughout the bronchial tree (both large and small airways) and are effective on parameters that directly or indirectly measure air trapping/airway closure. 相似文献
14.
Sensitivity analysis techniques are applied to two classic linear models of breathing mechanics to evaluate the expected accuracy
of the parameter estimates to be obtained in different experimental conditions. For this reason the characteristics of the
so-called indifference region have been studied, in which the objective function is not significantly affected by changes,
in the parameter values. A Mead type or a Otis type configuration was used to characterise the breathing mechanics by computer
simulation. For both models four different specific experiments have been simulated which correspond to two types of ventilation
(spontaneous breathing and mechanical ventilation) and to two different pathologies (obstructive lung disease and pulmonary
rigidness). The results obtained show that the use of the signals which are typical of mechanical ventilation allows very
accurate parameter estimates to be obtained in both cases. On the other hand, in spontaneous breathing the estimation of the
parameters is more critical, and in this case the Mead model is practically unusable whereas the Otis model supplies results
which are still acceptable, even if very sensitive to changes in pathology. 相似文献
15.
The utility of decellularized native tissues for tissue engineering has been widely demonstrated. Here, we examine the production of decellularized lung scaffolds from native rodent lung using two different techniques, principally defined by use of either the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) or sodium dodecyl sulfate (SDS). All viable cellular material is removed, including at least 99% of DNA. Histochemical staining and mechanical testing indicate that collagen and elastin are retained in the decellularized matrices with CHAPS-based decellularization, while SDS-based decellularization leads to loss of collagen and decline in mechanical strength. Quantitative assays confirm that most collagen is retained with CHAPS treatment but that about 80% of collagen is lost with SDS treatment. In contrast, for both detergent methods, at least 60% of elastin content is lost along with about 95% of native proteoglycan content. Mechanical testing of the decellularized scaffolds indicates that they are mechanically similar to native lung using CHAPS decellularization, including retained tensile strength and elastic behavior, demonstrating the importance of collagen and elastin in lung mechanics. With SDS decellularization, the mechanical integrity of scaffolds is significantly diminished with some loss of elastic function as well. Finally, a simple theoretical model of peripheral lung matrix mechanics is consonant with our experimental findings. This work demonstrates the feasibility of producing a decellularized lung scaffold that can be used to study lung matrix biology and mechanics, independent of the effects of cellular components. 相似文献
16.
Role of aquaporins in lung liquid physiology 总被引:7,自引:0,他引:7
Verkman AS 《Respiratory physiology & neurobiology》2007,159(3):324-330
Aquaporins (AQPs) are small, integral membrane proteins that facilitate water transport across cell membranes in response to osmotic gradients. Water transport across epithelia and endothelia in the peripheral lung and airways occurs during airway hydration, alveolar fluid transport and submucosal gland secretion. Several AQPs are expressed in the lung and airways: AQP1 in microvascular endothelia, AQP3 and AQP4 in airway epithelia, and AQP5 in type I alveolar epithelial cells, submucosal gland acini, and a subset of airway epithelial cells. Phenotype analysis of transgenic knockout mice lacking AQPs has defined their roles in the lung and airways. AQP1 and AQP5 provide the principal route for osmotically driven water transport between airspace and capillary compartments; however, alveolar fluid clearance in the neonatal and adult lung is not affected by their deletion, nor is lung fluid accumulation in experimental models of lung injury. In the airways, though AQP3 and AQP4 facilitate osmotic water transport, their deletion does not impair airway hydration, regulation of airway surface liquid, or fluid absorption. In contrast to these negative findings, AQP5 deletion in submucosal glands reduced fluid secretion by >50%. The substantially slower fluid transport in the lung compared to renal and secretory epithelia probably accounts for the lack of functional significance of AQPs in the lung and airways. Recent data outside of the lung implicating the involvement of AQPs in cell migration and proliferation suggests possible new roles for lung AQPs to be explored. 相似文献
17.
E. R. McFadden Jr. M.D. Nicholas A. Soter M.D. R. H. Ingram Jr. M.D. 《The Journal of allergy and clinical immunology》1980,66(6):472-477
In order to determine if there is a relationship among arterial histamine levels, state of disease activity, and the magnitude and site of obstruction in exercise-induced asthma, we recorded airway resistance, lung volumes, spirometry, and density dependence of maximum expiratory flow before and after an exercise challenge in 17 asymptomatic individuals. These observations were then related to the concentration of histamine in systemic arterial blood. This study demonstrates that those individuals whose disease process was the most active at the time of investigation had more depressed lung function and higher baseline histamine levels, and responded to the challenge with severe obstruction that involved the airways in the periphery of the lung. In contrast, those subjects whose underlying disease was more quiescent had lower histamine values and the response to provocation was less severe and predominated in the larger airways. In neither group did the postchallenge values for histamine increase. It is suggested that the factor that determines these patterns of response is the state of inflammation of the airways, for which histamine may serve as a marker. 相似文献
18.
Voltz JW Card JW Carey MA Degraff LM Ferguson CD Flake GP Bonner JC Korach KS Zeldin DC 《American journal of respiratory cell and molecular biology》2008,39(1):45-52
The roles of sex hormones as modulators of lung function and disease have received significant attention as differential sex responses to various lung insults have been recently reported. The present study used a bleomycin-induced pulmonary fibrosis model in C57BL/6 mice to examine potential sex differences in physiological and pathological outcomes. Endpoints measured included invasive lung function assessment, immunological response, lung collagen deposition, and a quantitative histological analysis of pulmonary fibrosis. Male mice had significantly higher basal static lung compliance than female mice (P < 0.05) and a more pronounced decline in static compliance after bleomycin administration when expressed as overall change or percentage of baseline change (P < 0.05). In contrast, there were no significant differences between the sexes in immune cell infiltration into the lung or in total lung collagen content after bleomycin. Total lung histopathology scores measured using the Ashcroft method did not differ between the sexes, while a quantitative histopathology scoring system designed to determine where within the lung the fibrosis occurred indicated a tendency toward more fibrosis immediately adjacent to airways in bleomycin-treated male versus female mice. Furthermore, castrated male mice exhibited a female-like response to bleomycin while female mice given exogenous androgen exhibited a male-like response. These data indicate that androgens play an exacerbating role in decreased lung function after bleomycin administration, and traditional measures of fibrosis may miss critical differences in lung function between the sexes. Sex differences should be carefully considered when designing and interpreting experimental models of pulmonary fibrosis in mice. 相似文献
19.
Dendritic cells in the respiratory tract 总被引:3,自引:0,他引:3
Studies from several laboratories on lung tissue samples from human and experimental animals have identified Ia+ cells with characteristic pleiomorphic (dendritic) morphology in the epithelium and underlying connective tissue, in both the conducting airways and in the distal lung. These dendritic cells (DC) are particularly prominent within the airway epithelium, forming a contiguous network equivalent to the Langerhans cells network of the epidermis. They may be readily concentrated from enzymatically disrupted respiratory tract tissue samples on the basis of their physical properties (notably non-adherence, lack of Fc-receptors and ultra-low density on percoll), and function as highly effective antigen presenting cells in vitro. Evidence is also accumulating that respiratory tract DC populations respond dynamically to local tissue inflammation, and as such may play a prominent role in immunoinflammatory disease processes in the airways and the distal lung. 相似文献
20.
Antonios Lalas Stavros Nousias Dimitrios Kikidis Aris Lalos Gerasimos Arvanitis Christos Sougles Konstantinos Moustakas Konstantinos Votis Sylvia Verbanck Omar Usmani Dimitrios Tzovaras 《BMC medical informatics and decision making》2017,17(3):173