Proteinase Imbalance versus Biomechanical Stress in Pulmonary Emphysema

Stehbens, William E.

doi:10.1006/exmp.2000.2307

Cited by 8 publications

(4 citation statements)

References 85 publications

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“…Although recent interest has focused on the cellular and molecular mechanisms contributing to emphysema, the study of lung mechanical stresses, one of the earliest postulated causes of emphysema (1), has received less attention. Weakened lung parenchyma is more likely to fracture during respiratory stress, and coalescence of a few alveoli can increase stress on adjacent units in a way that favors formation of large, localized cysts similar to the pattern seen in patients with advanced emphysema (2)(3)(4).…”

Section: Physiologic Basis For Impairment With Emphysemamentioning

confidence: 91%

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

Fessler¹,

Scharf²,

Ingenito³

et al. 2008

Proceedings of the American Thoracic Society

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It is not readily apparent how pulmonary function could be improved by resecting portions of the lung in patients with emphysema. In emphysema, elevation in residual volume relative to total lung capacity reduces forced expiratory volumes, increases inspiratory effort, and impairs inspiratory muscle mechanics. Lung volume reduction surgery (LVRS) better matches the size of the lungs to the size of the thorax containing them. This restores forced expiratory volumes and the mechanical advantage of the inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by cysts to be reclaimed by more normal lung. Newer, bronchoscopic methods for lung volume reduction seek to achieve similar ends by causing localized atelectasis, but may be hindered by the low collateral resistance of emphysematous lung. Understanding of the mechanisms of improved function after LVRS can help select patients more likely to benefit from this approach.Keywords: lung mechanics; emphysema surgery; lung recoil; airflow limitation; respiratory muscles PHYSIOLOGIC BASIS FOR IMPAIRMENT WITH EMPHYSEMAInflammatory changes associated with chronic obstructive pulmonary disease (COPD) initiate the changes in lung mechanical properties that characterize emphysema. Inflammation leads to destruction of elastin, which contributes to lung elasticity, and collagen, which provides tensile strength. Although recent interest has focused on the cellular and molecular mechanisms contributing to emphysema, the study of lung mechanical stresses, one of the earliest postulated causes of emphysema (1), has received less attention. Weakened lung parenchyma is more likely to fracture during respiratory stress, and coalescence of a few alveoli can increase stress on adjacent units in a way that favors formation of large, localized cysts similar to the pattern seen in patients with advanced emphysema (2-4). Effects of Emphysema on Expiratory FlowThese sequelae of inflammation ultimately decrease lung elastic recoil and small airway caliber, contributing to characteristic airflow limitation. The three classic determinants of expiratory flow limitation are lung elastic recoil, the propensity for airways to close, and airway resistance (5). Loss of elastic recoil in emphysema decreases the upstream pressure that drives expiratory flow, thereby decreasing maximal flows at any lung volume. Loss of elastic recoil also increases the unstressed volume of the lung (the volume remaining when elastic recoil is zero). Loss of radial traction on airways from lung parenchyma contributes to airway closure at higher lung volumes (increased trapped volume) because a higher transmural pressure is required to maintain airway patency. In addition, airway caliber at any lung volume is decreased (6). Coexisting small airway inflammation and fibrosis further increase airway resistance (7,8). These changes collectively reduce the rate of lung emptying.The rate of lung emptying may be expressed as its time constant, the time necessary for approximately 63% o...

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Section: Physiologic Basis For Impairment With Emphysemamentioning

confidence: 91%

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

Fessler¹,

Scharf²,

Ingenito³

et al. 2008

Proceedings of the American Thoracic Society

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“…It has been suggested that mechanical factors should contribute to disease progression 40 as measured by a decline in forced expiratory volume in 1 s (FEV1) 41 or by changes in the properties of low attenuation areas (LAA) in computed tomography (CT) images. 42 In fact, mechanical force-based tissue destruction serves as an organizing principle that can help explain how the various, apparently different, molecular mechanisms ultimately generate progressive airspace enlargement.…”

Section: Pulmonary Emphysemamentioning

confidence: 99%

Emergent Structure-Function Relations in Emphysema and Asthma

Winkler

Suki

2011

Crit Rev Biomed Eng

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Structure-function relationships in the respiratory system are often a result of the emergence self-organized patterns or behaviors that are characteristic of certain respiratory diseases. Proper description of such self-organized behavior requires network models that include nonlinear interactions among different parts of the system. This review focuses on 2 models that exhibit self-organized behavior: a network model of the lung parenchyma during the progression of emphysema that is driven by mechanical force-induced breakdown, and an integrative model of bronchoconstriction in asthma that describes interactions among airways within the bronchial tree. Both models suggest that the transition from normal to pathologic states is a nonlinear process that includes a tipping point beyond which interactions among the system components are reinforced by positive feedback, further promoting the progression of pathologic changes. In emphysema, the progressive destruction of tissue is irreversible, while in asthma, it is possible to recover from a severe bronchoconstriction. These concepts may have implications for pulmonary medicine. Specifically, we suggest that structure–function relationships emerging from network behavior across multiple scales should be taken into account when the efficacy of novel treatments or drug therapy is evaluated. Multiscale, computational, network models will play a major role in this endeavor.

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“…CS-induced emphysema is frequently associated with either an imbalance in proteinase and antiproteinase production or an increased oxidative status (Stehbens, 2000). However, the precise role of antioxidant enzymes in CS exposure-induced oxidative stress remains uncertain, and only a few studies address the association between the activities of these enzymes and oxidative status (Baskaran et al, 1999;Valenca et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Long-term exposure to cigarette smoke impairs lung function and increases HMGB-1 expression in mice

Bezerra

Valença

Pires

et al. 2011

Respiratory Physiology & Neurobiology

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Cigarette smoke (CS)-induced emphysema is caused by a continuous inflammatory response in the lower respiratory tract. The development of the condition is believed to be mediated by oxidant-antioxidant imbalance. This paper describes the effects of long-term CS exposure on alveolar cell recruitment, antioxidant defense systems, activity of extracellular matrix metalloelastases, expression of metalloelastase MMP-12, and high mobility group box-1 protein (HMGB-1). Ten C57Bl/6 mice were exposed to 12 cigarettes-a-day for 60 consecutive days, while 10 control animals were exposed to ambient air. After sacrifice, bronchoalveolar lavage fluid (BALF) was removed, and lung tissue underwent biochemical and histological analyses. In CS-exposed animals influx of alveolar macrophages and neutrophils into BALF, lung static elastance, and expression of MMP-12 and HMGB-1 were significantly increased while the activity of antioxidant enzyme was significantly reduced in comparison with control group. Thus, we demonstrated for the first time that long-term CS exposure decreased antioxidant defenses concomitantly with impaired lung function, which was associated with HMGB-1 expression.

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Proteinase Imbalance versus Biomechanical Stress in Pulmonary Emphysema

Cited by 8 publications

References 85 publications

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

Emergent Structure-Function Relations in Emphysema and Asthma

Long-term exposure to cigarette smoke impairs lung function and increases HMGB-1 expression in mice

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