Emphysema and Mechanical Stress-Induced Lung Remodeling

Suki, Bélâ; Sato, Susumu; Parameswaran, Harikrishnan; Szabari, Margit V.; Takahashi, Ayuko; Bartolák‐Suki, Erzsébet

doi:10.1152/physiol.00041.2013

Cited by 64 publications

(60 citation statements)

References 69 publications

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“…27 Standard computed tomography (CT) images of the thorax are useful clinically, however CT does not afford the necessary resolution to be able to characterize the structure and composition of the terminal airway and therefore does not yield information regarding tissue stretch or strain. 21,28 Micro-CT has been used to investigate the lung microstructure and quantify alveolar surface area, density, and volume. However, the resolution decreases with increasing sample thickness and the technique has a lower resolution than standard histopathology such that very thin alveolar septae may not be visible.…”

Section: Discussionmentioning

confidence: 99%

Airway Pressure Release Ventilation Reduces Conducting Airway Micro-Strain in Lung Injury

Kollisch-Singule

Emr

Smith

et al. 2014

Journal of the American College of Surgeons

120

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BACKGROUND Improper mechanical ventilation can exacerbate acute lung damage causing a secondary ventilator induced lung injury (VILI). We hypothesize that VILI can be reduced by modifying specific components of the ventilation waveform (mechanical breath) and studied the impact of airway pressure release ventilation (APRV) and controlled mandatory ventilation (CMV) on the lung micro-anatomy (alveoli and conducting airways). The distribution of gas during inspiration and expiration and the strain generated during mechanical ventilation in the micro-anatomy (micro-strain) were calculated. STUDY DESIGN Rats were anesthetized, surgically prepared and randomized into one uninjured Control group (n=2) and four groups with lung injury: 1)APRV 75% (n=2)–time at expiration (TLow) set to terminate appropriately at 75% of Peak Expiratory Flow Rate (PEFR); 2)APRV 10% (n=2)-TLow set to terminate inappropriately at 10% of PEFR; 3)CMV with PEEP 5cmH2O (PEEP 5;n=2) or 4)PEEP 16cmH2O (PEEP 16;n=2). Lung injury was induced in the experimental groups by Tween lavage and ventilated with their respective settings. Lungs were fixed at peak inspiration and end expiration for standard histology. Conducting airway and alveolar air space areas were quantified and conducting airway micro-strain calculated. RESULTS All lung injury groups redistributed inspired gas away from alveoli into the conducting airways. APRV 75% minimized gas redistribution and micro-strain in the conducting airways and provided the alveolar air space occupancy most similar to Control at both inspiration and expiration. CONCLUSIONS In an injured lung, APRV 75% maintained micro-anatomical gas distribution similar to that of the normal lung. The lung protection demonstrated in previous studies using APRV 75% may be due to a more homogeneous distribution of gas at the micro-anatomical level as well as a reduction in conducting airway micro-strain.

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Section: Discussionmentioning

confidence: 99%

Airway Pressure Release Ventilation Reduces Conducting Airway Micro-Strain in Lung Injury

Kollisch-Singule

Emr

Smith

et al. 2014

Journal of the American College of Surgeons

120

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“…(Gadkowski and Stout, 2008), primary cancer (Byers et al, 1984), and metastasis (Yanar et al, 2014), or even the presence of chronic obstructive pulmonary disease (COPD) due to the induction of emphysema (Suki et al, 2013). …”

Section: The Upper Lobes and Tropism For Tbmentioning

confidence: 99%

The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis

Cardona

2015

Front. Microbiol.

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A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed.

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“…Several disease conditions in the lung are associated with progressive ECM deposition or destruction and corresponding alterations in lung mechanics, including idiopathic pulmonary fibrosis (IPF), in which progressive fibrotic scarring is associated with decreases in lung compliance (1,2), and emphysema, in which destruction of elastic fibers is associated with increases in compliance (3). Recent evidence indicates that alterations in the matrix may shift resident cell functions in ways that promote disease progression rather than homeostasis (4,5).…”

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confidence: 99%

Matrix, Mesenchyme, and Mechanotransduction

Tschumperlin

2015

Annals ATS

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The extracellular matrix (ECM) of the lung serves as both a scaffold for resident cells and a mechanical support for respiratory function. The ECM is deposited during development and undergoes continuous turnover and maintenance during organ growth and homeostasis. Cells of the mesenchyme, including the tissue resident fibroblast, take a leading role in depositing and organizing the matrix and do so in an anatomically distinct fashion, with differing composition, organization, and mechanical properties within the airways, vessels, and alveoli of the lung. Recent technological advancements have allowed the lung's ECM biochemical composition and mechanical properties to be studied with improved resolution, thereby identifying novel disease-related changes in ECM characteristics. In parallel, efforts to study cells seeded on normal and disease-derived matrices have illustrated the powerful role the ECM can play in altering key functions of lung resident cells. The mechanical properties of the matrix have been identified as an important modifier of cell-matrix adhesions, with matrices of pathologic stiffness promoting profibrotic signaling and cell function. Ongoing work is identifying both mechanically activated pathways in mesenchymal cells and diseaserelated ECM molecules that biochemically regulate cell function. Uncovering the control systems by which cells respond to and regulate the matrix, and the failures in these systems that underlie aberrant repair, remains a major challenge. Progress in this area will be an essential element in efforts to engineer functional lung tissue for regenerative approaches and will be key to identifying new therapeutic strategies for lung diseases characterized by disturbed matrix architecture.

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Emphysema and Mechanical Stress-Induced Lung Remodeling

Cited by 64 publications

References 69 publications

Airway Pressure Release Ventilation Reduces Conducting Airway Micro-Strain in Lung Injury

Airway Pressure Release Ventilation Reduces Conducting Airway Micro-Strain in Lung Injury

The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis

Matrix, Mesenchyme, and Mechanotransduction

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