Role of Airway Recruitment and Derecruitment in Lung Injury

Abstract

The mechanical forces generated during the ventilation of patients with acute lung injury causes significant lung damage and inflammation. Low-volume ventilation protocols are commonly used to prevent stretch-related injury that occurs at high lung volumes. However, the cyclic closure and reopening of pulmonary airways at low lung volumes, i.e., derecruitment and recruitment, also causes significant lung damage and inflammation. In this review, we provide an overview of how biomedical engineering techniques are being used to elucidate the complex physiological and biomechanical mechanisms responsible for cellular injury during recruitment/derecruitment. We focus on the development of multiscale, multiphysics computational models of cell deformation and injury during airway reopening. These models, and the corresponding in vitro experiments, have been used to both elucidate the basic mechanisms responsible for recruitment/derecruitment injury and to develop alternative therapies that make the epithelium more resistant to injury. For example, models and experiments indicate that fluidization of the cytoskeleton is cytoprotective and that changes in cytoskeletal structure and cell mechanics can be used to mitigate the mechanotransduction of oscillatory pressure into inflammatory signaling. The continued application of biomedical engineering techniques to the problem of recruitment/derecruitment injury may therefore lead to novel and more effective therapies.

Cuffed vs. uncuffed tracheal tubes in children: a randomised controlled trial comparing leak, tidal volume and complications

“…Without accurate tidal volume monitoring, lung protective strategies become difficult. It is suggested that a cyclical process of recruitment and atelectasis may contribute to lung inflammation . However, evidence is lacking about whether there are advantages from ventilation with cuffed TT in children due to leak minimisation.…”

Influence of airway wall compliance on epithelial cell injury and adhesion during interfacial flows

“…VILI is a major source of trauma in intensive care units, and it is well established that interfacial flows during the reopening of collapsed pulmonary airways contribute to cellular injury during ventilation (24). Although previous studies have used rigid-walled in vitro systems to investigate how interfacial flows influence cell injury patterns (3,30,35,47,48), lung tissue is highly compliant, and many clinical disorders are characterized by changes in lung/airway wall compliance (32,41).…”

“…In addition to volutrauma, the cyclic collapse and reopening of fluid-occluded lung regions can also result in significant damage known as atelectrauma (24). Under these conditions, the closure and reopening of fluid-filled airways generates interfacial and microbubble flows that can significantly damage the lung epithelium.…”

Computational Analysis of Microbubble Flows in Bifurcating Airways: Role of Gravity, Inertia, and Surface Tension

“…However, during the acute respiratory distress syndrome (ARDS), bacterial/viral infections lead to disruption of the alveolar-capillary barrier and fluid-occlusion of pulmonary air ways [1][2][3]. This severely compromises gas transport within the lung and results in severe hypoxia and high mortality rates [4].…”

“…During ventilation, the cyclic closure and reopening of fluidfilled pulmonary airways leads to microbubble flows which are a significant source of cellular injury and inflammation [2,10]. The physics of microbubble flows has been studied for many decades.…”