Assessment of peripheral lung mechanics

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Abstract

The mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. In this review we examine the various experimental techniques that have provided data pertaining to the mechanical properties of the lung periphery, together with the mathematical models that have been used to interpret these data. These models seek to make a clear distinction between the central and peripheral compartments of the lung by encapsulating functional differences between the conducing airways, the terminal airways and the parenchyma. Such a distinction becomes problematic in disease, however, because of the inevitable onset of regional variations in mechanical behavior throughout the lung. Accordingly, lung models are used both in the inverse sense as vehicles for extracting physiological insight from experimental data, and in the forward sense as virtual laboratories for the testing of specific hypothesis about mechanisms such as the effects of regional heterogeneities. Pathologies such as asthma, acute lung injury and emphysema can alter the mechanical properties of the lung periphery through the direct alteration of intrinsic tissue mechanics, the development of regional heterogeneities in mechanical function, and the complete derecruitment of airspaces due to airway closure and alveolar collapse. We are now beginning to decipher the relative contributions of these various factors to pathological alterations in peripheral lung mechanics, which may eventually lead to the development and assessment of novel therapies.

Introduction

The structure of the lung has evolved to be uniquely suited for gas exchange, which of course is its primary function. A particular feature of the lung's specialized structure is the enormous surface area of the bloodā€“gas barrier, necessary because the transfer of oxygen and carbon dioxide between blood and alveolus takes place by passive diffusion. Blood and air are delivered to this huge diffusive interface via a system of branching conduits that begin with single conduits, the pulmonary artery and trachea, respectively, each having a cross-sectional area of only a few square centimeters in humans. The sequential branching of the vascular and airway trees, however, eventually results in a set of parallel conduits numerous enough to have a combined area of many square meters (West, 2004). In the case of the airway tree, this extreme change in cross-section is associated with a change in the dominant physical processes involved in gas transport, from convective to diffusive as one moves distally into the lung. There is also a change in physiological function; the majority of the airway tree is involved only in the bulk transport of gas, while gas exchange with the blood occurs only at the very end of the tree. These various features make it natural, and often useful, to consider the lung as having two distinct regions, central and peripheral.

Of course, a little thought shows that subdividing a very complicated organ such as the lung into two disparate regions can be problematic. The concept of central and peripheral regions might mesh well with the commonly invoked model of the lung as a single-compartment model served by a single airway, but reality is not nearly so simple. A key question is where to place the border between the central and distal regions. Should this border be defined anatomically or functionally? Is there even a definable border at all, given that the progression from conducting airway to respiratory zone (a region bordered by alveoli) is gradual? These issues become even more confusing in disease when the lung is likely to develop substantial regional differences in its structure and mechanical properties, invoking the concept of a multi-compartment system consisting of a collection of parallel balloon-and-pipe models connecting in parallel to a common central airway. Under these conditions, the distinction between the central and peripheral lung becomes blurred to the point that it becomes useful only to think of the periphery as being some region subtended by a sufficiently distal branch of the airway tree, yet it remains an important issue because all major lung diseases, such as asthma and emphysema, involve the lung parenchyma and small airways.

Our understanding of peripheral lung mechanics is thus not solely determined by the development of novel experimental techniques to study pressureā€“flow relationships in individual segments of the lung. As noted in a previous review (Bates and Lutchen, 2005), interpreting the mechanical data provided by these techniques has required the development of mathematical/computational models based on anatomical information from three-dimensional imaging modalities. In this review we examine the history of these methods and how they have brought us to our current understanding of lung peripheral mechanics.

Section snippets

The retrograde catheter

The first direct investigations of the lung periphery were provided by the retrograde catheter, introduced by Macklem and Mead in 1967. These investigators pulled a thin flexible catheter along the airways and out through a hole in the parenchyma until its flared end became wedged in a small airway (Fig. 1). By measuring the pressure at the other end of the catheter during ventilation of the lung, they were able to determine that most of the flow resistance of the normal airway tree was located

Probing peripheral lung mechanics indirectly

As is evident from the above discussion, most of the techniques developed for studying peripheral lung mechanics are highly invasive, and many suffer from severe sampling limitations. For these reasons, and because of the need to develop methods for probing the global mechanical properties of the lung periphery that can be applied in human patients, recent investigations have resorted to the analysis of pressure and flow signals measured at the airway opening. In principle, such signals can be

Asthma

Asthma is a complex disease defined on the basis of its symptoms, and which affects a large fraction of the population in developed countries (Masoli et al., 2004). A hallmark feature of asthma is airways hyperresponsiveness, defined as an abnormally pronounced decrement in lung function elicited by challenge with a standard dose of a smooth muscle agonist such as methacholine. This bronchoconstrictor response is also reversible by administration of a bronchodilator such as albuterol. Despite

Conclusions

It is clear that the mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. Understanding the precise role of the lung periphery, however, must be undertaken in the context of mathematical models of the lung that encapsulate functional differences between the conducing airways, the terminal airways and the parenchyma, because disease is invariably accompanied by the onset of regional variations in mechanical behavior

Acknowledgements

This work was supported by the National Heart, Lung, and Blood Institute Grants HL-59215, HL-67273, HL-75593 and HL-87788 and the Centers of Biomedical Research Excellence Grant P20 RR15557 from the National Center for Research Resources.

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