Treatment of Acute Lung Injury

Current and Emerging Pharmacological Therapies

Rob Mac Sweeney; Mark Griffiths; Danny McAuley

Disclosures

Semin Respir Crit Care Med. 2013;34(4):487-498. 

In This Article

Abstract and Introduction

Abstract

As a syndrome of injurious pulmonary inflammation resulting in deranged respiratory physiology, acute lung injury affords numerous potential therapeutic targets. Two main pharmacological treatment strategies have arisen—the attempted inhibition of excessive inflammation or the manipulation of the resulting physiological derangement causing respiratory failure. Additionally, such interventions may allow the delivery of less injurious mechanical ventilation. An emerging approach is the use of cell-based therapy, which, rather than inhibiting the inflammatory process, seeks to convert it from an injurious process to a reparative one. This review outlines previous, current, and emerging pharmacological therapies for acute lung injury.

Introduction

Acute lung injury (ALI) results from the development of excessive pulmonary inflammation consequential to an initial injury, which may be pulmonary or extrapulmonary in origin.[1] Although primary specific therapy aimed at the underlying cause is crucial for the resolution of critical illness, the various physiological and pathological derangements occurring during ALI provide multiple opportunities for pharmacological intervention in the natural history of this syndrome (Fig. 1). As an inflammatory pulmonary condition, many drug trials have attempted to inhibit the inflammatory cascade at various points. More recently, with the advent of cell-based therapy, focus has changed from preventing injurious inflammation to redirecting it to a reparative state. As well as the modulation of inflammation, the physiological alveolar processes of ventilation, perfusion, and gaseous diffusion have all been the subject of pharmacological intervention. This article provides an overview of previous and current clinical studies of pharmacotherapies investigated in ALI and highlights some promising potential therapies currently at early clinical or late preclinical stages of development.

Figure 1.

Pathological changes in acute lung injury providing multiple pharmacological targets for intervention.

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