ABSTRACT
This chapter examines combination therapies that simultaneously target
different aspects of lung injury pathophysiology to achieve additivity or
synergy in clinical efficacy. Interactive basic and clinical research on such
therapies is necessary, since it is not feasible todefine themechanisms, activity,
interactions, and efficacyof all relevant agents and interventions in human studies alone. Design, analysis, and other issues that impact clinical trials inves-
tigating combination therapies in severely ill patients are detailed and
discussed in the first part of the chapter. Coverage then focuses primarily on
agents and interventions of potential utility in combination therapies for clin-
ical acute lung injury (ALI) and the acute respiratory distress syndrome
(ARDS).Agents and interventions forboth theacute exudative phase and later
fibroproliferative phase ofALI=ARDS are described. Examples of pharmacologic agents for treating acute exudative lung injury include vasoactive agents and antithrombotics to improve perfusion, exogenous surfactants to improve
ventilation, and anti-inflammatory antibodies, receptor antagonists or antiox-
idants to antagonize overexuberant inflammation. Selected modalities or
strategies of mechanical ventilation and alveolar recruitment for use in
combination therapies forALI=ARDSare also covered, as are pharmacologic
agents relevant for treating fibroproliferative injury pathology. Many of these
agents and interventions have been discussed individually in Chapters 13-17,
and several have been shown tohave benefits in patientswith lung injury.How-
ever, their impact on survival and long-term patient outcomes may be
improved by combination therapy approaches.
