Control of ventilation in COPD and lung injury

Abstract

Breathing occurs in single breaths and in patterns which are altered by the onset, progression and resolution of respiratory diseases. Through modulations of rate, depth, and patterning of breathing, the ventilatory control system maintains numerous critical variables within their homeostatic ranges. A dynamic respiratory control system is critical to successful adaptation in the face of progressive pulmonary pathology. The objective of this review, is to illustrate functional changes and compensatory mechanisms which occur with the onset and progression of acute and chronic lung disease. Chronic obstructive pulmonary disease (COPD) will be considered as a model of a slowly progressive pulmonary process, where destruction of lung parenchyma and airway obstruction leads to hypoxemia and hypercapnia. Over time, adaptations of the respiratory control system to this disease include changes in the intrinsic properties of respiratory muscles, chemoreceptor signaling, and central respiratory drive which increase motor output to the respiratory muscles. In contrast, acute respiratory distress syndrome (ARDS) is an exemplar of an acute pulmonary process. The result of severe lung injury, ARDS is characterized by lung infiltrates, rapidly progressive hypoxemic respiratory failure, and possible progression to pulmonary fibrosis. Changes in breathing patterns result from these functional changes, as well as altered processing of afferent feedback by the central controller, possibly influenced by brainstem inflammation. Taken together, these disease models highlight the plasticity of the respiratory control system in response to the development and progression of lung disease.