Physiologic factors predisposing to chronic respiratory failure.

V(A)/Q mismatching and load/capacity imbalance are the major physiologic determinants of chronic respiratory failure. The former underlies lung failure and the consequent development of hypoxemia. The latter causes chronic ventilatory failure and hypercapnia. This is the consequence of an inefficient breathing pattern with lower VT and higher respiratory rate, probably due to the "wise choice" of preventing excessive inspiratory effort and eventually respiratory muscle fatigue. In many disorders, V(A)/Q mismatching and the load/capacity imbalance coexist, particularly in COPD, where the interplay between the two pathophysiologically represents the advanced stage of the disease. In other disorders, one of the two mechanisms prevails; for example, V(A)/Q mismatching in pure lung diseases, and chest wall mechanics in thoracic disorders. This has important therapeutic implications because oxygen administration can relieve hypoxemia, whereas mechanical ventilation can prevent excessive hypercapnia and respiratory acidosis. Although the role of oxygen therapy is well established, the role of chronic mechanical ventilation is still a matter of debate, particularly in COPD. A major task for future research is to achieve the best possible understanding of the pathophysiologic factors predisposing to chronic ventilatory failure, to prevent the progression of the respiratory diseases to the stage when chronic respiratory failure eventually develops.