The pathophysiology of breathlessness as it relates to neurological disease

The pathophysiology of breathlessness is described more fully in Chapter 1. While it is clear that multiple pathophysiological mechanisms are involved, some aspects of the complex mechanisms that control breathing and induce breathlessness are more critical for patients with neurological disease. Of the four main pathophysiological processes involved (increased afferent input from chemoreceptors, increased afferent input from upper airway and pulmonary receptors, increased sense of respiratory effort, and afferent mismatch), it is the increased sense of respiratory effort and the afferent mismatch that are key factors in neurological disease.

In patients with disorders such as amyotrophic lateral sclerosis or myasthenia gravis, the mechanical properties of the respiratory system maybe normal, but the weakened respiratory muscles require greater neural drive for activation.3 This has been demonstrated in patients with myasthenia gravis, who show greater electromyography activity, and higher airway pressures, as compared to controls.4 This greater neural drive increases sense of respiratory effort, and hence induces dyspnoea. The sense of effort is related to the ratio of the pressure generated by respiratory muscles to the maximum pressure-generating capacity of those muscles.5 Whenever there is muscle weakness, fatigue or paralysis, the maximum pressure-generating capacity is reduced, which increases the central motor command to the respiratory muscles, raises the sense of respiratory effort, and so induces dyspnoea. The greater neural drive may also add to 'mismatch' between the outgoing motor command, and incoming afferent information. It is as if the brain almost 'expects' a certain pattern of ventilation and afferent feedback according to particular circumstances, and 'mismatch' occurs when the expected and the actual patterns do not coincide. This mismatch further contributes to the sensation of dyspnoea.

Respiratory muscle weakness is a very frequent finding in neurological disease, and contributes directly to the increased sense of respiratory effort, as weak muscles need more neural drive to produce the required effect, as described above. Respiratory muscle weakness is also associated with an increased risk of respiratory infection, which complicates and further compromises respiratory function.

The general debility associated with many neurological diseases is likely to add to respiratory muscle weakness, although evidence for the role of debility in respiratory muscle weakness stems in part from non-neurological conditions. For example, in COPD patients it has been clearly shown that respiratory muscle strength is closely associated with body weight and lean body mass.6

ASSESSMENT OF BREATHLESSNESS IN NEUROLOGICAL DISEASE | 101

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