18.1: Occurrence and Forms of Dyspnea

Introduction

Dyspnea is the clinical term for "shortness of breath." However, the term "dyspnea" no longer describes one sensation but likely includes at least three distinctive sensations associated with breathing that have separate underlying neural mechanisms. This chapter will give you an overview of these sensations and the potential clinical importance of being able to distinguish them.

It might be worth putting dyspnea in a clinical context. Like pain, dyspnea can occur across a number of pathological conditions. It is the cardinal symptom of lung disease, but it is highly prevalent in heart diseases as well—in fact it is a more common sign of myocardial infarction in women than the classical symptom of chest pain that is more prevalent in men.

Dyspnea is also a strong predictor of mortality in most heart and lung diseases. As well as cardiopulmonary conditions, dyspnea is also prevalent in other conditions that affect breathing or metabolism, and (see figure 18.1) it is prevalent during end-stage disease where it is as common as pain and forms a significant problem for end-of-life care. Despite its prevalence there are few options for treating this symptom. Unlike pain, there are no specific drugs to reduce this sensation.

Figure 18.1: Conditions that can produce dyspnea. ARDS: Acute respiratory distress syndrome.

Forms of Dyspnea

So now let us look at the distinguishable sensations that the term dyspnea encompasses and begin to understand how they differ neurologically (see figure 18.2).

Effort to breathe: The first form of dyspnea is the sensation of work or effort to breathe. The healthy individual is usually unaware of the effort they are putting into breathing until breathing is significantly increased, such as during exercise when ventilation and work of breathing rises. The sensation of the work or effort to breathe is not particularly uncomfortable. If you jogged down the street now you might become more aware of the effort to breathe, but are not disturbed by it.

So where does this sensation come from?

An increase in motor drive is required to activate more tension or movement in any skeletal muscle, including the respiratory muscles. And like other skeletal muscles, such as limb muscles, we believe that the sensation of effort comes from a perception of that increased motor drive. Sensory information from the activated muscles, in our case the respiratory muscles, is thought to generate the sensation of work.

Figure 18.2: Types of dyspnea.

Getting laboratory subjects to report work and effort separately is very difficult, so for our purposes right now, we are grouping what might be two sensations together as one.

Chest tightness: The next form of dyspnea is primarily reported by asthmatic patients during bronchoconstriction. Similar to the sensation of work and effort, tightness was originally thought to arise from the increase in respiratory muscle activity associated with a rise in resistive work of breathing. But in 2002 we showed that "tightness" was unrelated to respiratory effort by removing respiratory muscle activity of bronchoconstricted asthmatics with mechanical ventilation. When we did this, "tightness" persisted, despite the respiratory muscles being inactive. So what does cause tightness? The next best, but so far unproven, alternative is that inflammation of the airways associated with an asthma attack leads to activation of airway irritant (or rapidly adapting) receptors, the afferent activity from which is perceived centrally as tightness.

Air hunger: Air hunger is arguably the most complex and clinically important form. "Air hunger" is the sensation of suffocation and can be described as a "desperate urge to breathe." You may have experienced this sensation at the end of a prolonged breath-hold, and it is the unpleasantness of air hunger that made you resume breathing. "Air hunger" is a warning signal that ventilation is insufficient and blood gases are becoming deranged; given the immediate importance of maintaining constant blood gases, air hunger is perhaps our most important homeostatic signal, and it has been referred to as the "suffocation alarm." The mechanisms underlying air hunger are still unclear, but again, they were once thought to involve the respiratory muscle motor and sensory signals and detection of a disparity between them—that is, the brain perceived that the respiratory muscles were not achieving the work they had been commanded to do. This hypothesis was developed in the sixties and still persists in texts today; however, it is wrong. In two separate labs, one at Harvard University and the other in Australia, pulmonary physiologists completely paralyzed each other to remove all motor activity; when they inhaled carbon dioxide, they still felt air hungry, suggesting the respiratory muscle signals were not essential to generate air hunger. So where does air hunger come from?

We see air hunger arise when P_aCO₂ rises, when P_aO₂ falls, or when arterial pH decreases. These changes are detected by chemoreceptors that reflexly increase the drive to breathe from the brainstem. While we are not usually aware of our reflex breathing drive, we think that once this drive increases to a critical level, a signal is sent upward that is perceived as air hunger.

So any signals to the brainstem respiratory networks that increase the drive to breathe are likely to promote air hunger, and these influences may not all be chemical (see figure 18.3). For example, emotions such as anxiety increase the drive to breathe, and this is a pertinent point with clinical ramifications that we will return to.

Likewise, any influences that reduce the drive to breathe also have a tendency to reduce air hunger (see figure 18.3). Perhaps the most interesting example of this is the effect of pulmonary stretch receptor activity. Pulmonary stretch receptors are mechanoreceptors in the airways that respond to lung inflation. Although this pulmonary afferent activity is thought to have little effect on the control of breathing in man, it reduces the drive to breathe in other species as part of the Hering–Breuer reflex. What we see in humans is that lung inflation, and presumably an increase in pulmonary stretch receptor firing, profoundly reduces air hunger, even in the absence of any blood gas improvements.

Figure 18.3: The proposed neural mechanism of air hunger.

This is easy to demonstrate to yourself by holding your breath; during the breath-hold CO₂ will gradually accumulate in your bloodstream and you will feel a gradually increasing urge to breathe that will become increasingly more uncomfortable to a point when it is intolerable and you must begin breathing again. That first big breath you take does not return your arterial CO₂ to normal, but despite this you get great relief from air hunger by taking it, probably because that big breath stretched the lung and caused a rapid increase of stretch receptor activity to the brainstem.

Figure 18.4: Balance of pulmonary stretch receptors and chemoreceptor firing.

So air hunger is really affected by a balance of influences: those that increase the drive to breathe (such as hypercapnia and hypoxia) promote air hunger, while inhibitory influences on the drive to breathe tend to promote comfort (see figure 18.4).