Results

LENGTH-TENSION INAPPROPRIATENESS

Figure 3 shows the relation between the factors ΔPtot and ΔVt for the two subgroups. There is a tendency towards a smaller slope in the group with CO₂ retention which indicates more length-tension inappropriateness in this group than in the group with no CO₂ retention. However, the analysis of covariance showed no significant relation between ΔVt and ΔPtot in the total group (β₂), nor in the two subgroups (β₃, table 5). When no length-tension inappropriateness is present a relationship between ΔVt and ΔPtot is expected, so we assume that in all these patients some length-tension inappropriateness is present but the magnitude of it is larger in the group with CO₂ retention.

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Figure 3

Graphical expression of ΔPtot against ΔVt for both subgroups of patients. The slopes of each line are an indication of length-tension inappropriateness. According to the analysis of covariance, no relation was found between Ptot and Vt, nor was there a significant difference in one group compared with the other. This might indicate that length-tension inappropriateness is present in both groups, but there is a tendency towards a lesser magnitude in the group without CO₂retention.

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Table 5

Relation between change in tidal volume (Vt) and change in pressure swing (Ptot) by analysis of covariance for the total group

Discussion

The aim of this study was to asses whether perception of dyspnoea during exercise was related to the chemical drive, the load on the inspiratory or expiratory muscles, or a combination or interaction of these parameters. We therefore investigated a group of patients with a wide range of severity of obstructive pulmonary disease. A subdivision was made between patients with or without CO₂ retention during exercise in order to distinguish between the effects of mechanical ventilatory loads and mechanical loads accompanied by a “chemical load” on the sensation of exertional dyspnoea, and to assess whether the sensations that lead to dyspnoea were qualitatively different in the two subgroups.

The results have shown that, in the total group and the group without CO₂ retention, a significant correlation existed between the Borg score for dyspnoea and the increase in time tension index for the inspiratory muscles. In the CO₂ retention group a significant correlation was seen between the Borg score for dyspnoea and ΔPaco ₂. Analysis of covariance showed that a significant relationship only existed in the group with CO₂ retention—that is, between the change in Paco ₂ and change in dyspnoea score. This was also confirmed by the multiple regression analysis. Moreover, there was no relationship between ΔPtot and ΔVt in the total group nor in either subgroup, which may indicate the presence of length-tension inappropriateness. The slope of this relationship tended to be smaller in the group with CO₂ retention which means that the magnitude of this inappropriateness is larger in the group with CO₂ retention than in those without.

It is questionable whether the two subgroups are, indeed, different from a pulmonary point of view, with different dyspnogenic mechanisms. CO₂ retention can be seen as an indication of ventilatory limitation.13-15 The group with CO₂ retention might therefore be considered as a group of subjects with ventilatory limitation, although it is debatable whether CO₂ retention is the same as ventilatory limitation. The question is whether subjects are really limited by the increase in Paco ₂ (a consequence of ventilatory limitation) or whether they would not go further because they simply did not want to. Looking at the ventilatory data at rest it can be seen that the CO₂ retention group had a ventilation of 25%MVV whereas the group without CO₂ retention had a ventilation of 13%. During exercise ventilation increased to 89.6% in the CO₂retention group and to 73.9% in the group without CO₂retention. This indicates that the CO₂ retention group reached almost maximal ventilation, which is hard to continue for a long time, so it seems that ventilatory limitation is indeed nearly reached. Furthermore, the increase in Paco ₂ (a consequence of ventilatory insufficiency) was the only factor that was significantly related to the change in dyspnoea score, which is one of the most important limiting factors in exercise in these patients. We therefore consider that the increase in Paco ₂was a true limiting factor and, as such, these subjects had a ventilatory limitation. In this ventilatory limited group the mechanisms that produce dyspnoea might indeed be qualitatively different from those in the group without CO₂ retention.

It is noteworthy that there is no correlation between dyspnoea and ventilation related indices. Other studies have shown highly significant correlations within subjects for these indices.10 ,25-27 It must be emphasised that, in this study, analysis has been done on differences between resting values and values at Wmax within the subgroups which might explain the absence of clear correlations. Furthermore, the measured oesophageal pressures are a better representation of the ventilatory effort than the actual ventilation since they were less modified by the mechanics of the respiratory system, although we are aware that oesophageal pressures are only a surrogate of the real inspiratory and expiratory activity. Nevertheless, the results of this study confirm the multifactorial aspect of the model of dyspnoea, with different stimuli contributing differently in various situations.2 ,3 ,8 ,28In normocapnic exercise in patients with obstructive pulmonary disease the sensation of dyspnoea seems to be mainly determined by the mechanical load on both groups of respiratory muscles and the ensuing length-tension inappropriateness. However, when patients become hypercapnic this chemical stimulus seems to override the perception of mechanical load and the hypercapnia becomes the main determinant of the sensation of dyspnoea.

The fact that muscular effort and other mechanical indices contribute to the sensation of dyspnoea has been found by several other studies, both in normal subjects and in patients.10 ,16 ,29 ,30 In contrast, some other studies found no relationship between mechanical load on the ventilatory muscles and the sensation of dyspnoea.11 The role of chemical sensation is more controversial. The additional dyspnogenic effect of Paco ₂ found in this study was also seen by Chonan et al 12 who hypothesised that an additional effect caused by afferent chemoreceptor inputs accentuates the difficulty in breathing. He confirmed this hypothesis by inducing hypercapnia in healthy subjects during exercise. In patients with ventilatory limitation who develop hypercapnia during exercise this phenomenon should also be present. Our results confirm this theory. In contrast, Kobayashiet al 31 found that hypercapnia had no additional dyspnogenic effect during a hypercapnic ventilatory response which was also seen by Clague et al. 32 Interestingly, Kobayashiet al also found a dyspnogenic effect of hypoxia during a hypoxic ventilatory response which occurred during moderate hypoxia (desaturation to 80%). Peripheral chemoreceptors normally respond to hypoxia only at very low levels of Pao ₂; the relationship between afferent impulse activity and Pao ₂ is hyperbolic. We therefore assumed that only increases in Paco ₂ act as dyspnogenic stimuli from chemical origin during exercise, which is confirmed in our study. Gandevia et al 6 studied the isolated effect of Paco ₂ which turned out to be a potent stimulus for dyspnoea. Although these findings appear to be inconsistent, we may at least conclude that the chemical drive does, indeed, play a part in the perception of dyspnoea. The precise mechanisms underlying the individual stimuli and the interactions between them need to be investigated further.

Furthermore, our results have shown that in the two subgroups with airflow limitation of different severity the perceived dyspnoea at Wmax is almost equal. This agrees with the findings of Killianet al 33 who found that the average subject stops exercise when either dyspnoea or leg effort reaches an intensity of approximately 7, regardless of whether they are normal subjects or patients with airflow limitation. Patients in both subgroups of our study stopped exercise when the dyspnoea intensity reached a Borg score of about 6, although the sensory inputs turned out to be quite different in the two groups. This dyspnoea score apparently does not discriminate between the type of stimulus responsible for the sensation of dyspnoea, which might be a consequence of what question was asked before selecting a number on the Borg scale. Some studies have shown that dyspnoea can be evoked by other sensations and that subjects are able to distinguish these.23 ,34 ,35Other studies have shown that, despite the fact that subjects can distinguish sensory sensations, they scored the same intensity on scales with different definitions of dyspnoea, based on qualitatively different inputs.26 ,36 Madoret al concluded that patients were unable to distinguish respiratory effort from respiratory discomfort when forced to make rapid decisions during incremental exercise, which suggests that the two different scales used were measuring a common element. Because most subjects name their experienced sensations “breathlessness” or “dyspnoea” despite the fact that different stimuli might have led to this perception of dyspnoea, we chose to ask for the effort of breathing, indicating breathlessness. We hoped that the assessed correlations between the different sensations and dyspnoea would give more insight into which stimuli give the general sensation of breathlessness.

As shown in fig 1, there are many inputs that may contribute to the sensation of dyspnoea. In this study we measured most of these inputs or indicators for them. One factor that we did not measure was the magnitude of hyperinflation which is also thought to be an important stimulus for the dyspnoea sensation.16 Nevertheless, we think that we measured enough mechanical and chemical parameters to get a good indication of these two groups of stimuli. In this study it seems that the load on the ventilatory muscles is one of the important factors that correlated with the sensation of dyspnoea in the group without CO₂ retention, whereas in the group with CO₂ retention an increase in Paco ₂seems to be the most important stimulus. The therapeutic consequence of this concept of dyspnoea may be that improving the strength of respiratory muscles by respiratory muscle training will lead to lower values for TTIi, TTIe, Ptot, and Paco ₂ during exercise, and subsequently to lower dyspnoea. When we know more about the effects of these single triggers it might be possible to say more about the multifactorial aspect of dyspnoea. Studying the effects of individual (isolated) stimuli is important, but might lead to paradoxical findings. Clague et al found no relation between the isolated CO₂ stimuli and dyspnoea sensation, whereas in our study and that of Chonanet al an additional dyspnogenic effect of CO₂ on top of mechanical stimuli was found. Both the role of isolated stimuli and of their interactions must therefore be studied further to achieve a better understanding of the mechanisms that produce dyspnoea. When we know more about this aspect of dyspnoea we may be able to determine what treatment is needed. For instance, training of isolated muscle groups might produce less CO₂than training more groups of muscles. Furthermore, training with negative work loads leads to a lesser production of CO₂also. Finally, inspiratory muscle training might result in better ventilation during exercise which may result in better exhalation of CO₂.