These results demonstrate the influence of changes in lung volume on apnoea severity and sleep architecture in OSA patients during non‐REM sleep. When EELV was increased the AHI, arousal index, and oxygen desaturation index all decreased significantly. Moreover, “light sleep”, as measured by the percentage of stage 1 and beta power, decreased when EELV was increased.
Previous animal and human studies suggest that the mechanism underlying these results is probably an increase in upper airway stiffness and size with increased lung volume due to caudal traction on the pharyngeal airway. Studies in normal adults (without OSA) have shown that, during wakefulness and sleep, changes in lung volume result in important variations in upper airway mechanics.
15,16,17,18 Moreover, pharyngeal airway size as measured by CT scanning
19,20 or acoustic reflection
21 increases with lung inflation and decreases at lower lung volume. Lastly, it has been shown that patients with OSA have greater lung volume related dependence of upper airway size than non‐apnoeic individuals both in men
20 and women.
21,22Because the subjects we studied were overweight or obese (like most patients with OSA), we suspect that their diaphragm was pushed upwards (cranially) when lying on their back. The negative extrathoracic pressure applied in the lung almost certainly pulled the diaphragm and trachea to a more caudal position, thereby increasing the traction on the upper airway and making it less collapsible. Other authors have found that the AHI can be considerably reduced when obese OSA patients sleep in a semi‐recumbent position,
23 which probably corroborates this hypothesis. In the present study there was also a trend toward a correlation between the extent of the reduction in AHI between baseline and LV2 and the BMI (correlation coefficient
=
0.53, p
=
0.077). This suggests that increases in lung volume may have a greater effect in more obese patients.
Another possibility is that an increase in EELV led to an overall increase in the Sao2 due to improved ventilation/perfusion matching that could lead to decreased Sao2 fluctuations. This reduction in chemical stimuli fluctuations may have stabilised respiratory control, decreasing the risk of cyclic breathing.
A previous study from our group showed that lung volume has an important effect on the CPAP level required to prevent upper airway flow limitation, which suggests that increments in lung volume may be one of the mechanisms by which CPAP eliminates disordered breathing during sleep. In the present study we have shown that an increase in lung volume alone (without CPAP) is able to decrease the apnoea and hypopnoea frequency significantly, which supports this hypothesis. The rest of the effect of CPAP is probably due to a splinting effect of positive airway pressure on the upper airway, maintaining a positive transmural pressure throughout the respiratory cycle.
Séries
et al conducted a study in which the EELV was increased by 500 ml during sleep in OSA subjects.
24,25 They observed a decrease in the severity of oxygen desaturation which is confirmed by our results. However, in contrast to our results, they found no effect on sleep structure and a non‐significant decrease in AHI when EELV was increased, despite studying their subjects for a longer period of time in each condition. There are several possible explanations for this discrepancy. Firstly, we induced a larger increase in lung volume (770 and 1300 ml compared with 500 ml) which probably achieved a greater traction on the trachea and on the upper airway. Secondly, we did not use the same technique to measure the changes in lung volume. Séries
et al determined the negative pressure required to induce a 500 ml increase in lung volume while awake and then applied this negative pressure during the night. It is possible that there were behavioural influences during the awake manoeuvre. In our study we constantly monitored the lung volume during sleep to be sure that the increase in lung volume was maintained during the night; this may have allowed us to achieve a more precise and constant increase in lung volume. Thirdly, the population we studied had 90.7% obstructive apnoeas at baseline (7.9% mixed and 1.4% central apnoea) whereas the subjects studied by Séries
et al had only 56.3% obstructive apnoeas (36.8% mixed and 6.9% central apnoea), even though the definition of central and mixed apnoea may have evolved between 1989 and 2005. It is therefore possible that upper airway mechanics was the main cause of sleep apnoea in our population, and that instability of respiratory control made a greater contribution to apnoea in the population studied by Séries
et al. Indeed, one of our subjects who had 14% central sleep apnoeas at baseline had an increase in time spent in apnoea when EELV was increased, despite the fact that the AHI decreased and Sa
o2 improved. It is possible that, for a subset of sleep apnoea patients with a high ventilatory instability, an increase in lung volume could trigger a “Hering Breuer” reflex inhibiting inspiration and thus extending the time in apnoea. Finally, our population was probably more obese (mean BMI 34.9) than that studied by Séries
et al (124% of ideal body weight). This could have induced a more important effect of increased lung volume in our study because the diaphragm of obese patients is pushed more rostrally by abdominal fat than in less obese patients. However, further work will be needed to define which subgroups of patients with sleep apnoea respond best to changes in lung volume.
There was a significant decrease in AHI between baseline and both LV1 and LV2, but the decrease in AHI between LV1 and LV2 did not reach significance and some patients even had a higher AHI at LV2 than at LV1. This may be due either to a ceiling effect on AHI of increasing EELV or to arousals secondary to the discomfort of higher negative pressure in the iron lung which could have induced some respiratory instability in these patients.
There are several limitations to this study. Firstly, because the subjects were studied only during supine non‐REM sleep, these results may not apply to other body positions or to REM sleep. The supine posture is usually the position in which the greatest respiratory disturbances are recorded, possibly in part due to abdominal fat applying pressure on the diaphragm leading to decreased lung volume and decreasing the traction on the upper airway by the trachea. If this assumption is correct, it is possible that, when subjects lie on their side or are prone, the effect of negative extrathoracic pressure would be smaller.
Secondly, while Séries et al studied their subjects for the whole night in each of the two conditions (baseline, +500 ml EELV), we studied our subjects for 1 hour in each of the three different conditions (baseline, +770 ml, +1300 ml). However, with our sample size (12 subjects) we had 80% power to detect a difference of 4 (3) events per hour between the three conditions using an ANOVA. Moreover, this design gave us homogeneous data collected in the exact same conditions during the same night. In addition, the randomisation of the order of the conditions prevented a “time of the night” bias. Thus, although this is a potential problem, we doubt it influenced our results.
Finally, a direct effect of the iron lung negative pressure on the neck and upper airway cannot be completely excluded. A decrease in the pressure around the neck when lung volume was increased could have “unloaded” the upper airway making it less collapsible. However, when the pressure in the iron lung was decreased, the webbing forming the seal around the neck was shifted inside the chamber which would only further decrease the neck area potentially exposed to the negative pressure in the lung. We therefore doubt that this contributed to the reduction in sleep disordered breathing
In summary, these results show that an increase in lung volume causes a decrease in sleep disordered breathing and improves sleep architecture in patients with sleep apnoea during non‐REM sleep. Although an iron lung may well be more cumbersome than nasal CPAP therapy, our data suggest that increments in lung volume may be one of the mechanisms by which sleep disordered breathing is improved by CPAP. Thus, increased lung volume could be a direct therapeutic target for patients with sleep apnoea using, for example, an expiratory resistance as suggested by Mahadevia
et al.
26