Abstract
Imaging
Almost all negative imaging studies reported were performed at altitudes below 4500 m, the altitude at which Cremona and colleagues (2002) found the indirect signs of extra vascular lung fluid accumulation, that is, the increase in closing volume (CV). Therefore, we think that all the imaging studies cited by Swenson are not valuable for this debate. Only Synder and colleagues (2006) performed a study at a comparable, but simulated, altitude. A possible explanation for their negative result could be either the different experimental setting or the possible concomitant presence of airway trapping, which could reduce lung density; the lack of a specific test for small-airways involvement does not allow confirmation. Therefore, this study also does not confirm the con hypothesis.
Respiratory Function
We agree with Swenson that one should move beyond spirometry because other factors can be implied in its changes, for example, in VC reduction. The problem of CV remains: we do not think that the increase in CV might be caused by exhaustive exercise; subjects rested for at least 1 h before the test (Cremona et al., 2002). And CV was still increased after 24-h rest at the same altitude (Senn et al., 2006). Further, in the Cremona study, the CV was significantly higher in subjects with radiological and clinical evidence of interstitial edema, and it is hard to concede that these subjects developed a more severe bronchial obstruction!
In the second part of his article, Swenson reports studies in which no impairment in exercise capacity was found in the presence of interstitial edema. We share the idea that lung interstitial edema may develop also at sea level during strenuous exercise when cardiac output and pulmonary vascular recruitment are maximal. In fact, this point was taken as proof that the lung is intrinsically very resistant to developing alveolar edema owing to the extreme rigidity of the extracellular matrix structure (Miserocchi et al., 1993). These results agree with the opinion that interstitial edema is present in healthy climbers and is not predictive of alveolar edema.
Finally, we wish to point out that the lack of correlation between arterial pulmonary pressure and changes in both respiratory function (Senn et al., 2006) and imaging (Pratali et al., 2010) poses the critical, still unsolved question to identify causes and effects between the vasomotor reflex and interstitial edema.
Our view is that interstitial edema, representing the physiological response to increased microvascular permeability, does occur in all subjects; in some of them the perturbation of lung water becomes directly or indirectly appreciable and, fortunately, only in a small percentage of people it evolves toward severe edema. We wish to stress the concept that interstitial edema represents a “critical narrow edge”: as shown by experimental animal models, “severe” lung edema occurs within minutes through an “accelerated” phase when the loss of integrity of the interstitial matrix proceeds beyond a critical threshold (Miserocchi et al., 2001). New promising techniques such as forced oscillation technique (FOT) could highlight the development of interstitial edema in both animal (Dallac à et al., 2008) and human studies (Pellegrino et al., 2010). Further research is certainly needed to find sensible, early predictive markers of this critical transition phase.
Up to now there is no evidence that a prophylactic treatment is needed, but this could be definitively confirmed only with appropriate studies.