My opponents argue most climbers develop interstitial edema based on changes in various pulmonary function parameters and lung-imaging modalities, all of which can be interpreted reasonably as consistent with edema formation. I have tried in my discussion of these alterations and the lack of consistency between studies to seek equally plausible factors, such as hypocapnia, mild respiratory muscle weakness, and simply the heavy exercise that evoke very similar changes. The fine work of Dr. Miserocchi on the lung interstitium and biochemical changes with hypoxia obtained in eucapnic, anesthetized ventilated animals with 12% oxygen gives us insight into the early sequence of events in interstitial fluid accumulation with critical hypoxic and/or hydrostatic stress, but may not be fully applicable to conscious, hyperventilating and hypocapnic climbers. Even if interstitial fluid formation increases with greater filtration during hypoxic (or normoxic) exercise, this does not mean that interstitial fluid necessarily increases to the same degree. Fluid clearance by active lymphatic pumping (not observed in anesthetized animals; Drake et al., 1991) and hyperventilation acting to wick lymphatic fluid toward the mediastinum (Staub, 1974, Koizumi et al., 2001) may limit fluid accumulation. Although hypoxia quite beyond that experienced by climbers (Po2 10 to 15 mmHg) increases endothelial cell permeability in vitro (Ogawa et al., 1990), increased sympathetic tone in vivo with β-adrenergic, receptor-mediated cAMP elevation strengthens the endothelium (Allen and Coleman, 1995; Yan et al., 1997). Results with two other methods are cited that find changes consistent with interstitial edema. The first is the ultrasonic lung comet score in Himalayan trekkers, but with no correlation to pulmonary artery systolic pressure (Pratali et al., 2010). Although very interesting, ultrasonography has not been rigorously tested in situations where lung fluid may only be slightly increased, but only in severely edematous states: acute lung injury (Jambrik et al., 2010), heart failure (Agricola et al., 2005), or HAPE (Fagenholz et al., 2007). In the original data from cardiac patients by Agricola ans colleagues (2005), the comet score can vary from almost zero to over 20 with very modest increases in lung water measured by thermodilution. Restricting the analysis to those with less than 750 mL of extravascular lung water (normal is <500 mL), there is no correlation with scores below 20. Another study used high-frequency forced oscillation and showed increases in resistance–reactance in climbers, but not those exposed to an equivalent hypoxia in a hypobaric chamber (Fasano et al., 2007). The influence of hypocapnia was not considered, but there is a similar magnitude of change in resting, normoxic, hypocapnic subjects (Twort et al., 1985).
Although my opponents are careful to describe the mild interstitial edema they believe to occur in nearly all climbers as “paraphysiological,” rather than pathological, many others nonetheless consider mild interstitial edema tantamount to impending HAPE. This is the undertone of references to this otherwise healthy state of affairs in many reviews of HAPE and lung function at high altitude. For instance, in the most-cited paper by Cremona and colleagues (2002), the authors conclude ominously that at altitude “the healthy human lung is on the edge of failure in terms of fluid balance.” As is the case in such pro–con debates, the truth is likely somewhere in the middle. But to which side it falls (few or most climbers), we agree it will require more precise measurements of lung water in the mountains than heretofore performed.
