High altitude pulmonary edema (HAPE) is the leading cause of death from altitude illness and rapid descent is often considered a life-saving foundation of therapy. Nevertheless, in the remote settings where HAPE often occurs, immediate descent sometimes places the victim and rescuers at risk. We treated 11 patients (7 Nepalese, 4 foreigners) for HAPE at the Himalayan Rescue Association clinic in Pheriche, Nepal (4240 m), from March 3 to May 14, 2006. Ten were admitted and primarily treated there. Seven of these (6 Nepalese, 1 foreigner) had serious to severe HAPE (Hultgren grades 3 or 4). Bed rest, oxygen, nifedipine, and acetazolamide were used for all patients. Sildenafil and salmeterol were used in most, but not all patients. The duration of stay was 31 +/- 16 h (range 12 to 48 h). Oxygen saturation was improved at discharge (84% +/- 1.7%) compared with admission (59% +/- 11%), as was ultrasound comet-tail score (11 +/- 4 at discharge vs. 33 +/- 8.6 at admission), a measure of pulmonary edema for which admission and discharge values were obtained in 7 patients. We conclude it is possible to treat even serious HAPE at 4240 m and discuss the significance of the predominance of Nepali patients seen in this series.

Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility.

The genes of the renin--angiotensin system (RAS) play an important role in the regulation of pulmonary vascular tone. Although studies on individual genes polymorphisms have reported association with high-altitude pulmonary oedema (HAPE), studies on multiple genes or epistasis are lacking. We therefore investigated the association of the RAS polymorphisms with HAPE. In a case-control design, we screened 163 HAPE-resistant/controls (HAPE-r) and 160 HAPEpatients (HAPE-p) of Indian origin for eight polymorphisms of four RAS genes, ACE, AGT, AGTR1 and AGTR2. Significant difference in genotype and allele frequencies of the ACE I/D and AGT M235T polymorphisms was observed between HAPE-p and HAPE-r (p< 0.05). In three-locus haplotype analysis of AGT the haplotype GTM was significantly higher in HAPE-p (29%) and haplotype GTT in HAPE-r (27%) after Bonferroni correction (p < 0.006). The differences were insignificant for polymorphisms from AGTR1 and AGTR2. The MDR (multifactor dimensional reduction) approach for gene--gene interaction depicted individual polymorphism M235T as the best disease predicting model (cross validation consistency, CVC = 10/10). We found a significant association of D allele of ACE and M allele of AGT with HAPE. The findings are supported at the haplotypic level as well as through nested genetic interaction between the RAS gene polymorphisms using the MDR approach.

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