In Response to ACE I/D Polymorphism and HAPE by Bhagi et al

To the Editor:

We read with profound interest the article titled “Positive Association of D Allele of ACE Gene With High Altitude Pulmonary Edema in Indian Population” by Bhagi et al. ¹ In this study, a total of 154 unrelated Indian lowlanders were acutely introduced to high altitude (HA) at Leh (>3500 m) during a period of approximately 2 years. It is apparent that 79 of these 154 subjects experienced high altitude pulmonary edema (HAPE) within 48 to 72 hours after ascent to HA ¹ while they were undergoing altitude-dependent acclimatization like the control group. Interestingly, subjects from both groups were staying in a controlled environment in terms of medical facilities during the period of acclimatization, but subjects who had HAPE were not started on medication or given oxygen supplementation until they were admitted to the hospital. It is likely that much discussion and deliberation must have taken place before this study protocol was approved by the institutional ethics committee of the Defence Institute of Physiology and Allied Sciences.

The authors also examined the possible association of gene polymorphisms of renin-angiotensin-aldosterone system pathways with arterial oxygen saturation (Sao₂) levels. However, the clinical significance of the use of Sao₂ for the diagnosis of HAPE remains obscure, predominantly because of the variability seen in its values in response to descent and supplemental oxygen. A significant amount of these variations in Sao₂ is likely to occur during evacuation from remote locations to medical facilities. Sao₂ is not part of the diagnostic criteria for HAPE as presented by the Lake Louise consensus. ² HAPE is diagnosed by the presence of at least 2 of these symptoms—dyspnea at rest, cough, weakness or decreased exercise performance, and chest tightness or congestion—and at least 2 of these signs—rales or wheezing in at least 1 lung field, central cyanosis, tachypnea, and tachycardia—in the setting of a recent gain of altitude. ² It would have been interesting had the authors also studied the association between the alleles of the ACE gene and other physiological parameters (such as heart rate and respiratory rate) included in the Lake Louise criteria for HAPE. This would have probably given a more comprehensive association of gene polymorphisms of renin-angiotensin-aldosterone system pathways with HAPE. ²

The authors concluded that the D/D genotype of the ACE gene appears to be associated with an increased risk of HAPE in an Indian population. The practical applications of these findings remain challenging, especially because HAPE is a disease with a very low incidence. ³ Apte et al ³ reported an incidence of HAPE of 0.31% in Indian male lowlanders after acute ascent (by air) to an altitude of 3400 m in the western Himalayas. Moreover, the incidence of HAPE and other HA-related illnesses can be reduced by following an altitude-dependent acclimatization schedule ³ ; therefore, it would be more cost-effective to disseminate the information about the importance of acclimatization in the population rather than using the outcome of this study as a screening tool for early identification of HAPE-susceptible individuals in the community.