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Highland population (HA) from the Andes, living above 3000 m, have a blunted ventilatory response to increasing hypoxia, breathe less compared to acclimatized newcomers, but more, compared to sea-level natives at sea level. Subjects with chronic mountain sickness (CMS) breathe like sea-level natives and have excessive erythrocytosis (EE). The respiratory stimulation that arises through the peripheral chemoreflex is modestly less in the CMS group when compared with the HA group at the same P(ET(O2)). With regard to CO(2) sensitivity, CMS subjects seem to have reset their central CO(2) chemoreceptors to operate around the sea-level resting P(ET(CO2)). Acetazolamide, an acidifying drug that increases the chemosensitivity of regions in the brain stem that contain CO(2)/H(+) sensitive neurons, partially reverses this phenomenon, thus, providing CMS subjects with the possibility to have high CO(2) changes, despite small changes in ventilation. However, the same type of adjustments of the breathing pattern established for Andeans has not been found necessarily in Asian humans and/or domestic animals nor in the various high altitude species studied. The differing time frames of exposure to hypoxia among the populations, as well as the reversibility of the different components of the respiratory process at sea level, provide key concepts concerning the importance of time at high altitude in the evolution of an appropriate breathing pattern.

We studied residents of high altitude in Ladakh, India, to determine the effects of altitude, age, gender, and ethnicity on gas exchange and pulmonary function. Physical examinations, including pulse oximetry, hemoglobin concentration, end-tidal PCO2, and pulmonary function, were conducted on resting Ladakhi and Tibetan subjects at altitudes of 3300, 4200, and 4500 m. A total of 574 men and women, ranging in age from 17 to 82, were studied. At 3300 m, Ladakhis had higher heart rates than Tibetans in both genders and higher PETCO2 in women. Above 4000 m, 21 of the 141 men studied (15%) had Hb concentrations higher than 20 g/dL, with one confirmed case of Monge's disease. There was no gender difference in SaO2 at any altitude except for pregnant women. At 4600 m, Tibetans had significantly higher peak flows and lower PETCO2 than Ladakhis. Ladakhi men had higher diastolic BP than women (91 vs. 81), with no difference in systolic BP. There was no gender difference in BP for Tibetans. An important spirometry finding for both groups was high air flows, with mid-maximal expiratory flow (MMEF) at 130% to 150% of predicted values, compared with 85% for sojourner controls, and FEV1/FVC at 115%, compared with sojourner controls at 98%. Improved lung mechanics may be an important adaptation to the lifelong sustained increase in resting ventilation as well as to indoor biomass smoke and outdoor dust exposure of these populations at high altitude.