Subclinical pulmonary dysfunction contributes to high altitude pulmonary edema susceptibility in healthy non-mountaineers.

HAPE susceptible (HAPE-S, had HAPE episode in past) subjects may have subclinical cardio-pulmonary dysfunction. We compared the results of pulmonary function tests in 25 healthy HAPE-S non-mountaineers and 19 matched HAPE resistant (HAPE-R, no HAPE episode in past). Acute normobaric hypoxia (FIo2 0.12) was administered at sea level to confirm hypoxia intolerance in HAPE-S. Unlike HAPE-R, HAPE-S subjects had elevated baseline and post-hypoxia systolic pulmonary arterial pressures (20.9 ± 3 vs 27.3 ± 5 mm Hg during normoxia and 26.2 ± 6 vs 45.44 ± 10 mm Hg during hypoxia, HAPE-R vs HAPE-S). Forced vital capacity (FVC) and single breath alveolar volume (SBVA) were significantly lower in HAPE-S compared to HAPE-R (FVC: 4.33 ± 0.5 vs 4.6 ± 0.4; SBVA: 5.17 ± 1 vs 5.6 ± 1 Lt; HAPE-S vs HAPE-R). Two subgroups with abnormal pulmonary function could be identified within HAPE-S; HAPE-S1 (n = 4) showed DLCO>140% of predicted, suggestive of asthma and HAPE-S2 (n = 12) showed restrictive pattern. Each of these patterns have previously been linked to early small airway disease and may additionally represent a lower cross-sectional area of the pulmonary vascular bed, related to lower lung volumes. HAPE susceptibility in healthy non-mountaineers may be related to sub-clinical pulmonary pathology that limits compensatory rise in ventilation and pulmonary circulation during hypoxic stress.

Raised HIF1α during normoxia in high altitude pulmonary edema susceptible non-mountaineers.

High altitude pulmonary edema (HAPE) susceptibility is associated with EGLN1 polymorphisms, we hypothesized that HAPE-susceptible (HAPE-S, had HAPE episode in past) subjects may exhibit abnormal HIF1α levels in normoxic conditions. We measured HIF1α levels in HAPE-S and HAPE resistant (HAPE-R, no HAPE episode) individuals with similar pulmonary functions. Hemodynamic responses were also measured before and after normobaric hypoxia (Fi02 = 0.12 for 30 min duration at sea level) in both groups. . HIF1α was higher in HAPE-S (320.3 ± 267.5 vs 58.75 ± 33.88 pg/ml, P < 0.05) than HAPE-R, at baseline, despite no significant difference in baseline oxygen saturations (97.7 ± 1.7% and 98.8 ± 0.7). As expected, HAPE-S showed an exaggerated increase in pulmonary artery pressure (27.9 ± 6 vs 19.3 ± 3.7 mm Hg, P < 0.05) and a fall in peripheral oxygen saturation (66.9 ± 11.7 vs 78.7 ± 3.8%, P < 0.05), when exposed to hypoxia. HIF1α levels at baseline could accurately classify members of the two groups (AUC = 0.87). In a subset of the groups where hemoglobin fractions were additionally measured to understand the cause of elevated hypoxic response at baseline, two of four HAPE-S subjects showed reduced HbA. In conclusion, HIF 1 α levels during normoxia may represent an important marker for determination of HAPE susceptibility.

Hypoxia-Induced Inflammatory Chemokines in Subjects with a History of High-Altitude Pulmonary Edema.

High altitude hypoxia is known to induce an inflammatory response in immune cells. Hypoxia induced inflammatory chemokines may contribute to the development of high altitude pulmonary edema (HAPE) by causing damage to the lung endothelial cells and thereby capillary leakage. In the present study, we were interested to know whether chronic inflammation may contribute to HAPE susceptibility. We examined the serum levels of macrophage inflammatory protein-1α (MIP-1α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 in group (1) HAPE Susceptible subjects (n = 20) who had past history of HAPE and group (2) Control (n = 18) consist of subjects who had stayed at high altitude for 2 years without any history of HAPE. The data obtained confirmed that circulating MCP-1, MIP-1α were significantly upregulated in HAPE-S individuals as compared to the controls suggestive of chronic inflammation. However, it is not certain whether chronic inflammation is cause or consequence of previous episode of HAPE. The moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence of enhanced level of inflammatory chemokines found in this study support the hypothesis that subjects with past history of HAPE have higher baseline chronic inflammation which may contribute to HAPE susceptibility.

Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers.

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.

Long-term stay at low altitude (1,200 m) promotes better hypoxia adaptation and performance.

Acute exposure to high altitude hypoxia is known to decrease physical performance. The exercise performance increases during moderate altitude training (2000-3000 m) but benefits are overshadowed by adverse effect associated with hypoxia. Therefore, the study was designed to address whether low altitude of 1200 m could increase exercise performance without any adverse effects and a correlation with stay period (stay > 6 month) was optimized. In the present study residents of lower altitude (1200 m altitude) (LA) and sea level (SL) residents were subjected to sub-maximal exercise test and their exercise response in terms of post-exercise heart rate and change in oxygen saturation was compared. Post-exercise peak heart rate (129.89 ± 13.42 vs 146.00 ± 11.81, p < 0.05) was significantly lower and arterial oxygen saturation (SpO2) after exercise had a significant fall (95.3 ± 2.26% vs 98 ± 0% p < 0.001) in LA residents. The hematological parameters like hemoglobin (Hb) and hematocrit (Hct) taken as markers of physiological adaptation, were also found to be significantly higher in LA as compared to SL residents (Hb 16.13 ± 0.70 vs 14.2 ± 0.87, p < 0.001 and Hct 47.4 ± ?2.08 vs 44.0 ± ?0.72, p <0.001). Overall, the study highlights that physiological adaptation at 1200 m results into a better exercise response and hematological benefit compared to sea level residents.