Life Expectancy at Altitude Depends on Which Disease You Have

Ezzati et al. (2011) examined the association with altitude of life expectancy and mortality from selected diseases using data from the National Elevation Dataset, National Center for Heath Statistics, and US Census. Counties above 1500 m had longer life expectancies than those within 100 m of sea level by 1.2–3.6 years for men and 0.5–2.5 years for women. Altitude had a beneficial association with ischemic heart disease (IHD) mortality and harmful association with chronic obstructive pulmonary disease (COPD), with a dose-response relationship. IHD mortality above 1000 m was 4–14 per 10,000 people lower than within 100 m of sea level; COPD mortality was higher by 3–4 per 10,000. The adjusted associations for stroke and cancers were not significantly different. Living at higher altitude may have a protective effect on IHD but a harmful effect on COPD.

Perceived Exertion of Chest and Leg Muscle in Hypoxic Work

Aliverti et al. (2011) compared power outputs to the perceived exertion for respiratory (RPE,resp) and leg (RPE,legs) muscles during incremental cycle exercise at sea level (SL) and high altitude (HA, 4559 m). Respiratory power output was calculated from breath-by-breath esophageal pressure and chest wall volume changes. RPE,resp scaled equally with total respiratory power output at SL and HA, while RPE,legs increased more at HA than at SL at each work rate. The authors conclude that RPE,resp uniquely relates to respiratory power output, while RPE,legs varies depending on muscle metabolic conditions.

Work Rate Limitations at Everest Base Camp

Factors contributing to the profile of work rate limitation in hypoxia at the Pyramid were examined in detail in 6 subjects performing cycle ergometry to the limit of tolerance, at which breathing reserve (estimated maximum voluntary ventilation minus end-exercise ventilation) approached zero with near-maximal dyspnea levels (Valli et al., 2011). Both the position and the shape of the hyperbolic relationship of power to the maximum tolerable time were reduced at HA compared to SL, considered to be consequent, in part, to reductions of muscle perfusion and oxygen delivery resulting from diversion of blood flow to respiratory muscles at the much higher ventilation at altitude.

Lung Diffusing Capacity at Everest Base Camp

Diffusing capacity of the lung includes alveolar membrane resistance and the red cell concentration and resistance. After two weeks at 5400 m, Everest Base Camp, Agostoni et al. (2011) report a small increase in lung diffusing capacity from 23.6±4.4 ml/min/mmHg to 25.1±5.3, but when normalized for alveolar volume (V_A) and pulmonary capillary volume (V_C) the increase of Dm, membrane diffusing capacity, rose 47%, from 10.9±5.2 ml/min/mmHg/L at sea level rising to 16.0±9.2 (p<0.01) at altitude. In 1965 Kreutzer and van Lookeren Campagne found no change in Dm after a week at 4560 m altitude, and in 1972 Weiskopf and Severinghaus reported a significant 20% decrease at 2–3 days at 4342 m, normalized to 60 torr PetO₂. Agostoni writes (May 25, 2011), “I have performed recently experiments at Capanna Regina Margherita (4600 m) after acute high altitude exposure and found in this setting a reduction of DL_CO and DM as you found. The data in our recent paper showed an increase of DL_CO which, in my opinion, is due to a different time exposure at altitude.”

Effects of Acetazolamide and Dexamethasone on Cerebral Hemodynamics in Hypoxia

Subudhi et al. (2011) investigated the effects of two drugs known to reduce symptoms of AMS (acute mountain sickness) to determine if cerebral hemodynamic hypoxic responses could explain the prophylactic effect. 20 healthy volunteers were given oral acetazolamide (250 mg), dexamethasone (4 mg), or placebo every 8 h for 24 h prior to and during a 10-h exposure to a simulated altitude of 4875 m in a hypobaric chamber, which included 2 h of exercise at 50% of altitude-specific Vo_2max. Cerebral hemodynamic parameters (autoregulation index, vasomotor reactivity, conductance index and vascular resistance) were derived from ultrasound recording of middle cerebral artery velocity, arterial pressure and response to increased Pco₂, before and after 9 h of hypoxia. Both drugs prevented AMS in those who became ill on placebo (LL score >3). None of the cerebral hemodynamic responses correlated with AMS.

Brain Natriuretic Peptide (BNP) Elevated in Trekkers with Acute Mountain Sickness (AMS)

AMS is associated with a relative failure of the natriuresis and diuresis that occurs at HA (high altitude). In 23 trekkers, mean BNP (pg/ml) was <7 at sea level, and unchanged at 3400 m and 4300 m. After reaching Everest base camp (5400 m) and descending to 5150 m, BMP mean was 17.7±5.1 in all, 21±8.6 in those with AMS (Lake Louise score 3.3±0.5) but 11.8±3.5 in 4 without AMS (LL 0.75±0.5). In 4 with LL ≥6, BNP mean was 24.6±9.3 (p=0.147). This is the first report to demonstrate a significant rise in BNP with exercise at HA (Woods et al., 2011).

In Repeated Exposure to Altitude, Acute Mountain Sickness (AMS) Recurs in Adults but Not in Children

Rexhaj et al. (2011) arranged a prospective controlled study in 27 children and 29 adults to learn whether AMS is likely to recur with repeat sojourn to altitude (3450 m, 9–12 mo apart). In adults, AMS recurred in 14 of the 18 adults but in no other adults, while none of the 6 children with AMS the first time had recurrences but 4 others developed AMS the second time. They conclude that prophylaxis is not appropriate in children with AMS history.

Spironolactone Useless in Acute Mountain Sickness (AMS) Prophylaxis

Because several small studies found spironolactone (S) helpful at altitude, Basnyat et al. (2011) mounted a double blind control study in comparison with acetazolamide (A) and a placebo (P) among 251 trekkers recruited at 4300 m and tested at 5000 m on the Everest Base Camp trek. Each received 3 doses of 50 mg S, 250 mg A or P. AMS incidence was 29% with S, 20% with P, and only 10.5% with A while Sp_O2 (at 5000 m) averaged 83% with A and 80% with either P or S.

Comparing a Visual Analog Scale and Self Reported Lake Louise Score

In an effort to simplify scaling acute mountain sickness (AMS), Van Roo et al. (2011) obtained data using both a new visual analog method and the self-reported Lake Louise score from 66 completed forms among 127 consenting volunteers. 77% developed AMS, with 48.5% being severe (LL >5). The authors found more scatter but similar linearity with VAS, and conclude that LLself remains the gold standard.

Angiotensin-Converting Enzyme (ACE) Allele D Correlates with High Altitude Pulmonary Edema (HAPE)

Using meta-analysis of 305 reported cases of HAPE and 662 controls, Qi et al. (2011) report a 1.55 fold greater probability of developing HAPE on ascent to altitude in subjects with the ACE D allele (p=0.004).

Genetic Differences in Susceptibility to High Altitude Pulmonary Edema

It is known that the genes of the renin-angiotensin system (RAS) affect pulmonary vascular tone. Stobdan et al. (2011) screened 163 HAPE-resistant/controls (HAPE-r) and 160 HAPE-patients (HAPE-p) of Indian origin for eight polymorphisms of four RAS genes, ACE, AGT, AGTR1, and AGTR2. HAPE-p subjects had significant differences in genotype and allele frequencies of the ACE I/D and AGT M235T polymorphisms. The haplotype GTM was significantly higher in HAPE-p (29%) and haplotype GTT was more common in HAPE-r (27%). Polymorphism M235T was the best predictor of HAPE susceptibility. The D allele of ACE and M allele of AGT also correlated with HAPE.

Exhaled NO Reduction at High Altitude Not Major Contributor to Hypoxic Pulmonary Vasoconstriction

In 11 healthy adults, exhaled NO fell at altitude to half the control value while pulmonary arterial pressure rose from 22.7 to 39.1 mmHg. However, the authors were not able to establish that this relationship was causative (Donnelly et al., 2011).

Hypoxic Pulmonary Vasoconstriction Not Mediated by Catechols

By measuring central venous and arterial epinephrine and norepinephrine levels, Berger et al. (2011) were able to show that the degree of pulmonary hypertension that occurs upon high-altitude exposure is largely independent of sympathetic nervous system activity in the pulmonary vasculature and adrenal gland.

Chronic Mountain Sickness (CMS) and Vasoactive Peptides

To investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS), Ge et al. (2011) sampled 24 patients with CMS and 50 control subjects residing at 4,300 m. In CMS patients, hematocrit was 70% vs 59% in controls, pulmonary arterial pressure was 27 torr vs 20 torr while Spo₂ was 85% vs 89%. With CMS, median concentrations of BNP were 50% greater, VEGF was 2.2 times higher and eNOS was 20% lower. The authors conclude that natriuretic and angiogenic peptides may modulate the adaptive response to chronic high-altitude exposure and serve as a marker of the severity of and perhaps pathophysiological trigger for CMS.

Chronic Kidney Disease in Tibetans

In a survey of 1289 Tibetans, Chen et al. (2011) found an increased incidence of albuminuria (16.2%) and hypertension (38.8%) strongly associated with hypertension, hyperuricemia, and polycythemia, similar to other high altitude populations. 19.1% of Tibetan adults had at least one indicator of kidney damage, which is higher than 12-13% in low altitude Chinese. The authors examine possible but unproven mechanisms including direct hypoxic injury, polycythemia, hyperuricemia and the high incidence of hypertension.

High Altitude Renal Syndrome

Humans on the Peruvian altiplano (>2400 m) have a high incidence of microalbuminuria, hyperuricemia associated with polycythemia, and systemic hypertension (Arestegui et al., 2011). The authors report improvement with use of ACE inhibitors and suggest that HARS be added to the pathologies of high altitude, HAPE and HACE.

Birth Weights Remain Low with Mothers Born at Low Altitude But Raised and Living at High Altitude

Low altitude native women while living at high altitude deliver lower weight infants than highland native women. Julian et al. (2011) report that this protective effect of highlanders does not occur in lowland women even after living at high altitude from childhood. The authors conclude that the causes of the protective effect in highlanders need both genomic and epigenetic studies (Moore et al., 2011).

Consensus Recommendations on Working in Hypoxia

The consensus Statement of the Medical Commission of the Union Internationale des Associations d'Alpinisme (UIAA MedCom) published recommendations on how to provide health and safety for employees in different kinds of low oxygen atmospheres. Typical situations of work in hypoxia were defined and their specific risks described. They defined four main groups working in hypoxia with some subgroups (main risk in parentheses): short exposure (pressure change), limited exposure (acute altitude disease), expatriates (chronic altitude disease), and high-altitude populations (re-entry pulmonary edema) (Kupper et al., 2011).

Impact of HIF Discovery on Understanding Altitude Hypoxic Stress

Cerretelli and Gelfi (2011) reinterpret and reexamine energy metabolic mechanisms related to acute and chronic adaptation to high altitude. They discuss (1) the role of stress response proteins in the maintenance of ROS homeostasis, (2) the activity of the PDK1 gene on the shunting of pyruvate away from the TCA cycle in rodents and in humans, (3) the COX-4/COX-2 ratio in hypoxic rodents, (4) the overall efficiency of oxidative phosphorylation in humans during exercise in hypoxia, (5) some features of muscle mitochondrial autophagy in humans undergoing subchronic and chronic altitude exposure.

Raymond Greene: Physician, Mountaineer, and Raconteur

Rodway, Gibbs, and Windsor (2011) remember Greene as the leader of a 1933 attempt to climb Everest. He was a notable early UK thyroid endocrinologist, student of altitude physiology, medical publisher and story teller.