Andrew D. Miller

Exercise-induced interstitial pulmonary edema at sea-level in young and old healthy humans

We asked whether aged adults are more susceptible to exercise-induced pulmonary edema relative to younger individuals. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (Dm) and pulmonary-capillary blood volume (Vc) were measured before and after exhaustive discontinuous incremental exercise in 10 young (YNG; 27±3 years) and 10 old (OLD; 69±5 years) males. In YNG subjects, Dm increased (11±7%, P=0.031), Vc decreased (-10±9%, P=0.01) and DLCO was unchanged (30.5±4.1 vs. 29.7±2.9mL/min/mmHg, P=0.44) pre- to post-exercise. In OLD subjects, DLCO and Dm increased (11±14%, P=0.042; 16±14%, P=0.025) but Vc was unchanged (58±23 vs. 56±23mL, P=0.570) pre- to post-exercise. Group-mean Dm/Vc was greater after vs. before exercise in the YNG and OLD subjects. However, Dm/Vc was lower post-exercise in 2 of the 10 YNG (-7±4%) and 2 of the 10 OLD subjects (-10±5%). These data suggest that exercise decreases interstitial lung fluid in most YNG and OLD subjects, with a small number exhibiting evidence for exercise-induced pulmonary edema.

Incidence and symptoms of high altitude illness in South Pole workers: Antarctic study of altitude physiology (ASAP)

Introduction Each year, the US Antarctic Program rapidly transports scientists and support personnel from sea level (SL) to the South Pole (SP, 2835 m) providing a unique natural laboratory to quantify the incidence of acute mountain sickness (AMS), patterns of altitude related symptoms and the field effectiveness of acetazolamide in a highly controlled setting. We hypothesized that the combination of rapid ascent (3 hr), accentuated hypobarism (relative to altitude), cold, and immediate exertion would increase altitude illness risk. Methods Medically screened adults (N = 246, age = 37 ± 11 yr, 30% female, BMI = 26 ± 4 kg/m2) were recruited. All underwent SL and SP physiological evaluation, completed Lake Louise symptom questionnaires (LLSQ, to define AMS), and answered additional symptom related questions (eg, exertional dyspnea, mental status, cough, edema and general health), during the 1st week at altitude. Acetazolamide, while not mandatory, was used by 40% of participants. Results At SP, the barometric pressure resulted in physiological altitudes that approached 3400 m, while T °C averaged -42, humidity 0.03%. Arterial oxygen saturation averaged 89% ± 3%. Overall, 52% developed LLSQ defined AMS. The most common symptoms reported were exertional dyspnea-(87%), sleeping difficulty-(74%), headache-(66%), fatigue-(65%), and dizziness/lightheadedness-(46%). Symptom severity peaked on days 1-2, yet in >20% exertional dyspnea, fatigue and sleep problems persisted through day 7. AMS incidence was similar between those using acetazolamide and those abstaining (51 vs. 52%, P = 0.87). Those who used acetazolamide tended to be older, have less altitude experience, worse symptoms on previous exposures, and less SP experience. Conclusion The incidence of AMS at SP tended to be higher than previously reports in other geographic locations at similar altitudes. Thus, the SP constitutes a more intense altitude exposure than might be expected considering physical altitude alone. Many symptoms persist, possibly due to extremely cold, arid conditions and the benefits of acetazolamide appeared negligible, though it may have prevented more severe symptoms in higher risk subjects.

Physiological variables associated with the development of acute mountain sickness at the South Pole

Exposure to altitudes >2500u2005m can result in acute mountain sickness (AMS), a mild and usually self-limiting condition. Research has attempted to identify factors associated with developing AMS without controlling important factors related to the ascent or collecting a comprehensive set of variables. Objectives The Antarctic Study of Altitude Physiology (ASAP) investigated variables associated with the development of AMS in adults experiencing rapid passive transport to altitude by airplane. Design Our prospective observational trial collected data, including personal history, anthropometrics, vital signs, blood samples and pulmonary function, at sea level and at altitude. Statistical analysis utilised independent sample t tests to investigate between-group differences (p<0.05) and a forward, step-wise binary logisitic regression analysis was performed. Participants Of 248 eligible ASAP participants, those who did not use acetazolamide (N=98) were included in the present analysis. Primary outcome measures The diagnosis of AMS using the Lake Louise Symptom Score. Results Analysis of participants not using acetazolamide (n=90) found 30 participants developed AMS and 60 participants did not. Estimated plasma volume decreased significantly at altitude (p=0.025) in the AMS group as compared with the No AMS group while body weight did not change (p=0.125). Serum sodium (p=0.045) and low-density lipoprotein (LDL) (p=0.049) levels were higher in the No AMS group. A logistic regression analysis emphasised the contributions of LDL and eosinophil levels in the development of AMS. Conclusions These results suggest that the body water regulation and inflammation are key factors in AMS development when all other factors such as the level of physical exertion during ascent, the rate and magnitude of ascent and the use of acetazolamide are controlled.

Oral contraceptive use and acute mountain sickness in South Pole workers.

INTRODUCTIONnProgesterone has a number of properties that could influence the development of acute mountain sickness (AMS), including anti-inflammation, respiratory smooth muscle relaxation, ventilatory stimulation, and antidiuretic characteristics. Oral contraceptive (OC) use decreases levels of circulating progesterone by preventing ovulation. We hypothesized rates of AMS development would be significantly higher in OC users as compared to Non-OC users in a population traveling rapidly to the South Pole.nnnMETHODSnThere were 50 female subjects (OC N = 13, no OC N = 37) who traveled by airplane from Sea Level (SL) to Altitude (ALTD) (-3200 m) in < 4 h and were monitored for the development of AMS. SL and ALTD measurements of anthropometrics, vital signs, hematologic variables, blood chemistries, electrolytes, endocrine responses, and pulmonary function were assessed with t-test and Chi-square analyses, P < 0.05.nnnRESULTSnAs compared to Non-OC users, OC users had lower progesterone levels (ng x ml(-1)) at SL (0.7 +/- 0.5 vs. 3.2 +/- 4.6) and at ALTD (0.7 +/- 0.7 vs. 3.1 +/- 4.6). AMS was significantly more prevalent in OC users (85%) as compared to Non-OC users (51%). Acetazolamide prophylaxis was not protective, with a greater proportion of OC users (100%) developing AMS despite its use as compared to Non-OC users (50%). Blood pressure responses also differed significantly, with OC users displaying higher mean arterial pressures at ALTD vs. Non-OC users.nnnCONCLUSIONnOC use at ALTD is associated with an increased risk for the development of AMS. Acetazolamide prophylaxis with OC use was also associated with an increased rate of AMS development.

The effect of aging and cardiorespiratory fitness on the lung diffusing capacity response to exercise in healthy humans

Aging is associated with deterioration in the structure and function of the pulmonary circulation. We characterized the lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary-capillary blood volume (Vc) response to discontinuous incremental exercise at 25, 50, 75, and 90% of peak work (Wpeak) in four groups: 1) Young [27u2009±u20093 yr, maximal oxygen consumption (V̇o2max): 110u2009±u200918% age predicted]; 2) Young Highly Fit (27u2009±u20093 yr, V̇o2max: 147u2009±u20098% age predicted); 3) Old (69u2009±u20095 yr, V̇o2max: 116u2009±u200913% age predicted); and 4) Old Highly Fit (65u2009±u20095 yr, V̇o2max: 162u2009±u200918% age predicted). At rest and at 90% Wpeak, DLCO, DmCO, and Vc were decreased with age. At 90% Wpeak, DLCO, DmCO, and Vc were greater in Old Highly Fit vs. Old adults. The slope of the DLCO-cardiac output (Q̇) relationship from rest to end exercise at 90% Wpeak was not different between Young, Young Highly Fit, Old, and Old Highly Fit (1.35 vs. 1.44 vs. 1.10 vs. 1.35 mlCO·mmHg-1·liter blood-1, P = 0.388), with no evidence of a plateau in this relationship during exercise; this was also true for DmCO-Q̇ and Vc-Q̇. V̇o2max was positively correlated with 1) DLCO, DmCO, and Vc at rest; and 2) the rest to end exercise change in DLCO, DmCO, and Vc. In conclusion, these data suggest that despite the age-associated deterioration in the structure and function of the pulmonary circulation, expansion of the pulmonary capillary network does not become limited during exercise in healthy individuals regardless of age or cardiorespiratory fitness level.NEW & NOTEWORTHY Healthy aging is a crucial area of research. This article details how differences in age and cardiorespiratory fitness level affect lung diffusing capacity, particularly during high-intensity exercise. We conclude that highly fit older adults do not experience a limit in lung diffusing capacity during high-intensity exercise. Interestingly, however, we found that highly fit older individuals demonstrate greater values of lung diffusing capacity during high-intensity exercise than their less fit age-matched counterparts.

Expiratory loading improves cardiac output during exercise in heart failure

PURPOSEnThe objective of this study was to investigate the effect of changes in expiratory intrathoracic pressure on stroke volume (SV) at rest and during moderate exercise in patients with heart failure versus healthy individuals.nnnMETHODSnSV was obtained by echocardiography during spontaneous breathing and during expiratory loads of 5 and 10 cm H2O produced by a ventilator in 11 patients with heart failure (61 ± yr, ejection fraction: 32 ± 4%, New York Heart Association, 32% ± 4%; NYHA class I-II) and 11 age-matched healthy individuals at rest and during exercise at 60% of aerobic capacity on a semirecumbent cycle ergometer.nnnRESULTSnAt rest, expiratory loading did not change HR, SV index (SVI), or cardiac index (CI) in either group. During moderate exercise, expiratory loading increased SVI and CI in patients with heart failure but decreased SVI and CI in healthy individuals. There was a negative correlation between changes in gastric pressure and SVI (r = -0.51, P < 0.05) in healthy individuals, whereas there was a positive correlation between changes in gastric pressure accompanying expiratory loading and CI (r = 0.83, P < 0.01) in patients with heart failure.nnnCONCLUSIONnExpiratory loading during moderate exercise elicited increases in SVI and CI in patients with heart failure but decreased SVI and CI in healthy individuals. Improvements in cardiac function during submaximal exercise in patients with heart failure may be caused by a beneficial reduction in left ventricular preload.

Variability in pulmonary function following rapid altitude ascent to the Amundsen–Scott South Pole station

The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835xa0m). The mean FEF between 25 and 75% (FEF25–75) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF25–75 increased by an average of 12% with changes ranging from −26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF25–75 (41 vs. 22%, Pxa0=xa00.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF25–75. Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF25–75. Greater levels of endothelin-1 in individuals with decreased FEF25–75 suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of β2-adrenergic receptors.

Acute Mountain Sickness Symptom Severity at the South Pole: The Influence of Self-Selected Prophylaxis with Acetazolamide.

Introduction Acetazolamide, a carbonic anhydrase inhibitor, remains the only FDA approved pharmaceutical prophylaxis for acute mountain sickness (AMS) though its effectiveness after rapid transport in real world conditions is less clear. Methods Over 2 years, 248 healthy adults traveled by airplane from sea level (SL) to the South Pole (ALT, ~3200m) and 226 participants provided Lake Louise Symptom Scores (LLSS) on a daily basis for 1 week; vital signs, blood samples, and urine samples were collected at SL and at ALT. Acetazolamide was available to any participant desiring prophylaxis. Comparisons were made between the acetazolamide with AMS (ACZ/AMS) (n = 42), acetazolamide without AMS (ACZ/No AMS)(n = 49), no acetazolamide with AMS (No ACZ/AMS) (n = 56), and the no acetazolamide without AMS (No ACZ/No AMS) (n = 79) groups. Statistical analysis included Chi-squared and one-way ANOVA with Bonferroni post-hoc tests. Significance was p≤0.05. Results No significant differences were found for between-group characteristics or incidence of AMS between ACZ and No ACZ groups. ACZ/AMS reported greater LLSS, BMI, and red cell distribution width. ACZ/No AMS had the highest oxygen saturation (O2Sat) at ALT. No significant differences were found in serum electrolyte concentrations or PFT results. Discussion Acetazolamide during rapid ascent provided no apparent protection from AMS based on LLSS. However, it is unclear if this lack of effect was directly associated with the drug or if perhaps there was some selection bias with individuals taking ACZ more likely to have symptoms or if there may have been more of perceptual phenomenon related to a constellation of side effects.

Sleep disordered breathing and acute mountain sickness in workers rapidly transported to the South Pole (2835 m)

BACKGROUNDnSleep disordered breathing may be a risk factor for high altitude illness. Past Antarctic sleep studies suggest that rapid transport from sea level (SL) to the Amundsen Scott South Pole Station (SP, 2835 m) increases risk of Acute Mountain Sickness (AMS). We analyzed sleep studies in 38 healthy polar workers to explore the association between sleep disordered breathing and AMS after rapid transport to the South Pole.nnnMETHODSnSubjects completed a baseline questionnaire, performed basic physiology tests, and were evaluated for AMS and medication use using an extended Lake Louise Questionnaire (LLQ) during their first week at the South Pole. Participants were included in this study if they took no medications and underwent polysomnography on their first nights at Sea Level and the South Pole using the Vivometrics LifeShirt(®). Within group changes were assessed with Wilcoxon signed rank tests and between group differences were assessed with Kruskal-Wallis rank sum tests.nnnRESULTSnOverall, 21/38 subjects met criteria for AMS at some time on or prior to the third morning at the South Pole. Subjective poor sleep quality was reported by both AMS (65%) and no AMS (41%) groups. The Apnea Hypopnea Index (AHI) increased significantly in both the AMS and no AMS groups, but the difference in the increase between the two groups was not statistically significant. Increased AHI was not associated with increased AMS symptoms. Previous altitude illness (p=0.06) and residence at low altitudes (p = 0.02) were risk factors for AMS.nnnCONCLUSIONnAMS was not significantly associated with sleep architecture changes or increased AHI. However, AHI sharply increased at South Pole (19/38 participants) primarily due to central apneas. Those developing AMS were more likely to have experienced previous problems at altitude and reported living at lowland altitudes within the 3 months prior to rapid transport to the South Pole than those without AMS.

Peripheral blood mononuclear cell gene expression in healthy adults rapidly transported to high altitude

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Advances in Genomics and Genetics 2015:5 1–9 Advances in Genomics and Genetics Dovepress