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Richalet, Jean-Paul, Chantal Julia, and Francois J. Lhuissier. Evaluation of the Lake Louise Score for acute mountain sickness and its 2018 version in a cohort of 484 trekkers at high altitude. Hig...

Periodic breathing is a respiratory phenomenon frequently observed in patients with heart failure and in normal subjects sleeping at high altitude. However, until recently, periodic breathing has not been studied in wakefulness and during exercise. This review relates the latest findings describing this ventilatory disorder when a healthy subject is submitted to simultaneous physiological (exercise) and environmental (hypoxia, hyperoxia, hypercapnia) or pharmacological (acetazolamide) stimuli. Preliminary studies have unveiled fundamental physiological mechanisms related to the genesis of periodic breathing characterized by a shorter period than those observed in patients (11~12 vs. 30~60 s). A mathematical model of the respiratory system functioning under the aforementioned stressors corroborated these data and pointed out other parameters, such as dead space, later confirmed in further research protocols. Finally, a cardiorespiratory interdependence between ventilatory oscillations and heart rate variability in the low frequency band may partly explain the origin of the augmented sympathetic activation at exercise in hypoxia. These nonlinear instabilities highlight the intrinsic “homeodynamic” system that allows any living organism to adapt, to a certain extent, to permanent environmental and internal perturbations.

Heart rate variability (HRV) may be influenced by several factors, such as environment (hypoxia, hyperoxia, hypercapnia) or physiological demand (exercise). In this retrospective study, we tested the hypothesis that inter-beat (RR) intervals in healthy subjects exercising under various environmental stresses exhibit oscillations at the same frequency than ventilatory oscillations.Spectra from RR intervals and ventilation ([Formula: see text]E) were collected from 37 healthy young male subjects who participated in 5 previous studies focused on ventilatory oscillations (or periodic breathing) during exercise in hypoxia, hyperoxia and hypercapnia. Bland and Altman test and multivariate regressions were then performed to compare respective frequencies and changes in peak powers of the two signals.Fast Fourier analysis of RR and [Formula: see text]E signals showed that RR was oscillating at the same frequency than periodic breathing, i.e., ~ 0.09 Hz (11 s). During exercise, in these various conditions, the difference between minimum and maximum HRV peak power was positively correlated to the same change in ventilation peak power (P 0.05). Low-frequency (LF) peak power was correlated to tidal volume (P 0.01) and breathing frequency (P 0.001).This study suggests that low-frequency ventilatory oscillations in hypoxia are a major contributor to the LF band power of heart rate variability. CLINICAL TRIAL REG. NO.: NCT02201875.

This study aims to evaluate the accuracy of the Garmin Forerunner 245 heart rate (HR) and pulse O2 saturation (SpO2) sensors compared with electrocardiogram and medical oximeter, from sea level to high altitude. Ten healthy subjects underwent five tests in normoxia and hypoxia (simulated altitudes from 3000 to 5500 m), consisting in a 5-min rest phase, followed by 5-min of mild exercise. Absolute error (±10 bpm for HR and ±3% for SpO2, around criterion) and intraclass correlations (ICC) were calculated. Error rates for HR remained under 10%, except at 3000 m, and ICCs evidenced a good reliability between Garmin and criterion. Overall SpO2 was higher than criterion (P50% error rate (>80% above 4800 m), and a poor reliability with criterion. The Garmin device displayed acceptable HR data at rest and exercise for all altitudes, but failed to provide trustworthy SpO2 values, especially at high altitude, where a pronounced arterial O2 desaturation could lead to acute mountain sickness in hypoxia-sensitive subjects, and its life-threatening complications; moreover, readings of overestimated SpO2 values might induce trekkers into further hazardous behavior by pursuing an ascent while being already at risk. Therefore, its use to assess SpO2 should be proscribed in altitude for acclimatization evaluation.

International audience; Purpose: A decision tree based on a clinico-physiological score (SHAI score) has been developed to detect subjects susceptible to Severe High Altitude Illness (SHAI). We aimed to validate this decision tree, to rationalize the prescription of acetazolamide (ACZ) and to specify the rule for a progressive acclimatization.Methods: Data were obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of SHAI score, ACZ prescription and use and fulfillment of the acclimatization rule.Results: The occurrence of SHAI was 22.6%, similar to what was observed 18 years before (23.7%), while life-threatening forms of SHAI (High Altitude Pulmonary and Cerebral Edema) were less frequent (2.6% to 0.8%, P=0.007). The negative predictive value of the decision tree based was 81%, suggesting that the procedure is efficient to detect subjects who will not suffer from SHAI, therefore limiting the use of ACZ. The maximal daily altitude gain that limits the occurrence of SHAI was established at 400 m. The occurrence of SHAI was reduced from 27% to 12% when the recommendations for ACZ use and 400 m daily altitude gain were respected (P

Background Infertility is defined as the inability to conceive after 12 months of unprotected intercourse. It affects approximately one in six couples seeking pregnancy in France or western countries. Many lifestyle factors of the couples’ pre and peri-conceptional environment (weight, diet, alcohol, tobacco, coffee, drugs, physical activity, stress, sleep…) have been identified as risk factors for infertility in both males and females. The high prevalence rates of unhealthy diets and lifestyles in the reproductive population of industrialized countries are worrisome. Nevertheless, adoption of a healthy lifestyle may improve fertility but lifestyle changes are difficult to achieve and to maintain due notably to behavioral factors. Methods Consequently, we decided to propose an interventional study aimed at improving the quality of life of infertile couples before the start of assisted reproductive technology treatment. It is a randomized controlled multicentre trial. Both members of the couples are involved in an integrated global care program (PEPCI for “Parcours Environnement PériConceptionnel en Infertilité”) vs. usual care. This global intervention not only considers diet and/or physical activity but follows a holistic approach, including a multidisciplinary assessment to address complete physical, psychological and social well-being. According to patient needs, this includes interventions on weight, exercise, diet, alcohol and drugs, mental and social health. Discussion The main objective of trial is to demonstrate that periconceptional multidisciplinary care has a positive impact on reproductive functions. We will also focus on feasibility, acceptance, compliance and conditions of success of a multifaceted lifestyle intervention. Trial registration The trial was registered at ClinicalTrials.gov, Identifier: NCT02961907 on November 11, 2016.

International audience; The purpose of this study was to define a new method to estimate the adult height of an individual from data recorded during a single and nonintrusive childhood examination. The data required are maturity stage and stature in a standing position. Specific growth curves were obtained from longitudinal data collected from 125 sedentary boys aged from 12 to 17.5 years, during 5 consecutive years. The sample comprise of 1234 measurements.The puberty stages were based on facial, axillary hair growth and changing voice with four stages: stage 1 (ST1, below the puberty), stage 2 (ST2, prepubescent), stage 3 (ST3, para pubescent), and stage 4 (ST4, pubescent). They were classified as early, standard, or late maturation.Between the different maturation groups, significant differences were found for the age of peak height velocity (APHV). From 160 to 164 months, we found a connection between the pubertal stages and the APHV without possible intersection. Significant differences were observed between APHV for each maturation group, which enable to model average curves of the stature for each puberty group.To validate the new model, we predicted young basketball players’ adult stature. First, data were collected (height and stage of puberty) a single time for age between 160 and 164 months. From our models of sedentary reference subjects we estimated the adult stature. In a second time, these estimations were compared to the real measured stature at 18 years old (216 months).For each basketball player we calculated the deviation from the average value obtained on the first population expressed as standard deviation (Z‐score).The relation between the predicted stature and the adult stature for overall basketball population shows a correlation with r = 0.98 and SEE = 1.65 cm. The predictions lie within +/− 0.3cm, 98% of the time.This study shows that the knowledge of biological maturation (peak of height velocity) and maturity (delayed, standard or advanced puberty) make possible to develop new stature growth curves, and to predict adult stature.This technique is a new valid nonintrusive and accurate method, which permits to predict adult stature. It was validated with a population of basketball players and constitutes an advance in the detection and the orientation of future basketball players.

Introduction: Tolerance to high altitude in women might be influenced by hormonal status since female hormones modulate ventilation. Methods: Our objectives were (i) to explore in 1060 women, the i...

International audience; Recent studies have shown that normal subjects exhibit periodic breathing when submitted to concomitant environmental (hypoxia) and physiological (exercise) stresses. A mathematical model including mass balance equations confirmed the short period of ventilatory oscillations and pointed out an important role of dead space in the genesis of these phenomena. Ten healthy subjects performed mild exercise on a cycloergometer in different conditions: rest/exercise, normoxia/hypoxia and no added dead space / added dead space (aDS). Ventilatory oscillations (E peak power) were augmented by exercise, hypoxia and aDS (P

Objectives The current study aimed to determine whether acute hypoxia exposure in laboratory conditions associated with exercise induces an increase in systemic blood pressure (BP) in normotensive and hypertensive patients, and whether hypertensive patients are more prone to develop severe acute mountain sickness (sAMS). Finally, to determine if BP changes at exercise in acute hypoxia in hypertensive patients are predictive factors for sAMS. Methods From 2012 to 2015, 852 normotensive and 106 hypertensive patients went through an acute hypoxia exercise test before a sojourn at high altitude. A subgroup of 228 normotensive was selected to match age, sex ratio, body weight and BMI and compared with the hypertensive group. Results In normotensive and hypertensive patients, for a given workload, BP was higher in hypoxia than in normoxia, whereas, for a given heart rate, it was lower in hypoxia than in normoxia. Hypertensive patients treated by beta-blockers showed lower arterial oxygen saturation (vs. other treatments) and blunted cardiac and ventilatory responses to hypoxia at exercise. Based on questionnaires filled out at high altitude, hypertensive patients were not more prone than normotensive patients to develop sAMS. During the laboratory acute hypoxic exercise test, hypertensive patients suffering from sAMS, although taking acetazolamide showed similar BP than hypertensive patients without sAMS and without acetazolamide. Discussion and conclusion We hypothesize that acute hypoxia with exercise in laboratory conditions induces a peripheral vasodilation that balances vasoconstriction and tachycardia centrally induced through the adrenergic system. Hypertensive and normotensive patients behave similarly during exercise in acute hypoxia. Acute hypoxia does not exacerbate the exercise-induced increase in BP. BP variation, during the acute hypoxia exercise test, is not a useful predictor of intolerance to high altitude. Based on laboratory tests in acute hypoxia, hypertensive patients may not be at higher risk to develop sAMS at high altitude.

International audience; We evaluated the mechanisms responsible for the instability of ventilation control system under simultaneous metabolic (exercise) and environmental (hypoxia) stresses, promoting the genesis of periodic breathing. A model following the main concepts of ventilatory control has been tested, including cardiovascular and respiratory parameters, characteristics of peripheral and central chemoreceptors, at mild exercise in hypoxia (FIO 2 =0.145). Interaction between O 2 and CO 2 sensing was introduced following three different modalities. A sensitivity and multivariate regression analyses closely matched with physiological data for magnitude and period of oscillations. Low FIO 2 and long circulatory delay from lungs to peripheral chemoreceptors (DeltaTp) lengthen the period of oscillations, while high peripheral and central chemoresponses to O 2 and CO 2 , low FIO 2 and high DeltaTp increased their magnitude. Peripheral and central O 2 / CO 2 interactions highlight the role of CO 2 on peripheral gain to O 2 and the contribution of peripheral afferences on central gain to CO 2. Our model supports the key role of peripheral chemoreceptors in the genesis of ventilatory oscillations. Differences in the dynamics of central and peripheral components might be determinant for the system stability.

Resume La pratique de plus en plus frequente d’activites sportives ou de loisir en haute altitude amene a se poser la question des facteurs de risque de la pathologie engendree par l’exposition aigue a l’hypoxie : mal aigu des montagnes, œdeme pulmonaire et œdeme cerebral de haute altitude. Des etudes epidemiologiques recentes ont permis d’identifier ces facteurs de risque : antecedents de pathologie d’altitude lors de sejours precedents, montee rapide en altitude, migraine, entrainement regulier en endurance, ainsi que des donnees physiologiques obtenues lors d’un test d’effort en hypoxie : reponse ventilatoire et cardiaque a l’hypoxie a l’exercice, desaturation a l’exercice en hypoxie. Ces dernieres donnees physiologiques evaluent la sensibilite des chemorecepteurs a l’hypoxie et permettent une bonne detection des sujets a risque. Lors d’une consultation specialisee de medecine d’altitude, on s’attachera dans un premier temps a eliminer les contre-indications medicales a un sejour en altitude et, a l’aide du score clinicophysiologique elabore a l’issu du test d’effort en hypoxie, on donnera des conseils adaptes au profil du consultant desireux de se rendre en haute altitude.

Richalet, Jean-Paul, and François J. Lhuissier. Aging, tolerance to high altitude, and cardiorespiratory response to hypoxia. High Alt Med Biol. 16:117-124, 2015.--It is generally accepted that aging is rather protective, at least at moderate altitude. Some anecdotal reports even mention successful ascent of peaks over 8000 m and even Everest by elderly people. However, very few studies have explored the influence of aging on tolerance to high altitude and prevalence of acute high altitude related diseases, taking into account all confounding factors such as speed of ascent, altitude reached, sex, training status, and chemo-responsiveness. Changes in physiological responses to hypoxia with aging were assessed through a cross-sectional 20-year study including 4675 subjects (2789 men, 1886 women; 14-85 yrs old) and a longitudinal study including 30 subjects explored at a mean 10.4-year interval. In men, ventilatory response to hypoxia increased, while desaturation was less pronounced with aging. Cardiac response to hypoxia was blunted with aging in both genders. Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with aging. These adaptive responses were less pronounced or absent in post-menopausal untrained women. In conclusion, in normal healthy and active subjects, aging has no deleterious effect on cardiac and ventilatory responses to hypoxia, at least up to the eighth decade. Aging is not a contraindication for high altitude, as far as no pathological condition interferes and physical fitness is compatible with the intensity of the expected physical demand of one's individual. Physiological evaluation through hypoxic exercise testing before going to high altitude is helpful to detect risk factors of severe high altitude-related diseases.

Periodic breathing is frequent in heart failure or ventilatory disorders during sleep, and common during sleep at high altitude, but has been rarely studied in wakefulness and during exercise. A retrospective analysis of ventilation from hypoxia exercise tests was realized in 82 healthy subjects separated into two groups with either high or low ventilatory response to hypoxia at exercise (HVRe). A fast Fourier transform spectral analysis of the breath-by-breath ventilation (V̇e) signal, O2 saturation, and end-tidal PCO2 evidenced a periodic pattern with a period of 11.1 to 12.0 s. The peak power of the V̇e spectrum was higher in the high HVRe group ( P < 0.001). A prospective study (25 subjects) was performed to evaluate the influence of cardiorespiratory factors on the amplitude and period of oscillations in various conditions of exercise (20 to 40% maximal aerobic power) and hypoxia (0 to 4,000 m altitude). The period of V̇e was shorter at exercise (vs. rest, P < 0.001) and hypoxia (vs. normoxia, P < 0.001), and inversely related with cardiac output and V̇e ( P < 0.001). V̇e peak power was higher at exercise ( P < 0.001) and hypoxia ( P < 0.001), and was positively related with cardiac output and V̇e ( P < 0.001). V̇e peak power in hypoxia was positively related with the ventilatory response to CO2 (HCVR). This novel observation suggests that healthy subjects demonstrate a spontaneous periodic breathing, not clearly observable at rest and in normoxia, but triggered by hypoxic exercise. The periodic pattern is enhanced in subjects with high HVRe and high HCVR, suggesting that oxygen and CO2 play synergistic roles in the modulation of these oscillations.

Background and objectives Little is known about the consequences of chronic sarcoidosis on daily life physical activity (DLPA). The aim of this prospective study was to measure DLPA in patients with chronic sarcoidosis and to determine its relationship to clinical and functional parameters. Methods Fifty‐three patients with chronic sarcoidosis and 28 healthy control subjects were enrolled in this multicenter prospective study. Two markers of DLPA (number of steps walked per day [SPD]) and total daily energy expenditure (TEE) were assessed for five consecutive days with a physical activity monitor. Pulmonary function, aerobic capacity (maximal oxygen uptake [VO2max]), exercise capacity (6‐min walk test [6MWT]), and quality of life (self‐reported questionnaires) were also evaluated. Comparisons of DLPA parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DLPA parameters and patient characteristics were assessed in multivariable linear regression models. Results Patients with sarcoidosis walked significantly fewer SPD than did the control subjects (6395 ± 4119 and 11 817 ± 3600, respectively; P

The risk of severe altitude-induced diseases is related to ventilatory and cardiac responses to hypoxia and is dependent on sex, age and exercise training status. However, it remains unclear how ageing modifies these physiological adaptations to hypoxia. We assessed the physiological responses to hypoxia with ageing through a cross-sectional 20 year study including 4675 subjects (2789 men, 1886 women; 14-85 years old) and a longitudinal study including 30 subjects explored at a mean 10.4 year interval. The influence of sex, training status and menopause was evaluated. The hypoxia-induced desaturation and the ventilatory and cardiac responses to hypoxia at rest and exercise were measured. In men, ventilatory response to hypoxia increased (P < 0.002), while desaturation was less pronounced (P < 0.001) with ageing. Cardiac response to hypoxia was blunted with ageing in both sexes (P < 0.001). Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with ageing. These adaptive responses were less pronounced or absent in post-menopausal women (P < 0.01). At exercise, desaturation was greater in trained subjects but cardiac and ventilatory responses to hypoxia were preserved by training, especially in elderly people. In conclusion, respiratory response to hypoxia and blood oxygenation improve with ageing in men while cardiac response is blunted with ageing in both sexes. Training aggravates desaturation at exercise in hypoxia, improves the ventilatory response and limits the ageing-induced blunting of cardiac response to hypoxia. Training limits the negative effects of menopause in cardiorespiratory adaptations to hypoxia.

International audience; Periodic breathing has been found in patients with heart failure and sleep apneas, and in healthy subjects in hypoxia, during sleep and wakefulness, at rest and, recently, at exercise. To unravel the cardiorespiratory parameters liable to modulate the amplitude and period of ventilatory oscillations, 26 healthy subjects were tested under physiological (exercise) and environmental (hypoxia, hyperoxia, hyperoxic hypercapnia) stresses, and under acetazolamide (ACZ) treatment. A fast Fourier transform spectral analysis of breath‐by‐breath ventilation urn:x-wiley:2051817X:media:phy212446:phy212446-math-0001 evidenced an increase in urn:x-wiley:2051817X:media:phy212446:phy212446-math-0002 peak power under hypercapnia (vs. normoxia and hyperoxia, P < 0.001) and a decrease under ACZ (vs. placebo, P < 0.001), whereas it was not modified in hyperoxia. urn:x-wiley:2051817X:media:phy212446:phy212446-math-0003 period was shortened by exercise in all conditions (vs. rest, P < 0.01) and by hypercapnia (vs. normoxia, P < 0.05) but remained unchanged under ACZ (vs. placebo). urn:x-wiley:2051817X:media:phy212446:phy212446-math-0004 peak power was positively related to cardiac output (urn:x-wiley:2051817X:media:phy212446:phy212446-math-0005) and urn:x-wiley:2051817X:media:phy212446:phy212446-math-0006 in hyperoxia (P < 0.01), in hypercapnia (P < 0.001) and under ACZ (P < 0.001). urn:x-wiley:2051817X:media:phy212446:phy212446-math-0007 period was negatively related to urn:x-wiley:2051817X:media:phy212446:phy212446-math-0008 and urn:x-wiley:2051817X:media:phy212446:phy212446-math-0009 in hyperoxia (P < 0.01 and P < 0.001, respectively), in hypercapnia (P < 0.05 and P < 0.01, respectively) and under ACZ (P < 0.05 and P < 0.01, respectively). Total respiratory cycle time was the main factor responsible for changes in urn:x-wiley:2051817X:media:phy212446:phy212446-math-0010 period. In conclusion, exercise, hypoxia, and hypercapnia increase ventilatory oscillations by increasing urn:x-wiley:2051817X:media:phy212446:phy212446-math-0011 and urn:x-wiley:2051817X:media:phy212446:phy212446-math-0012, whereas ACZ decreases ventilatory instability in part by a contrasting action on O2 and CO2 sensing. An intrinsic oscillator might modulate ventilation through a complex system where peripheral chemoreflex would play a key role.

Periodic breathing has been rarely studied in wakefulness during exercise in healthy humans. Spectral analyses of 82 healthy subjects breath-by-breath ventilation (VE) signals, from hypoxia exercise tests, evidenced a periodic pattern with a period from 11.1 to 12.0 seconds. VE Peak power was higher in the group 'high ventilatory response to hypoxia at exercise' (HVRe) group (vs low HVRe, P

Background— The goals of this study were to compare ECG at moderate exercise in normoxia and hypoxia at the same heart rate, to provide evidence of independent predictors of hypoxia-induced ECG changes, and to evaluate ECG risk factors of severe high-altitude illness. Methods and Results— A total of 456 subjects performed a 20-minute hypoxia exercise test with continuous recording of ECG and physiological measurements before a sojourn above 4000 m. Hypoxia did not induce any conduction disorder, arrhythmias, or change in QRS axis. The amplitude of the P wave in V 1 was lower in hypoxia than in normoxia. The amplitudes of the R, S, and T waves and the Sokolow index decreased in hypoxia. Under hypoxia, the amplitude of the ST segment decreased in II and V 6 and increased in V 1 , the ST slope rose in V 5 and V 6 , and the J point was lower in II, V 5 , and V 6 . Multivariate regression of hypoxic/normoxic ratios of electrophysiological parameters and clinical characteristics showed a correlation between the decrease in Sokolow index and T-wave amplitude in V 5 with desaturation at exercise. Trained status and low body mass index were associated with a smaller decrease in T-wave amplitude in V 5 and V 6 . Comparison of ECG between subjects suffering or not suffering from severe high-altitude illness failed to show any difference. Conclusions— During a hypoxia exercise test, a dose-dependent hypoxia-induced decrease in the amplitude of the P/QRS/T waves was observed. No standard ECG characteristic predicted the risk of developing severe high-altitude illness. Further studies are required to clarify the cause of these electric changes and their potential predictive role in cardiac events.

to the editor: We followed with great interest the recent exchanges between Drs. Teppema and Berendsen ([4][1]) on one hand and Dr. Swenson on the other hand regarding the mechanisms of effects of acetazolamide (AZ) in the prevention of Acute Mountain Sickness (AMS) ([3][2]). One of the essential

The hypoxic exercise test combining a 4,800-m simulated altitude and a cycloergometer exercise at 30% of normoxic maximal aerobic power (MAP) is used to evaluate the individual chemosensitivity to hypoxia in submaximal exercise conditions. This test allows the calculation of three main parameters: the decrease in arterial oxygen saturation induced by hypoxia at exercise (ΔSae) and the ventilatory (HVRe) and cardiac (HCRe) responses to hypoxia at exercise. The aim of this study was to determine the influence of altitude and exercise intensity on the values of ΔSae, HVRe, and HCRe. Nine subjects performed hypoxic tests at three simulated altitudes (3,000 m, 4,000 m, and 4,800 m) and three exercise intensities (20%, 30%, and 40% MAP). ΔSae increased with altitude and was higher for 40% MAP than for 20% or 30% ( P < 0.05). For a constant heart rate, the loss in power output induced by hypoxia, relative to ΔSae, was independent of altitude (4,000–4,800 m) and of exercise intensity. HVRe and HCRe were independent of altitude (3,000–4,800 m) and exercise intensity (20%-40% MAP). Moreover, the intraindividual variability of responses to hypoxia was lower during moderate exercise than at rest ( P < 0.05 to P < 0.001). Therefore, we suggest that HVRe and HCRe are invariant parameters that can be considered as intrinsic physiological characteristics of chemosensitivity to hypoxia.