Anne Charloux

ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy)

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalised in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.

Dynamic heart rate variability: a tool for exploring sympathovagal balance continuously during sleep in men

We have recently demonstrated that the overnight profiles of cardiac interbeat autocorrelation coefficient of R-R intervals (rRR) calculated at 1-min intervals are related to the changes in sleep electroencephalographic (EEG) mean frequency, which reflect depth of sleep. Other quantitative measures of the Poincaré plots, i.e., the standard deviation of normal R-R intervals (SDNN) and the root mean square difference among successive R-R normal intervals (RMSSD), are commonly used to evaluate heart rate variability. The present study was designed to compare the nocturnal profiles of rRR, SDNN, and RMSSD with the R-R spectral power components: high-frequency (HF) power, reflecting parasympathetic activity; low-frequency (LF) power, reflecting a predominance of sympathetic activity with a parasympathetic component; and the LF-to-HF ratio (LF/HF), regarded as an index of sympathovagal balance. rRR, SDNN, RMSSD, and the spectral power components were calculated every 5 min during sleep in 15 healthy subjects. The overnight profiles of rRR and LF/HF showed coordinate variations with highly significant correlation coefficients (P < 0.001 in all subjects). SDNN correlated with LF power (P < 0.001), and RMSSD correlated with HF power (P < 0.001). The overnight profiles of rRR and EEG mean frequency were found to be closely related with highly cross-correlated coefficients (P < 0. 001). SDNN and EEG mean frequency were also highly cross correlated (P < 0.001 in all subjects but 1). No systematic relationship was found between RMSSD and EEG mean frequency. In conclusion, rRR appears to be a new tool for evaluating the dynamic beat-to-beat interval behavior and the sympathovagal balance continuously during sleep. This nonlinear method may provide new insight into autonomic disorders.We have recently demonstrated that the overnight profiles of cardiac interbeat autocorrelation coefficient of R-R intervals ( r RR) calculated at 1-min intervals are related to the changes in sleep electroencephalographic (EEG) mean frequency, which reflect depth of sleep. Other quantitative measures of the Poincaré plots, i.e., the standard deviation of normal R-R intervals (SDNN) and the root mean square difference among successive R-R normal intervals (RMSSD), are commonly used to evaluate heart rate variability. The present study was designed to compare the nocturnal profiles of r RR, SDNN, and RMSSD with the R-R spectral power components: high-frequency (HF) power, reflecting parasympathetic activity; low-frequency (LF) power, reflecting a predominance of sympathetic activity with a parasympathetic component; and the LF-to-HF ratio (LF/HF), regarded as an index of sympathovagal balance. r RR, SDNN, RMSSD, and the spectral power components were calculated every 5 min during sleep in 15 healthy subjects. The overnight profiles of r RR and LF/HF showed coordinate variations with highly significant correlation coefficients ( P < 0.001 in all subjects). SDNN correlated with LF power ( P < 0.001), and RMSSD correlated with HF power ( P < 0.001). The overnight profiles of r RR and EEG mean frequency were found to be closely related with highly cross-correlated coefficients ( P < 0.001). SDNN and EEG mean frequency were also highly cross correlated ( P < 0.001 in all subjects but 1). No systematic relationship was found between RMSSD and EEG mean frequency. In conclusion, r RR appears to be a new tool for evaluating the dynamic beat-to-beat interval behavior and the sympathovagal balance continuously during sleep. This nonlinear method may provide new insight into autonomic disorders.

Aldosterone release during the sleep-wake cycle in humans

The aim of this study was to assess the relative influence on the 24-h aldosterone profile of the adrenocorticotropic system, primarily modulated by a circadian rhythmicity, and the renin-angiotensin system, which is influenced by sleep. Cortisol, plasma renin activity (PRA), and aldosterone were measured for 24 h in healthy subjects under basal conditions, once with nocturnal sleep and once with a night of sleep deprivation followed by 8 h of daytime sleep. The sleep period displayed high mean aldosterone levels, pulse amplitude, and frequency that were reduced during waking periods. During sleep, aldosterone pulses were mainly related to PRA oscillations, whereas they were mainly associated with cortisol pulses during waking periods. Cross-correlation analysis between sleep electroencephalographic activity in the delta band and aldosterone levels yielded significant results, aldosterone following delta waves by ∼30 min. This study demonstrates that the 24-h aldosterone profile is strongly influenced by sleep processes. A dual influence, by the renin-angiotensin system during sleep and by the adrenocorticotropic system during wakefulness, is exerted on aldosterone pulses throughout the 24-h period.The aim of this study was to assess the relative influence on the 24-h aldosterone profile of the adrenocorticotropic system, primarily modulated by a circadian rhythmicity, and the renin-angiotensin system, which is influenced by sleep. Cortisol, plasma renin activity (PRA), and aldosterone were measured for 24 h in healthy subjects under basal conditions, once with nocturnal sleep and once with a night of sleep deprivation followed by 8 h of daytime sleep. The sleep period displayed high mean aldosterone levels, pulse amplitude, and frequency that were reduced during waking periods. During sleep, aldosterone pulses were mainly related to PRA oscillations, whereas they were mainly associated with cortisol pulses during waking periods. Cross-correlation analysis between sleep electroencephalographic activity in the delta band and aldosterone levels yielded significant results, aldosterone following delta waves by approximately 30 min. This study demonstrates that the 24-h aldosterone profile is strongly influenced by sleep processes. A dual influence, by the renin-angiotensin system during sleep and by the adrenocorticotropic system during wakefulness, is exerted on aldosterone pulses throughout the 24-h period.

The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective?; split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy?; the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated?

Skeletal muscle response to short endurance training in heart transplant recipients

OBJECTIVES We sought to examine the effects of endurance training on the ultrastructural characteristics of skeletal muscle in heart transplant recipients (HTRs) and age-matched control subjects (C). BACKGROUND Deconditioning is one of the factors involved in the peripheral limitation of exercise capacity of HTRs, and training has proven to be beneficial. METHODS Biopsies of the vastus lateralis muscle, analyzed by ultrastructural morphometry, and quadriceps muscle cross-sectional area, assessed by computed tomography (CT), were performed in 12 HTRs and 7 age-matched C before and 6 weeks after an endurance training program. Maximal oxygen uptake (peak VO2) was determined by an incremental exercise test. Additionally muscle biopsies were performed before and after a 6-week control period in four HTRs to check for spontaneous improvement. RESULTS Training resulted in similar increases in peak VO2 (11% in HTRs, 8.5% in C), ventilatory threshold (23% in HTRs, 32% in C) and total endurance work (54% in HTRs, 31% in C). Volume density of total mitochondria increased significantly (26% in HTRs, 33% in C) with a predominant increase of subsarcolemmal mitochondrial volume density (74% in HTRs, 70% in C). The capillary/fiber ratio increased by 19% in C only. In the nontrained group, none of the structural markers was spontaneously modified. CONCLUSIONS Six weeks of endurance training in HTRs and C led to similar improvements of aerobic work capacity. However, the decreased muscular capillary network in HTRs remained unchanged with training. Immunosuppressive therapy might be responsible for the discrepancy between the normal mitochondrial content and the reduced capillary supply of these patients.

Age-related changes in cardiac autonomic control during sleep

Aging is commonly associated with decreased sleep quality and increased periodic breathing (PB) that can influence heart rate variability (HRV). Cardiac autonomic control, as inferred from HRV analysis, was determined, taking into account the sleep quality and breathing patterns. Two groups of 12 young (21.1 ± 0.8 years) and 12 older (64.9 ± 1.9 years) volunteers underwent electroencephalographic, cardiac, and respiratory recordings during one experimental night. Time and frequency domain indices of HRV were calculated in 5‐min segments, together with electroencephalographic and respiratory power spectra. In the elderly, large R–R oscillations in the very‐low frequency (VLF) range emerged, that reflected the frequency of PB observed in 18% of the sleep time. PB occurred more frequently during rapid eye movement sleep (REM) sleep and caused a significant (P < 0.02) increase in the standard deviation of normal R–R intervals (SDNN) and absolute low‐frequency (LF) power. With normal respiratory patterns, SDNN, absolute VLF, LF, and high frequency (HF) power fell during each sleep stage (P < 0.01) compared with young subjects, with no significant sleep‐stage dependent variations. An overall decrease (P < 0.01) in normalized HF/(LF + HF) was observed in the elderly, suggesting a predominant loss of parasympathetic activity which may be related to decreased slow‐wave sleep duration. These results indicate that two distinct breathing features, implying different levels of autonomic drive to the heart, influence HRV in the elderly during sleep. The breathing pattern must be considered to correctly interpret HRV in the elderly.

Lung membrane diffusing capacity, heart failure, and heart transplantation

The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure and remains decreased after heart transplantation. This decrease in DLCO may depend on a permanent alteration after transplantation of one or the other of its components: diffusion of the alveolar capillary membrane or the pulmonary capillary blood volume (Vc). Therefore, we measured DLCO, the membrane conductance, and Vc before and after heart transplantation. At the time of hemodynamic measurements, the Roughton and Forster method of measuring DLCO at varying alveolar oxygen concentrations was used to determine the membrane conductance, Vc, DLCO/alveolar volume (VA), the membrane conductance/VA and thetaVc/VA (theta = carbon monoxide conductance of blood, VA = alveolar volume) in 21 patients with class III to IV heart failure before and after transplantation, and in 21 healthy controls. Transplantation normalized pulmonary capillary pressure and increased cardiac index. DLCO was decreased before transplantation (7.11 vs 10.0 mmol/min/kPa in controls), but DLCO/VA was normal (1.67+/-0.44 vs 1.71+/-0.26 mmol/min/kPa/L in controls). DLCO/VA remained unchanged after transplantation, because the decrease in Vc (82+/-30 vs 65+/-18 ml before and after transplantation) and thetaVc/VA was not compensated by the changes in membrane conductance (11+/-4 vs 12+/-5 mmol/min/kPa before and after transplantation, respectively) and membrane conductance/VA. We conclude that the decrease in DLCO in patients with chronic heart failure is due to a restrictive ventilatory pattern because their DLCO/VA remains normal; the decrease in the membrane conductance is compensated by the increase in Vc. After transplantation, the decrease in Vc due to normalization of pulmonary hemodynamics is not completely compensated for by an increase in membrane conductance. Because the membrane conductances, measured before and after transplantation, are negatively correlated with duration of heart failure, its abnormal pulmonary hemodynamics may have irreversibly altered the alveolar capillary membrane.

Skeletal muscle mitochondrial dysfunction during chronic obstructive pulmonary disease: central actor and therapeutic target

•  What is the topic of this review? Muscle dysfunction is a common complication and an important independent prognostic factor in chronic obstructive pulmonary disease (COPD). •  What advances does it highlight? In COPD patients, the vastus lateralis muscle presents with alterations that include a decrease in mitochondrial density and biogenesis, impaired mitochondrial respiration and coupling, as well as increased mitochondrial production of reactive oxygen species, possibly associated with increased mitochondrial apoptosis. These mitochondrial changes are accessible to conventional therapies, such as exercise and tobacco cessation, but potentially also to innovative management strategies, such as antioxidant treatment and supplementation with polyunsaturated fatty acids. Mitochondrial pathophysiology represents an emerging area of research in muscle dysfunction associated with COPD and has promising therapeutic implications.

Sleep deprivation blunts the night time increase in aldosterone release in humans

The aim of this study was to determine the effect of sleep deprivation on the 24‐h profile of aldosterone and its consequences on renal function. Aldosterone and its main hormonal regulatory factors, ACTH (evaluated by cortisol measurement) and the renin‐angiotensin system [RAS, evaluated by plasma renin activity (PRA) measurement] were determined every 10 min for 24 h in eight healthy subjects in the supine position, once with nocturnal sleep and once during total 24‐h sleep deprivation. Plasma Na+ and K+ were measured every 10 min in four of these subjects. In an additional group of 13 subjects under enteral nutrition, diuresis, natriuresis and kaliuresis were measured once during the sleep period (23.00–07.00 h) and once during a 23.00–07.00 hours sleep deprivation period. During sleep deprivation, aldosterone displayed lower plasma levels and pulse amplitude in the 23.00–07.00‐hour period than during sleep. Similarly, PRA showed reduced levels and lower pulse frequency and amplitude. Plasma cortisol levels were slightly enhanced during sleep deprivation. Overnight profiles of plasma K+ and Na+ were not affected. Diuresis and kaliuresis were not influenced by sleep deprivation. In contrast, natriuresis significantly increased during sleep deprivation. This study demonstrates that sleep deprivation modifies the 24‐h aldosterone profile by preventing the nocturnal increase in aldosterone release and leads to altered overnight hydromineral balance.

Time‐courses in renin and blood pressure during sleep in humans

We previously described a strong concordance between nocturnal oscillations in plasma renin activity (PRA) and the rapid eye movement (REM) and non‐REM (NREM) sleep cycles, but the mechanisms inducing PRA oscillations remain to be identified. This study was designed to examine whether they are linked to sleep stage‐related changes in arterial blood pressure (ABP). Analysis of sleep electroencephalographic (EEG) activity in the delta frequency band, intra‐arterial pressure, and PRA measured every 10 min was performed in eight healthy subjects. Simultaneously, the ratio of low frequency power to low frequency power + high frequency power [LF/(LF + HF)] was calculated using spectral analysis of R–R intervals. The cascade of physiological events that led to increased renin release during NREM sleep could be characterized. First, the LF/(LF + HF) ratio significantly (P < 10−4) decreased, indicating a reduction in sympathetic tone, concomitantly to a significant (P < 10−3) decrease in mean arterial pressure (MAP). Delta wave activity increased (P < 10−4) 10–20 min later and was associated with a lag of 0–10 min with a significant rise in PRA (P < 10−4). Rapid eye movement sleep was characterized by a significant increase (P < 10−4) in the LF/(LF + HF) ratio and a decrease (P < 10−4) in delta wave activity and PRA, whereas MAP levels were highly variable. Overnight cross‐correlation analysis revealed that MAP was inversely correlated with delta wave activity and with PRA (P < 0.01 in all subjects but one). These results suggest that pressure‐dependent mechanisms elicit the nocturnal PRA oscillations rather than common central processes controlling both the generation of slow waves and the release of renin from the kidney.