[Variation in ventilatory response to CO2 in patients treated by non-invasive ventilation]. / Variation de la réponse ventilatoire au CO2 chez des patients appareillés par ventilation non invasive.

INTRODUCTION: There are many mechanisms for improving the clinical and blood gas status of patients with the obesity hypoventilation syndrome (OHS) or chronic obstructive pulmonary disease (COPD) by non-invasive ventilation (NIV) at home. Our objective was to set up a pilot study to evaluate the potential modification of the sensitivity of the respiratory centers to CO2 by NIV in paired new COPD and OHS patients. METHODS: We assessed the sensitivity of the respiratory centers to CO2 by the Read method in 3 COPD patients and 3 OHS patients newly treated by NIV and again 3 months later. We compared their results to those of 6 control subjects. RESULTS: All the patients included had altered ventilatory responses to CO2 with slopes of less of than 1 L.min-1.mmHg-1. Mean coefficients of variation were significantly higher in patients than in healthy subjects (P=0.007). Patients who improved their CO2 sensitivity slope were those most observant of NIV. CONCLUSION: This work showed significant changes in the ventilatory response to hypercapnia in patients with either OHS or COPD after NIV therapy. The significance of these changes deserves to be studied.

[Approaches to the pre-operative functional assessment of patients with lung cancer and preoperative rehabilitation]. / Bilan fonctionnel préopératoire du cancer bronchique et réhabilitation préopératoire.

Surgery is the best treatment for early lung cancer but requires a preoperative functional evaluation to identify patients who may be at a high risk of complications or death. Guideline algorithms include a cardiological evaluation, a cardiopulmonary assessment to calculate the predicted residual lung function, and identify patients needing exercise testing to complete the evaluation. According to most expert opinion, exercise tests have a very high predictive value of complications. However, since the publication of these guidelines, minimally-invasive surgery, sublobar resections, prehabilitation and enhanced recovery after surgery (ERAS) programmes have been developed. Implementation of these techniques and programs is associated with a decrease in postoperative mortality and complications. In addition, the current guidelines and the cut-off values they identified are based on early series of patients, and are designed to select patients before major lung resection (lobectomy-pneumonectomy) performed by thoracotomy. Therefore, after a review of the current guidelines and a brief update on prehabilitation (smoking cessation, exercise training and nutritional aspects), we will discuss the need to redefine functional criteria to select patients who will benefit from lung surgery.

Radiation-induced lung toxicity predictors: Retrospective analysis of 90 patients treated with stereotactic body radiation therapy for stage I non-small-cell lung carcinoma.

BACKGROUND: The main complication after hypofractionated radiotherapy for lung carcinoma is radiation-induced lung toxicity, which can be divided into radiation pneumonitis (acute toxicity, occurring within 6 months) and lung fibrosis (late toxicity, occurring after 6 months). The literature describes several predictive factors related to the patient, to the tumor (volume, central location), to the dosimetry and to biological factors. MATERIALS AND METHODS: This study is a retrospective analysis of 90 patients treated with stereotactic body irradiation for stage I non-small-cell lung carcinoma between December 2010 and May 2015. RESULTS: Radiation pneumonitis was observed in 61.5% of the patients who were mainly asymptomatic (34%). Chronic obstructive pulmonary disease was not predictive of radiation pneumonitis, whereas active smoking was protective. Centrally located tumors were not more likely to result in this complication if the radiation schedule utilized adapted fractionation. In our study, no predictive factor was identified. Whereas the mean lung dose was a predictive factor in 3D radiotherapy, the lung volume irradiated at high doses seemed to be involved in the pathogenesis after hypofractionated radiotherapy. CONCLUSION: The discovery of predictive factors for radiation pneumonitis is difficult due to the rarity of this complication, especially with an 8×7.5Gy schedule. Radiation pneumonitis seems to be correlated with the volume irradiated at high doses, which is in contrast to the known knowledge about the organs in parallel. This finding leads us to raise the hypothesis that vessel damage, organs in series, occurring during hypofractionated radiotherapy could be responsible for this toxicity.

Respiratory sound analysis in the era of evidence-based medicine and the world of medicine 2.0.

OBJECTIVE: This paper describes the state of the art, scientific publications, and ongoing research related to the methods of analysis of respiratory sounds. METHODS AND MATERIAL: Narrative review of the current medical and technological literature using Pubmed and personal experience. RESULTS: We outline the various techniques that are currently being used to collect auscultation sounds and provide a physical description of known pathological sounds for which automatic detection tools have been developed. Modern tools are based on artificial intelligence and techniques such as artificial neural networks, fuzzy systems, and genetic algorithms. CONCLUSION: The next step will consist of finding new markers to increase the efficiency of decision-aiding algorithms and tools.

[Vocal cord dyskinesia and/or asthma]. / Dyskinésie des cordes vocales et/ou asthme.

INTRODUCTION: Vocal cord dyskinesia or vocal cord dysfunction (VCD) is characterized by intermittent abnormal adduction of the vocal cords leading to airflow limitation at the level of the larynx, in the absence of local organic disease. It may occur in isolation or in association with asthma. The pathophysiology is complex and poorly understood. Wheeze, stridor or apparent upper airway obstruction are the most common symptoms. It occurs in a wide age range, more commonly in women, and diagnosis is often delayed and leads to unnecessary treatments (intubation, tracheostomy and high dose steroids). METHODS: A retrospective study of 15 cases of VCD (8 cases of isolated VCD and 7 cases of VCD with associated asthma) describing the main clinical features and the diagnosis strategy. RESULTS: Apparent upper airway obstruction, with or without associated asthma, requires an ear nose and throat examination with laryngoscopy to confirm the paradoxical adduction of the vocal cords during an acute episode of dyspnoea or during a provocation test with triggers like exercise or exposure to irritants, and for the purpose of differential diagnosis. CONCLUSIONS: VCD remains under-appreciated and misdiagnosed, often by mimicking asthma with which it can be associated. A delayed diagnosis by emergency specialists, pulmonologists and ear nose and throat surgeons leads to unnecessary treatments and morbidity before specific therapy can be given.

Diffusing capacity of the lung for CO and pulmonary blood flow during incremental and intermittent exercise.

The aims of this study were to evaluate the feasibility of successive diffusing capacity of the lung for carbon monoxide (DLCO) measurements during two different exercise tests (upright cycling), and to compare the relationships between DLCO and pulmonary blood flow (Qc). Eight healthy subjects performed an incremental test (1-min step) and a strenuous 30-min intermittent-work exercise test (4 min at low and 2 min at high workload). Intrabreath DLCO and Qc were calculated by assessing the uptake of CO and C2H2 during exhalation. DLCO could be measured reliably up to 73-90% of peak oxygen consumption (VO2) during the incremental test, and up to 85-95% of peak VO2 during the intermittent test. The coefficients of variation of DLCO and Qc measured during two successive constant-load exercise tests were 5-6% and 7-11%, respectively. The highest values of DLCO, Qc and VO2 measured during the incremental and intermittent tests were similar (56 and 51 mL/mmHg/min for DLCO, 18.7 and 18.3 L/min, for Qc and 2.4 and 2.3 L/min for VO2, respectively). The main observed result was that the linear relationships between DLCO and Qc were similar whatever the exercise type. This allows DLCO comparisons, with regards to Qc, during different exercise protocols.

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 finalized 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.

A comparison of four algorithms for the measurement of interrupter respiratory resistance in adults.

The aim of our study was to compare four algorithms for the measurement of respiratory resistance in adults using the interrupter technique. Four methods to estimate alveolar pressure from the mouth pressure during occlusion were assessed in 122 normal adults (57 males, 65 females, aged 18-79 yr, mean 41.2 +/- 15.6): taking the mean oscillation pressure (Rint), performing a linear back extrapolation (RintL) or a linear regression for the whole curve (RintRL), taking the end-occlusion pressure (RintE). Mean values for Rint, RintL and RintRL in males were respectively 0.23 +/- 0.04, 0.22 +/- 0.04 and 0.22 +/- 0.04 kPa s L(-1), not statistically different. In females values were respectively 0.27 +/- 0.05, 0.26 +/- 0.05 and 0.26 +/- 0.05 kPa s L(-1), not statistically different. RintE was higher than the remainder and was the only measure correlating weakly with morphometric variables: RintE = 1.152 - (0.00152 x age (yr)) - (0.00382 x height (cm)), r = 0.31 (p < 0.05) in females; RintE = 0.227 - (0.00122 x age (yr)) + (0.00830 x body mass index (kg m(-2))) with r = 0.34 (p < 0.05) in males. We conclude that it is equivalent to estimate alveolar pressure from or extrapolating it to the beginning of occlusion in healthy adults but when taking the end-occlusion pressure, resistance is higher and depends in part on morphometric parameters.

[Preoperative assessment of lung cancer patients before lung resection]. / L'évaluation cardio-respiratoire avant la chirurgie thoracique du cancer bronchique.

The aim of the functional evaluation of lung cancer patients before lung resection is to evaluate the risk of peri-operative cardio-respiratory complications. The successive steps of the functional assessment are determined according to the predictive value, the invasiveness, and the sophistication of the tests. The cardiovascular risk is evaluated using clinical predictors and ECG findings. If both are negative, the first step of the respiratory function assessment will be FEV1 measurement. Simultaneous measurement of CO diffusing lung capacity (DLCO), which has a high predictive value of complications, is highly recommended by some authors. The second and the third steps will be either exercise testing or split function studies based on quantitative perfusion scan results, the position of the test in the algorithm depending on the authors. Formal exercise testing has been found to be the best predictor of postoperative complications in several studies. However, it does not evaluate the functional contribution of the parenchyma to be resected, which required a perfusion scan. On the other hand, patients with low values of predicted post-operative FEV1 or DLCO should undergo exercise tests. Eventually, clinical, surgical and anesthetic factors should also be taken into account in addition to the functional evaluation to assess the perioperative risk of the patient.

Relationship between very high physical activity energy expenditure, heart rate variability and self-estimate of health status in middle-aged individuals.

In middle-aged persons, moderate physical activity energy expenditure (PAEE) has been shown to be associated with increased vagal-related heart rate variability (HRV) indexes and better health status. The purpose of this study was to determine whether a very high PAEE has greater effect on vagal-related HRV indexes and self-estimates of well-being in middle-aged subjects having distinct long-term physical activity profiles. Forty-four subjects were divided into three groups on the basis of the sport score of the Modified Baecke Questionnaire for Older Adults: sedentary (SED, n = 15), moderately-trained (MT, n = 16), and highly-trained subjects (HT, n = 13). PAEE was estimated by triaxial accelerometry during one week. Time and frequency domain HRV indexes were determined during quiet periods in the morning on 5-min R-R interval segments under controlled breathing. Quality of life was evaluated using the SF-36 health survey questionnaire. PAEE was significantly different for each group (374.5 +/- 13.8, 616.8 +/- 22.4, and 1086.6 +/- 43.2 kcal . day (-1) for SED, MT, and HT, respectively, p < 0.001). MT presented significantly higher vagal-related HRV indexes than SED and HT (p < 0.05). None of the HRV indexes was significantly greater in HT than in SED. MT and HT had similar health status scores, which were significantly higher than for SED. These results indicate that in middle-aged subjects, habitual moderate PAEE is associated with greater vagal tone and self-estimates of well-being compared to low PAEE. In contrast, very high PAEE is associated with similar vagal-related indexes as low PAEE, despite better overall health status.

Mechanisms of renal hyporesponsiveness to ANP in heart failure.

The atrial natriuretic peptide (ANP) plays an important role in chronic heart failure (CHF), delaying the progression of the disease. However, despite high ANP levels, natriuresis falls when CHF progresses from a compensated to a decompensated state, suggesting emergence of renal resistance to ANP. Several mechanisms have been proposed to explain renal hyporesponsiveness, including decreased renal ANP availability, down-regulation of natriuretic peptide receptors and altered ANP intracellular transduction signal. It has been demonstrated that the activity of neutral endopeptidase (NEP) is increased in CHF, and that its inhibition enhances renal cGMP production and renal sodium excretion. In vitro as well as in vivo studies have provided strong evidence of an increased degradation of intracellular cGMP by phosphodiesterase in CHF. In experimental models, ANP-dependent natriuresis is improved by phosphodiesterase inhibitors, which may arise as new therapeutic agents in CHF. Sodium-retaining systems likely contribute to renal hyporesponsiveness to ANP through different mechanisms. Among these systems, the renin-angiotensin-aldosterone system has received particular attention, as angiotensin II and ANP have renal actions at the same sites and inhibition of angiotensin-converting enzyme and angiotensin-receptor blockade improve ANP hyporesponsiveness. Less is known about the interactions between the sympathetic nervous system, endothelin or vasopressin and ANP, which may also blunt ANP-induced natriuresis. To summarize, renal hyporesponsiveness to ANP is probably multifactorial. New treatments designed to restore renal ANP efficiency should limit sodium retention in CHF patients and thus delay the progression to overt heart failure.

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.

Non-invasive cardiac output evaluation during a maximal progressive exercise test, using a new impedance cardiograph device.

One of the greatest challenges in exercise physiology is to develop a valid, reliable, non-invasive and affordable measurement of cardiac output (CO). The purpose of this study was to evaluate the reproducibility and accuracy of a new impedance cardiograph device, the Physio Flow, during a 1-min step incremental exercise test from rest to maximal peak effort. A group of 12 subjects was evaluated to determine the reproducibility of the method as follows: (1) each subject performed two comparable tests while their CO was measured by impedance cardiography using the new device (COImp1, COImp2), and (2) in a subgroup of 7 subjects CO was also determined by the direct Fick method (COFick) during the second test. The mean difference between the values obtained by impedance (i.e. COImp1-COImp2) was -0.009 l.min-1 (95% confidence interval: -4.2 l.min-1, 4.2 l.min-1), and CO ranged from 3.55 l.min-1 to 26.75 l.min-1 (n = 146). When expressed as a percentage, the difference (COImp1-COImp2) did not vary with increasing CO. The correlation coefficient between the values of COImp and COFick obtained during the second exercise test was r = 0.94 (P < 0.01, n = 50). The mean difference expressed as percentage was -2.78% (95% confidence interval: -27.44%, 21.78%). We conclude that COImp provides a clinically acceptable evaluation of CO in healthy subjects during an incremental exercise.

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.

Exercise training with a heart device: a hemodynamic, metabolic, and hormonal study.

PURPOSE: The mechanisms of the training-induced improvements in left ventricular assist (LVAD) patients are unknown. METHODS: We measured the hemodynamic, gas exchange, and metabolic and hormonal effects of 6-wk exercise training in a cardiogenic shock patient who was assisted by an LVAD. RESULTS: After training, the peak power and VO2 increased by 166% and 56%, respectively (80 W and 16.1 mL x min(-1) x kg(-1)), whereas the ventilatory drive decreased. Although the LVAD output increased little with exercise, the systemic cardiac output rose (adequately for the VO2) from 5.91 and 4.90 L x min(-1) at rest to 9.75 and 9.47 L x min(-1) at peak work rate, before and after training, respectively. Thus, the left ventricle ejected again through the aortic valve. Unloading and/or retraining resulted in a left ventricular filling pressure decrease. Although the right ventricular ejection fraction increased with exercise, it decreased again at the maximal load after training. For a given work rate the arterial lactate, the norepinephrine (NE) and epinephrine (E) concentrations fell after training, but the enhanced maximal work rate elicited higher NE and E concentrations (4396 and 1848 pg x mL(-1), respectively). The lack of right ventricular unloading might have kept the atrial natriuretic peptide higher after training, but the blood cyclic GMP and endothelin were lower after training. CONCLUSION: In an LVAD patient, retraining returns the exercise capacity to the class III level by peripheral and left ventricular hemodynamic improvements, but the safety of maximal exercise remains to be proven in terms of right ventricular function and orthosympathetic drive.

A new impedance cardiograph device for the non-invasive evaluation of cardiac output at rest and during exercise: comparison with the "direct" Fick method.

The objectives of this study were to evaluate the reliability and accuracy of a new impedance cardiograph device, the Physio Flow, at rest and during a steady-state dynamic leg exercise (work intensity ranging from 10 to 50 W) performed in the supine position. We compared cardiac output determined simultaneously by two methods, the Physio Flow (QcPF) and the direct Fick (QcFick) methods. Forty patients referred for right cardiac catheterisation, 14 with sleep apnoea syndrome and 26 with chronic obstructive pulmonary disease, took part in this study. The subjects' oxygen consumption values ranged from 0.14 to 1.19 l x min(-1). The mean difference between the two methods (QcFick - QcPF) was 0.04 l x min(-1) at rest and 0.29 l x min(-1) during exercise. The limits of agreement, defined as mean difference +/- 2SD, were -1.34, +1.41 l x min(-1)] at rest and -2.34, +2.92 l x min(-1) during exercise. The difference between the two methods exceeded 20% in only 2.5% of the cases at rest, and 9.3% of the cases during exercise. Thoracic hyperinflation did not alter QcPF. We conclude that the Physio Flow provides a clinically acceptable and non-invasive evaluation of cardiac output under these conditions. This new impedance cardiograph device deserves further study using other populations and situations.

Exercise-induced increase in circulating adrenomedullin is related to mean blood pressure in heart transplant recipients.

Adrenomedullin (ADM) is a newly discovered potent vasorelaxing and natriuretic peptide that recently has been shown to be increased after heart transplantation. To investigate the hemodynamic factors modulating its release and the eventual role of ADM in blood pressure regulation after heart transplantation, seven matched heart-transplant recipients (Htx) and seven normal subjects performed a maximal bicycle exercise test while monitoring for heart rate, blood pressure, and circulating ADM. Baseline heart rate and systemic blood pressure were higher in Htx; left ventricular mass index and ADM tended to be higher after heart transplantation and correlated positively in Htx (r = 0.79, P = 0.03). As expected, exercise-induced increase in heart rate was lower in Htx than in controls (60 +/- 11 % vs. 121 +/- 14 %, respectively) and blood pressure increase was similar in both groups. Maximal exercise increased significantly plasma ADM in both groups (from 25.3 +/- 3.1 to 30.7 +/- 3.5 pmol/L, P < 0.05 and from 15.2 +/- 1.4 to 29.1 +/- 4.4 pmol/L, P = 0.02 in Htx and controls, respectively), the hypotensive peptide level remaining elevated until the 30th min of recovery. A significant inverse relationship was observed between peak mean blood pressure and circulating ADM in Htx (r = -0.86, P < 0.02). Besides showing that circulating ADM is increased after heart transplantation, the present study demonstrates a positive relationship between baseline ADM and left ventricular mass index. Furthermore, maximal exercise-induced increase in ADM is inversely related to mean blood pressure in Htx, suggesting that ADM might participate in blood pressure regulation during exercise after heart transplantation.

Lack of acute cyclosporine nephrotoxicity in late heart-transplant recipients.

BACKGROUND: Cyclosporine induces daily renal hypoperfusion in subjects with normal atrial natriuretic peptide (ANP) levels, but its acute effects in heart transplant patients with increased ANP remain to be determined. METHODS: Cyclosporinemia and creatinine clearance were monitored during 7 hours following cyclosporine administration in 6 heart transplant patients. CONCLUSIONS: No acute cyclosporine-induced decrease in creatinine clearance was observed after heart transplantation. These data suggest that maintenance cyclosporine dose may be less nephrotoxic than suspected and that increased ANP might protect the renal function late after heart transplantation.