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Retrospective study of prospectively collected data to assess the reliability of cervical magnetic stimulation (CMS) to detect prolonged phrenic nerve (PN) conduction time at the bedside. Because PN injuries may cause diaphragm dysfunction, their diagnosis is relevant in intensive care units (ICU). This is achieved by studying latency and amplitude of diaphragm response to PN stimulation. Electrical stimulation (ES) is the gold standard, but it is difficult to perform in the ICU. CMS is an easy noninvasive tool to assess PN integrity, but co-activates muscles that could contaminate surface chest electromyographic recordings. In a first set of 56 ICU patients with suspected PN injury, presence and latency of compound motor action potentials elicited by CMS and ES were compared. With ES as the reference method, CMS was evaluated as a test designed to indicate presence or absence of PN injury. In eight additional patients, intramuscular diaphragm recordings were compared with surface diaphragm recordings and with the electromyograms of possible contamination sources. The sensitivity of CMS to diagnose abnormal PN conduction was 0.91, and specificity was 0.84, whereas positive and negative predictive values were 0.81 and 0.92, respectively. Passing–Bablok regression analysis suggested no differences between the two measures. The correlation between PN latency in response to CMS and ES was significant. The “diaphragm surface” and “needle” latencies were close, and were significantly different from those of possibly contaminating muscles. One hemidiaphragm showed likely signal contamination. CMS provides an easy reliable tool to detect prolonged PN conduction time in the ICU.

To determine the prevalence and risk factors of symptoms of anxiety, depression, and posttraumatic stress disorder-related symptoms in patients with chronic obstructive pulmonary disease and their relatives after an intensive care unit stay.Prospective multicenter study.Nineteen French intensive care units.One hundred twenty-six patients with chronic obstructive pulmonary disease who survived an intensive care unit stay and 102 relatives.None.Patients and relatives were interviewed at intensive care unit discharge and 90 days later to assess symptoms of anxiety and depression using Hospital Anxiety and Depression Scale (HADS) and posttraumatic stress disorder-related symptoms using the Impact of Event Scale (IES). At intensive care unit discharge, 90% of patients recollected traumatic psychological events in the intensive care unit. At day 90, we were able to conduct telephone interviews with 53 patients and 47 relatives. Hospital Anxiety and Depression Scale scores indicated symptoms of anxiety and depression in 52% and 45.5% of patients at intensive care unit discharge and in 28.3% and 18.9% on day 90, respectively. Corresponding prevalence in relatives were 72.2% and 25.7% at intensive care unit discharge and 40.4% and 14.9% on day 90, respectively. The Impact of Event Scale indicated posttraumatic stress disorder-related symptoms in 20.7% of patients and 29.8% of relatives on day 90. Peritraumatic dissociation assessed using the Peritraumatic Dissociative Experiences Questionnaire was independently associated with posttraumatic stress disorder-related symptoms in the patients and relatives. Previous intensive care unit experience and recollection of bothersome noise in the intensive care unit predicted posttraumatic stress disorder-related symptoms in the patients.Psychiatric symptoms were found to be common in a group of 126 patients with chronic obstructive pulmonary disease who survived an intensive care unit stay and their relatives at intensive care unit discharge and 90 days later. Peritraumatic dissociation at intensive care unit discharge was found to independently predict posttraumatic stress disorder-related symptoms in this sample of patients and relatives.

In humans, anatomy indicates that the phrenic nerve mainly arises from the C4 cervical root, with variable C3 and C5 contributions. How this translates into functional innervation is unknown. The diaphragm response to electrical stimulation of C3, C4 and C5 was described in three patients undergoing surgical laryngeal reinnervation with an upper phrenic root (surface chest electrodes at anterior, lateral and posterior sites; oesophageal and gastric pressures (Pes and Pga) to derive transdiaphragmatic pressure (Pdi)). Anatomically, the phrenic nerve predominantly originated from C4. Phrenic stimulation elicited motor responses at the three sites in the three patients, as did C4 stimulation. It produced Pdi values of 9, 11, and 14 cm H 2 O in the three patients, respectively, vs. 9, 9, and 7 cm H 2 O for C4. C3 stimulation produced modest Pdi responses, whereas C5 stimulation could produce Pdi responses close to those observed with C4 stimulation. These singular observations confirm the dominance of C4 in diaphragm innervation but suggest than C5 can be of importance.

International audience; Rationale. Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans. Objectives: To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena. Methods: Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-kappa B, and calpains). Measurements and Main Results: TwPtr decreased progressively during MV, with a mean reduction of 32 +/- 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 +/- 4.8 vs. 4.7 +/- 0.6% area), decreased cross-sectional area of muscle fibers (1,904 +/- 220 vs. 3,100 +/- 329 mu m(2)), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-kappa B (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm. Conclusions: Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.

Congenital central hypoventilation syndrome (CCHS), or Ondine's curse syndrome, is a rare genetic disorder associated with mutations of the PHOX2B gene. It is characterized by sleep-related life-threatening hypoventilation that requires mechanical ventilation. The ventilatory response to hypercapnia and hypoxia is absent or dramatically reduced. Spontaneous or pharmacologically induced recovery has never been reported. We have fortuitously observed a case of CO(2)-chemosensitivity recovery in a woman with CCHS who took a progestin contraceptive - desogestrel. We hypothesized that the desogestrel could be responsible for this effect. We tested this hypothesis in a second adult patient. Her lack of CO(2)-chemosensitivity was documented 5 months before she was prescribed desogestrel. Three weeks after initiation of the treatment she exhibited a ventilatory and sensory response to hypercapnia. This response persisted 3 weeks later. This is the first documented case of pharmacologically restored chemosensitivity in CCHS. It suggests that a very potent progestin such as desogestrel could unveil latent chemosensitive neural circuits.

Humans can program and control movements, including breathing-related movements. On the electroencephalogram (EEG), this preparation is accompanied by a low-amplitude negativity starting ∼2.5 s before inspiration that is best known as a Bereitschaftspotential (BP). The presence of BPs has been described during the compensation of mechanical inspiratory loading, thus identifying a cortical involvement in the corresponding ventilatory behavior. The pathophysiological interpretation of this cortical involvement depends on its transient or enduring nature. This study addressed this issue by looking for BPs during sustained inspiratory loading (1 h). Nine healthy male volunteers were studied during unloaded quiet breathing and inspiratory threshold loading (with unloaded expiration). Analyses of EEG signal and ventilatory variables were used to compare beginning and end of sessions. Inspiratory threshold loading caused ventilatory modifications that persisted, unchanged, for an hour. The presence of a BP at the beginning and end of a session was the most frequent occurrence (6 of 9 cases with a 17-cmH2O threshold load; 8 of 9 cases with a 23-cmH2O load). These observations support the hypothesis that the cerebral cortex is involved in the compensation of sustained experimental inspiratory loading. How this translates to respiratory disease involving acute changes in respiratory mechanics remains to be determined.

Expulsive maneuvers (EMs) caused by simultaneous contraction of diaphragm and abdominal muscles shift substantial quantities of blood from the splanchnic circulation to the extremities. This suggests that the diaphragm assisted by abdominal muscles might accomplish ventilation and circulation simultaneously by repeated EMs. We tested this hypothesis in normal subjects by measuring changes (Δ) in body volume (Vb) by whole body plethysmography simultaneously with changes in trunk volume (Vtr) by optoelectronic plethysmography, which measures the same parameters as whole body plethysmography plus the volume of blood shifts (Vbs) between trunk and extremities: Vbs = ΔVtr − ΔVb. We also measured abdominal pressure, pleural pressure, the arterial pressure wave, and cardiac output (Q̇c). EMs with abdominal pressure ∼100 cmH2O for 1 s, followed by 2-s relaxations, repeated over 90 s, produced a “stroke volume” from the splanchnic bed of 0.35 ± 0.07 (SD) liter, an output of 6.84 ± 0.75 l/min compared with a resting Q̇c of 5.59 ± 1.14 l/min. Refilling during relaxation was complete, and the splanchnic bed did not progressively empty. Diastolic pressure increased by 25 mmHg during each EM. Between EMs, Q̇c increased to 7.09 ± 1.14 l/min due to increased stroke volume and heart rate. The circulatory function of the diaphragm assisted by simultaneous contractions of abdominal muscles with appropriate pressure and duration at 20 min−1can produce a circulatory output as great as resting Q̇c, as well as ventilation. These combined functions of the diaphragm have potential for cardiopulmonary resuscitation. The abdominal circulatory pump can act as an auxiliary heart.

Mouth (PmT), esophageal (PesT), and transdiaphragmatic pressure twitches (PdiT) in response to single supramaximal bilateral phrenic nerve shocks were recorded during relaxation between total lung capacity (TLC) and functional residual capacity (FRC) in five normal volunteers. The PmT versus PesT or PmT versus PdiT relationships, which were linearly correlated (all r greater than 0.76), were not affected by diaphragm fatigue and were reproducible on repeated determinations over a period exceeding 1 yr. The PmT versus lung volume relationship was also linear (all r greater than 0.72) and reproducible, and its changes following diaphragm fatigue reliably reflected the changes in diaphragm contractility. We conclude that PmT is a reliable measure of diaphragm pressure-generating capacity in normal individuals and has the potential of providing similar information in patients.

The transdiaphragmatic pressure twitches (PdiT) in response to single maximal shocks delivered bilaterally to the phrenic nerves were recorded as a function of lung volume when the diaphragm was fresh and when fatigued. All relationships were linear and negatively sloped (all r greater than 0.85). From these relationships PdiT was found to decrease with fatigue more rapidly and to recover more quickly at high than at low lung volumes. Complete recovery of PdiT at all lung volumes was greater than 1 h. Contraction and relaxation rate constants of PdiT did not change significantly with fatigue. We conclude that fatigue affects diaphragm contractility more at high than at low lung volumes and that changes in diaphragm contractility are best reflected in the measurement of PdiT as a function of lung volume.

Resume Par opposition au hoquet aigu, frequent, de duree limitee et de pronostic benin, le hoquet chronique — defini par la poursuite de secousses de hoquet pendant plus de 48 heures — est rare, invalidant et difficile a traiter. Nous en rapportons 18 cas, recueillis en quatre ans. Il s'agit d'adultes d'âge souvent avance (moyenne = 58,6 ans) qui apres un mode de declenchement variable ont installe un hoquet dont la duree va de 10 jours a 30 ans. Les differentes manœuvres physiques, medications et interventions œsophagiennes se sont revelees dans l'ensemble inefficaces. Pourtant, un reflux gastro-œsophagien existe des l'apparition du hoquet chronique dans 50 % et apparait secondairement dans 5 % de cas supplementaires. Si les medicaments anti-secretoires gastriques, les pansements gastriques et les prokinetiques ont parfois un certain succes au stade precoce du hoquet chronique associe a un reflux, a un stade ulterieur le hoquet semble s'autoperpetuer. De nombreux medicaments neurotropes ont ete proposes (neuroleptiques, antidepresseurs tricycliques, benzodiazepines, anticomitiaux); aucun n'est regulierement efficace. Le baclofene a donne des resultats interessants (taux de reponse = 60%). L'etude systematique de ces 18 cas selon un plan uniforme montre que le hoquet chronique est une entite a part entiere. La decouverte d'une etiologie permet parfois un traitement adapte.

Inspiratory loading in awake humans is associated with electroencephalographic signs of supplementary motor area (SMA) activation. To provide evidence for a functional connection between SMA and the diaphragm representation in the primary motor cortex (M1DIA), we tested the hypothesis that modulating SMA activity using repetitive transcranial magnetic stimulation (rTMS) would alter M1DIA excitability. Amplitude and latency of diaphragm motor evoked potentials (MEPDIA), evoked through single pulse M1DIA stimulation, before and up to 16 min after SMA stimulation, were taken as indicators of M1DIA excitability. MEPs from the first dorsal interosseous muscle (FDI, MEPFDI) served as a control. Four SMA conditioning sessions were performed in random order at 1-wk intervals. Two aimed at increasing SMA activity (5 and 10 Hz, both at 110% of FDI active motor threshold; referred to as 5Hz and 10Hz, respectively), and two aimed at decreasing it (1 Hz either at 110% of FDI active or resting motor threshold, referred to as aMT or rMT, respectively). The 5Hz protocol increased MEPDIA and MEPFDI amplitudes with a maximum 11–16 min poststimulation ( P = 0.04 and P = 0.02, respectively). The 10Hz protocol increased MEPFDI amplitude with a similar time course ( P = 0.03) but did not increase MEPDIA amplitude ( P = 0.32). Both aMT and rMT failed to decrease MEPDIA or MEPFDI amplitudes ( P = 0.23 and P = 0.90, respectively, for diaphragm and P = 0.48 and P = 0.14 for FDI). MEPDIA and MEPFDI latencies were unaffected by rTMS. These results demonstrate that 5-Hz rTMS over the SMA can increase the excitability of M1DIA. These observations are consistent with the hypothesis of a functional connection between SMA and M1DIA.

Background Upper airway collapse does not occur during wake in obstructive sleep apnea patients. This points to wake-related compensatory mechanisms, and possibly to a modified corticomotor control of upper airway dilator muscles. The objectives of the study were to characterize the responsiveness of the genioglossus to transcranial magnetic stimulation during respiratory and non-respiratory facilitatory maneuvers in obstructive sleep apnea patients, and to compare it to the responsiveness of the diaphragm, with reference to normal controls. Methods Motor evoked potentials of the genioglossus and of the diaphragm, with the corresponding motor thresholds, were recorded in response to transcranial magnetic stimulation applied during expiration, inspiration and during maximal tongue protraction in 13 sleep apnea patients and 8 normal controls. Main Results In the sleep apnea patients: 1) combined genioglossus and diaphragm responses occurred more frequently than in controls (P < 0.0001); 2) the amplitude of the genioglossus response increased during inspiratory maneuvers (not observed in controls); 3) the latency of the genioglossus response decreased during tongue protraction (not observed in controls). A significant negative correlation was found between the latency of the genioglossus response and the apnea-hypopnea index; 4) the difference in diaphragm and genioglossus cortico-motor responses during tongue protraction and inspiratory loading differed between sleep apnea and controls. Conclusion Sleep apnea patients and control subjects differ in the response pattern of the genioglossus and of the diaphragm to facilitatory maneuvers, some of the differences being related to the frequency of sleep-related events.

Cardioventilatory coupling (CVC), a transient temporal alignment between the heartbeat and inspiratory activity, has been studied in animals and humans mainly during anesthesia. The origin of the coupling remains uncertain, whether or not ventilation is a main determinant in the CVC process and whether the coupling exhibits chaotic behavior. In this frame, we studied sedative-free, mechanically ventilated patients experiencing rapid sequential changes in breathing control during ventilator weaning during a switch from a machine-controlled assistance mode [assist-controlled ventilation (ACV)] to a patient-driven mode [inspiratory pressure support (IPS) and unsupported spontaneous breathing (USB)]. Time series were computed as R to start inspiration (RI) and R to the start of expiration (RE). Chaos was characterized with the noise titration method (noise limit), largest Lyapunov exponent (LLE) and correlation dimension (CD). All the RI and RE time series exhibit chaotic behavior. Specific coupling patterns were displayed in each ventilatory mode, and these patterns exhibited different linear and chaotic dynamics. When switching from ACV to IPS, partial inspiratory loading decreases the noise limit value, the LLE, and the correlation dimension of the RI and RE time series in parallel, whereas decreasing intrathoracic pressure from IPS to USB has the opposite effect. Coupling with expiration exhibits higher complexity than coupling with inspiration during mechanical ventilation either during ACV or IPS, probably due to active expiration. Only 33% of the cardiac time series (RR interval) exhibit complexity either during ACV, IPS, or USB making the contribution of the cardiac signal to the chaotic feature of the coupling minimal. We conclude that 1) CVC in unsedated humans exhibits a complex dynamic that can be chaotic, and 2) ventilatory mode has major effects on the linear and chaotic features of the coupling. Taken together these findings reinforce the role of ventilation in the CVC process.

Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunosuppressed patients. The number of non-HIV immunosuppressed patients at risk for Pneumocystis pneumonia is rapidly growing. In contrast to HIV patients, there are no guidelines for Pneumocystis prophylaxis in other immunocompromised hosts. A detailed analysis of current literature data allowed us hereby to define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.

In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm.In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion).At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa).The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.

International audience; Human ventilation at rest exhibits complexity and chaos. The aim of this study was to determine whether suprapontine interferences with the automatic breathing control could contribute to ventilatory chaos. We conducted a post hoc analysis of a previous study performed in awake volunteers exhibiting cortical pre-motor potentials during inspiratory loading. In eight subjects, flow was recorded at rest, while breathing against inspiratory threshold loads (median 21.5 cm H(2)O) and resistive loads (50 cm H(2)Ol(-1)s(-1)) loads, and while inhaling 7% CO(2)-93% O(2). Chaos was identified through noise titration (noise limit, NL) and the sensitivity to initial conditions was assessed through the largest Lyapunov exponent (LLE). Breath-by-breath variability was evaluated using the coefficient of variation of several ventilatory variables. Chaos was consistently present in ventilatory flow recordings, but mechanical loading did not alter NL, LLE, or variability. In contrast, CO(2) altered chaos and reduced variability. In conclusion, inspiratory loading - and any resultant respiratory-related cortical activity - were not associated with changes in ventilatory chaos in this study, arguing against suprapontine contributions to ventilatory complexity.

Upper airway stabilizing muscles play a crucial role in the maintenance of upper airway patency. Transcranial magnetic stimulation allows the investigation of the corticomotor activation process for respiratory muscles. This technique has also been used to evaluate the genioglossus corticomotor response. The aims of this study were to characterize the response of different upper airway stabilizing muscles to focal cortical stimulation of the genioglossus. Alae nasi, genioglossus, levator palatini, palatoglossus and diaphragm motor-evoked potential responses to transcranial magnetic stimulation were recorded during expiration, tidal inspiration and deep inspiration in nine normal awake subjects. A concomitant response of the four studied upper airway muscles was observed in the majority of cortical stimuli. The response of these muscles was independent of the diaphragmatic one that was only occasionally observed. Significant positive relationships were found between alae nasi, levator palatini and palatoglossus motor-evoked potential latencies and amplitudes and the corresponding values of the genioglossus. We conclude that transcranial magnetic stimulation applied in the genioglossus area induces a concomitant motor response of upper airway stabilizing muscles with consistent changes in their motor responses during inspiratory manoeuvres.

International audience; (1) makes important points relating to life most cogently. What we observe on the surface of the earth is most decidedly not what we might immediately predict from the Second Law of Thermodynamics, and this arises only through the constant supply of energy. In a sense, however, this is a permissive explanation-it says that we may observe ordered systems, but not necessarily that we should. Why should we observe ordered systems? At the heart of this lies an asymmetry. On the one hand, disordered configurations are much more likely than ordered configurations, but because of their very nature (disordered) they cannot replicate. On the other hand, rare ordered configurations have the potential through their very nature (ordered) to self-replicate. It is this asymmetry that allows imposition of order onto disorder and that generates the phenomena that we observe on earth. Within his article, Peter Macklem (1) describes autocatalytic sets in peptide chemistry as examples of such systems that have been generated in the laboratory. We lack, however, a more abstract understanding of the process. Questions include what sorts of objects and interactions have to be present for self-replicating systems to develop; how big do such sets have to be; how long do interactions have to run; and, so important to life, how do hierarchical layers of self-replicating systems develop? In this sense, life should be seen as the remarkable result of some physical law concerning a fundamental asymmetry between order and disorder. REFERENCE 1. Macklem PT. Viewpoint: Emergent phenomena and the secrets of life.

Ventilatory flow measured at the airway opening in humans exhibits a complex dynamics that has the features of chaos. Currently available data point to a neural origin of this feature, but the role of respiratory mechanics has not been specifically assessed. In this aim, we studied 17 critically ill mechanically ventilated patients during a switch form an entirely machine-controlled assistance mode (assist-controlled ventilation ACV) to a patient-driven mode (inspiratory pressure support IPS). Breath-by-breath respiratory variability was assessed with the coefficient of variation of tidal volume, total cycle time, inspiratory time, expiratory time, mean inspiratory flow, duty cycle. The detection of chaos was performed with the noise titration technique. When present, chaos was characterized with numerical indexes (correlation dimension, irregularity; largest Lyapunov exponent, sensitivity to initial conditions). Expectedly, the coefficients of variations of the respiratory variables were higher during IPS than during ACV. During ACV, noise titration failed to detect nonlinearities in 12 patients who did not exhibit signs of spontaneous respiratory activity. This indicates that the mechanical properties of the respiratory system were not sufficient to produce ventilatory chaos in the presence of a nonlinear command (ventilator clock). A positive noise limit was found in the remaining 5 cases, but these patients exhibited signs of active expiratory control (highly variable expiratory time, respiratory frequency higher than the set frequency). A positive noise limit was also observed in 16/17 patients during IPS (p < 0.001). These observations suggest that ventilatory chaos predominantly has a neural origin (intrinsic to the respiratory central pattern generators, resulting from their perturbation by respiratory afferents, or both), with little contribution of respiratory mechanics, if any.

Background Inspiratory occlusion evoked cortical potentials (the respiratory related-evoked potentials, RREPs) bear witness of the processing of changes in respiratory mechanics by the brain. Their impairment in children having suffered near-fatal asthma supports the hypothesis that relates asthma severity with the ability of the patients to perceive respiratory changes. It is not known whether or not chronic respiratory defects are associated with an alteration in brain processing of inspiratory loads. The aim of the present study was to compare the presence, the latencies and the amplitudes of the P1, N1, P2, and N2 components of the RREPs in children with chronic lung or neuromuscular disease. Methods RREPs were recorded in patients with stable asthma (n = 21), cystic fibrosis (n = 32), and neuromuscular disease (n = 16) and in healthy controls (n = 11). Results The 4 RREP components were significantly less frequently observed in the 3 groups of patients than in the controls. Within the patient groups, the N1 and the P2 components were significantly less frequently observed in the patients with asthma (16/21 for both components) and cystic fibrosis (20/32 and 14/32) than in the patients with neuromuscular disease (15/16 and 16/16). When present, the latencies and amplitudes of the 4 components were similar in the patients and controls. Conclusion Chronic ventilatory defects in children are associated with an impaired cortical processing of afferent respiratory signals.

Mammalian ventilation is driven by automatic structures producing "metabolic" ventilation. Respiratory neuroplasticity can adapt this control to developmental, environmental, and disease-related changes. A corticospinal diaphragm pathway accounts for behavioural disruptions of metabolic ventilation. It should be sensitive to use-dependent short-term plasticity. However, the brainstem-generated permanent diaphragm activity could alter the learning-related corticospinal plasticity (metaplasticity). To test this hypothesis, eight healthy volunteers (six women, 21-25) were studied before and after having learnt to produce prominent diaphragm contractions during voluntary inspiratory manoeuvres. Diaphragm training resulted in (1) a decreased liminal stimulation intensities; (2) an increased number of responding sites on the diaphragm mapping with focal stimulation (5.1+/-3.3 versus 9+/-4.4, p=0.004 in relaxed conditions; 8.9+/-5 versus 15.3+/-4.5, p0.0001, with underlying voluntary facilitation); (3) shortened motor evoked potentials latencies in response to non-focal stimulation (17.2+/-1.6 ms versus 16.2+/-1.4 ms, p=0.03 in relaxed conditions, and 16.8+/-1.1 ms versus 15.2+/-1.6 ms, p=0.003, with facilitation). These results are closely comparable with similar data in locomotor muscle. They provide a neurophysiological basis for the capacity of normal humans to rapidly acquire diaphragmatic skills.

Purpose To measure phrenic nerve conduction velocity in the neck in humans. Scope We studied 15 healthy subjects (9 men, 32.4±6.7). We performed bipolar electrical phrenic stimulation in the neck, from a distal and a proximal stimulation site, and recorded diaphragm electromyographic responses on the surface of the chest. The ratio of the between-site distance to the latency difference provided phrenic velocities. Ulnar motor velocity was assessed similarly. In addition, five homogeneous patients with Charcot-Marie-Tooth disease type 1A (CMT1A) were studied for validation purposes. We obtained diaphragmatic responses from the two stimulation sites in all cases. The distal latencies (anterior axillary line recording) were 6.51±0.63ms (right) and 6.13±0.64ms (left). The minimal between site distance was 39mm. Phrenic motor velocity was 55.2±6.3ms −1 (right) and 56.3±7.2ms −1 (left). In CMT1A, phrenic velocities were 17.1±8.1ms −1 (from 7 to 32ms −1 ) and were similar to ulnar and median velocities. Conclusions Phrenic nerve velocities can be estimated in humans and compare with upper limb motor conduction velocities. This should refine the investigation of phrenic function in peripheral neuropathies.

International audience; Dyspnea, a leading respiratory symptom, shares many clinical, physiological, and psychological features with pain. Both activate similar brain areas. The neural mechanisms of dyspnea are less well described than those of pain. The present research tested the hypothesis of common pathways between the two sensations. Six healthy men (age 30-40 yr) were studied. The spinal nociceptive flexion reflex (RIII) was first established in response to electrical sural stimulation. Dyspnea was then induced through inspiratory threshold loading, forcing the subjects to develop 70% of their maximal inspiratory pressure to inhale. This led to progressive inhibition of the RIII reflex that reached 50 +/- 12% during the fifth minute of loading (P < 0.001), was correlated to the intensity of the self-evaluated respiratory discomfort, and had recovered 5 min after removal of the load. The myotatic H-reflex was not inhibited by inspiratory loading, arguing against postsynaptic alpha motoneuron inhibition. Dyspnea, like pain, thus induced counterirritation, possibly indicating a C-fiber stimulation and activation of diffuse noxious inhibitory descending controls known to project onto spinal dorsal horn wide dynamic range neurons. This confirms the noxious nature of certain types of breathlessness, thus opening new physiological and perhaps therapeutic perspectives.

Introduction Congenital central hypoventilation syndrome (CCHS, or Ondine's curse syndrome), a rare genetic disease, is characterized by a deficient respiratory response to hypoxia and hypercapnia, associated to vagal dysfunction. Serendipitous observations of restored ventilatory response to hypercapnia associated to progestin led to the hypothesis that oral contraceptive treatment (desogestrel or levonorgestrel) might also improve vagal activity. This was assessed by analyses of heart rate variability (HRV) during hypercapnic and hypoxic challenges. Methods ECG was recorded in 5 CCHS adult women enrolled in the RESPIRONDINE study ( NCT01243697 ): – during normoxia; – during hypercapnia (CO 2 rebreathing); – during progressive hypoxia. High frequency versus high plus low frequency (HF n.u., reflects parasympathetic control) and high frequency versus low frequency power (LF/HF, reflects sympathetic activity) were calculated, without (before or after a washout of 4 months) or during oral contraceptive treatment. Results During normoxia, LF/HF (2.43 ± 0.17 ms 2 ), HF n.u. (0.31 ± 0.03) and HR (82.6 ± 2.18 bpm) remained statistically unaffected by the progestative treatment ( P = 0.85, P = 0.83 and P = 0.93, respectively). During hypercapnic challenges and independently of contraceptive treatment ( n = 5), we observed a decrease in LF/HF ( P = 0.004 and P P P = 0.005). During hypoxic challenges and independently of the progestative treatment ( n = 3), an increase in LF/HF was always observed. Conclusions CCHS patients display an increase in the parasympathetic tone and a decrease in the sympathetic tone during hypercapnia. They also display an increase in sympathetic tone during hypoxia. This is similar to what occurs in healthy subjects. These results suggest a relative preservation of chemoreception that influences the cardiac function but probably not ventilation.

Background Pilot studies have evidenced the possibility of altering corticospinal projections to phrenic motoneurons (PMNs) and modifying respiratory behavior using repetitive transcranial magnetic stimulation (rTMS). Similar evidence lacks regarding induced neuroplasticity at the spinal level. Objective This study was designed to investigate the immediate and long-lasting effects of a single session of transcutaneous spinal direct current stimulation (tsDCS), a non-invasive way of modulating spinal cord functions, on corticophrenic excitability in healthy humans. Methods Using a double-blind, controlled, randomized crossover approach, we examined the effects of anodal, cathodal, and sham tsDCS delivered to C3–C5 on: – diaphragm motor-evoked potentials (DiMEP) elicited by transcranial magnetic stimulation (TMS); – resting motor threshold (rMT) of the diaphragm and short interval intracortical inhibition (sICI) thought to reflect GABAergic inhibition in the motor cortex; – spontaneous ventilation, as measured by respiratory inductance plethysmography and a measure of ventilatory mathematical complexity (noise limit). Results and conclusions Both anodal and cathodal tsDCS induced a progressive increase of DiMEP amplitude during stimulation that persisted for at least 20 min after current offset. They also lowered rMT. sICI and noise limit were unchanged, suggesting that enhanced excitability was spinal rather than cortical or medullary. Cathodal tsDCS induced a persistent increase in tidal volume. tsDCS can therefore result in polarity-dependent breathing pattern changes, which opens the perspective of harnessing respiratory plasticity as a therapeutic tool in disorders altering the central ventilatory command or its spinal transmission.

Objectifs La dyspnee est un determinant majeur de la qualite de vie au cours de la BPCO. Son impact est etroitement lie a l’intolerance a l’exercice. La dyspnee, comme la douleur, est multidimensionnelle, avec des composantes sensorielle (S) et affective (A). Cette etude decrit les relations entre « S » et « A » et differents criteres de jugement au cours de la BPCO. Methodes Deux cent soixante-seize patients, recrutes par 74 praticiens a l’occasion d’un ajustement therapeutique (âge 66 ; VEMS 44 % ; CRF 149 % ; GOLD 2, 3, 4 : 34, 36, 30 % ; GOLD ABCD : 8, 20, 8, 64 % ; comorbidites cardiovasculaires 56 % ; exacerbations au cours de la derniere annee : 144 patients). Le critere de jugement principal etait le « profil multimensionnel de dyspnee » ( multidimensional dyspnea profile [MDP]). Resultats Le MDP avait une bonne validite multidimensionnelle et une bonne coherence interne (Cronbach's α > 0,8). « S » etait mieux correle que « A » aux scores MMRC, CAT, et DIRECT (handicap). « A » etait mieux correle aux scores SF-12 et HADS-anxiete. « S » augmentait lineairement avec MMRC, tandis que « A » augmentait de facon disproportionnee lors du passage de MMRC 3 a MMRC 4. En analyse multivariee, « A » etait lie au VEMS, a la presence d’elements depressifs, et au type d’activite physique (d’autant plus intense qu’activite limitee aux actions de la vie quotidienne). Conclusion 1) le MDP est psychometriquement robuste au cours de la BPCO ; 2) il est possible d’evaluer separement les composantes sensorielle et affective de la dyspnee en pratique pneumologique courante ; 3) ces composantes ont des impacts differents sur les caracteristiques cliniques de la BPCO.

Objectif La compression osteopathique du ganglion pterygo-palatin (GPP), relais du systeme sympathique et des nerfs crâniens mixtes, ameliore potentiellement la permeabilite des voies aeriennes superieures (VAS) et est utilisee empiriquement dans le traitement du ronflement. Cette etude en evaluait l’effet dans le syndrome d’apnees obstructives du sommeil (SAOS). Methodes Les compressions bilaterales active (CA) et simulee (CS) du GPP, validees par test de Schirmer, etaient comparees. Etaient recueillis avant CA et CS, a 30 min et 24 h, la pression critique de fermeture (Pcrit) des VAS et le debit de pointe intra-nasal (DPIN). Une polysomnographie etait realisee avant et 24 h apres. Resultats Trente patients (6F), 57 ± 11 ans, 92 ± 20 kg, Pcrit –22 ± 17,1 cmH2O, IAH 37 ± 21/h ont ete inclus. Par rapport a CS, CA a ameliore le DPIN (mediane [Q1 ; Q3] (L/min) a 30 min (14,8 [14,8 ; 39], p = 0,0001) et 24 h (30 [10 ; 45], p = 0,0001) et la Pcrit a 24 h (–2,2 [–5,3 ; –0,2] pour CA et –0,8 [-2,8 ; 1,8] pour CS ; difference –2,2[–6,4 ; 1,3] cmH2O ; p = 0,047). Il n’y avait pas de difference entre CA et CS sur l’index d’apnees-hypopnees, ni sur la Pcrit a 30 min. Conclusion La CA ameliore la stabilite des VAS a 24 h et la permeabilite nasale a 30 min et 24 h sans modifier l’index d’apnees-hypopnees. La compression du GPP semble affecter le controle neuro-vegetatif des VAS. Ces resultats preliminaires soutiennent la poursuite de l’investigation. Cette technique pourrait representer dans l’avenir un complement aux traitements conventionnels du SAOS. Financement PHRC 2011.

Objectif Evaluation en vie reelle, a long terme sur une cohorte de grande taille, peu d’etudes etant disponibles. Methodes Un volet retrospectif sur dossier chez tous les patients adresses au specialiste dentaire pour OAM entre janvier 2010 et juillet 2013 puis evaluation a 3–6 mois. Un volet prospectif (recueil telephonique) chez les patients traites depuis au moins un an au 16/09/14 (suivi 1–4 ans). Resultats Volet retrospectif : 458 patients inclus dont 309 (71 % H, 56 ± 12 ans, IMC 28 ± 6 kg/m 2 , IAH 30/h ± 17 [IAH > 30 : 40 %]) ont eu une pose d’OAM : Narval Cadcam n = 270, Narval non Cadcam n = 17, Somnomed n = 13, Orthosom n = 9. Cent quarante-neuf n’ont pas ete traites (83 contre-indication dentaire). Trente-quatre (11 %) ont arrete prematurement l’OAM. Deux cent vingt-trois patients (72 %) evalues, avec un IAH de 12 ± 10 au controle, un taux de succes (reduction ≥ 50 % de l’IAH) de 68 % (IAH p = 0,0002). Le controle polysomnographique etait disponible chez 78 % des patients du reseau mais seulement chez 39 % des patients hors reseau ( p Conclusion Cette etude apporte des donnees sur le parcours en vie reelle des patients ayant une prescription d’OAM. L’efficacite et la tolerance a court terme sont comparables a celles des essais cliniques. Environ 2/3 des patients poursuivent le traitement a long terme avec une efficacite clinique, une tolerance et une observance satisfaisantes. Le reseau a permis d’identifier en amont les contre-indications dentaires et d’augmenter le pourcentage de patients ayant une PSG de controle.

Objectif La compression osteopathique du ganglion pterygo-palatin (GPP), relais du systeme sympathique et des nerfs cr‚niens mixtes, ameliore potentiellement la permeabilite des voies aeriennes superieures (VAS). Elle est utilisee empiriquement en osteopathie, dans le traitement du ronflement et de la rhinite chronique. Cette etude en evaluait l’effet, chez des patients presentant un syndrome d’apnees obstructives du sommeil (SAOS) en methodologie prospective, randomisee, controlee, croisee, contre manœuvre factice, en simple aveugle pour l’osteopathe et double aveugle pour le medecin investigateur. Methodes Les compressions bilaterales active (CA) et simulee (CS) du GPP etaient comparees. Etaient recueillis avant CA et CS, a 30 min et 24 h, la pression critique de fermeture (Pcrit) des VAS et le debit de pointe intranasal. Une polysomnographie etait realisee avant et 24 h apres. Un test de Shirmer permettait de valider l’administration effective de CA (chez le sujet sain nous avions montre que la compression du GPP induisait une lacrymation). Resultats Trente patients (6F, 57 ± 11 ans, 92 ± 20 kg) avec une Pcrit basale de–22,5 ± 17,1 cmH 2 O et un index d’apnees-hypopnees de 37 ± 21/h ont ete inclus. Le test de Schirmer a montre que CA avait ete administree correctement ( p p = 0,0001) et 24 h (30 L/min [10 ; 45], p = 0,0001) et la Pcrit a 24 h (–2,2 cmH 2 O [–5,3 ;–0,2] pour CA et–0,8 cmH 2 O [–2,8 ; 1,8] pour CS ; difference–2,2 [–6,4 ; 1,3] ; p = 0,047). Il n’y avait pas de difference entre CA et CS sur l’index d’apnees-hypopnees, ni sur la Pcrit a 30 min. Conclusion La compression osteopathique du GPP ameliore la stabilite des VAS a 24 h et la permeabilite nasale a 30 min et 24 h, sans modifier l’index d’apnees-hypopnees. Elle semble affecter le controle neuro-vegetatif des VAS. Ces resultats preliminaires soutiennent la poursuite de l’investigation (duree de l’effet, identification des repondeurs). Cette technique pourrait representer dans l’avenir un complement aux traitements conventionnels du SAOS.

Les emotions negatives majorent la perception des sensations respiratoires. Le potentiel evoque respiratoire (PER) est une mesure electroencephalographique de la perception des sensations respiratoires. Nous avons teste l’hypothese que les emotions negatives diminuent le filtrage cerebral du PER. Deux PER (S1 et S2) etaient produits a 500 ms d’intervalle par occlusion inspiratoire. Le filtrage du PER etait calcule comme la difference d’amplitude entre les pics N1 du 2e (N1S2) et du 1er PER (N1S1). Les resultats etaient compares entre 2 conditions experimentales : emotion neutre et negative produites par la visualisation d’images affectives issues du systeme IAPS. Treize sujets sains ont participe (7 femmes, 6 hommes). Les resultats sont exprimes par la mediane [min ; max]. L’amplitude du pic N1 du 1er PER (N1S1) etait diminue en condition negative comparativement a la condition neutre (−3,37 μV [−4,62 ; −1,37] versus −4,59 μV [−6,08 ; −1,36] ; p = 0,017). Il n’y avait pas de difference d’amplitude des pics N1 du 2e PER (N1S2) entre les 2 conditions emotionnelles (−0,26 [−3,24 ; 2,36] versus −0,7 [−1,54 ; 3,6] ; p = 0,68). Le filtrage du PER etait significativement diminue en condition negative (score S2–S1 a 3,73 μV [0 ;5,82] versus 4,79 μV [3 ;6,2] ; p = 0,038). En conclusion, une stimulation emotionnelle negative produit 2 effets sur le PER : d’une part, une diminution d’amplitude du pic N1S1 probablement liee a un effet de distraction attentionnelle vers les images affectives au detriment des sensations respiratoires ; d’autre part, une diminution du filtrage du PER. Ce dernier mecanisme pourrait etre implique dans l’hyperperception des stimuli respiratoires repetes observee dans les situations d’emotion negative.

International audience; Background: Breathing in humans is dually controlled for metabolic (brainstem commands) and behavioral purposes (suprapontine commands) with reciprocal modulation through spinal integration. Whereas the ventilatory response to chemical stimuli arises from the brainstem, the compensation of mechanical loads in awake humans is thought to involve suprapontine mechanisms. The aim of this study was to test this hypothesis by examining the effects of inspiratory resistive loading on the response of the diaphragm to transcranial magnetic stimulation. Results: Six healthy volunteers breathed room air without load (R0) and then against inspiratory resistances (5 and 20 cmH 2 O/L/s, R5 and R20). Ventilatory variables were recorded. Transcranial magnetic stimulation (TMS) was performed during early inspiration (I) or late expiration (E), giving rise to motor evoked potentials (MEPs) in the diaphragm (Di) and abductor pollicis brevis (APB). Breathing frequency significantly decreased during R20 without any other change. Resistive breathing had no effect on the amplitude of Di MEPs, but shortened their latency (R20:-0.903 ms, p = 0.03) when TMS was superimposed on inspiration. There was no change in APB MEPs. Conclusion: Inspiratory resistive breathing facilitates the diaphragm response to TMS while it does not increase the automatic drive to breathe. We interpret these findings as a neurophysiological substratum of the suprapontine nature of inspiratory load compensation in awake humans. Background Breathing in humans fulfils both metabolic and behavioral functions. The automatic activity of brainstem central pattern generators continuously adapts ventilation to the production of carbon dioxide by the tissues. Suprapontine descending pathways convey voluntary and emotional respiratory commands that are independent of bodily requirements. Spinal respiratory motoneurons integrate

Objectives: To compare descriptors of the breath-to-breath respiratory variability during a 60-min spontaneous breathing trial in patients successfully and unsuccessfully separated from the ventilator and the endotracheal tube and to assess the usefulness of these predictors in discriminating these two categories of patients. Design: Prospective observational study. Setting: Four general intensive care units in university hospitals. Patients: A total of 51 consecutive patients mechanically ventilated for >24 hrs. Interventions: None. Measurements and Main Results: Tidal volume, respiratory period, inspiratory time, expiratory time, mean inspiratory flow (tidal volume/inspiratory time), and duty cycle (inspiratory time/ respiratory period) were obtained from the flow signal. Breathby-breath variability was expressed in terms of their coefficients of variation (CV), the number of breaths among which a significant correlation was found (lag), and the autocorrelation coefficient between one breath and the following one. Five patients were excluded because of nonstationarity of the data, leaving 46 cases for analysis. Between-group comparison was conducted with the Mann-Whitney test, and a nonparametric classification and regression tree was used to identify variables discriminating “success” (n 32) and “failure” patients (n 14). All coefficients of variation were significantly higher in success patients, who also exhibited significantly less respiratory autocorrelation (shorter “short memory”). The classification and regression tree analysis allocated all success patients to a group defined by a coefficient of variation of tidal volume/inspiratory time of >19% and a coefficient of variation of inspiratory time/respiratory period of >10% that did not contain any failure patient. All failure patients belonged to a group with coefficient of variation of tidal volume/inspiratory time of 11, and that contained no success patient. Conclusions: In intensive care unit patients undergoing a spontaneous breathing trial, breathing variability is greater in patients successfully separated from the ventilator and the endotracheal tube. Variability indices are sufficient to separate success from failure cases. (Crit Care Med 2006; 34:2076‐2083)

Background Opportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis. Case presentation We describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and agressive symptomatic treatment. Conclusion Invasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities.

The home ventilator market has grown in size and complexity. The aim of this study was to determine if common home ventilators are user-friendly for trained intensive care unit (ICU) physicians. Eleven ventilator models were tested by 13 ICU physicians without practical experience in home mechanical ventilation. Six tests were defined (start-up, unlocking, mode and setting recognition, mode change, pressure setting and alarm). For each test, the physicians were timed and their performance compared with a reference time established by a technician. The physicians also had to rate their global assessment of each machine on a visual analogue scale. The start-up test was the only test for which there was no significant difference between the physicians and the technician, except for two ventilators. The physicians were slower than the technician to unlock the ventilator and change the ventilatory mode, with some complete failures during these tests and heterogeneous results between physicians and between ventilators. Mistakes occurred in close to 50% of cases during the ventilatory mode and settings recognition test. The mean time for the most rapid of the physicians for all the tests was 58+/-53 s, compared with 15+/-9 s for the technician. In conclusion, trained intensive care unit physicians perform poorly when confronted with home mechanical ventilators without specific prior training. Therefore, it is hypothesised that the user-friendliness of home ventilators for other categories of users might be questionable.