Search

BackgroundWhereas first-line bronchial artery embolisation (BAE) is considered standard of care for the management of severe haemoptysis, it is unknown whether this approach is warranted for non-severe haemoptysis.Research questionTo assess the efficacy on bleeding control and the safety of first-line BAE in non-severe haemoptysis of mild abundance.Study design and methodsThis multicentre, randomised controlled open-label trial enrolled adult patients without major comorbid condition and having mild haemoptysis (onset ResultsBleeding recurrence at day 30 after randomisation (primary outcome) occurred in 4 (11.8%) of 34 patients in the BAE strategy and 17 (44.7%) of 38 patients in the medical strategy (difference −33%; 95% CI −13.8% to −52.1%, p=0.002). The 90-day bleeding recurrence-free survival rates were 91.2% (95% CI 75.1% to 97.1%) and 60.2% (95% CI 42.9% to 73.8%), respectively (HR=0.19, 95% CI 0.05 to 0.67, p=0.01). No death occurred during follow-up and no bleeding recurrence needed surgery.Four adverse events (one major with systemic emboli) occurred during hospitalisation, all in the BAE strategy (11.8% vs 0%; difference 11.8%, 95% CI 0.9 to 22.6, p=0.045); all eventually resolved.ConclusionIn non-severe haemoptysis of mild abundance, BAE associated with medical therapy had a superior efficacy for preventing bleeding recurrences at 30 and 90 days, as compared with medical therapy alone. However, it was associated with a higher rate of adverse events.Trial registration numberNCT01278199

Background Phrenic pacing is an alternative to positive-pressure ventilation in selected patients, mostly in cases of upper spinal cord injury. We evaluated results of phrenic pacing performed by video-assisted thoracic surgery (VATS). Method Between 1997 and 2007, after complete neuromuscular investigations, 20 patients requiring full-time ventilation were selected for phrenic pacing (19 with posttraumatic tetraplegia and 1 with congenital central hypoventilation syndrome). Quadripolar cuff electrodes were fixed around each intrathoracic phrenic nerve via bilateral VATS. They were connected to a subcutaneous radiofrequency receiver coupled to an external radiofrequency transmitter. All patients participated in a reconditioning program beginning 2 weeks after implantation and continued until ventilatory weaning. Results Phrenic pacing was successful in all cases. No intraoperative complications or perioperative mortality were observed. Intraoperative testing detected stimulation thresholds in 19 patients (range, 0.05-2.9 mA). Ventilatory weaning was obtained in 18 patients. Median diaphragm reconditioning time was 6 weeks (2 weeks–11 months). Reconditioning was still in process in a young woman and was not achieved in an elderly woman with a 4-year history of tetraplegia. All the patients weaned from mechanical ventilation reported improved quality of life. Failure or delay in recovery of effective diaphragm contraction was due to nonreversible amyotrophy. Conclusions VATS implantation of 4-pole electrodes around the intrathoracic phrenic nerve is a safe procedure. Ventilatory weaning correlates with the degree of diaphragmatic amyotrophy. Phrenic pacing, performed as soon as neurologic and orthopedic stabilization is achieved, is the most important prognostic factor for successful weaning.

High cervical spinal cord injuries induce extreme handicap and tactile isolation. Tracheotomised tetraplegic patients are also bound to be olfaction deprived. By restoring negative pressure inspiration, diaphragm pacing (DP) should improve olfaction. We tested olfaction in 10 consecutive tetraplegics during positive pressure mechanical ventilation and DP, using the University of Pennsylvania Smell Identification Test (UPSIT). Quality of life was assessed using the Satisfaction with Life Scale (SWLS). Self-perceived benefits of DP were studied using an in-house questionnaire. Olfaction was very poor during positive pressure mechanical ventilation (UPSIT, mean+/-SD 17.1+/-6.4, anosmia or severe microsmia). It improved during DP (35.2+/-1.9, normosmia or mild microsmia; p0.0001) and SWLS was 18.5+/-4.2. Nine patients stated that DP had improved their quality of life. This was driven by better mobility (ranked first), improved self-image and relationships with others (ranked second), improved olfaction and better feeling of security (both ranked third). Improved olfaction is among the benefits of DP and should be mentioned to patients considered for this therapy. Furthermore, attention to olfaction is warranted in tracheotomised ventilator-dependent patients, as a putative path towards improvement of quality of life.

Resume Position du probleme La ventilation par tracheotomie est efficace chez des patients atteints de maladies neuromusculaires, mais contraignante. Le « retour » a une ventilation au masque (VNI) peut etre envisage, mais cette pratique n’est pas repandue, en partie faute de procedures standardisees permettant une transition sure. Methodes Une procedure de relais tracheotomie-ventilation au masque a ete elaboree a partir de la litterature et de l’experience locale (faisabilite de la ventilation non-invasive : absence de lesions laryngo-tracheales, compensation de fuites adequate ; efficacite de la toux). Elle a ete testee chez trois patients atteints de maladies neuromusculaires severes mais stables (polyradiculonevrite chronique dans deux cas, amyotrophie spinale progressive dans un cas), a titre preliminaire. Resultats Les trois patients ont pu etre decanules et adaptes a une ventilation a domicile en 6, 7, et 10 jours, au terme desquels ils etaient tous rentres a leur domicile. Apres 4 mois dans 2 cas, 6 mois dans l’autre, aucune complication significative n’etait relevee, l’etat respiratoire sous ventilation au masque etait comparable a l’etat anterieur (tracheotomie), et les patients etaient satisfaits du changement. Conclusion L’algorithme propose semble permettre un passage rapide et sur de la tracheotomie a la ventilation au masque. Il reste, par des etudes a grande echelle, a verifier cette notion, et, au-dela, a identifier dans quelle population une telle demarche peut raisonnablement etre appliquee.

Recently, it has been suggested that peak expiratory flow (PEF) may be determined by the wave speed flow-limiting mechanism. In six normal male subjects (age = 33 +/- 8 years) performing expiratory forced vital capacity (FVC) maneuvers, a negative expiratory pressure (NEP) of -10 cm H2O was randomly applied at the beginning of maximal expiration to assess changes in PEF as compared with baseline. During FVC maneuvers, the expiratory effort was measured by changes in esophageal pressure (Pes), as either peak expiratory Pes-Pes at end expiratory lung volume (DeltaPes(peak)) or maximal rate of rise of Pes (dPes/dt(max)). In each experimental condition, at least three FVC maneuvers with comparable expiratory effort were selected for analysis for each subject. With similar DeltaPes(peak) (107.2 +/- 34.9 versus 111.7 +/- 40.5 cm H2O) and dPes/dt(max) (1181 +/- 518 versus 1177 +/- 546 cm H2O/second) PEF amounted to 10.84 +/- 1.08 L/second and to 10.82 +/- 1.03 L/second with and without NEP, respectively. These data show that PEF obtained by normal subjects to the best of their abilities (best PEF) does not increase with NEP and indicate that the best PEF is a flow-limited and effort-independent parameter, reflecting only lung and airways mechanics as the other subsequent maximal expiratory flows achieved during the FVC maneuver.

The eosinophilic inflammatory response in asthma is associated with protein nitration, detected as immunostaining for 3-nitrotyrosine (3NT). As the presence of 3NT is strongly correlated with upregulation of the inducible form of nitric oxide synthase (NOS II), it has been hypothesized that 3NT formation results from the action of peroxynitrite (ONOO-), a highly reactive NO derivative produced from the reaction of molecular NO and O2-. However, recent observations have suggested that the action of peroxidases, including eosinophil peroxidase (EPO), may be responsible for protein nitration. In this study, we used murine models of allergic asthma to address the relative contribution of EPO and NOS II to protein nitration. We studied EPO-deficient New Zealand White (NZW) mice, which were sensitized and challenged intranasally with ovalbumin (OVA). Despite comparable levels of eosinophilia, NO, and superoxide production, NZW mice exhibited markedly decreased 3NT staining around the airways after OVA challenge when compared with two other strains (A/J and C57BL/6J). Immunocytochemical analysis of bronchoalveolar lavage (BAL) cells and lung sections suggested that 3NT staining was largely confined to eosinophils. This was confirmed by Western Blot analysis of proteins from different subsets of BAL cells that demonstrated a marked decrease in 3NT formation in eosinophils from NZW mice. These results contrast with those obtained in OVA-sensitized and -challenged NOS II deficient mice, which despite decreased NO production, exhibited similar 3NT staining in the airways after OVA challenge as in wild-type control mice. In this model, protein nitration was thus not a function of NO production by NOS II. We conclude that in the mouse, 3NT formation after specific allergen challenge is dependent on EPO activity, particularly in eosinophils themselves. In contrast, 3NT formation is not driven by upregulation of NOS II expression in this model and does not appear to depend on increases in the level of NO production.

To explore the possible role of eosinophils in NO-mediated tissue injury, we studied a murine model of allergic asthma. Male A/J mice were sensitized and challenged intranasally with ovalbumin (OVA). Following challenge, the number of eosinophils in bronchoalveolar lavage fluid (BALF) increased from 0.4% of total cells at baseline (0.02 x 10(4) cells/ml) to 60.2% at 48 h after the challenge (9.34 x 10(4) cells/ml). The rise in eosinophil count was accompanied by a 40.3% increase in total NO(2-) plus NO(3-) (NO(x)) in BALF. This in turn was accompanied by expression of inducible NO synthase (NOS II) in airway epithelial and inflammatory cells, as well as by evidence of staining for 3-nitrotyrosine (3NT) in peribronchial inflammatory cells and at the epithelial surface. Both NO(x) production and 3NT were significantly reduced by pretreatment of the challenged mice with the highly specific NOS II inhibitor N-3-aminomethyl-benzyl-acetamidine-dihydrochloride (1400W), as well as by the nonselective NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). L-NAME and 1400W also reduced the number of BALF eosinophils (37.2% and 61.5%, respectively, as compared with the control value), suggesting that NO production by NOS II contributes to eosinophil recruitment. To further examine the role of eosinophils, we pretreated additional mice with an anti-interleukin (IL)-5 antibody, which reduced BALF eosinophilia following OVA challenge by 90.1%. In concert with the decrease in eosinophils, the anti-IL-5 antibody reduced NO(x) in BALF almost to the baseline value, and decreased the number of 3NT-positive cells in the peribronchial region by 74.4%. Western blot analysis of protein extracted from whole lung confirmed the reduction in tyrosine nitration by anti-IL-5 antibody. These findings indicate that NO and eosinophilic inflammation are closely coupled, and suggest that eosinophils are an important source of tyrosine nitration.

International audience; Rationale: Diaphragmatic insults occurring during intensive care unit (ICU) stays have become the focus of intense research. However, diaphragmatic abnormalities at the initial phase of critical illness remain poorly documented in humans. Objectives: To determine the incidence, risk factors, and prognostic impact of diaphragmatic impairment on ICU admission. Methods: Prospective, 6-month, observational cohort study in two ICUs. Mechanically ventilated patients were studied within 24 hours after intubation (Day 1) and 48 hours later (Day 3). Seventeen anesthetized intubated control anesthesia patients were also studied. The diaphragm was assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Measurements and Main Results: Eighty-five consecutive patients aged 62 (54-75) (median [interquartile range]) were evaluated (medical admission, 79%; Simplified Acute Physiology Score II, 54 [44-68]). On Day 1, Ptr, stim was 8.2 (5.9-12.3) cm H2O and 64% of patients had Ptr, stim less than 11 cm H2O. Independent predictors of low Ptr, stim were sepsis (linear regression coefficient, -3.74; standard error, 1.16; P = 0.002) and Simplified Acute Physiology Score II (linear regression coefficient, -0.07; standard error, 1.69; P = 0.03). Compared with nonsurvivors, ICU survivors had higher Ptr, stim (9.7 [6.3-13.8] vs. 7.3 [5.5-9.7] cm H2O; P = 0.004). This was also true for hospital survivors versus nonsurvivors (9.7 [6.3-13.5] vs. 7.8 [5.5-10.1] cm H2O; P = 0.004). Day 1 and Day 3 Ptr, stim were similar. Conclusions: A reduced capacity of the diaphragm to produce inspiratory pressure (diaphragm dysfunction) is frequent on ICU admission. It is associated with sepsis and disease severity, suggesting that it may represent another form of organ failure. It is associated with a poor prognosis.

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.

Background Intensive care unit (ICU) admission of adults with cystic fibrosis (CF) is controversial because of poor outcome. This appraisal needs re-evaluation following recent changes in both CF management and ICU daily practice. Objectives were to determine long-term outcome of adults with CF admitted in ICU and to identify prognostic factors. Methods Retrospective multicenter study of 60 ICU hospitalizations for 42 adult CF patients admitted between 2000 and 2003. Reason for ICU admission, ventilatory support provided and one-year survival were recorded. Multiple logistic analysis was used to determine predictors of mortality. Results Prior to ICU admission, all patients (mean age 28.1 ± 8 yr) had a severe lung disease (mean FEV1 28 ± 12% predicted; mean PaCO2 47 ± 9 mmHg). Main reason for ICU hospitalization was pulmonary infective exacerbation (40/60). At admission, noninvasive ventilation was used in 57% of cases and was successful in 67% of patients. Endotracheal intubation was implemented in 19 episodes. Overall ICU mortality rate was 14%. One year after ICU discharge, 10 of the 28 survivors have been lung transplanted. Among recognized markers of CF disease severity, only the annual FEV1 loss was associated with a poor outcome (HR = 1.47 [1.18–1.85], p = 0.001). SAPSII (HR = 1.08 [1.03–1.12], p < 0.001) and endotracheal intubation (HR = 16.60 [4.35–63.34], p < 0.001) were identified as strong independent predictors of mortality. Conclusion Despite advanced lung disease, adult patients with CF admitted in ICU have high survival rate. Endotracheal intubation is associated with a poor prognosis and should be used as the last alternative. Although efforts have to be made in selecting patients with CF likely to benefit from ICU resources, ICU admission of these patients should be considered.

Methacholine (MCh)-induced bronchoconstriction in vivo produces greater maximal increases in pulmonary and airway resistances in immature than in mature rabbits. Our recent findings of lower shear modulus and greater airway distensibility suggest a lower elastic load limiting airway smooth muscle (ASM) shortening in immature rabbit lungs. We hypothesized that a lower elastic load should result in greater velocity of airway narrowing. Lung explants were prepared from three immature and five mature rabbits. Dynamic narrowing of intraparenchymal airways after maximal MCh stimulation was assessed by video microscopy. Immature airways (n = 80) compared with mature airways (n = 110) demonstrated greater peak velocity of shortening (6.98 +/- 0.32 versus 4.22 +/- 0.18% of baseline perimeter/s) and greater maximal airway narrowing, expressed as percentage of baseline area (31.9 +/- 1.6 versus 42.2 +/- 1.8%). For both groups, a greater velocity of shortening resulted in greater airway narrowing. As available data do not support maturational differences in rabbit ASM, our results are consistent with a lower elastic load limiting ASM shortening in the immature rabbit.

To investigate the relationship between bronchial responsiveness and airway smooth-muscle (ASM) contractile properties, we studied inbred mice with known interstrain differences in airway responsiveness. Using oscillatory mechanics, we confirmed that A/J mice were hyperresponsive to methacholine (MCh) as compared with mice of the C3H/HeJ and C57BL/6J strains. Analysis of respiratory system resistance and elastance at different flow oscillation frequencies indicated that interstrain differences in responsiveness are present in both central and peripheral airways of these mice. We used video microscopy to measure the rate of contraction of explanted airways, and found that the airways of A/J mice contracted more rapidly than those of C3H/HeJ or C57BL/6J mice. In studies of a fourth strain (Balb/C) of mice, we found both bronchial hyperresponsiveness and increased ASM shortening velocity. The rank order of responsiveness among strains was the same as that for shortening velocity (A/J > Balb/C > C3H/HeJ > C57BL/6J). Furthermore, in each strain of mice, shortening velocity correlated with the achieved degree of airway narrowing and with a greater likelihood of airway closure in individual airways. In contrast, generation of isometric tension in trachealis, morphometric measurements of tracheal ASM, tracheal myosin content, and dose-response curves for MCh of explanted intraparenchymal bronchi failed to correspond to the in vivo phenotype of airway reactivity. These results indicate that bronchial responsiveness is related to ASM shortening velocity, and underscore the importance of smooth-muscle dynamics in understanding the mechanisms of bronchial responsiveness.

Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1

The twitch occlusion technique is a promising tool for use in accessing central drive to the diaphragm and determining maximal transdiaphragmatic pressure (Pdi) from submaximal efforts. It clinical use is limited by difficulties inherent to bilateral electrical stimulation (BES) of the phrenic nerves. This study was designed to revisit the technique using cervical magnetic stimulation (CMS). In addition, the effects of a voluntary contraction on diaphragm response to magnetic stimulation of the cortex (CxMS) were studied. Seven volunteers aged 23-33 yrs were studied. Pdi was determined at relaxed functional residual capacity (FRC) in response to BES (Pdi,P-ES) and CMS (Pdi,p-CMS), and the effects of an increasing voluntary contraction (Pdi, vol) were assessed, The same procedure was applied to CxMS. Pdi,p-CMS at relaxed FRC was 27.5 +/- 2.2 cmH2O (mean+/-SEM), about 20% higher than Pdi,p-ES, and reported previously. Pd,p-CMS linearly decreased with Pdi, vol, and six out of seven subjects were capable of producing voluntary contractions sufficient to extinguish the twitch. More complex patterns were observed with CxMS. Cervical magnetic stimulation provides diaphragmatic twitch occlusion data very similar to bilateral electrical phrenic stimulation. Magnetic stimulation, be it cervical or cortical, could probably be helpful for the assessment of central and peripheral mechanisms of diaphragmatic dysfunction in the clinical setting.

Introduction : Le rythme ventilatoire, comme le rythme cardiaque, n’est pas monotone mais variable au cours du temps. La nature chaotique deterministe de la commande ventilatoire sous-tend une variabilite des cycles les uns par rapport aux autres (decrite par exemple par le coefficient de variation —CoV— du volume courant —Vt—, de la frequence —Fr— et de la periode —Tt— respiratoire, du temps inspiratoire —Ti—, de Vt/Ti et de Ti/Tt. La variabilite ventilatoire diminue au cours de certaines situations pathologiques et de facon generale lorsque la charge imposee au systeme respiratoire augmente (index d’adequation charge-capacite). Le neuro-asservissement de la ventilation assistee (NAVA) ajuste l’assistance delivree par le ventilateur a l’activite electromyographique du diaphragme (Edi), dans le but d’optimiser le couplage neuro-mecanique et donc l’harmonie patient-ventilateur. Cette etude teste l’hypothese que la variabilite ventilatoire augmente lors de l’application du NAVA a des patients prealablement en aide inspiratoire (AI), et ce a niveau ventilatoire constant. Methodes : Chez 7 patients intubes, la variabilite ventilatoire a ete caracterisee en AI puis en mode NAVA a 4 niveaux croissants d’assistance (NAVA 1, 2, 3, 4 cmH2O/µV Edi), de la facon suivante : 1) detection du chaos ventilatoire par titration de bruit —TdB— et quantification de la sensibilite aux conditions initiales par calcul du plus grand exposant de Lyapunov —LLE— ; 2) calcul du CoV des descripteurs du cycle ventilatoire (Vt, Fr, Tt, Ti, Vt/ Ti, Ti/Tt). Lorsque cela s’est avere possible, le confort du patient a ete evalue par le calcul du score composite « ATICE” » et la mesure de l’intensite de la dyspnee sur une echelle visuelle analogique (EVA). Resultats : Le passage de AI a NAVA ne modifie pas la ventilation- minute ni les valeurs moyennes des differents descripteurs du cycle ventilatoire. Le CoV de ces descripteurs est significativement superieur en mode NAVA par rapport a l’AI, et augmente significativement a mesure que le niveau d’assistance croit (p Conclusion : Le NAVA est associe a une variabilite ventilatoire plus elevee que le mode AI, a niveau constant de ventilation. Ceci laisse supposer que l’adequation charge-capacite et/ou le couplage neuromecanique sont ameliores par le NAVA Avec le soutien de l’ANTADIR, du FERH, et de la societe Maquet France.

Background Phrenic nerve pacing is a recognized substitute to positive pressure ventilation via tracheotomy in patients with high cervical cord lesions or central hypoventilation. Although its indications are infrequent, reliable strategies need to be used in the determinations of patients who may benefit from this treatment; contraindications should be carefully respected. Study objectives To determine whether modern and noninvasive means to study the motor pathway to the diaphragm, namely cortical magnetic stimulation (CxMS) and cervical magnetic stimulation (CMS), can contribute to the selection of patients who may benefit from phrenic pacing. Design and setting Prospective study (18 months), on a consecutive basis, of patients referred for possible phrenic pacing to a 10-bed ICU associated with a respiratory neurophysiology laboratory. Patients Seven patients (high cervical cord injury, n=5; central hypoventilation following neurosurgery, n=1; idiopathic acquired central hypoventilation, n=1). Intervention, measurements, and results Electromyography of the diaphragm and transdiaphragmatic pressure were assessed in response to CxMS and CMS. In three eases, no interruption of the corticodiaphragmatic pathway was evidenced, the decision of pacing was postponed, and the patients eventually recovered a spontaneous breathing activity. In two cases, the diagnosis of irreversible peripheral phrenic dysfunction was reached and pacing was denied. In two cases, complete interruption of the corticodiaphragmatic pathway and integrity of peripheral conduction led to the decision of phrenic pacemaker implantation. Conclusion CxMS and CMS can be used to refine the assessment of patients proposed for phrenic pacing. CxMS can possibly identify those in whom there is a possibility for eventual recovery, and therefore substantiate a decision to postpone the pacing.