Lung Volume Reduction Coil Treatment vs Usual Care in Patients With Severe Emphysema: The REVOLENS Randomized Clinical Trial:

IMPORTANCE: Therapeutic options for severe emphysema are limited. Lung volume reduction using nitinol coils is a bronchoscopic intervention inducing regional parenchymal volume reduction and restoring lung recoil. OBJECTIVE: To evaluate the efficacy, safety, cost, and cost-effectiveness of nitinol coils in treatment of severe emphysema. DESIGN, SETTING, AND PARTICIPANTS: Multicenter 1:1 randomized superiority trial comparing coils with usual care at 10 university hospitals in France. Enrollment of patients with emphysema occurred from March to October 2013, with 12-month follow-up (last follow-up, December 2014). INTERVENTIONS: Patients randomized to usual care (n = 50) received rehabilitation and bronchodilators with or without inhaled corticosteroids and oxygen; those randomized to bilateral coil treatment (n = 50) received usual care plus additional therapy in which approximately 10 coils per lobe were placed in 2 bilateral lobes in 2 procedures. MAIN OUTCOMES AND MEASURES: The primary outcome was improvement of at least 54 m in the 6-minute walk test at 6 months (1-sided hypothesis test). Secondary outcomes included changes at 6 and 12 months in the 6-minute walk test, lung function, quality of life as assessed by St George's Respiratory Questionnaire (range, 0-100; 0 being the best and 100 being the worst quality of life; minimal clinically important difference, ≥4), morbidity, mortality, total cost, and cost-effectiveness. RESULTS: Among 100 patients, 71 men and 29 women (mean age, 62 years) were included. At 6 months, improvement of at least 54 m was observed in 18 patients (36%) in the coil group and 9 patients (18%) in the usual care group, for a between-group difference of 18% (1-sided 95% CI, 4% to ∞; P = .03). Mean between-group differences at 6 and 12 months in the coil and usual care groups were +0.09 L (95% CI, 0.05 L to ∞) (P = .001) and +0.08 L (95% CI, 0.03 L to ∞) (P = .002) for forced expiratory volume in the first second, +21 m (95% CI, -4 m to ∞) (P = .06) and +21 m (95% CI, -5 m to ∞) (P = .12) for 6-minute walk distance, and -13.4 points (95% CI, -8 points to ∞) and -10.6 points (95% CI, -5.8 points to ∞) for St George's Respiratory Questionnaire (1-sided P < .001 for both). Within 12 months, 4 deaths occurred in the coil group and 3 in the usual care group. The mean total 1-year per-patient cost difference between groups was $47,908 (95$47,879-$48,073) (P < .001); the incremental cost-effectiveness ratio was$782,598 per additional quality-adjusted life-year. CONCLUSIONS AND RELEVANCE: In this preliminary study of patients with severe emphysema followed up for 6 months, bronchoscopic treatment with nitinol coils compared with usual care resulted in improved exercise capacity with high short-term costs. Further investigation is needed to assess durability of benefit and long-term cost implications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822795.Comment in : *Lung Volume Reduction Coils for Severe Emphysema--Reply. [JAMA. 2016] *Coils implanted into lungs show promise for emphysema. [BMJ. 2016] *Lung Volume Reduction Coils for Severe Emphysema. [JAMA. 2016] *Bronchoscopic Lung Volume Reduction in COPD: Lessons in Implementing Clinically Based Precision Medicine. [JAMA. 2016

Assistance ventilatoire à domicile : justifications et contraintes physiopathologiques

[Home mechanical ventilation: indications and pathophysiological limitations] Introduction Domiciliary assisted ventilation (DAV) may be undertaken invasively or non-invasively. Non-invasive DAV is used for patients suffering from alveolar hypoventilation due to restrictive pathology. Invasive DAV is reserved for "indications of necessity" that is when non-invasive ventilation is contraindicated due to the absence of adequate cough and for alveolar hypoventilation leading to hypercapnoea during spontaneous ventilation. State of the art The main pathophysiological limitation to noninvasive ventilation is the interference of the glottis. In this mode the glottis imposes a variable resistance to the ventilation delivered. Its behaviour is more predictable during volume controlled than during pressure controlled ventilation. The control parameters of a volume controlled ventilator are very different from those used in invasive ventilation during which the respiratory system may be regarded as a single compartment (provided a cuffed tube bypasses the upper airway). In non-invasive DAV: mode VCM, tidal volume 13 mls kg(-1), rate 20 cycles min(-1), insp/exp ratio 1/1.2. In invasive DAV: mode VCM, tidal volume 8-10 mls kg(-1), rate 12 cycles min(-1), insp/exp ratio depending on the pathology 1/2. Perspectives As non-invasive DAV is essentially delivered during sleep the parameters for each patient can be optimised during polysomnography because waking, leading to a partial glottic occlusion, interferes with the ventilation delivered. Conclusions Recent understanding of the way the glottis interferes with mechanical ventilation when delivered non-invasively should lead to a revision of earlier practices based on invasive ventilation

Effects of nasal positive-pressure hyperventilation on the glottis in normal sleeping subjects.

We have previously observed that, in normal awake subjects passively hyperventilated with intermittent positive-pressure ventilation delivered through nasal access (nIPPV), the glottis could interfere with the ventilation. We report on data obtained in the same subjects during stable sleep. In all cases, the glottis was continuously observed through a fiber-optic bronchoscope, and other indexes were also continuously recorded. Mechanical ventilation was progressively increased up to 30 l/min. We have observed during passive nIPPV in stable sleep that increases in delivered minute ventilation (VEd) resulted in progressive narrowing of the glottic aperture, with increases in inspiratory resistance and progressive reductions in the percentage of the delivered tidal volume effectively reaching the lungs. For a given level of VEd, comparisons showed that the glottis was significantly narrower during sleep than during wakefulness and that the glottis was significantly narrower during stage 2 than during stages 3/4 non-rapid-eye-movement sleep. Moreover, when CO2 is added to the inspired air, glottic aperture increased in five of nine trials without changes in sleep stage. We also observed a significant negative correlation between glottic width and the VED, independent of the CO2 level. We conclude that during nIPPV glottis narrowing results in a decrease in the proportion of the delivered tidal volume reaching the lungs

Effects of nasal positive-pressure hyperventilation on the glottis in normal awake subjects.

We have recently observed obstructive apneas during nasal intermittent positive-pressure ventilation (nIPPV) and suggested that they were due to hypocapnia-induced glottic closure. To confirm this hypothesis, we studied seven healthy subjects and submitted them to nIPPV while their glottis was continuously monitored through a fiber-optic bronchoscope. During wakefulness, we measured breath by breath the widest inspiratory angle formed by the vocal cords at the anterior commissure along with several other indexes. Mechanical ventilation was progressively increased up to 30 l/min. In the absence of diaphragmatic activity, increases in delivered minute ventilation resulted in progressive narrowing of the vocal cords, with an increase in inspiratory resistance and a progressive reduction in the percentage of the delivered tidal volume effectively reaching the lungs. Adding CO2 to the inspired gas led to partial widening of the glottis in two of three subjects. Moreover, activation of the diaphragmatic muscle was always associated with a significant inspiratory abduction of the vocal cords. Sporadically, complete adduction of the vocal cords was directly responsible for obstructive laryngeal apneas and cyclic changes in the glottic aperture resulted in waxing and waning of tidal volume. We conclude that in awake humans passive ventilation with nIPPV results in vocal cord adduction that depends partly on hypocapnia, but our results suggest that other factors may also influence glottic width

Determinants of effective ventilation during nasal intermittent positive pressure ventilation

Our aim was to verify in healthy subjects submitted to nasal intermittent positive pressure ventilation (nIPPV) with a volumetric ventilator on controlled mode, whether changes in ventilator settings (delivered tidal volume (VT), respiratory frequency (fR) and inspiratory flow (V'I) could influence effective minute ventilation (V'E), thus allowing identification of the settings resulting in the highest V'E during nIPPV. We then compared these experimentally obtained "best" settings to those obtained retrospectively in a group of patients submitted to long-term nIPPV for clinical reasons. We studied 10 healthy subjects awake and asleep, and 33 patients with restrictive ventilatory disorders. Changes in delivered V'I (for a constant delivered VT and fR) led to significant changes in V'E. V'E was significantly higher when a given delivered V'E was obtained using higher fR and lower VT than when it was obtained using lower delivered fR and higher VT. Increases in fR generally resulted in increases in V'E. The "best" settings derived from these results were: VT: 13 mL.kg-1 of body weight; fR: 20 breaths.min-1 and V'I: 0.56-0.85 L.s-1. The corresponding average values found in the patient group were: delivered VT: 14 mL.kg-1; fR: 23 breaths.min-1 and delivered V'I: 0.51 L.s-1. Changes in minute ventilation resulting from modifications in ventilator settings can be attributed to the glottic response to mechanical influences. This leads to "ideal" settings quite different from the standard ones in intubated patients. Values derived from nasal intermittent positive pressure ventilation in healthy subjects seem to apply to patients submitted to long-term nasal intermittent positive pressure ventilation

Etude BPCO-EP: prévalence et prédiction de l'embolie pulmonaire dans l'exacerbation de la broncho-pneumopathie obstructive chronique [The COPD-PE study: prevalence and prediction of pulmonary embolism in acute exacerbations of chronic obstructive pulmonary disease].

INTRODUCTION: Patients suffering from chronic obstructive pulmonary disease (COPD) are often admitted to hospital with an exacerbation of their disease that manifests itself with an increase in cough and/or sputum, increased dyspnoea and sometimes chest pain. These episodes are most often attributed to an acute exacerbation of bronchial infection but the real cause is often unknown. COPD is considered a risk factor for pulmonary embolism (PE) and PE is part of the differential diagnosis of an acute exacerbation of COPD. However, the symptoms of these two conditions overlap to a considerable extent and the investigation of PE is often ignored in these patients. Therefore the true prevalence of PE in this situation is unknown. Nevertheless several small series suggest that up to 30% of patients seen as emergencies with exacerbations of COPD may have a deep vein thrombosis or PE. The aims of this study are therefore: 1. To evaluate the prevalence of PE in patients admitted as emergencies with exacerbations of COPD; and 2. To attempt to develop a prediction guide for PE in this population in order to identify the patients in whom PE should be investigated. MATERIALS AND METHODS: 600 consecutive patients admitted as emergencies with exacerbations of COPD will be included in a cross sectional study in three university hospitals (Geneva and Lausanne in Switzerland, and Amiens in France). Patients fulfilling the inclusion criteria will be investigated by a diagnostic algorithm appropriate for the study of PE, including D-dimer levels and, in those with abnormal results, ultrasonic scan of the deep veins of the legs and spiral CT scan. The patient characteristics on admission will be incorporated in a multivariate regression analysis in an attempt to identify the predictive factors for PE in these patients. The expected duration of the study is 24 months. EXPECTED RESULTS: This study should determine the prevalence of PE in patients admitted as emergencies with exacerbations of COPD and therefore help decide when, and in which patients, a systematic search for PE should be undertaken