Sylvie Leroy

Efficacy predictors of lung volume reduction with zephyr valves in a european cohort

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n=111) or medical management (n=60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean±sd change in forced expiratory volume in 1 s (7±20% versus 0.5±19%; p=0.067), cycle ergometry (2±14 W versus -3±10 W; p=0.04) and St George’s Respiratory Questionnaire (-5±14 points versus 0.3±13 points; p=0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean±sd lobar volume reduction of -80±30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.

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 Georges 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 Georges 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

Colistin in multi-drug resistant Pseudomonas aeruginosa blood-stream infections: a narrative review for the clinician.

47,908 (95% CI,

Bone loss in adults with cystic fibrosis: Prevalence, associated factors, and usefulness of biological markers

47,879-

Bronchoscopic Coil Treatment for Patients with Severe Emphysema: A Meta-Analysis.

48,073) (P < .001); the incremental cost-effectiveness ratio was

Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease

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.

Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer

Antimicrobial resistance to Pseudomonas aeruginosa is on the rise. In the absence of new anti-pseudomonal drugs, clinicians have had to resort to older antimicrobials such as colistin for the treatment of multi-drug resistant (MDR) strains. This polymyxin compound acts on the outer membrane of the bacteria resulting in its permeability and cell-death. Its bactericidal action is concentration-dependant. This antibiotic is mainly used as salvage therapy in the treatment of often life-threatening infections due to MDR P. aeruginosa blood-stream infections (BSI). Its potential nephrotoxicity and neurotoxicity have been overestimated and have limited the use in its intravenous form. A better understanding of its pharmacokinetics and pharmacodynamics, has facilitated more appropriate dosing strategies with a standard 9 million-unit daily-dose that should be adapted to kidney function. Combination treatment that involves the association of colistin with classical anti-pseudomonal treatment has rarely been clinically tested. In vitro synergy has been reported for certain combinations that could be used to prevent or limit the risk of induced resistance in MDR strains. Positioning colistin in antimicrobial strategies especially as a first-line treatment remains to be properly assessed.

A multicenter randomized controlled trial of Zephyr endobronchial valve treatment in heterogeneous emphysema (TRANSFORM)

BACKGROUND Osteoporosis is a common complication of cystic fibrosis. OBJECTIVE To determine the prevalence of osteopenia and osteoporosis in adults with cystic fibrosis and to look for factors associated with low bone mineral density (BMD) values. METHODS During this prospective 2-year study, we collected clinical data (history, body mass index, and treatments) and laboratory data (nutritional and hormonal status, markers for inflammation and bone turnover, and calcium and phosphate levels). Lung function tests and a 6-meter walking test were performed. BMD was measured at the spine, total hip, and femoral neck. RESULTS We included 55 patients (31 women) with a mean age of 31.9 years; 14 were homozygous and 25 heterozygous for the deltaF508 mutation and 20 (36%) had a history of fractures. BMD values indicated osteopenia in 32 (58.2%) patients and osteoporosis in 11 (20%) patients at one or more measurement sites. At all three sites, BMD values correlated with the body mass index, forced vital capacity as % predicted, and forced expiratory volume in 1 s as % predicted; at the femoral neck and total hip, BMD values correlated with the 6-meter walking test result and grip strength. CONCLUSION BMD was low in 78.2% of adults with cystic fibrosis. Three factors reflecting lung disease severity were associated with low BMD values, namely, respiratory function, physical function (walking test and grip strength), and nutritional status.

Endobronchial Phototoxicity of WST 09 (Tookad®), a New Fast-Acting Photosensitizer for Photodynamic Therapy: Preclinical Study in the Pig¶

Background: Bronchoscopic coil treatment has been shown to improve pulmonary function, exercise capacity, and quality of life in patients with severe emphysema. Objectives: To perform a meta-analysis of the results of four independent European clinical trials investigating this coil therapy for emphysema. Methods: Data on all patients included in the four European clinical trials were analyzed for efficacy and safety outcomes. Results: A total of 2,536 coils were placed during 259 procedures in 140 patients. A total of 37 chronic obstructive pulmonary disease exacerbations and 27 pneumonias were recorded as serious adverse events up to 1 year after treatment. The pneumothorax rate was 6.4%. Both 6 and 12 months after treatment, significant (all p < 0.001) improvements were observed for: forced expiratory volume in 1 s [+0.08 liters (±0.19) and +0.08 liters (±0.21)], residual volume [RV; -510 ml (±850) and -430 ml (±720)], 6-min walking distance [6MWD; +44.1 m (±69.8) and +38.1 m (±71.9)], and St. Georges Respiratory Questionnaire score [SGRQ; -9.5 points (±14.3) and -7.7 points (±14.2)]. No differences in any outcome measures were observed between heterogeneous and homogeneous emphysema patients. Only a high baseline RV was found to be an independent predictor of successful treatment. Conclusions: Bronchoscopic coil treatment improves pulmonary function, 6MWD, and quality of life in patients with severe emphysema up to 1 year after treatment, independent of the distribution of the disease.

Phenotyping Adults with Non-Cystic Fibrosis Bronchiectasis: A 10-Year Cohort Study in a French Regional University Hospital Center

OBJECTIVE To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting. METHODS A multicentre observational study investigated adverse events, treatment discontinuation, FEV1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV1 below 40% predicted. RESULTS Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV1 was +2.06% after one month of treatment (P=0.086) and +3.19% after 3 months (P=0.009). BMI was unchanged. CONCLUSIONS Treatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials.