A Prototype Implantable Artificial Bronchus Reduces Lung Hyperinflation in Recently Deceased Patients with Emphysema.

BACKGROUND: Several minimally invasive treatments have been offered to patients with severe emphysema over the last two decades. Currently, endobronchial valves (EBVs) are the only approved therapeutic option, but this method has drawbacks: only a few can undergo this therapy and the incidence of pneumothorax remains high. A minimally invasive technique, appropriate for a broader patient population and posing fewer risks, would represent a desirable alternative to improve lung function in these patients. OBJECTIVE: The objective of this study was to demonstrate whether a new prototype implantable artificial bronchus (IAB) releases trapped air from the lungs of recently deceased patients with emphysema. METHOD: Seven recently deceased patients with emphysema were mechanically ventilated and the respiratory rate increased from 12 bpm (resting) to 30 bpm (exercise), inducing air trapping and dynamic hyperinflation. This protocol was performed twice, before and after IAB placement. Ventilation parameters and the fraction of inspired oxygen were similar in all patients. Respiratory system plateau pressure (Pplat,rs) and intrinsic positive end-expiratory pressure (iPEEP) were measured. RESULTS: IAB implantation significantly reduced Pplat,rs (p = 0.017) in 6 of 7 deceased patients with emphysema and iPEEP (p = 0.03) in 5 of 7 patients. CONCLUSIONS: Placement of one or two IABs in segmental bronchi (up to 15th generation) proved to be feasible and improved lung function. These findings should provide a basis for subsequent clinical studies to assess the safety and efficacy of IAB in patients with emphysema, as well as identify short- and long-term effects of this innovative procedure.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Combined Bone Marrow-Derived Mesenchymal Stromal Cell Therapy and One-Way Endobronchial Valve Placement in Patients with Pulmonary Emphysema: A Phase I Clinical Trial.

One-way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients. However, local inflammation may result and can contribute to worsening of clinical status in these patients. We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients. This initial study sought to investigate the safety of this approach. For this purpose, a phase I, prospective, patient-blinded, randomized, placebo-controlled design was used. Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow-derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one-way EBVs. Patients were evaluated 1, 7, 30, and 90 days after therapy. All patients completed the study protocol and 90-day follow-up. MSC delivery did not result in acute administration-related toxicity, serious adverse events, or death. No significant between-group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease. Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes. However, quality-of-life indicators were higher in EBV + MSC compared with EBV. EBV + MSC patients presented decreased levels of circulating C-reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores. Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy. Stem Cells Translational Medicine 2017;6:962-969.

Fissure Integrity and Volume Reduction in Emphysema: A Retrospective Study.

BACKGROUND: One-way endobronchial valves (EBVs) relieve symptoms of emphysema, particularly in patients without collateral ventilation between the target and adjacent lobes. Pretreatment knowledge of fissure integrity could serve as an aid in indicating EBV interventions. OBJECTIVE: This study aimed to investigate the relationship between software-measured lung fissure integrity and clinically relevant lung volume reduction (≥350 ml) in emphysema patients treated with one-way EBVs using a lobar exclusion strategy. METHODS: Of 108 patients treated between March 2008 and July 2014, 38 had both baseline and follow-up computed tomography (CT) scans acquired following a specific protocol for quantitative CT analysis and were included in the study (total of 39 treatments, two lungs treated in 1 patient). Outcome measures were fissure integrity measured on baseline CT scans, difference between pre- and postoperative lung volume (considering the lowest measured postoperative volume), and correlation between fissure integrity and volume change. RESULTS: Fissure integrity ≥75% correlated with volume reduction ≥350 ml (Spearman coefficient: -0.65; p < 0.01). The mean and median volume reductions were 1,223.96 ± 907.5 ml and 663 ml, respectively, for lungs with fissure integrity ≥75% (n = 31). The accuracy of fissure integrity ≥75% in predicting a volume reduction was 87.2%. The positive predictive value of fissure integrity ≥75% to predict a volume reduction ≥350 ml was 83.9%, and it was 70% for fissure integrity 75-90% and 90.5% for fissure integrity >90%. CONCLUSIONS: A target lobe volume reduction using EBVs is possible with lung fissure integrity ≥75%. For patients with fissure integrity between 75 and 90%, a further evaluation of interlobar ventilation should be performed. A clinically relevant volume reduction following treatment with EBVs is likely with any level of fissure integrity >90%.

Insuficiência respiratória aguda causada por hiperinfecçäo pelo "Strongyloides Stercoralis": relato de um caso / Acute respiratory failure due to hyperinfection by \"Strongyloides Stercoralis\": a case report

O presente trabalho aborda um caso de hiperinfecçäo por Strongyloides stercoralis em um paciente idoso, com DPOC e Cor Pulmonale. Descrevem-se as manifestaçöes clínicas atuais, relacionadas à infecçäo respiratória aguda grave que segue curso inusitado, apontam-se aspectos diagnósticos e terapêuticos relevantes para o sucesso da intervençäo médica. É ressaltada a importância das informaçöes fornecidas pela radiologia, fibrobroncoscopia e microbiologia do lavado broncoalveolar, para a elucidaçäo diagnóstica. Enfatiza-se que, sendo uma doença curável, de terapêutica simples e pouco dispendiosa, näo haja retardo no início do tratamento pois, uma vez estabelecida, a hiperinfecçäo pelo S. Stercoralis apresenta alto risco de mortalidade