Esophageal Manometry and Regional Transpulmonary Pressure in Lung Injury.

RATIONALE: Esophageal manometry is the clinically available method to estimate pleural pressure, thus enabling calculation of transpulmonary pressure (Pl). However, many concerns make it uncertain in which lung region esophageal manometry reflects local Pl. OBJECTIVES: To determine the accuracy of esophageal pressure (Pes) and in which regions esophageal manometry reflects pleural pressure (Ppl) and Pl; to assess whether lung stress in nondependent regions can be estimated at end-inspiration from Pl. METHODS: In lung-injured pigs (n = 6) and human cadavers (n = 3), Pes was measured across a range of positive end-expiratory pressure, together with directly measured Ppl in nondependent and dependent pleural regions. All measurements were obtained with minimal nonstressed volumes in the pleural sensors and esophageal balloons. Expiratory and inspiratory Pl was calculated by subtracting local Ppl or Pes from airway pressure; inspiratory Pl was also estimated by subtracting Ppl (calculated from chest wall and respiratory system elastance) from the airway plateau pressure. MEASUREMENTS AND MAIN RESULTS: In pigs and human cadavers, expiratory and inspiratory Pl using Pes closely reflected values in dependent to middle lung (adjacent to the esophagus). Inspiratory Pl estimated from elastance ratio reflected the directly measured nondependent values. CONCLUSIONS: These data support the use of esophageal manometry in acute respiratory distress syndrome. Assuming correct calibration, expiratory Pl derived from Pes reflects Pl in dependent to middle lung, where atelectasis usually predominates; inspiratory Pl estimated from elastance ratio may indicate the highest level of lung stress in nondependent "baby" lung, where it is vulnerable to ventilator-induced lung injury.

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).

Use of MDCT to Assess the Results of Bronchial Thermoplasty.

OBJECTIVE: The purpose of this study was to evaluate the use of MDCT to assess response to bronchial thermoplasty treatment for severe persistent asthma. MATERIALS AND METHODS: MDCT data from 26 patients with severe persistent asthma who underwent imaging before and after bronchial thermoplasty were analyzed retrospectively. Changes in the following parameters were assessed: total lung volume, mean lung density, airway wall thickness, CT air trapping index (attenuation < -856 HU), and expiratory-inspiratory ratio of mean lung density (E/I index). Asthma Quality of Life Questionnaire score changes were also assessed. RESULTS: Median total lung volumes before and after bronchial thermoplasty were 2668 mL (range, 2226-3096 mL) and 2399 mL (range, 1964-2802 mL; p = 0.08), respectively. Patients also showed a pattern of obstruction improvement in air trapping values (median before thermoplasty, 14.25%; median after thermoplasty, 3.65%; p < 0.001] and in mean lung density values ± SD (before thermoplasty, -702 ± 72 HU; after thermoplasty, -655 ± 66 HU; p < 0.01). Median airway wall thickness also decreased after bronchial thermoplasty (before thermoplasty, 1.5 mm; after thermoplasty, 1.1 mm; p < 0.05). There was a mean Asthma Quality of Life Questionnaire overall score change of 1.00 ± 1.35 (p < 0.001), indicating asthma clinical improvement. CONCLUSION: Our study showed improvement in CT measurements after bronchial thermoplasty, along with Asthma Quality of Life Questionnaire score changes. Thus, MDCT could be useful for imaging evaluation of patients undergoing this treatment.

Design of the exhale airway stents for emphysema (EASE) trial: an endoscopic procedure for reducing hyperinflation.

BACKGROUND: Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612). METHODS/DESIGN: The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1 ≤ 50% of predicted or FEV1 < 1 liter, RV/TLC ≥ 0.65 at screening, marked dyspnea score ≥ 2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥ 12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥ 1 point at the 6-month follow-up visit. DISCUSSION: If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00391612.

Airway bypass treatment of severe homogeneous emphysema: taking advantage of collateral ventilation.

Airway bypass is being investigated as a new form of minimally invasive therapy for the treatment of homogeneous emphysema. It is a bronchoscopic catheter-based procedure that creates transbronchial extra-anatomic passages at the bronchial segmental level. The passages are expanded, supported with the expectation that the patency is maintained by paclitaxel drug-eluting airway bypass stents. The concept of airway bypass has been demonstrated in two separate experimental studies. These studies have shown that airway bypass takes advantage of collateral ventilation present in homogeneous emphysema to allow trapped gas to escape and reduce hyperinflation. It improves lung mechanics, expiratory flow, and volume. Airway bypass stent placements have been shown to be feasible and safe in both animal and human studies. Paclitaxel-eluting airway bypass stents were found to prolong stent patency and were adopted for clinical studies. A study evaluating the early results of the clinical application of airway bypass with paclitaxel-eluting stents found that airway bypass procedures reduced hyperinflation and improved pulmonary function and dyspnea in selected subjects who have severe emphysema. The duration of benefit appeared to correlate with the degree of pretreatment hyperinflation. These preliminary clinical results supported further evaluation of the procedure and led to the EASE Trial. The EASE Trial is a prospective, multicenter, randomized, double-blind, sham-controlled study. The trial aims to evaluate the safety and effectiveness of the airway bypass to improve pulmonary function and reduce dyspnea in homogeneous emphysema subjects who have severe hyperinflation. The trial is presently ongoing worldwide, though enrollment was completed.

Nonfunctioning paraganglioma of the aortopulmonary window.

Aortopulmonary paraganglioma is a rare tumor of the mediastinum. The only effective treatment is complete resection, which may pose a surgical challenge because of its proximity to the heart, great vessels, and trachea, often rendering a complete resection difficult to achieve. We report a case in which the tumor was excised under cardiopulmonary bypass and resulted in massive bleeding only controlled by means of packing the pleural cavity during 48 hours, known as damage control strategy. The patient survived and has been disease-free for 2 years.

Peritoneal free autologous fat graft for the control of pulmonary air leaks in emphysematous rat lungs.

BACKGROUND: Persistent pulmonary air leak is the most frequent complication after lung resection, resulting in an increase in postoperative morbidity and mortality. We evaluated the viability, integration, and efficacy of a free peritoneal fat graft as a method for controlling air leak in normal and emphysematous rat lungs. METHODS: Sixty Wistar rats were divided into two groups: elastase-produced lung emphysema (n=30) and control (normal) lungs (n=30). Pulmonary air leak was produced by puncture of the right lower lobe, and aerostasis was attempted by means of intrapulmonary injection of autologous free peritoneal fat graft. Rats in each group (n=6) were randomly allocated to subgroups and were sacrificed at 7, 14, 21, 30, and 60 days. Then, lungs were removed for histology, morphometry, vessel identification and counting, and immunohistochemistry for caspase 3, vascular endothelial growth factor, and factor VIII. RESULTS: Tissue integration of the free fat grafts was found in all animals in both groups. Vessels stained with India ink inside the fat grafts were present at all assessment periods in both groups. Vascular endothelial growth factor expression was significantly higher in all periods in the emphysema group compared with normal lungs (p<0.001). There was a significant increase in caspase 3 expression in the emphysema group at 7, 21, 30, and 60 days (p<0.001). Factor VIII showed a significant increase (p<0.001) at 30 and 60 days in emphysematous lungs. CONCLUSIONS: The use of free peritoneal fat graft was able to control the air leaks in normal and emphysematous rat lungs, with persisting graft viability for as long as 60 days after implantation.

Clinical application of airway bypass with paclitaxel-eluting stents: early results.

OBJECTIVE: To assess the safety and early clinical results of a multicenter evaluation of airway bypass with paclitaxel-eluting stents for selected patients with severe emphysema. METHODS: Airway bypass was performed with a fiberoptic bronchoscope in three steps: identification of a blood vessel-free location with a Doppler probe at the level of segmental bronchi, fenestration of the bronchial wall, and placement of a paclitaxel-eluting stent to expand and maintain the new passage between the airway and adjacent lung tissue. All adverse events were recorded, as well as 1- and 6-month pulmonary function tests and dyspnea index. RESULTS: Thirty-five patients received the airway bypass procedure with a median of 8 stents implanted per patient. At 1-month follow-up, statistically significant differences in residual volume, total lung capacity, forced vital capacity, forced expiratory volume, modified Medical Research Council scale, 6-minute walk, and St George's Respiratory Questionnaire were observed. At the 6-month follow-up, statistically significant improvements in residual volume and dyspnea were demonstrated. One death occurred after bleeding during the procedure. Retrospective analysis revealed that the degree of pretreatment hyperinflation may be an important indicator of which patients achieve the best short- and long-term results. CONCLUSIONS: The airway bypass procedure reduces hyperinflation and improves pulmonary function and dyspnea in selected patients with severe emphysema. Duration of benefit appears to correlate with the degree of pretreatment hyperinflation. These preliminary clinical results support further evaluation of the procedure.

Estenoses benignas da via aérea: tratamento endoscópico / Benign airway stenosis: endoscopic treatment

O objetivo do presente trabalho é uma revisão do tratamento endoscópico das estenoses laringotraqueais benignas. O tratamento de eleição para este tipo de estenose é a ressecção com anastomose primária. Entretanto, nem sempre essa situação pode ser alcançada devido a natureza, extensão e localização das estenoses. O tratamento endoscópico é uma alternativa em casos nos quais a ressecção não é possível ou após complicações ou insucessos nas ressecções prévias. O tratamento endoscópico inclui dilatações, ressecção endoscópica com eletrocautério, laser, argon plasma coagulation, crioterapia, braquiterapia e a utilização de endopróteses. Todos esses métodos de dilatação mecânica produzem um resultado imediato satisfatório, com aumento da via aérea e melhora dos sintomas clínicos, mas a durabilidade da terapia continua problemática. Em poucos dias ou semanas retornam os sintomas que obrigam repetidas reintervenções. As endopróteses são divididas em: silicone rígido e metálico autoexpansível. As endopróteses de silicone são as mais utilizadas na literatura e com o maior seguimento em longo prazo. As endopróteses metálicas autoexpansíveis foram introduzidas mais recentemente, e, devido à facilidade de aplicação, ocorreram abusos na utilização com diversas complicações. Mais recentemente, as endopróteses chamadas “híbridas” congregam componentes metálicos autoexpansíveis com uma cobertura de silicone.

This review focuses on endoscopic treatment of benign laryngotracheal stenoses. The standard treatment for laryngotracheal stenoses is surgical resection and reconstruction of the primary airway. However, when surgical resection is not feasible due to the nature, extent, or location of the stenosis, endoscopy presents an alternative for treating complications and for the management of previous unsuccessful resections. Endoscopic treatment includes electrocauterization, laser resection, argon plasma coagulation, cryotherapy, brachytherapy,and stent placement. Although endoluminal approaches have been shown to improve luminal patency, none have produced consistent results and the durability of their effects remains problematic, resulting in a high rate of repeat interventions. There are two basic types of stents: silicon stents; and self-expandable metal stents. Silicon stents are less expensive, more widely available, and still the most often studied. However, the newer, metal stents are easier to insert and position. Therefore, metal stents have been overused, resulting in complications. Recently, “hybrid” stents, such as one composed of a metal scaffold and a silicon coating with self-expandable capabilities, have been introduced.

Desmoid tumor of the mediastinum

A desmoid tumor of the mediastinum was diagnosed and terated in a 35 year-old white male who presented with a right supraclavicular mass. He was treated with resection, which involved several vascular structures, requiring multiple vascular reconstructions followed by postoperative radiotherapy. The authors concluded that, when located in tha mediastinum, the invasive character of such tumors and its tendency to recur may pose a considerable surgical challenge, requiring careful preoperative planing and postoperative planning follow-up. The role of radiation therapy is limited to the control of local recurrences