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).

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial.

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation.Objectives:Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported.Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George's Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy).Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P < 0.05 and P < 0.001, respectively). Reduction in CAT was through improvements in breathlessness (P < 0.05), energy level (P < 0.05), activities (P < 0.001), and increased confidence when leaving home (P < 0.05). The TDI measures of effort, task, and functional impairment were uniformly improved (P < 0.001). The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group. Improvements correlated with changes in residual volume and residual volume/TLC ratio.Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months.Clinical trial registered with www.clinicaltrials.gov (NCT01796392).

Esthesioneuroblastoma with widespread distant metastasis: Case report and literature review.

Esthesioneuroblastoma (ENB) is an uncommon sinonasal tract tumor, and it is even more uncommon among all neoplasms. Literature regarding the incidence and spread of the disease is limited. The prognosis of metastatic disease is poor. In this report, we present a case of recurrent ENB in a young woman involving metastasis to the neck, lungs, and ovary. Metastasis to the cervical lymph nodes is relatively common, but metastasis to the lungs is rare. Furthermore, to our knowledge, no cases of ovarian metastases of ENB have been reported. This case highlights the potential for widespread metastatic disease, suggesting the need for more frequent and thorough surveillance of patients diagnosed with recurrences of this tumor.

A 52-year-old man with palpitations and a solitary pulmonary nodule.

A 52-year-old white man presented to a pulmonary clinic for evaluation of a 2.3 × 1.7 cm lung nodule. The patient had originally presented to his cardiologist for palpitations. The palpitations were described as a "fluttering" sensation, occurring daily, more often at rest, but not associated with syncope. At the time, he denied dyspnea, paroxysmal nocturnal dyspnea, or orthopnea. The patient had a coronary artery calcium scoring test done, which revealed a lobulated, well-circumscribed, smoothly marginated lower lobe nodule, and he was sent to a pulmonary clinic for further evaluation. The patient denied shortness of breath, chest pain, cough, wheezing, or hemoptysis. He denied fatigue, night sweats, or weight loss. He had a 1 pack-year smoking history and stopped cigarettes 30 years ago but still smoked two to three cigars monthly. His family history was only significant for early coronary artery disease. He was an avid marathon runner who worked as an athletic equipment manager for a prominent sports team in Arizona.

Hydrostatic mechanisms may contribute to the pathogenesis of human re-expansion pulmonary edema.

OBJECTIVE: The primary objective was to test the hypothesis that clinical re-expansion pulmonary edema is predominantly due to increased permeability of the alveolar-capillary barrier. A secondary objective was to determine if the alveolar epithelium was functionally intact in patients with re-expansion pulmonary edema by measuring net alveolar epithelial fluid transport in a subset of patients. DESIGN: Retrospective study of mechanically ventilated patients with re-expansion pulmonary edema. SETTING: Two academic tertiary care hospitals. PATIENTS: Seven patients with acute onset of re-expansion pulmonary edema after tube thoracostomy or thoracentesis. INTERVENTIONS: Pulmonary edema fluid and plasma were collected at the time of onset of re-expansion edema. MEASUREMENTS AND RESULTS: Contrary to our hypothesis, the mean initial edema fluid to plasma protein ratio was 0.58+/-0.21, supporting a hydrostatic mechanism of edema formation. Four of the patients had an initial edema fluid to plasma protein ratio of less than 0.65, consistent with pure hydrostatic pulmonary edema, while the others had a slight increase in permeability (edema fluid to plasma ratios of 0.67, 0.71 and 0.77), perhaps due to capillary stress failure from hydrostatic stress. Alveolar fluid clearance (mean 9.8+/-8.0%/h) was intact in the subset of three patients in whom it was measured. CONCLUSIONS: This study provides the first direct evidence that hydrostatic forces may contribute to the development of re-expansion pulmonary edema.

Long-term complications of artificial airways.

In summary, long-term complications of artificial airways are rare but important sequelae of artificial airways. Many of the potential long-term complications of translaryngeal intubation and tracheotomy are similar and overlapping. Although most patients who undergo these procedures tend to tolerate them without difficulties, significant morbidity and mortality may occur. Identifying the exact cause of the complication may not be possible at times, due to the multiple risk factors involved in the pathogenesis. It is hoped that understanding these potential complications will lead to a more vigilant preventive measures during the institution of long-term artificial airways and a judicious early search for the underlying pathology when a complication is suspected.

"Corkscrew stenosis": defining and preventing a complication of percutaneous dilatational tracheostomy.

OBJECTIVE: The short-term safety of percutaneous dilatational tracheostomy has been widely demonstrated. However, less is known about their long-term complications. Through an illustrative case series, we present and define "corkscrew stenosis," a type of tracheal stenosis uniquely associated with percutaneous dilatational tracheostomy. METHODS: Patients treated at our institution for tracheal stenosis after percutaneous dilatational tracheostomy were reviewed. Demographic data including gender, age, history of presentation, lesion morphology, imaging, and management was collected and evaluated. The pathology of the stenosis and the strategies for prevention are presented. RESULTS: From January, 2008 through December 2011, 11 patients had tracheal stenosis after percutaneous dilatational tracheostomy. The mean age was 54 ± 17 years and 55% were male. The stenotic lesions were characterized by a corkscrew morphology at the stoma site with a mean distance of 2.3 ± 0.8 cm from the vocal cords. Images of these lesions demonstrated disruption and fracture of the proximal tracheal cartilages and displacement of the anterior tracheal wall into the tracheal lumen. The majority of our patients required tracheal resection for definitive repair. CONCLUSIONS: We suggest that a unique form of tracheal stenosis can result from percutaneous dilatational tracheostomy. We observed corkscrew stenosis to be located proximally, associated with fractured tracheal rings, and morphologically appearing as interdigitation of these fractured rings. Recognizing corkscrew stenosis, its unique mechanism of formation, and technical means of prevention may be important in advancing the long-term safety of this procedure for critically ill patients who require prolonged ventilatory support.

CXCR2 is critical to hyperoxia-induced lung injury.

Hyperoxia-induced lung injury is characterized by infiltration of activated neutrophils in conjunction with endothelial and epithelial cell injury, followed by fibrogenesis. Specific mechanisms recruiting neutrophils to the lung during hyperoxia-induced lung injury have not been fully elucidated. Because CXCL1 and CXCL2/3, acting through CXCR2, are potent neutrophil chemoattractants, we investigated their role in mediating hyperoxia-induced lung injury. Under variable concentrations of oxygen, murine survival during hyperoxia-induced lung injury was dose dependent. Eighty percent oxygen was associated with 50% mortality at 6 days, while greater oxygen concentrations were more lethal. Using 80% oxygen, we found that lungs harvested at day 6 demonstrated markedly increased neutrophil sequestration and lung injury. Expression of CXCR2 ligands paralleled neutrophil recruitment to the lung and CXCR2 mRNA expression. Inhibition of CXC chemokine ligands/CXCR2 interaction using CXCR2(-/-) mice exposed to hyperoxia significantly reduced neutrophil sequestration and lung injury, and led to a significant survival advantage as compared with CXCR2(+/+) mice. These findings demonstrate that CXC chemokine ligand/CXCR2 biological axis is critical during the pathogenesis of hyperoxia-induced lung injury.