Steven C. Springmeyer

A Multicenter Pilot Study of a Bronchial Valve for the Treatment of Severe Emphysema

Background: Chronic obstructive pulmonary disease (COPD) affects millions of people and has limited treatment options. Surgical treatments for severe COPD with emphysema are effective for highly selected patients. A minimally invasive method for treating emphysema could decrease morbidity and increase acceptance by patients. Objective: To study the safety and effectiveness of the IBV® Valve for the treatment of severe emphysema. Methods: A multicenter study treated 91 patients with severe obstruction, hyperinflation and upper lobe (UL)-predominant emphysema with 609 bronchial valves placed bilaterally into ULs. Results: Valves were placed in desired airways with 99.7% technical success and no migration or erosion. There were no procedure-related deaths and 30-day morbidity and mortality were 5.5 and 1.1%, respectively. Pneumothorax was the most frequent serious device-related complication and primarily occurred when all segments of a lobe, especially the left UL, were occluded. Highly significant health-related quality of life (HRQL) improvement (–8.2 ± 16.2, mean ± SD change at 6 months) was observed. HRQL improvement was associated with a decreased volume (mean –294 ± 427 ml, p = 0.007) in the treated lobes without visible atelectasis. FEV1, exercise tests, and total lung volume were not changed but there was a proportional shift, a redirection of inspired volume to the untreated lobes. Combined with perfusion scan changes, this suggests that there is improved ventilation and perfusion matching in non-UL lung parenchyma. Conclusion: Bronchial valve treatment of emphysema has multiple mechanisms of action and acceptable safety, and significantly improves quality of life for the majority of patients.

Multicentre European study for the treatment of advanced emphysema with bronchial valves

This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis. Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n=37) or without (n=36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥4-point improvement in St George’s Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography. At 3 months, there were eight (24%) positive responders in the treated group versus none (0%) in the control group (p=0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean±sd -7.3±9.0%) to the non-treated lobes (6.7±14.5%), with minimal change in the control group (p<0.05). Mean SGRQ total score improved in both groups (treatment: -4.3±16.2; control: -3.6±10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups. Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.

Computed tomography assessment of lung volume changes after bronchial valve treatment

The aim of the present study was to correlate clinical outcome measures following treatment with bronchial valves with regional lung volume. Computed tomography (CT) scan data from 57 subjects with severe emphysema were obtained from nine North American clinical trial sites. IBV® Valves (Spiration, Inc., Redmond, WA, USA) were placed to occlude segmental and subsegmental bronchi in right and left upper lobes using a flexible bronchoscope. Subjects completed a St Georges Respiratory Questionnaire (SGRQ), pulmonary function test (PFT) and exercise capacity test. CT scans were analysed at baseline and at 1, 3 or 6 months after treatment to measure total and lobar lung density, volume and mass. Total lung volumes measured using CT were strongly correlated with PFT and did not change with treatment. However, the treated upper lobes significantly decreased in volume in 88% of the observations, by mean±sd 335±444 mL, or a decrease of 10.2% in the 6 month data. The untreated lobes had an 11.6% increase in volume. Changes in regional lung volume were associated with clinically meaningful improvements in SGRQ (-8.95±16.22), but not clinically meaningful PFT changes. The significant health status improvements reported by subjects following bilateral bronchial valve treatment are associated with regional lung volume changes and interlobar shift measured using computed tomography.

Mycobacterial infections in marrow transplant patients

Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealed Mycobacterium tuberculosis in two patients, Mycobacterium fortuitum in two patients, and Mycobacterium kansasii in one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.

Endobronchial Valve Treatment for Prolonged Air Leaks of the Lung: A Case Series

PURPOSE An endobronchial valve developed for treatment of severe emphysema has characteristics favorable for bronchoscopic treatment of air leaks. We present the results of a consecutive case series treating complex alveolopleural fistula with valves. DESCRIPTION Patients with air leaks that persisted after treatment gave consent and compassionate use approval was obtained. Bronchoscopy with balloon occlusion was used to identify the airways to be treated. IBV Valves (Spiration, Redmond, WA) were placed after airway measurement. EVALUATION During a 15-month period, 8 valve placement procedures were performed in 7 patients and all had improvement in the air leak. The median duration of air leakage was 4 weeks before and 1 day after treatment, with a mean of 4.5 days. Discharge within 2 to 3 days of the procedure occurred in 57% of the patients. A median of 3.5 valves (mode, 2.4) were used, and all valve removals were successful. There were no procedural or valve-related complications. CONCLUSIONS Removable endobronchial valves appear to be a safe and effective intervention for prolonged air leaks.

Treatment of Heterogeneous Emphysema Using the Spiration IBV Valves

Ninety-eight emphysema patients were treated at 13 international sites during a 3-year series of single-arm, open-label studies with the IBV valve and a multi-lobar treatment approach. Fifty six percent of subjects had a clinically meaningful improvement in health-related quality of life, but standard pulmonary function and exercise studies were insensitive effectiveness measures. Quantitative CT analyses of regional lung changes showed lobar volume changes in over 85% of subjects. Lung volume reduction was an uncommon mechanism for a treatment response with bilateral upper lobe treatment. A redirection of inspired air, an interlobar shift to health-ier lung tissue, was the most common mechanism for a valve treatment response.

Bronchoscopic Management of Prolonged Air Leak

Prolonged pulmonary parenchymal air leaks are an important clinical problem. Standard treatment of prolonged air leaks include continued chest tube drainage, pleural sclerosis, or surgery. Approaches that are less invasive than bedside sclerosis or surgery are desirable but bronchoscopy approaches tried over the years have had limited success. In 2001, an American College of Chest Physicians (ACCP) consensus statement concluded there was no role for bronchoscopy for the treatment of prolonged air leaks. The development of bronchial valves for treatment of emphysema allowed the use of these devices for air leaks under compassionate use regulations. Multiple reports of successful bronchial valve treatments, along with the US Food and Drug Administrations (FDA) humanitarian use approval of a bronchial valve for certain postsurgical air leaks, provide new evidence that there is likely a role for endobronchial treatment of prolonged air leaks in selected patients.

Lung Volume Reduction Surgery

AbstractBackground: Observational studies have suggested that lung volume reduction surgery (LVRS) is superior to optimal medical therapy for selected subsets of patients with advanced emphysema. Randomized clinical trials (RCTs) with the exception of the National Emphysema Treatment Trial (NETT), failed to enroll a sufficient number of patients to provide clinicians and patients with convincing outcome data on the usefulness of LVRS. It was postulated that a meta-analysis of these RCTs (3–12 months’ follow up) may provide more compelling information on the value of LVRS in patients with emphysema. Methods: A comprehensive search of the MEDLINE database between January 1994 and January 2004 for RCTs on LVRS was performed. Results: From a total of eight RCTs on record, six studies (306 patients) with 3- to 12-month follow up were deemed suitable for meta-analysis. Key baseline features of these RCT populations included heterogeneous emphysema, comparable inclusion/exclusion criteria and, in retrospect, low walking capacity as measured by the 6-minute walk distance (6MWD). This profile closely resembles NETT’s ’predominantly upper lobe — low exercise tolerance emphysema’ cohort.The LVRS arm of the meta-analysis population showed better results than the medical cohort in terms of pulmonary function (FEV1 p < 0.0001, FVC p < 0.0001, residual volume p < 0.0001, total lung capactiy p = 0.004), gas exchange (arterial partial pressure of oxygen p < 0.0001) and exercise capacity (6MWD p = 0.0002). Although information on quality-of-life measures was not sufficiently uniform to qualify for meta-analysis, a survey of available data revealed better results in the surgical than in the medical arms of each RCT. Mortality 6–12 months after random assignment to treatment was similar in the two study arms, suggesting that the operative mortality from LVRS was offset, within months, by deaths in the medical arm. Conclusions: This meta-analysis showed that a selected subset of patients with advanced, heterogeneous emphysema and low exercise tolerance (6MWD) experienced better outcomes from LVRS than from medical therapy.

The IBV Valve trial: a multicenter, randomized, double-blind trial of endobronchial therapy for severe emphysema.

Background:Lung volume reduction surgery improves quality of life, exercise capacity, and survival in selected patients but is accompanied by significant morbidity. Bronchoscopic approaches may provide similar benefits with less morbidity. Methods:In a randomized, sham procedure controlled, double-blind trial, 277 subjects were enrolled at 36 centers. Patients had emphysema, airflow obstruction, hyperinflation, and severe dyspnea. The primary effectiveness measure was a significant improvement in disease-related quality of life (St. George’s Respiratory Questionnaire) and changes in lobar lung volumes. The primary safety measure was a comparison of serious adverse events. Results:There were 6/121 (5.0%) responders in the treatment group at 6 months, significantly >1/134 (0.7%) in the control group [Bayesian credible intervals (BCI), 0.05%, 9.21%]. Lobar volume changes were significantly different with an average decrease in the treated lobes of −224 mL compared with −17 mL for the control group (BCI, −272, −143). The proportion of responders in St. George’s Respiratory Questionnaire was not greater in the treatment group. There were significantly more subjects with a serious adverse event in the treatment group (n=20 or 14.1%) compared with the control group (n=5 or 3.7%) (BCI, 4.0, 17.1), but most were neither procedure nor device related. Conclusions:This trial had technical and statistical success but partial-bilateral endobronchial valve occlusion did not obtain clinically meaningful results. Safety results were acceptable and compare favorably to lung volume reduction surgery and other bronchial valve studies. Further studies need to focus on improved patient selection and a different treatment algorithm. Trial Registry:ClinicalTrials.gov NCT00475007.

Diffusing Capacity for Carbon Monoxide Correlates Best With Tissue Volume From Quantitative CT Scanning Analysis

BACKGROUND Quantitative analysis of high-resolution chest CT scan (QCT) is an established method for determining the severity and distribution of lung parenchymal destruction inpatients with emphysema. Diffusing capacity of the lung for carbon monoxide (D(LCO)) is a traditional physiologic measure of emphysema severity and is probably influenced more by destruction of the alveolar capillary bed than by membrane diffusion per se. We reasoned that D(LCO) should correlate with tissue volume from QCT. METHODS A total of 460 patients with upper-lobe-predominant emphysema were enrolled in the study. Th e mean (SD) of percent predicted values for FEV 1 , total lung capacity, and D(LCO) were 30.6% (8.0%), 129.5% (18.1%), and 6.7% (13.1%), respectively. QCT was performed using custom soft ware; the relationship between D(LCO) and various metrics from QCT were evaluated using Pearson correlation coefficients. RESULTS On average, whole-body plethysmography volumes were higher by 841 mL compared with QCT-calculated total lung volume. However, there was a strong correlation between these measurements (r=0.824, P < .0001). D(LCO) correlated with total lung volume (r=0.314, P<.0001), total tissue volume (r=0.498, P<.0001), and percentage of lung with low density (-950 Hounsfield units) (r=-0.337, P<.0001). CONCLUSIONS In patients with severe emphysema, D(LCO) correlates best with total tissue volume,supporting the hypothesis that pulmonary capillary blood volume is the main determinant of D(LCO) in the human lung. Th e relationships between D(LCO) and various anatomic metrics of lung parenchymal destruction from QCT inform our understanding of the relationship between structure and function of the human lung.