Utilizing Clinical Trial Data to Assess Timing of Surgical Treatment for Emphysema Patients.

BACKGROUND: Lung volume reduction surgery (LVRS) and medical therapy are 2 available treatment options in dealing with severe emphysema, which is a chronic lung disease. However, or there are currently limited guidelines on the timing of LVRS for patients with different characteristics. OBJECTIVE: The objective of this study is to assess the timing of receiving LVRS in terms of patient outcomes, taking into consideration a patient's characteristics. METHODS: A finite-horizon Markov decision process model for patients with severe emphysema was developed to determine the short-term (5 y) and long-term timing of emphysema treatment. Maximizing the expected life expectancy, expected quality-adjusted life-years, and total expected cost of each treatment option were applied as the objective functions of the model. To estimate parameters in the model, the data provided by the National Emphysema Treatment Trial were used. RESULTS: The results indicate that the treatment timing strategy for patients with upper-lobe predominant emphysema is to receive LVRS regardless of their specific characteristics. However, for patients with non-upper-lobe-predominant emphysema, the optimal strategy depends on the age, maximum workload level, and forced expiratory volume in 1 second level. CONCLUSION: This study demonstrates the utilization of clinical trial data to gain insights into the timing of surgical treatment for patients with emphysema, considering patient age, observable health condition, and location of emphysema. HIGHLIGHTS: Both short-term and long-term Markov decision process models were developed to assess the timing of receiving lung volume reduction surgery in patients with severe emphysema.How clinical trial data can be used to estimate the parameters and obtain short-term results from the Markov decision process model is demonstrated.The results provide insights into the timing of receiving lung volume reduction surgery as a function of a patient's characteristics, including age, emphysema location, maximum workload, and forced expiratory volume in 1 second level.

Comparative outcomes of lung volume reduction surgery and lung transplantation: a systematic review and meta-analysis.

Background: Lung volume reduction (LVR) and lung transplantation (LTx) have been used in different populations of chronic obstructive pulmonary disease (COPD) patients. To date, comparative study of LVR and LTx has not been performed. We sought to address this gap by pooling the existing evidence in the literature. Methods: An electronic search was performed to identify all prospective studies on LVR and LTx published since 2000. Baseline characteristics, perioperative variables, and clinical outcomes were extracted and pooled for meta-analysis. Results: The analysis included 65 prospective studies comprising 3,671 patients [LTx: 15 studies (n=1,445), LVR: 50 studies (n=2,226)]. Mean age was 60 [95% confidence interval (CI): 58-62] years and comparable between the two groups. Females were 51% (95% CI: 30-71%) in the LTx group vs. 28% (95% CI: 21-36%) in LVR group (P=0.05). Baseline 6-minute walk test (6MWT) and pulmonary function tests were comparable except for the forced expiratory volume in 1 second (FEV1), which was lower in the LTx group [21.8% (95% CI: 16.8-26.7%) vs. 27.3% (95% CI: 25.5-29.2%), P=0.04]. Postoperatively, both groups experienced improved FEV1, however post-LTx FEV1 was significantly higher than post-LVR FEV1 [54.9% (95% CI: 41.4-68.4%) vs. 32.5% (95% CI: 30.1-34.8%), P<0.01]. 6MWT was also improved after both procedures [LTx: 212.9 (95% CI: 119.0-306.9) to 454.4 m (95% CI: 334.7-574.2), P<0.01; LVR: 286 (95% CI: 270.2-301.9) to 409.1 m (95% CI: 392.1-426.0), P<0.01], however, with no significant difference between the groups. Pooled survival over time showed no significant difference between the groups. Conclusions: LTx results in better FEV1 but otherwise has comparable outcomes to LVR.

The nodule in the emphysematous lung: an appeal for surgery in a lung volume reduction concept.

Background: Emphysema patients, who are candidates for lung volume reduction surgery (LVRS) usually present with an extensive smoking history and thus have an increased risk for lung. The incidence of pulmonary nodules in emphysematous lungs is high. We therefore aimed to analyse the incidence and histological findings of pulmonary nodules in our LVRS program. Methods: We conducted a retrospective review of all patients who underwent LVRS between 2016 and 2018. Data concerning preoperative workup, 30 days mortality and histopathological findings analysed. Results: Between 2016 and 2018, LVRS was performed in 66 patients. In 18 (27%) a nodule was found in the preoperative computed tomography (CT) scan. Histological findings revealed in two cases squamous cell lung cancer. In two other cases, histopathological findings revealed an anthracotic intrapulmonary lymph node. In eight cases, a tuberculoma was found with a positive culture in one case. The other six histopathological findings were hamartoma, granuloma or sequelae of pneumonia. Conclusions: Malignancy was found in 11.1% of patients presenting with a nodule in preoperative LVRS workup. The relative risk of lung cancer in emphysema patients is increased and if LVRS criteria are fulfilled surgical resection of a pulmonary nodule is a meaningful way to verify the histology.

Critical Analysis of the National Emphysema Treatment Trial Results for Lung-Volume-Reduction Surgery.

The National Emphysema Treatment Trial compared medical treatment of severe pulmonary emphysema with lung-volume-reduction surgery in a multiinstitutional randomized prospective fashion. Two decades later, this trial remains one of the key sources of information we have on the treatment of advanced emphysematous lung disease. The trial demonstrated the short- and long-term effectiveness of surgical intervention as well as the need for strict patient selection and preoperative workup. Despite these findings, the key failure of the trial was an inability to convince the medical community of the value of surgical resection in the treatment of advanced emphysema.

Value of a Multidisciplinary Team Approach to Treatment of Emphysema.

Lung volume reduction surgery can significantly improve quality of life for properly selected patients who are symptomatic despite maximal medical management for emphysema. This requires a well-constructed multidisciplinary team (including transplant) to evaluate and treat these patients.

Discretization of Learned NETT Regularization for Solving Inverse Problems.

Deep learning based reconstruction methods deliver outstanding results for solving inverse problems and are therefore becoming increasingly important. A recently invented class of learning-based reconstruction methods is the so-called NETT (for Network Tikhonov Regularization), which contains a trained neural network as regularizer in generalized Tikhonov regularization. The existing analysis of NETT considers fixed operators and fixed regularizers and analyzes the convergence as the noise level in the data approaches zero. In this paper, we extend the frameworks and analysis considerably to reflect various practical aspects and take into account discretization of the data space, the solution space, the forward operator and the neural network defining the regularizer. We show the asymptotic convergence of the discretized NETT approach for decreasing noise levels and discretization errors. Additionally, we derive convergence rates and present numerical results for a limited data problem in photoacoustic tomography.

Endoscopic Lung Volume Reduction: Review of the EMPROVE and LIBERATE trials.

Endoscopic lung volume reduction is now included in the guidelines for treatment in severe chronic obstructive pulmonary disease. Since December 2018, 2 valve systems have been approved by the US Food and Drug Administration (FDA). To date, there is no head-to-head trial comparing both valve systems and no clear benefit of one over the other. This article provides an overview of the two largest prospective trials performed with the FDA-approved valve systems.

Hypercapnia in Advanced Chronic Obstructive Pulmonary Disease: A Secondary Analysis of the National Emphysema Treatment Trial.

RATIONALE: Hypercapnia develops in one third of patients with advanced chronic obstructive pulmonary disease (COPD) and is associated with increased morbidity and mortality. Multiple factors in COPD are thought to contribute to the development of hypercapnia including increased carbon dioxide (CO2) production, increased dead space ventilation, and the complex interactions of deranged respiratory system mechanics, inspiratory muscle overload and the ventilatory control center in the brainstem. However, these factors have not previously been systematically analyzed in a large, well-characterized population of severe COPD patients. METHODS: This is a secondary analysis of the clinical, physiologic and imaging data from the National Emphysema Treatment Trial (NETT). All patients with complete baseline data for the key predictor variables were included. An inclusive list of 32 potential predictor variables were selected a priori based on consensus of the investigators and literature review. Stepwise variable selection yielded 10 statistically significant associations in multivariate regression. RESULTS: A total of 1419 patients with severe COPD were included in the analysis; mean age 66.4 years (standard deviation 6.3), 38% females, and 422 (29.7%) had baseline hypercapnia. Key variables associated with hypercapnia were low resting partial pressure of oxygen in blood, low minute ventilation (Ve), high volume of exhaled carbon dioxide, low forced expiratory volume in 1 second, high residual volume, lower % emphysema on chest computed tomography, use of oxygen, low ventilatory reserve (high Ve/maximal voluntary ventilation), and not being at high altitude. Low diffusing capacity for carbon monoxide showed a positive association with hypercapnia in univariate analysis but a negative correlation in multivariate analysis. Measures of dyspnea and quality of life did not associate with degree of hypercapnia in multivariable analysis. CONCLUSION: Hypercapnia in a well-characterized cohort with severe COPD and emphysema is chiefly related to poor lung mechanics, high CO2 production, and a reduced ventilatory capability. Hypercapnia is less impacted by gas exchange abnormalities or the presence of emphysema.

Loneliness and ED Visits in Chronic Obstructive Pulmonary Disease.

The primary objective of this study was to investigate the association of loneliness and the incidence of ED visits in a large and well-characterized cohort of patients with severe chronic obstructive pulmonary disease (COPD); the association of loneliness with performance measures and health perception was the secondary objective. Baseline data were used from the National Emphysema Treatment Trial (NETT), which investigated the effectiveness of lung volume reduction surgery in patients with moderate-to-severe COPD. Patients received Quality of Wellbeing questionnaires, which asked about loneliness and social isolation. For comparing baseline variables between lonely and non-lonely subjects, we used χ2 tests for categorical variables and Wilcoxon tests for continuous variables. The association of loneliness with ED visits and health perception was assessed with a logistic model that adjusted for multiple critical confounders. The study took place from December 2002, to December 2004, with a follow-up period of 5 years to assess loneliness and 24 months to assess use of the emergency department. There were 1218 patients analyzed, mean age 65 (standard deviation [SD] 12), 47% were women, FEV 1% 41 (SD 12); 7.9% of participants reported feeling lonely. These individuals had worse health ratings, 6-minute walk tests (6MWTs), and breathlessness. Loneliness was independently associated with ED visits after adjusting for age, lung function, dyspnea, 6MWT, treatment, and gender, odds ratio (OR) 1.57 (95% confidence interval [CI], 1.005-2.466), P=.04. This study suggests that loneliness in patients with COPD is significantly and independently associated to ED visits and reduced health perception. Addressing loneliness of patients with COPD in the outpatient setting may contribute to improved health perception and less health care utilization.

Lung volume reduction surgery in the post-National Emphysema Treatment Trial era.

Lung volume reduction surgery (LVRS) as means to improve the pulmonary function and quality of life of patients with chronic obstructive pulmonary disease (COPD) can be traced back to the 1950's and early work by Otto Brantigan. Joel Cooper revived this concept with pioneering work in the 1990's. His work, along with others, led to the National Emphysema Treatment Trial (NETT) which demonstrated a quality of life and survival benefit for certain subsets of patients with emphysema. While the outcomes of carefully selected patients are excellent, with proven benefits in both quality of life and overall survival, the volume of LVRS being performed remains low. The procedure is highly regulated in the United States and is only performed in Centers for Medicare and Medicaid Services (CMS) approved programs. Programs are required to follow the NETT selection criteria. The program at Columbia University Medical Center/New York Presbyterian Hospital remains active. Utilizing the NETT criteria, we continue to perform LVRS with no operative mortality and excellent long-term outcomes.

Long-term survival and symptomatic relief in lower lobe lung volume reduction surgery.

OBJECTIVES: Lung volume reduction surgery (LVRS) has been demonstrated to provide symptomatic relief and improve lung function in patients with end-stage emphysema. The National Emphysema Treatment Trial specifically noted functional benefits in patients with predominantly upper lobe emphysema and demonstrated improvement in quality-of-life parameters, in patients with non-upper lobe emphysema and a low-baseline exercise capacity. We aimed to investigate whether physiological and health status benefits correlated with lower lobe LVRS. METHODS: A retrospective analysis was performed from our prospectively collected patient database. A total of 36 patients with severe, non-upper lobe predominant emphysema underwent lower lobe LVRS in our institution, over a 20-year period. The assessments consisted of measurements of body mass index, pulmonary function tests and health-related quality of life using the Short Form 36-item questionnaires. RESULTS: Forced expiratory volume in 1 s was seen to improve 3 months [coefficient of time = 1.55 (0.88, 2.21); P < 0.0001] after the procedure, maintained until the first 6 months [0.48 (0.12, 0.85); P = 0.010], decline over the second half of the first year and gradually return to preoperative levels after 2 years, while residual volume to total lung capacity (%) ratio was seen to follow a similar pattern with significant decrease from baseline after 3 months [coefficient of time = -1.76 (-2.75, -0.76); P = 0.001] and 6 months [-1.05 (-1.51, -0.59); P < 0.0001]. Quality-of-life improvements were mainly noted in physical components. CONCLUSIONS: Contrary to a widely held misconception following the National Emphysema Treatment Trial that lower lobe lung volume reduction does not offer significant benefits to patients with non-upper lobe predominant emphysema, we feel justified in offering lower lobe LVRS in these patients when they meet the same selection criteria as upper lobe LVRS.

A randomized, single-blinded, prospective study that compares complications between cuffed and uncuffed nasal endotracheal tubes of different sizes and brands in pediatric patients.

STUDY OBJECTIVE: To compare any association between the problematic distal placement of cuffed and uncuffed nasal endotracheal tubes (NETTs) of different sizes and brands in pediatric patients. DESIGN: Randomized, single-blinded, prospective study. SETTING: Operating room at The Children's Hospital. PATIENTS: Pediatric patients (aged 2-18 years) scheduled for dental surgery under general anesthesia whose American Society of Anesthesiologists physical status is not greater than 2. INTERVENTION: Patients were randomly assigned to preformed cuffed (1) RAE (Ring-Adair-Elwyn) endotracheal tube by Mallinckrodt or (2) nasal AGT NETT by Rüsch. MEASUREMENTS: The distance between the tube's distal end and the carina was measured using a fiber optic bronchoscope. Problematic placements were defined where the tip of the tubes was within 0.5 cm of carina. MAIN RESULTS: The odds of a problematic placement was 7 times higher (95% confidence interval of odds ratio, 2.06, 23.4) in patients managed with cuffed tubes than those with uncuffed tubes (P = .002). The distance between the tip of cuffed NETT tubes and carina was significantly less than with uncuffed tubes. CONCLUSIONS: The chances of possible complications were significantly higher with cuffed NETT. The NETT should be kept at least 0.5 cm above carina to avoid possible complications.

Maximal Oxygen Uptake--Risk Predictor of NSCLC Resection in Patients With Comorbid Emphysema: Lessons From NETT.

We compared VO2 max values from ACCP Guidelines and from NETT's homogenous NULPD surrogate for predicting operative mortalities. Estimated mid and long-term non-cancer related survival in NETT's subset was also obtained. NETT and ACCP Guideline VO2 max values were similar in the "low" and "mid" risk operative mortality categories but NETT's "high" risk subset showed lower mortality (14% vs. 26%). Estimated non-cancer related survival in NETT "low", "mid" and "high" risk VO2 max categories at two and eight years were 100%, 74%, 59% and 48%, 26%, 14%, respectively. The lower predicted risk in NETT's "high- risk" subset raises the possibility of extending indications for potential curative resection in selected patients. The NETT surrogate also provides hitherto unavailable estimate on long-term non-cancer related survival after potential curative resection of NSCLC and suggests that the operation does not shorten eight-year longevity.