The importance of baseline variables for when comparing bronchoscopic lung volume reduction (BLVR) vs. lung volume reduction surgery (LVRS)

Chronic obstructive pulmonary disease (COPD) is a disease of the lungs that stems from cigarette smoking (1). The disease is characterized by airway obstruction and parenchymal destruction with loss of elastic recoil. These changes can lead to significant air trapping and hyperinflation. Emphysema-related hyperinflation results in a mechanical disadvantage for the respiratory muscles leading to shortness of breath, inactivity, and deconditioning. This downward spiral can lead to poor quality of life and increased mortality.

Treatment options for emphysema are traditionally focused on inhaler therapy, pulmonary rehabilitation, and supplemental oxygen. While these options aim to prevent progression of dyspnea and deconditioning, they do not provide substantial therapeutic improvements. Instead, procedural interventions such as bronchoscopic lung volume reduction (BLVR) and lung volume reduction surgery (LVRS) significantly reduce hyperinflation, leading to improvements in expiratory airflow, inspiratory capacity, and diaphragm function. While both BLVR and LVRS effectively reduce hyperinflation, the more invasive nature of LVRS carries higher morbidity and mortality. As a result, individuals who are frail or suffer from more severe emphysema are typically not candidates for LVRS, but instead are considered for BLVR. The trend of more ill individuals qualifying for BLVR often leads to selection bias when comparing outcomes between the two treatments.

While procedural these therapies for emphysema can be effective, the risk of complication in a patient population with multiple comorbidities is significant. The National Emphysema Treatment Trial (NETT) demonstrated significant improvements in dyspnea and survival in patients treated with LVRS for upper lobe predominant disease and low exercise capacity (2). Unfortunately, the incidence of post-surgical complications along with a 7.9% 90-day mortality led LVRS to be performed in very few institutions across the country (2). This not only resulted from complication risk, but also due to the narrow patient population. Additionally, the perceived notion that patients may be too sick to undergo a median sternotomy procedure, as was performed in many NETT patients, was another deterrent for treatment. Today, LVRS is commonly performed by minimally invasive surgical techniques along with improved post-surgical care. These changes bring into question the true morbidity and mortality associated with the surgical techniques used in the NETT trial.

BLVR remains a less invasive alternative for the treatment of emphysema compared to LVRS, with multiple randomized controlled trials, including the LIBERATE and EMPROVE studies, demonstrating significant improvements in dyspnea and spirometry compared to standard of care (SOC) therapy (3,4). The use of small, one-way valves placed into segmental and sub-segmental airways result in induction of lobar atelectasis, essentially emulating the anatomic changes seen following LVRS. While pneumothorax can occur between 14–26 percent of individuals undergoing BLVR, this bronchoscopic therapy was considered less invasive with less morbidity (3,4). As a result, patients who would not tolerate LVRS due to poorer lung health would be considered for BLVR. This self-selects sicker patients and more comorbidities to undergo BLVR.

This issue of The Annals of Thoracic Surgery features an article by Hayanga et al. entitled endobronchial valve (EBV) therapy vs. LVRS in the United States (5). This is a retrospective comparison of LVRS and BLVR by reviewing patients undergoing these interventions based on the United States Centers for Medicare and Medicaid Services between 2018 and 2020. The group reviewed 2,378 patients treated with LVRS and 841 patients treated with BLVR. The primary outcome of the study was difference in mortality between the two groups, with secondary outcomes included post-treatment complications and cost. Importantly, risk adjustments were performed using inverse probability weighting, multilevel regression models, and competing-risk time-to-event analysis. The Elixhauser comorbidity index and the claims based frailty index (CFI) were incorporated to establish risk, as both use multiple data points to assess the baseline health of patients.

This study described the BLVR group as having a higher 30-day mortality (7.37% vs. 4.62%; P=0.003), 60-day mortality (8.69% vs. 5.33%; P<0.001), 1-year mortality (13.7% vs. 10%; P=0.004). The EBV patients also had higher 1-year readmission rate (38.6% vs. 30.6%; P<0.001) and readmission with EBV procedure within 1 year after discharge (9.51% vs. 0.168%; P<0.001). Furthermore, at all-time points, LVRS was associated with higher odds of survival. While findings may make LVRS appear to have superior outcomes compared to BLVR, it reflects BLVR patients are more ill than patients who are eligible for LVRS. A blanket statement that BLVR patients displayed a higher mortality compared to LVRS is not a commentary on the procedure, but more so a representation of the medical complexity of patients undergoing BLVR.

While the analysis by Hayanga et al. is thought-provoking, there are multiple concerns and questions left unanswered in this study. A major limitation to the study is the retrospective nature of the analysis in which the enrollment criteria for the two groups was not consistent. Furthermore, the retrospective data was included over a 2-year period that included 2020, during the height of the global coronavirus disease 2019 (COVID-19) pandemic. This has significant bearing as there is no information on the respiratory severity of the BLVR group and COVID-19 related morality. Additionally, no description of treatment center expertise and treatment capabilities are presented. Did all institutions offer BLVR and LVRS? This is a salient point as centers with only one treatment option drive patient selection, while institutions with both options will tend to send more frail patients for BLVR if eligible and more robust patients for LVRS. Additionally, there was no description of the number of bilateral vs. unilateral LVRS procedures. The weighting of bilateral vs. unilateral is important as conclusions of safety compared to BLVR cannot be appropriately made if most surgeries were unilateral.

The most concerning limitation of the study by Hayanga et al. is the lack of lung function variables, 6-minute walk distance (6MWD), BODE score (body mass index, obstruction, dyspnea, exercise) index, and patient related outcome measures (PROM) score as baseline variables between the two groups. make comparisons for mortality invalid. The comparison between BLVR and LVRS should not be viewed in the procedure or surgery itself, but, more importantly, the baseline health of the patients involved. Salient factors related to patient selection for BLVR and LVRS involve patient comorbidities and functional status. Without clarifying these baseline variables, comparisons of mortality cannot be ascertained. In this study cohort, while the CFI was higher in the patients undergoing BLVR, the Elixhauser comorbidity index was more favorable in LVRS patients. These may reflect degrees of hyperinflation which directly affect respiratory muscle activity and function. Appropriately, the BLVR group may have represented a frail cohort with more severe parenchymal damage, thus resulting in poorer outcomes and worse survival. A more representative indicator of lung health and parenchymal destruction is seen by assessing the use of supplemental oxygen two groups: 50.1% in the BLVR group and 15.9% in the LVRS group. Analysis and comparison of 6MWD, forced expiratory value at 1 second (FEV1), BODE index, PROM score, and diffusing capacity of the lung for carbon dioxide (DLCO) for these cohorts is essential to validate any conclusions described in this study.

The publication of this study remains essential in driving the development of comprehensive COPD programs. Too often, physicians attempt to decide between BLVR or LVRS for therapeutic approaches to emphysema. Furthermore, lung transplantation in appropriate patients should also be considered. These treatment options should not the competitive, but complementary. Multi-disciplinary meetings conducted on a regular basis including thoracic surgeons, interventional pulmonologists, transplant pulmonologists, and radiologists are essential. These meetings should review COPD patients optimized on medical therapy for possible procedural treatment. Following review of treatment options, recommendations can be developed and treatment plans can be facilitated. A recent study by Janssens et al. high-light the importance of a multi-disciplinary lung volume reduction program. (6). This study described improved outcomes and prognoses of highly symptomatic patients with severe emphysema with implementation of a lung volume reduction program providing both surgical and bronchoscopic interventions to maximize eligibility.

The analysis from Hayanga et al. high-lights the importance of both BLVR and LVRS for patients suffering from COPD. While additional baseline data is necessary to validate the conclusions drawn from the Hayanga et al. study, this study will hopefully serve as a springboard for future randomized control trials comparing LVRS and BLVR. Until then, a multi-disciplinary approach to address candidacy for LVRS or BLVR will remain essential.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-61/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-61/coif). The author has no conflicts of interest to declare.

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