Background: Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. Objective: The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. Methods: Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. Results: Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥30% difference in tissue destruction. Conclusion: Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones.

Emphysema is often distributed heterogeneously throughout the lungs, even at the segmental level. It is important for interventional lung volume reduction therapies to target and treat the most diseased regions of the lung while preserving the less diseased functional regions. Identification and determination of the severity of emphysema can be done using the various quantification measures reviewed in this article. However, all of these measures are similar in what they quantify and are equally good indicators of emphysema. The tissue/air ratio was chosen for our purposes. Software capable of quantifying emphysema severity at the segmental level exists, and can be utilized to identify the most diseased segments while following anatomical boundaries. The segmental heterogeneity index is a new measure being introduced to help quantify differences in emphysema severity at the segmental level. The goal of segmental targeting is to improve efficacy and safety outcomes of vapor ablation patients. The Sequential Staged Treatment of Emphysema with Upper Lobe Predominance (STEP-UP, NCT01719263) trial is currently enrolling patients with upper lobe heterogeneous emphysema using these techniques.

BackgroundAn innovative approach to lung volume reduction (LVR) for emphysema is introduced in the design of the Sequential Segmental Treatment of Emphysema with Upper Lobe Predominance (STEP-UP) trial where vapour ablation is administered bilaterally over the course of two sessions and is used to target only the most diseased upper lobe segments. By dividing the procedure into two sessions, there is potential to increase the total volume treated per patient but reduce volume treated and energy delivered per session. This is expected to correlate with improvements in vapour ablation’s safety and efficacy profiles.MethodsThe STEP-UP trial is a randomized, controlled, open-label, 12 month study of patients with upper lobe predominant emphysema (ULPE). The trial compares patients receiving standard medical management alone against patients receiving bilateral vapour ablation in addition to standard medical management. An intended sixty nine subjects will be randomized at a 2:1 (treatment arm:control arm) ratio. Inclusion criteria include a forced expiratory volume in 1 second (FEV1) between 20% and 45% predicted, total lung capacity > 100% predicted, residual volume > 150% predicted, marked dyspnea scoring ≥ 2 on the modified Medical Research Council (mMRC) scale, and PaCO2 ≤ 50 mm Hg. The primary endpoints are the change in FEV1 %predicted and St. George Respiratory Questionnaire (SGRQ) score between the treatment and control arm at 12 months. Adverse events will be monitored as secondary endpoints along with other efficacy outcomes at 6 and 12 months.DiscussionVapour ablation can reduce lung volume in the presence of collateral ventilation (CV). Due to this ability, it can be used to target specifically the more diseased segments of each upper lobe. Safety and efficacy outcomes are expected to improve by considering which segments to treat along with the volume treated per session and per patient.Trial registrationClinicalTrials.gov NCT01719263.

Background: Various methods for ablating peripheral lung lesions are being investigated; however, none have been successfully adapted for delivery via bronchoscopy. Vapor ablation is currently being used to bronchoscopically create lung volume reduction in emphysema patients. Objectives: In this study, an adaptation of that technology is evaluated for potential treatment of lung lesions in a live pig model. Methods: In 5 anesthetized healthy pigs, vapor of varying energy levels was delivered bronchoscopically to 66 different lung subsegments with airway diameters of 2-5 mm. Two hours after treatment, a necropsy was performed and the ablated regions were assessed for ablation and tissue structure disruption. In 6 additional pigs, vapor was applied to 3 subsegments each. To evaluate the progression of the response to treatment, 2 were kept alive for 10 days, 2 for 21 days, and 2 for 32 days. Results: Histopathological evaluation of the sections demonstrated that vapor is capable of creating a uniform field of necrosis following the subsegment anatomical boundary. The reliability of a uniform field is dependent on the level of energy delivered. An energy level that reliably creates a uniform field of necrosis was applied in chronic animals. The animals tolerated the procedure and posttreatment care. No cardiac arrhythmias, hemorrhage, stroke, respiratory distress, or pneumothorax occurred during or after treatment. Conclusions: Vapor ablation is a potentially safe and efficient means of ablating a targeted region of the lung. We hypothesize that vapor may be useful in treating lesions of the lung in humans.

BackgroundQuantification of lung tissue via analysis of computed tomography (CT) scans is increasingly common for monitoring disease progression and for planning of therapeutic interventions. The current study evaluates the quantification of human lung tissue mass by software analysis of a CT to physical tissue mass measurements.MethodsTwenty-two ex vivo lungs were scanned by CT and analyzed by commercially available software. The lungs were then dissected into lobes and sublobar segments and weighed. Because sublobar boundaries are not visually apparent, a novel technique of defining sublobar segments in ex vivo tissue was developed. The tissue masses were then compared to measurements by the software analysis.ResultsBoth emphysematous (n = 14) and non-emphysematous (n = 8) bilateral lungs were evaluated. Masses (Mean ± SD) as measured by dissection were 651 ± 171 g for en bloc lungs, 126 ± 60 g for lobar segments, and 46 ± 23 g for sublobar segments. Masses as measured by software analysis were 598 ± 159 g for en bloc lungs, 120 ± 58 g for lobar segments, and 45 ± 23 g for sublobar segments. Correlations between measurement methods was above 0.9 for each segmentation level. The Bland-Altman analysis found limits of agreement at the lung, lobe and sublobar levels to be −13.11% to −4.22%, –13.59% to 4.24%, and –45.85% to 44.56%.ConclusionThe degree of concordance between the software mass quantification to physical mass measurements provides substantial evidence that the software method represents an appropriate non-invasive means to determine lung tissue mass.