Body composition impacts outcome of bronchoscopic lung volume reduction in patients with severe emphysema: a fully automated CT-based analysis.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s [FEV1], r = 0.440; ΔInspiratory vital capacity [IVC], r = 0.397; Δ6Minute walking distance [6MWD], r = 0.509 and ΔCOPD assessment test [CAT], r = -0.324; all p < 0.001). Group stratification by bone adjusted muscle volume changes revealed that groups with substantial muscle gain experienced a greater clinical benefit in pulmonary function improvements, QoL and physical performance (ΔFEV1%, 5.5 vs. 39.5; ΔIVC%, 4.3 vs. 28.4; Δ6MWDm, 14 vs. 110; ΔCATpts, -2 vs. -3.5 for groups with ΔMuscle, BAR% < -10 vs. > 10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV1) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% -5 vs. 3.4 and ΔIMAT, BAR% -0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients.

[Bronchoscopic lung volume reduction]. / Endoskopische Lungenvolumenreduktion.

Bronchoscopic lung volume reduction is as a safe and effective therapy for patients with advanced emphysema, suffering from breathlessness despite optimal medical therapy. By reducing hyperinflation, it improves lung function, exercise capacity and quality of life. The technique includes one-way endobronchial valves, thermal vapor ablation and endobronchial coils. Patient selection is the key to a successful therapy; hence the indication should be evaluated in a multidisciplinary emphysema team meeting. The procedure can lead to a potentially life-threatening complication. Therefore, an adequate post-procedural patient management is crucial.

Clinical Impact of Compensatory Hyperinflation of the Nontreated Adjacent Lobe After Bronchoscopic Lung Volume Reduction with Valves.

Background: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) can be a successful treatment for end-stage emphysema patients. The reduction of hyperinflation enhances ventilatory mechanics and diaphragm function. Understanding predictors for treatment success is crucial for further improvements. Purpose: The aim of this study was to assess the effect of the target lobe volume reduction (TLVR) in relation to the ipsilateral lung volume reduction (ILVR), affected by the compensatory expansion of the adjacent lobe, on the outcome after BLVR with valves. Patients and Methods: The volumetric relationship of ILVR% to TLVR%, addressed as Reduction Ratio (R), was recorded in 82 patients and compared to changes in lung function, physical performance and quality of life. A small value for R implies a relatively low volume reduction of the ipsilateral lung (ILVR) compared to the volume reduction of the target lobe (TLVR). Additionally, the minimal clinically important difference (MCID) for R was calculated. Results: Patients with a smaller Reduction Ratio (R <0.2) showed minor improvements at the 3 months follow-up compared to patients with R ≥0.2 (mean changes of 39 mL (5.8%), -395 mL (-4.9%) and 96 mL (7.1%) versus 231 mL (33%), -1235 mL (-20%) and 425 mL (29%) in the forced expiratory volume in 1s (FEV1), residual volume (RV) and inspiratory vital capacity (IVC), respectively, and -3 m and 0 points versus 20.4 m and -3.4 points in the 6-minute-walking-distance (6MWD) and COPD assessment test (CAT) score respectively). With a combined value of 0.185, a MCID for R was calculated with established anchors (FEV1, RV, and 6MWD) for emphysema patients. Conclusion: Extensive compensatory hyperinflation of the adjacent non-treated lobe after BLVR results in decreased ILVR, which is responsible for a lack of meaningful improvements in ventilatory mechanics and clinical outcome, despite technically successful lobe volume reduction.

Predictive value of Chartis measurement for lung function improvements in bronchoscopic lung volume reduction.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) via valve implantation can be achieved by targeting severely hyperinflated and emphysematously destructed lung areas in patients with chronic obstructive lung disease. Lack of collateral ventilation (CV) is important for good outcomes with BLVR. CV can be measured using the catheter-based Chartis system. The aim of this study was to evaluate the correlation between total exhaled volume drained from the target lobe measured by Chartis and clinical outcomes after BLVR in CV-negative patients. METHODS: From January 2016 to March 2019, 60 patients were included in this retrospective single-center analysis. Drained volume (TVol) measured by Chartis was recorded and compared with lung function and physical performance parameters. Outcome variables included the percentage change in lung function [forced expiratory volume in 1 s (FEV1), residual volume (RV), and inspiratory vital capacity (IVC)]. Secondary outcomes were the degree of target lobe volume reduction (TLVR), change in 6-min walk distance (6MWD), and change in chronic obstructive pulmonary disease (COPD) assessment test (CAT) score. RESULTS: Drained volume correlated significantly with post-BLVR change in FEV1 (r = 0.663), IVC (r = 0.611), RV (r = -0.368), and TLVR (r = 0.635) (all p < 0.05). In a priori-defined patient subgroups based on drained volume [<100 ml (n = 19), 100-400 ml (n = 33), and >400 ml (n = 8)]; mean changes in FEV1 were 2.6%, 17.4%, and 51.3%; in RV were -3.9%, -10.6%, and -23.8%; in IVC were -4.0%, 10.6%, and 62.4%; and in TLVR were 525 ml (39%), 1375 ml (73%) and 1760 ml (100%), respectively. There were no significant correlations between absolute and percentage changes in 6MWD and the CAT score. Lung volume reduction was diagnosed in 32 (53%) cases. CONCLUSION: Drained volume measured by the Chartis system correlated with functional improvement in CV-negative patients undergoing BLVR. The reviews of this paper are available via the supplemental material section.

Integration of Bronchoscopic Transesophageal Ultrasound Examination of the Left Adrenal Gland into Routine Lung Cancer Staging Workup: A Prospective Trial.

BACKGROUND: Endobronchial ultrasound (EBUS) with transbronchial needle aspiration increases the diagnostic yield of lung cancer staging. The left adrenal gland (LAG) is a common site for lung cancer metastasis. The modality of transesophageal examination with an EBUS bronchoscope (EUS-B) routinely for LAG has not been assessed. OBJECTIVE: The aim of this study was to prospectively assess if evaluation and tissue sampling of the LAG could routinely be implemented in an EBUS procedure. METHODS: Patients referred for EBUS between March and August 2017 had assessment of the LAG via EUS-B. Fine-needle aspiration (FNA) was performed in cases with a suspicious LAG. The detection rate, procedure time, and learning curve of four experienced EBUS-bronchoscopists was assessed, plus the diagnostic accuracy and complication rate of FNA. RESULTS: In total, 313 consecutive patients were included. The overall LAG detection rate was 87.5%. After the initial learning curve, the detection rate for all four bronchoscopists was >93%. The detection rate did not correlate with any patient characteristics. EUS-B-FNA revealed nine LAG metastases, with a sensitivity, specificity, and accuracy of 75%, 100%, and 99%, respectively. The mean EUS-B operation time was 194.4 s, with 594.8 s for FNA. There were no FNA-associated complications. CONCLUSIONS: Evaluation of the LAG with EUS-B could routinely be included in an EBUS procedure if necessary. A high detection rate can be achieved after an initial learning period. FNA of the LAG was feasible and safe. EUS-B of the LAG could be integrated into the usual EBUS/EUS-B procedure in lung cancer staging workup.

A summary statistic approach to sequence variation in noncoding regions of six schizophrenia-associated gene loci.

In order to explore the role of noncoding variants in the genetics of schizophrenia, we sequenced 27 kb of noncoding DNA from the gene loci RAC-alpha serine/threonine-protein kinase (AKT1), brain-derived neurotrophic factor (BDNF), dopamine receptor-3 (DRD3), dystrobrevin binding protein-1 (DTNBP1), neuregulin-1 (NRG1) and regulator of G-protein signaling-4 (RGS4) in 37 schizophrenia patients and 25 healthy controls. To compare the allele frequency spectrum between the two samples, we separately computed Tajima's D-value for each sample. The results showed a smaller Tajima's D-value in the case sample, pointing to an excess of rare variants as compared to the control sample. When randomly permuting the affection status of sequenced individuals, we observed a stronger decrease of Tajima's D in 2400 out of 100,000 permutations, corresponding to a P-value of 0.024 in a one-sided test. Thus, rare variants are significantly enriched in the schizophrenia sample, indicating the existence of disease-related sequence alterations. When categorizing the sequenced fragments according to their level of human-rodent conservation or according to their gene locus, we observed a wide range of diversity parameter estimates. Rare variants were enriched in conserved regions as compared to nonconserved regions in both samples. Nevertheless, rare variants remained more common among patients, suggesting an increased number of variants under purifying selection in this sample. Finally, we performed a heuristic search for the subset of gene loci, which jointly produces the strongest difference between controls and cases. This showed a more prominent role of variants from the loci AKT1, BDNF and RGS4. Taken together, our approach provides promising strategy to investigate the genetics of schizophrenia and related phenotypes.