Lung Volume Reduction Research Articles

Lung Point in a Case of Bronchoscopy Lung Volume Reduction: Consider Its Mimics Before Inserting the Tube

Point of Care Ultrasound (POCUS) is used to evaluate many clinical scenarios. Chest POCUS has been integrated as a part of a clinical protocol to assess patients with lung pathology [1]. The ability to detect pneumothorax using chest POCUS has been shown to be superior to chest radiography, with specificity reported to be as high as 100% when a lung point sign is identified. In addition to improved diagnostic accuracy, chest POCUS has the added benefits of ease of access and absence of ionizing radiation. Here we describe a case where a patient with a high pre-test probability for pneumothorax had a detected lung point sign, but pneumothorax was ruled out via Computed Tomography (CT). This case highlights the importance of considering the mimics of the lung point sign. This case also shows a unique and interesting finding related to pleural movement restriction post-Bronchoscopic lung volume reduction (BLVR).

Impact of deep inspiration breath hold, surface-guided radiotherapy, and daily CBCT on the organs at risk in breast cancer radiotherapy.

The goal of the study was to assess the impact of deep inspiration breath hold technique (DIBH), surface-guided radiotherapy (SGRT), and daily kilovoltage cone-beam computed tomography (kV-CBCT) on the dose to organs at risk (OAR) in left-sided breast cancer radiotherapy. Twenty-six consecutive left-sided breast cancer patients treated using Volumetric Intensity Modulated Arc Therapy (VMAT), DIBH, SGRT, and a hypofractionated regimen were retrospectively evaluated in this study. Dose parameters were extracted from dose-volume histograms (DVH). The Wilcoxon Matched Pairs test was used to test dose parameters obtained in free breathing (FB) and DIBH for statistical significance. Multivariable analysis of variance (ANOVA) and receiver operating characteristics (ROC) analysis were used to identify parameters and cut-off points associated with the reduction of the mean heart dose (MHD) by DIBH. Based on published models, the risk of cardiac and lung toxicity (pneumonitis) using SGRT or daily kV-CBCT was estimated and compared. DIBH substantially reduced the MHD (median, 43.6%; range, 4.2% to 75.1%; P < 0.00001). The risk of cardiac toxicity using SGRT increased by 1%, compared to 3.6% to 20.5% using daily kV-CBCT. No significant difference in the risk of radiation-induced pneumonitis using SGRT versus daily kV-CBCT was detected. The ANOVA revealed the relative increase of the left lung volume by DIBH as the only significant impact factor for the MHD. The ROC analysis of this parameter showed an area under the curve (AUC) of 0.89 (95%CI, 0.71 to 0.98; P < 0.0001). DIBH can substantially reduce the MHD in left-sided breast cancer patients treated with modern radiotherapy techniques and hypofractionation. Patient setup using SGRT compared to daily kV-CBCT may be the preferred option for many patients. In our patient cohort, the relative reduction of the left lung volume by DIBH can be used as a predictor to select patients who benefit from DIBH.

Chronic airway diseases: a new frontier in interventional pulmonology

As medical science has advanced, the incidence of central airway lesions, traditionally the primary focus of interventional pulmonology, has decreased significantly. However, the large population suffering from chronic airway diseases, coupled with unmet treatment needs and a high demand for new technologies and methods, has greatly driven the innovation and application of interventional respiratory techniques. The development and clinical application of techniques such as lung volume reduction, targeted lung denervation, pulsed electric field technology, bronchial thermoplasty, and regenerative medicine for chronic airway diseases are providing new treatment options. Chronic airway diseases are becoming a new frontier in interventional pulmonology.

Clinical application and challenges of thermal vapor lung volume reduction

There are major clinical challenges in the management of chronic obstructive pulmonary disease (COPD). Recent studies suggest that thermal vapor lung volume reduction may be an important interventional method in the treatment of emphysema phenotype of COPD. In this article, we reviewed and summarized the research and development, the current situation of clinical application, and the clinical challenges of thermal vapor lung volume reduction, to provide further clinical evidence for the standardized application of thermal vapor lung volume reduction.

Application and innovation of bronchoscopic lung volume reduction with endobronchial valve

Bronchoscopic lung volume reduction with endobronchial valve (BLVR-EBV) involves the placement of an endobronchial valve (EBV) in the emphysema area of patients with chronic obstructive pulmonary disease (COPD) via bronchoscopy, resulting in the collapse of the target lung lobe. This procedure has been shown to improve pulmonary function, quality of life, and activity endurance in COPD patients. Strict selection criteria and thorough preoperative evaluation are essential to ensure the success of BLVR-EBV. Due to its excellent postoperative performance, BLVR-EBV has been widely used in the treatment of patients with end-stage COPD, including those with conditions such as pulmonary tuberculosis cavities or those requiring surgical treatment. This paper provided a brief overview of the application and innovation of BLVR-EBV in patient assessment, perioperative management, and postoperative outcomes.

Bronchoscopic Lung Volume Reduction: Effect on Symptoms and Lung Function in Patients with Emphysema That Qualify for Lung Transplant

BackgroundBronchoscopic lung volume reduction (BLVR) studies excluded patients meeting the listing criteria for lung transplantation (LT). Research QuestionWhat are the outcomes of BLVR in a sicker group of emphysematous patients compared to patients not meeting the criteria for LT listing? Study Design and MethodsReal-world retrospective study (June 2018 to December 2022) assessing the effect of BLVR in patients with severe emphysema considered for LT. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), symptoms, and 6-minute walk distance (6-MWD) were measured at baseline and 45 days and 6 months post-BLVR. ResultsOf 76 fully evaluated patients (median age 62 years old, 60% female), 42 underwent BLVR (30 sicker patients met the criteria for LT listing). At baseline, patients that met the criteria for listing had shorter baseline 6-MWD (234.72 ± 68.86, p < 0.001), higher BODE index (6.79 ± 1.11, p = 0.001), and lower FEV1 (617.5 ± 139.2 mL, p = 0.005). All patients treated with BLVR experienced a decrease in BODE index and Borg dyspnea by -0.5 to -2 points, respectively. DLco %pred increased by 4.5%, FEV1 increased by 115 mL, FVC increased by 450 mL, and 6-MWD increased by 20 meters. In the sicker group, FEV1 at 45 days post-BLVR increased by 180.8 ± 231 mL (FEV1 %pred 5.84 ± 5.66) compared to baseline; a persistent effect was seen at 6 months in 62% of patients with available data (18/30). Median hospital length of stay was 3.27 ± 3.07 days. Valves were removed in 6 patients (3 in each group) due to complications. The pneumothorax rate was 24% (10/42; 5 in each group). InterpretationsImprovement in lung function after BLVR was observed regardless of disease severity. BLVR might represent an alternative to LT for some patients.

Endobronchial valve treatment improves chest-CT diaphragm configuration in COPD

This study investigated the impact of bronchoscopic lung volume reduction treatment using endobronchial valves (EBV) on diaphragm configuration. We successfully analyzed the diaphragm index using a newly developed quantitative computed tomography (QCT) tool before and after EBV treatment in forty patients with severe emphysema. We evaluated whether changes in the diaphragm index were associated with improvements in forced expiratory volume in 1 s (FEV1), residual volume (RV), Saint Georges Respiratory Questionnaire (SGRQ), and 6-min walking distance (6MWD) using Spearman's rho. The EBV treatment influenced the diaphragm configuration only on the treated side, resulting in an increased diaphragm curvature. There were significant associations of relative diaphragm index changes on the treated lung side or the entire diaphragm with improvements in FEV1 and 6MWD. These findings provide valuable insights into how EBV treatment affects the diaphragm in COPD patients.

Lessons learned: Risk factors and clinical impact of severe pneumothorax after endoscopic lung volume reduction with endobronchial valves

BackgroundPneumothorax is a major complication following endoscopic lung volume reduction with valves with a prevalence of up to 34%. While some patients benefit from valve implantation despite pneumothorax, others are significantly impaired after lung collapse. Research questionWhat are the differences in the severity grades of pneumothorax and how does that affect our clinical practice? Study design and MethodsThis single-center retrospective study analyzed patients undergoing endoscopic valve implantation with and without post-interventional pneumothorax. Emphysema characteristics, collateral ventilation, management, and outcome of patients with pneumothorax 3 months after valve implantation were assessed. Pneumothorax was categorized as “severe pneumothorax” (chest tube insertion, prolonged air leak requiring valve removal), “moderate pneumothorax” (chest tube, no valve removal), and “mild pneumothorax” (no chest tube). ResultsPneumothorax occurred in 102/532 patients (19%) and was significantly more common after valve placement in the upper lobes (31.3%) compared to the lower lobes (11.3%, p < 0.001). Fissure integrity was significantly higher in patients with pneumothorax (mean 96.6 ± 6.3 % vs. 93.4 ± 10.3 %, p = 0.002). Of all pneumothoraces, 30.4% were mild, 30.4% moderate, 39.2% severe. Severe pneumothorax caused multiple complications and prolonged hospitalization. Valve placement in the left upper lobe and a larger size of the target lobe were identified as risk factors for severe pneumothorax. Patients with pneumothorax developed complete lobar atelectasis in >60% as a sign of therapeutic success, but obviously only when valves could be left in place or re-implanted. However, valve re-implantation resulted in re-pneumothorax in 42.9%. InterpretationPatients could be more individually informed about their risk of pneumothorax, which varies with target lobe location, fissure integrity and re-implantation. The poor outcome and high complication rate of severe pneumothorax calls for future research into the prediction of severe pneumothorax.

Polyhexamethylene Guanidine Phosphate Induces Restrictive Ventilation Defect and Alters Lung Resistance and Compliance in Mice

Polyhexamethylene guanidine phosphate (PHMG-p), a major ingredient of humidifier disinfectants, is known to induce inflammation, interstitial pneumonitis, and fibrosis in the lungs. While its histopathologic toxicities have been studied in rodents, research on pulmonary function test (PFT) changes following PHMG-p exposure is limited. This study aimed to investigate the acute and chronic effects, as well as the dose and time response, of PHMG-p on the lungs in mice using PFT and histopathologic examinations. In the single instillation model, mice received PHMG-p and were sacrificed at 2, 4, and 8 weeks. In the five-time instillation model, PHMG-p was administered five times at one-week intervals, and mice were sacrificed 10 weeks after the first instillation. Results showed that PHMG-p exposure reduced lung volume, increased resistance, and decreased compliance, indicating a restrictive ventilation defect. Histopathologic examination showed increases in lung inflammation and fibrosis scores. Changes in several lung volume and compliance parameters, as well as histopathology, were dose-dependent. Lung resistance and compliance parameters had significant correlations with lung inflammation and fibrosis scores. PHMG-p exposure in mice resulted in a restrictive ventilation defect with altered lung resistance and compliance, along with histopathologic lung inflammation and fibrosis.

Reference formulas for chest CT-derived lobar volumes in the lung-healthy general population.

Lung hyperinflation, a key contributor to dyspnea in chronic obstructive pulmonary disease (COPD), can be quantified via chest computed tomography (CT). Establishing reference equations for lobar volumes and total lung volume (TLV) can aid in evaluating lobar hyperinflation, especially for targeted lung volume reduction therapies. The Imaging in Lifelines study (ImaLife) comprises 11,729 participants aged 45 and above with analyzed inspiratory low-dose thoracic CT scans. Lung and lobar volumes were measured using an automatic AI-based segmentation algorithm (LungSeg). For the main analysis, participants were excluded if they had self-reported COPD/asthma, lung disease on CT, airflow obstruction on lung function testing, were currently smoking, aged over 80 years, or had height outside the 99% confidence interval. Reference equations for TLV and lobar volumes were determined using linear regression considering age and height, stratified by sex. For the subanalysis, participants who were currently smoking or experiencing airflow obstruction were compared to the group of the main analysis. The study included 7306 lung-healthy participants, 97.5% Caucasian, 43.6% men, with mean age of 60.3 ± 9.5 years. Lung and lobar volumes generally increased with age and height. Men consistently had higher volumes than women when adjusted for height. R2 values ranged from 7.8 to 19.9%. In smokers and those with airway obstruction, volumes were larger than in lung-healthy groups, with the largest increases measured in the upper lobes. The established reference equations for CT-derived TLV and lobar volumes provide a standardized interpretation for individuals aged 45 to 80 of Northern European descent. Question Lobar lung volumes can be derived from inspiratory CT scans, but healthy-lung reference values are lacking. Findings Lung and lobar volumes generally increased with age and height. Reference equations for lung/lobar volumes were derived from a sizeable lung-healthy population. Clinical relevance This study provides reference equations for inspiratory CT-derived lung and lobar volumes in a lung-healthy population, potentially useful for assessing candidates for lung volume reduction therapies, for lobe removal in lung cancer patients, and in case of restrictive pulmonary diseases.

Clinical Improvements after Endoscopic Lung Volume Reduction with Valves in Patients with advanced Emphysema and a 6-Minute-Walk-Test ≤140 m at Baseline

BackgroundData regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with very low 6-Minute Walk Test (6-MWT) is limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6-MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutics benefits and increased complication risk.Study Designs and MethodsThis study utilized data from the Lungenemphysemregister e.V., a large German national multi-center prospective open label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6-MWT ≤140 m and dyspnea primarily attributed to hyperinflation.ResultsFifty-four patients with a baseline 6-MWT ≤140 m and 365 patients with a baseline 6-MWT between 140 m and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6-MWT ≤140 m at baseline had a lower FEV1, DLCO and higher symptom burden. In the 3-month-follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6-MWT ≤140 m at baseline showed significantly more 6-MWT improvement compared to patients with baseline 6-MWT between 140 m–450 m. Moreover, complication rates were similar in both groups.InterpretationIn summary, the data indicates that ELVR may be an effective and safe treatment for emphysema patients with a very low 6-MWT ≤140 m, if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6-MWT.

Systemic pro-inflammatory response following bronchoscopic lung volume reduction using endobronchial valves

RationaleBronchoscopic lung volume reduction treatment using endobronchial valves (EBV) is an effective treatment for severe COPD patients by improving lung function and quality of life. However, little is known about its effects on systemic inflammation. Therefore, the aim of our study was to investigate whether EBV treatment impacts the inflammatory cytokine profile.MethodsThis study was a predefined substudy of the SoLVE trial (NCT03474471) that investigated the combination of EBV treatment with pulmonary rehabilitation (PR). The substudy included the collection of blood samples with assessment of 10 inflammatory markers prior to EBV treatment and 6 months after EBV or EBV+PR treatment.ResultsIn 66 patients, six months after treatment a pro-inflammatory cytokine profile was observed, with an increase in all pro-inflammatory markers and a decrease in the anti-inflammatory cytokine IL-10. The changes in plasma cytokine profile were not associated with changes in clinical outcomes such as lung function or exercise capacity.DiscussionIn conclusion, our study demonstrated an elevation in systemic pro-inflammatory cytokine levels following successful EBV-treatment, which was not associated with adverse clinical outcomes. It would be interesting to further explore, whether this increase is attributed to a foreign body response or if other factors contribute to this phenomenon.

Biofilm infections of endobronchial valves in COPD patients after endoscopic lung volume reduction: a pilot study with FISHseq

Endoscopic lung volume reduction (ELVR) using endobronchial valves (EBV) is a treatment option for a subset of patients with severe chronic obstructive pulmonary disease (COPD), suffering from emphysema and hyperinflation. In this pilot study, we aimed to determine the presence of bacterial biofilm infections on EBV and investigate their involvement in lack of clinical benefits, worsening symptomatology, and increased exacerbations that lead to the decision to remove EBVs. We analyzed ten COPD patients with ELVR who underwent EBV removal. Clinical data were compared to the microbiological findings from conventional EBV culture. In addition, EBV were analyzed by FISHseq, a combination of Fluorescence in situ hybridization (FISH) with PCR and sequencing, for visualization and identification of microorganisms and biofilms. All ten patients presented with clinical symptoms, including pneumonia and recurrent exacerbations. Microbiological cultures from EBV detected several microorganisms in all ten patients. FISHseq showed either mixed or monospecies colonization on the EBV, including oropharyngeal bacterial flora, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus spp., and Fusobacterium sp. On 5/10 EBV, FISHseq visualized biofilms, on 1/10 microbial microcolonies, on 3/10 single microorganisms, and on 1/10 no microorganisms. The results of the study demonstrate the presence of biofilms on EBV for the first time and its potential involvement in increased exacerbations and clinical worsening in patients with ELVR. However, further prospective studies are needed to evaluate the clinical relevance of biofilm formation on EBV and appropriate treatment options to avoid infections in patients with ELVR.

Bilateral lung volume reduction surgery outperforms the unilateral approach in functional improvement.

Lung volume reduction surgery (LVRS) is an established treatment approach for patients with severe pulmonary emphysema, enhancing lung function and quality of life in selected patients. Functional benefits and outcomes after uni- versus bilateral lung volume reduction remain a topic of debate. A retrospective analysis of patients undergoing LVRS from January 2018 to October 2022 was conducted. After encouraging initial results, the standard unilateral LVRS approach was switched to bilateral. The goal of this study was to assess the impact on functional outcomes at 3 and 6 months post-surgery compared to preoperative levels for the uni- versus the bilateral approach. A total of 83 patients were included (43 bilateral, 40 unilateral). Baseline demographic and functional parameters were comparable between groups. The most common complication was prolonged air leak in 19 patients (11 in the unilateral group, 8 in the bilateral group). Two patients died perioperatively (2.4%). Overall, LVRS improved forced expiratory volume in 1 s by 8.3% after 3 and 12.5% after 6 months postoperatively compared to baseline. Bilateral surgery presented significantly superior forced expiratory volume in 1 s improvement than unilateral approach at both 3 (29.2% versus 2.9%; P = 0.0010) and 6 months (21.5% versus 3%; P = 0.0310) postoperatively. Additionally, it reduced hyperinflation (residual volume) by 23.1% after 3 months and by 17.5% after 6 months, compared to reductions of 16% and 9.1% in the unilateral group. Bilateral approach resulted in better functional outcomes 3 and 6 months postoperatively compared to unilateral surgery.

Is It Time to Expand the Criteria for Bronchoscopic Lung Volume Reduction in Very Low FEV1 and DLCO Emphysema.

Is It Time to Expand the Criteria for Bronchoscopic Lung Volume Reduction in Very Low FEV1 and DLCO Emphysema.

Outcomes of lung volume reduction surgery for emphysema: unilateral and bilateral

Outcomes of lung volume reduction surgery for emphysema: unilateral and bilateral

Pulmonary and Systemic Immune Profiles Following Lung Volume Reduction Surgery and Allogeneic Mesenchymal Stromal Cell Treatment in Emphysema.

Emphysema in patients with chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation. Preclinical studies suggest that lung volume reduction surgery (LVRS) and mesenchymal stromal cell (MSC) treatment dampen inflammation. We investigated the effects of bone marrow-derived MSC (BM-MSC) and LVRS on circulating and pulmonary immune cell profiles in emphysema patients using mass cytometry. Blood and resected lung tissue were collected at the first LVRS (L1). Following 6-10 weeks of recovery, patients received a placebo or intravenous administration of 2 × 106 cells/kg bodyweight BM-MSC (n = 5 and n = 9, resp.) in week 3 and 4 before the second LVRS (L2), where blood and lung tissue were collected. Irrespective of BM-MSC or placebo treatment, proportions of circulating lymphocytes including central memory CD4 regulatory, effector memory CD8 and γδ T cells were higher, whereas myeloid cell percentages were lower in L2 compared to L1. In resected lung tissue, proportions of Treg (p = 0.0067) and anti-inflammatory CD163- macrophages (p = 0.0001) were increased in L2 compared to L1, while proportions of pro-inflammatory CD163+ macrophages were decreased (p = 0.0004). There were no effects of BM-MSC treatment on immune profiles in emphysema patients. However, we observed alterations in the circulating and pulmonary immune cells upon LVRS, suggesting the induction of anti-inflammatory responses potentially needed for repair processes.

Retrospective Review of Pneumothorax Rates in a Rural, Micropolitan Area After Bronchoscopic Lung Volume Reduction.

Retrospective Review of Pneumothorax Rates in a Rural, Micropolitan Area After Bronchoscopic Lung Volume Reduction.

The influence of sex, age, and body height on the pulmonary vascular permeability index – a prospective observational study

The pulmonary vascular permeability index (PVPI) is a quotient of the extravascular lung water (EVLW) and the pulmonary blood volume (PBV). In acute respiratory distress syndrome (ARDS), the alveolar-capillary membrane integrity is disrupted. The result is a disproportionate increase of EVLW compared to the PBV and, hence, an increase in PVPI. Thus, PVPI has repetitively been discussed to extend the definition of ARDS. Besides sex, the influence of other anthropometric variables on PVPI has not been studied so far. However, since it is known that EVLW depends on body height and sex, we hypothesize that PVPI depends on anthropometric variables as well. This prospective single-center observational study included 1533 TPTD measurements of 251 non-critically ill patients (50.6% men) undergoing elective neuro-, thoracic, or abdominal surgery at the Munich Clinic Bogenhausen of the Technical University of Munich. Multivariate regressions were used to measure the influence of sex, age, and body height on PVPI. In all patients, PVPI was significantly higher in women (P < 0.001), with 34.4% having a PVPI > 2 compared to 15.9% of men. Mean PVPI significantly decreased with height (P < 0.001) and age (P < 0.001). Multivariate regressions allowed the calculation of mean reference surfaces. The 95th percentile surface for PVPI was > 3 for small and young women and well above 2 for all but tall and elderly men. In patients who underwent (lung reduction) thoracic surgery, the PVPI before and after surgery did not differ significantly (P = 0.531), and post-surgical PVPI did not correlate with the amount of lung resected (P = 0.536). Hence, we conclude that PVPI may be independent of the extent of lung volume reduction. However, PVPI is heavily dependent on sex, age, and body height. Anthropometric variables thus have a significant impact on the likelihood of misclassified abnormal PVPI. This warrants further studies since an increased PVPI, e.g. in the context of an ARDS, may be overlooked if anthropometric variables are not considered. We suggest reference surfaces based on the 95th-percentile corrected for sex, age, and height as a novel approach to normalize PVPI.

Lung Tensioning Device Coil Treatment in Patients with Severe Emphysema: A Prospective Safety and Feasibility Trial (EFFORT)

Introduction: Currently, there is a lack of bronchoscopic lung volume reduction options that do not depend on fissure integrity. Endobronchial coils have been extensively studied to address this need but exhibited variable patient response and have been discontinued. Lung tension device (LTD) coils represent the next-generation coil treatment. This study aimed to evaluate safety, feasibility, and efficacy of LTD-coil treatment. Methods: Patients with advanced emphysema and hyperinflation were enrolled at two European sites. LTD-coils (Free Flow Medical, Fremont, CA, USA) were implanted in the two most destructed lobes, as determined by quantitative CT analysis, in two separate procedures. The primary endpoint was 3-month follow-up after the last treatment. Results: Fourteen patients (50% male, median age 64 years, FEV1 23%predicted, RV 249%predicted) received LTD-coil treatment: 12 received bilateral and 2 unilateral treatment. Six serious respiratory adverse events occurred within the initial 3 months posttreatment, including one device-associated death. Treatment significantly reduced in- and expiratory volume of the treated lobes (−410 [−710, −340], p = 0.004 and −650 [−730, −190] mL, p < 0.001, respectively) and improved quality of life (SGRQ total score −4.6 [−21.0, −2.6], p < 0.001). However, at a group level, no significant improvements in pulmonary function or 6-min walk distance were observed. Responder rates ranged from 18% to 54% for the different endpoints. Conclusion: This first-in-human study shows that the new LTD-coil procedure is feasible with a safety profile comparable to the previous coil treatment. While the treatment effectively reduced lobar volume and modestly improved quality of life up to 3 months’ follow-up, at a group level it did not significantly enhance pulmonary function or exercise capacity.