Impact of Ventilation Modes on Bronchoscopic Chartis Assessment Outcome in Candidates for Endobronchial Valve Treatment

Background: Endobronchial valve therapy has proven to reduce lung hyperinflation and decrease disease burden in patients with severe lung emphysema. Exclusion of collateral ventilation (CV) of the targeted lobe by using an endobronchial assessment system (Chartis; PulmonX, Drive Redwood City, CA, USA) in combination with software-based fissure integrity analysis (FCS [fissure completeness score]) of computed tomography scans of the lung are established tools to select appropriate patients for endobronchial valve treatment. So far, there is no conclusive evidence if the ventilation mode during bronchoscopy impacts the outcome of Chartis assessments. Methods: Patients with Chartis assessments and software-based quantification of FCS (StratX; PulmonX, Drive Redwood City, CA, USA) were enrolled in this retrospective study. During bronchoscopy, pulmonary fissure integrity was evaluated with the Chartis assessment system in each patient first under spontaneous breathing and subsequently under high-frequency (HF) jet ventilation. Results: In total, 102 patients were analyzed. Four Chartis phenotypes CV positive (CV+), CV negative (CV-), low flow, and low plateau in spontaneous breathing and HF jet ventilation were identified. The frequency of each Chartis phenotype per lobe was similar in both settings. When comparing Chartis assessments in spontaneous breathing and HF jet ventilation, there was an overall good concordance rate for all analyzed fissures. In agreement, receiver operating characteristic analysis of the FCS showed an almost similar prediction for CV+ and CV- status independent of the ventilation modes. Conclusion: Chartis assessment in spontaneous breathing and HF jet ventilation had similar rates in detecting CV in lung emphysema. Our results suggest that both modes are equivalent for the assessment of CV

Endoscopic Lung Volume Reduction: An Expert Panel Recommendation

Chronic obstructive pulmonary disease (COPD) is a progressive condition comprising a constellation of disorders from chronic bronchitis, airflow obstruction through to emphysema. The global burden of COPD is estimated at more than 6% of the population. The standard of care is based on a combination of smoking cessation, immunization, pharmacological treatments and pulmonary rehabilitation. However, the more advanced stages of COPD are challenging to manage. In this situation, our current standards of care do not adequately control patient symptoms nor halt the progressive decline. For the emphysema phenotype, lung volume reduction surgery has shown a beneficial effect in selected patients but is counterbalanced by the morbidity experienced by some patients. Bronchoscopic volume reduction technologies have been developed to improve the clinical situation of emphysema patients. This expert statement provides broad guidance regarding patient selection and the current position of the available techniques for patients with advanced emphysema

Bronchoscopic lung volume reduction for Emphysema: physiological and radiological correlations

Introduction: Patient selection in lung volume reduction (LVR) plays a pivotal role in achieving meaningful clinical outcomes. Currently, LVR patients are selected based on three established criteria: heterogeneity index, percentage of low attenuation area (%LAA), and fissure integrity score. Quantitative computed tomography (QCT) has been developed to quantify lung physiological indices at the lobar level and could potentially revolutionise patient selection in LVR procedures. We developed an in-house QCT software, LungSeg, and used its radiological indices for the purposes of this thesis. The aim of this thesis is to discover potential physiological and radiological indices that could serve as predictors for superior LVR outcomes for better patient selection. Methods: This thesis took two studies and analysed them using LungSeg. The first study was the long-term coil study, a randomised controlled study that had the control group crossing over to the treatment arm at 12 months. At 12 months post-procedure the baseline measurements were assessed against the 12-months post-procedural measurements. The second study was the short-term valve study which was another randomised controlled study that compared the primary and secondary endpoints between the control and the valve-treated group at three months post-procedure. Results: In the long-term coil study, we found that the best statistically significant combination of predictors for change in target lobar volume at inspiration was found to be the combination of baseline target LV at inspiration, -950HU EI at inspiration, and TLCabs with a model adjusted R2 of 0.407 (p = 0.0001). In a subsequent multivariate analysis using ≥45% LAA on the -950HU at Inspiration, the R2 of the same prediction model did improve to 0.493 (P-value = 0.002). Meanwhile, the best statistically significant combination of predictors for change in target lobar volume at inspiration following valve treatment was found to be the combination of baseline target LV at inspiration, target lobar fissure integrity and baseline FEV1abs with a model adjusted R2 of 0.193 (p = 0.105). Conclusion: Using QCT, we have improved the proposed patient selection algorithm for LVR procedures based on the best QCT and lung function predictors.Open Acces

Determinants of Lung Fissure Completeness

RATIONALE: New advanced bronchoscopic treatment options for patients with severe COPD have led to increased interest for COPD phenotyping, including fissure completeness. OBJECTIVES: We investigated clinical, environmental, and genetic factors contributing to fissure completeness in patients with and without COPD. METHODS: We used data of 9926 participants of the COPDGene study who underwent chest computed tomography (CT). Fissure completeness was calculated from CT scans following quantitative CT analysis at baseline and five-year follow-up. The clinical and environmental factors sex, race, smoking, COPD, emphysema, maternal smoking during pregnancy and maternal COPD were tested for impact on fissure completeness. Genome-wide association analyses were performed separately in non-Hispanic whites and African-Americans. MEASUREMENTS AND MAIN RESULTS: African-Americans had significant higher fissure completeness than non-Hispanic whites for all three fissures (p<0.001). There was no change in fissure completeness between baseline and five-year follow-up. For all fissures, No clinically relevant differences in fissure completeness were found for other clinical or environmental factors, including COPD severity. Rs2173623, rs264866, rs2407284, rs7310342, rs4904145, rs6504172, and rs7209556 showed genome-wide significant associations with fissure completeness in non-Hispanic whites. In African-Americans, rs264866, rs4904145 and rs6504172 were identified as significant associations. Rs2173623, rs6504172, and rs7209556 lead to WNT5A and HOXB antisense RNA expression, which play an important role during embryogenesis. CONCLUSIONS: Fissure completeness is genetically determined and not dependent on age, sex, smoking status, the presence and severity of COPD including exacerbation frequency, maternal smoking during pregnancy, or maternal COPD

Measuring pulmonary function in COPD using quantitative chest computed tomography analysis

COPD is diagnosed and evaluated by pulmonary function testing (PFT). Chest computed tomography (CT) primarily serves a descriptive role for diagnosis and severity evaluation. CT densitometry-based emphysema quantification and lobar fissure integrity assessment are most commonly used, mainly for lung volume reduction purposes and scientific efforts. A shift towards a more quantitative role for CT to assess pulmonary function is a logical next step, since more, currently underutilised, information is present in CT images. For instance, lung volumes such as residual volume and total lung capacity can be extracted from CT; these are strongly correlated to lung volumes measured by PFT. This review assesses the current evidence for use of quantitative CT as a proxy for PFT in COPD and discusses challenges in the movement towards CT as a more quantitative modality in COPD diagnosis and evaluation. To better understand the relevance of the traditional PFT measurements and the role CT might play in the replacement of these parameters, COPD pathology and traditional PFT measurements are discussed

Advances in bronchoscopic lung volume reduction:Improved patient selection and assessment of treatment response

Bronchoscopic lung volume reduction is a relatively new treatment for patients with severe COPD, a chronic and progressive lung disease. The aim of this treatment is to decrease the increased residual volume, in order to improve disease symptoms and quality of life. Not every patient with COPD is eligible to undergo this treatment, and treatment outcomes vary between patients. The aim of this thesis was to improve patient selection for bronchoscopic lung volume reduction, and to improve the identification of patients who achieved a relevant treatment effect.Only one out of five patients that are referred, are actually eligible for treatment. This finding highlights the importance of the development of new treatments for the large group of patients that are currently not eligible for bronchoscopic treatments. In one of the studies in this thesis, we have introduced an innovative approach to measure oxygen uptake capacity of individual lobes of the lung, which can prove a valuable contribution to the identification of the least functional lobe, and thus best treatment target. Two other studies demonstrated that the measurement of interlobar collateral ventilation, an essential measurement before treatment with endobronchial valves, is easier and faster to perform under general anesthesia than under conscious sedation. This finding supports the clinical practice to perform both this measurement as well as the treatment in one session under general anesthesia. Finally, we have introduced a new threshold for a clinically relevant treatment effect for two important outcome parameters after treatment: lung volume reduction measured on a CT scan and a quality of life questionnaire

Endobronchial Valves for the Treatment of Advanced Emphysema

Bronchoscopic lung volume reduction with one-way endobronchial valves is a guideline treatment option for patients with advanced emphysema that is supported by extensive scientific data. Patients limited by severe hyperinflation, with a suitable emphysema treatment target lobe and with absence of collateral ventilation, are the responders to this treatment. Detailed patient selection, a professional treatment performance, and dedicated follow up of the valve treatment, including management of complications, are key ingredients to success. This treatment does not stand alone; it especially requires extensive knowledge of COPD for which the most appropriate treatment is discussed in a multidisciplinary approach. We discuss the endobronchial valve treatment for emphysema and provide a guideline for patient selection, treatment guidance, and practice tools, based on our own experience and literature

Bronchoscopic lung volume reduction treatment in severe COPD: from improving patient selection to management of complications

Chronic Obstructive Pulmonary Disease (COPD) is a common disease, often characterized by shortness of breath and coughing and this can lead to a poor quality of life. In patients with severe COPD, there can be hyperinflation and an increased residual volume. In some patients with severe increased residual volume, bronchoscopic lung volume reduction treatment using one-way valves can be an option. It has been proven that valve treatment can lead to improvements in shortness of breath, exercise capacity and quality of life. For treatment, it is important that there is sufficient emphysema in the treatment lobe and no collateral ventilation between the treated lobe and the adjacent lobe.Currently, the CT scan of the lungs is the most important tool to determine whether a patient is potentially suitable for the treatment with one-way valves. With quantitative CT scan analysis, various parameters can be assessed automatically (e.g. severity of emphysema and fissure completeness).In this thesis, we investigate whether the use of quantitative CT scan analysis can be optimized in patients who are evaluated for treatment with valves and to improve the selection of the right patients and the optimal treatment lobe. Additionally, we discuss several methods to improve the measurement of collateral ventilation (Chartis measurement) and to discuss the main complications after valve treatment