Isolation of a new steroid from phytochemical investigation on Caralluma lasiantha.

A new steroid (acylated C21 pregnane steroid) was isolated from chloroform extract in phytochemical screening of Caralluma lasiantha. The isolated compound is found to be 3ß-hydroxy-14ß-(6'- carboxyphenyl)propionyloxypregn-5-en-20-one based on spectroscopic studies (IR, 1H NMR, 13C NMR, DEPT, COSY, HSQC, HMBC and ESI-MS). The isolated new steroid was tested against four bacterial strains and the activity was related to the structure of the molecule.

Predicting Lung Volume Reduction after Endobronchial Valve Therapy Is Maximized Using a Combination of Diagnostic Tools.

BACKGROUND: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) has been proven to be effective in patients with severe emphysema. However, the selection of patients without collateral ventilation prior to treatment is critical for procedural success. Collateral ventilation can be assessed directly with the Chartis system or indirectly using computed tomography (CT) fissure analysis. OBJECTIVES: We retrospectively evaluated the diagnostic value of a combination of the quantitative CT interlobar fissure completeness score (FCS) and Chartis in predicting responders to EBV therapy. METHODS: CT data from four prospective studies were pooled and analyzed using semiautomated software to quantify the completeness of interlobar fissures. These FCSs were compared to a reference standard of achieving ≥350 ml of target lobe volume reduction after EBV treatment. Using a receiver operating characteristic curve, optimal thresholds predictive of complete fissures (responders) and incomplete fissures (non-responders) were determined. A subgroup of patients with partially complete fissures was identified, where software had lower accuracy. The complementary value of Chartis was investigated in this group. RESULTS: A fissure was defined as complete (FCS >95%), incomplete (FCS <80%), or partially complete (80% < FCS < 95%). The positive predictive value (PPV) of complete fissures is 88.1%, and the negative predictive value (NPV) is 92.9%, with an overall accuracy of 89.2%. Chartis was utilized in patients with partially complete fissures, with a PPV of 82.3%, an NPV of 84.6%, and an accuracy of 83.3%. CONCLUSION: Combining diagnostic tools could reduce the burden on patients and the healthcare system while providing clinicians with a better means for patient selection for EBV therapy.

Comparing Clinical Outcomes in Upper versus Lower Lobe Endobronchial Valve Treatment in Severe Emphysema.

BACKGROUND: Lung volume reduction surgery has been recommended for patients with upper lobe predominant emphysema and was associated with less favorable outcomes in patients with non-upper lobe predominant emphysema. The value of endobronchial valve (EBV) treatment in lower lobe predominant emphysema has not been studied. OBJECTIVES: To confirm the equivalence of upper and lower lobe valve treatments in patients with heterogeneous emphysema. METHODS: A retrospective analysis from the Endobronchial Valve for Emphysema Palliation Trial (VENT), where patients with heterogeneous emphysema received Zephyr® EBV (Pulmonx Corp., Redwood City, Calif., USA) or medical treatment, was performed. Patients with low interlobar collateral ventilation and accurate placement of valves in the target lobes were identified. Safety and efficacy were compared between patients who underwent upper versus lower lobe treatment. RESULTS: Of the 331 patients, 60 had low interlobar collateral ventilation and successful lobar exclusion (45 patients with upper lobe treatment and 15 patients with lower lobe treatment). There was no difference in baseline characteristics between the groups except for a higher destruction score (70.3 vs. 60.7%; p = 0.0010) and a higher heterogeneity index (24 vs. 13%; p = 0.0005) for the upper lobe cohort. At 180 days, both groups had improved clinically. There were no significant differences in mean changes or responder rates of forced expiratory volume in 1 s (+23.8 vs. +22.9%), the St. Georges Respiratory Questionnaire (-6.50 vs. -7.53 points), the 6-min walk test (+24.1 vs. +44.0 m), target lobe volume reduction (-1,199 vs. -1,042 ml), or in the adverse event rate between both cohorts. CONCLUSION: Patients with lower and upper lobe predominant emphysema benefit equally from EBV therapy when interlobar collateral ventilation is low and lobar exclusion is achieved. Patients with lower lobe disease did not have increased adverse events compared to patients with upper lobe emphysema.

Diagnostic performance comparison of the Chartis System and high-resolution computerized tomography fissure analysis for planning endoscopic lung volume reduction.

BACKGROUND AND OBJECTIVE: Endobronchial valve (EBV) therapy is optimized in patients who demonstrate little or no collateral ventilation (CV). The accuracy of the Chartis System and visual assessment of high-resolution computerized tomography (HRCT) fissure completeness by a core radiology laboratory for classifying CV status was compared by evaluating the relationship of each method with target lobe volume reduction (TLVR) after EBV placement. METHODS: Retrospective HRCT fissure analysis of a study population who underwent catheter-based measurement of CV followed by complete occlusion of the targeted lobe by EBV. Accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the HRCT fissure analysis and the catheter-based measurement of CV for predicting TLVR was determined. RESULTS: Accuracy for correctly classifying TLVR with EBV was similar for Chartis System and HRCT fissure analysis (74 vs 77%). The sensitivity and specificity of the Chartis measurement were 86% and 61% and those of HRCT fissure analysis 75% and 79%. Patients with TLVR ≥ 350 mL had statistically significant improvement in respiratory function, exercise performance and quality of life measures. CONCLUSIONS: When evaluating patients for likelihood of successful EBV therapy, the Chartis System CV assessment and HRCT fissure analysis appear to have comparable accuracy. Both techniques were found to be beneficial for EBV procedure planning.

VT20 method for Chartis assessment of collateral ventilation with flexible bronchoscopy under procedural sedation.

VT20 is applicable for Chartis assessments with conscious sedation and spontaneous ventilation or high-frequency jet ventilation, and the cut-off of ≤6 mL remains the same to distinguish between CV- and CV+ phenotypes https://bit.ly/3HG9iMQ.

A multicenter, prospective, single-arm clinical investigation of a modified staged treatment algorithm using the AeriSeal system - The STAGE trial.

INTRODUCTION: Treatment with AeriSeal is an alternate treatment option to achieve lung volume reduction in patients with severe COPD and emphysema who are not eligible for valve treatment. This study aimed to assess the safety and mode of action of a modified staged treatment algorithm with a staged treatment with lower dose of AeriSeal. METHODS: We performed a prospective, multicenter feasibility study. AeriSeal was administered during two sequential bronchoscopies: 2 subsegments of a lobe treated with two 5 mL doses, followed by two 10 mL doses in a contralateral lobe after 6 weeks. RESULTS: A total of 14 patients (36% male, mean FEV1 28.4% ± 6.7% of predicted) were enrolled. Ten patients completed both treatments, four were treated unilaterally. AeriSeal treatment resulted in significant TLVR (median 220.5 mL) at 3 months follow up. There were no significant changes from baseline at 12 months in lung function, exercise capacity and quality of life. During the 3-month post-treatment period, respiratory SAEs included 5 COPD exacerbations in 4 (28.6%) subjects, post-treatment acute inflammatory response (PAIR) in 2 (14.3%) subjects, and 1 respiratory failure event in 1 (7.1%) subject. CONCLUSION: The staged and lower dosed administration of AeriSeal does not impact the overall safety profile in terms of reducing the type and frequency of respiratory SAEs previously reported for a single-stage treatment. A larger volume of AeriSeal than used in this study may be necessary to provide meaningful clinical benefits.

An adjusted and time-saving method to measure collateral ventilation with Chartis.

INTRODUCTION: Bronchoscopic lung volume reduction with endobronchial valves is an important treatment option in selected patients with severe emphysema and absence of collateral ventilation in the treatment target lobe. The Chartis system provides an important physiological assessment of the presence or absence of collateral ventilation. We aimed to evaluate a new feature and determine whether low flow during a Chartis measurement is predictive for the absence of collateral ventilation, and whether this allows for a procedure to be shortened by earlier terminating the Chartis measurement. This is measured with the "volume trend for the previous 20 s" (VT20). METHODS: We retrospectively evaluated 249 Chartis assessments of patients scheduled for bronchoscopic lung volume reduction procedures. The VT20 was calculated, and several thresholds were compared between patients with collateral ventilation (CV positive) and without collateral ventilation (CV negative). RESULTS: 100% of the CV negative patients reached a threshold of VT20 ≤6 mL, whereas all CV positive patients reached a VT20 ≥7 mL. The median "time saved" between VT20=6 mL and end of assessment was 60 s (range 5-354 s). CONCLUSION: The threshold of VT20 ≤6 mL is a reliable method to exclude the presence of collateral ventilation when air flow rates are low and can therefore reduce bronchoscopic lung volume procedure times.

Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial.

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation.Objectives:Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported.Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George's Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy).Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P < 0.05 and P < 0.001, respectively). Reduction in CAT was through improvements in breathlessness (P < 0.05), energy level (P < 0.05), activities (P < 0.001), and increased confidence when leaving home (P < 0.05). The TDI measures of effort, task, and functional impairment were uniformly improved (P < 0.001). The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group. Improvements correlated with changes in residual volume and residual volume/TLC ratio.Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months.Clinical trial registered with www.clinicaltrials.gov (NCT01796392).