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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.

The presence or absence of collateral ventilation can be predicted based on the fissure completeness between lobes [7,8]. However, a more accurate assessment can be performed using the Chartis Pulmonary Assessment System (Pulmonx Inc., Redwood City, CA, USA), which provides a physiological assessment of airflow through the target lobe [5,9]. The Chartis system consists of a catheter with a balloon at the distal tip, designed to be inserted into the airways through the working channel of a bronchoscope. The open lumen at the distal tip of the Chartis catheter can be placed into the target airway, and inflation of the balloon causes the airway to become sealed and isolated. The catheter is connected to the Chartis console that measures the air flow and pressure from the occluded lobe and quantifies the collateral ventilation status [5,10,11].
The Chartis assessment can be performed in patients breathing spontaneously with procedural sedation, or under general anaesthesia. Compared to sedation, Chartis measurement performed under general anaesthesia is more feasible with shorter procedure times [12,13]. Absence of collateral ventilation in patients under general anaesthesia is confirmed if the air flow from the occluded lobe reaches zero, with an immediate return of airway flow after deflating and removing the balloon catheter [6,13]. In many cases, there may be an evident reduction of flow, suggesting absence of collateral ventilation; however, because of the very low flow rate, it can take a significant amount of time for the flow rate to reach "zero" [10].
During some Chartis assessments, the momentary appearance of sudden spikes in the flow rate can confound the assessment. Integration of the flow rate over a fixed period of time during this situation can attenuate this artefact. Therefore, the Chartis software (version 6.0.5) has been updated to continually measure and display the total expired volume over the last 20 s: the "volume trend for the previous 20 s" (VT20).
With this feature, the expired volume in the last 20 s is measured, and this is shown continuously on the Chartis console, next to the currently used flow curve (figure 1). The VT20 value is shown after the first 20 s of the Chartis assessment.
The present study aimed to validate whether there is a threshold of the VT20 which is predictive for the absence of collateral ventilation in situations where the flow rate during a Chartis measurement is low, and potentially shortening the Chartis procedure by earlier termination of the Chartis measurement. For this, we measured and continuously monitored VT20 based on the hypothesis that if a low flow is predictive of the absence of collateral ventilation, it would lead to shorter procedure time. This results in an easier procedure, with less manipulation of the airway wall by the Chartis balloon and catheter.

Study design and population
This is a single-centre retrospective study conducted at the University Medical Center Groningen, the Netherlands. Anonymised Chartis assessments previously performed in a routine clinical care setting were analysed. Patients with severe emphysema and hyperinflation who were eligible for valve treatment and were scheduled for Chartis assessment as part of regular care in the Bronchoscopic Emphysema Treatment in the Netherlands registry (BREATHE-NL) were included. All patients provided informed consent regarding their treatment and use of their data for future scientific purposes (BREATHE-NL registry; ClinicalTrials.gov Identifier: NCT02815683).

Chartis measurements
All Chartis assessments included in the analysis were performed under general anaesthesia with patients intubated with a flexible 9-mm endotracheal tube. Positive pressure ventilation was applied in all patients as per routine practice, with low ventilation frequency (8-10 times per minute), with an inspiratory/ expiratory ratio of 1:3 to 1:4 and preferably a positive end-expiratory pressure of 3 cmH 2 O [10,13].
Collateral ventilation over the fissure of the target lobe was measured and scored as presence of collateral ventilation (CV positive), absence of collateral ventilation (CV negative) or inconclusive. In some patients, multiple measurements were performed in several lobes, e.g. when there was more than one treatment target.

Chartis VT20 measurements
The original raw output data of the Chartis assessments performed during bronchoscopy were used to evaluate the effectiveness of the new VT20 feature on the Chartis 6.0.5 software. An example of a CV negative and a CV positive Chartis assessment is shown in figures 1 and 2, respectively.
The selection of Chartis assessments for inclusion in the analysis was based on the algorithm shown in table 1, to indicate whether an assessment was valid or inconclusive. The valid Chartis assessments were evaluated to determine whether the VT20 data were valid or invalid. For VT20 data to be valid, there   should be presence of air flow at the end of the assessment (in CV positive patients) or the presence of air flow when the VT20 reached a value of 6 mL and below so that the VT20 could reasonably be used to indicate the end of an assessment. The time of the end of the assessment was recorded. The lowest VT20 value was recorded in all assessments and for CV negative assessments, the time point at which the VT20 was 6 mL, 5 mL, 4 mL, 3 mL, 2 mL, 1 mL or 0 mL.

Statistical analysis
To compare outcomes between the CV negative and CV positive groups, we used an independent-samples t-test in case of normal distribution and a Mann-Whitney U test in case of non-normal distribution, p-values below 0.05 were considered statistically significant and mean or median data were calculated per group. All statistical analyses were performed using SPSS version 22 (IBM, New York, NY, USA).

Results
A total of 279 Chartis assessments were evaluated. Thirty assessments were excluded because the VT20 values were invalid to use, as described in the Methods section. Ultimately, 249 Chartis assessments were analysed (187 CV negative and 62 CV positive).

VT20
Of the 187 CV negative patients, 100% reached a minimum value of VT20⩽6 mL during the last 2 minutes of assessment. Additionally, 98.9% reached a value of VT20⩽3 mL and 90.4% a VT20⩽1 mL. Of the 62 CV positive patients, 100% did not reach a VT20⩽6 mL, and the lowest VT20 was 7 mL. The distribution is shown in figure 3.

Time assessment
The median time of the Chartis measurements was 240 s (range 77-864) in all patients. In CV positive patients the median time was 304 s (range 122-533) and in CV negative patients, 226 s (range 77-864) ( p=0.021) (see table 2). The median time to VT20=6 mL was 168 s (range 36-546). The median time difference between the end of measurement and the VT20=6 mL time point ("time saved") was 60 s (range 5 to 354), as shown in figure 4.

Volume
The median measured expiratory volume was 320 mL (range 15-1780) in all patients (table 2). In CV negative patients this was 240 mL (range 15-983), compared to 1014 mL (range 115-1780) in CV positive patients ( p<0.005). The median difference between the total expired volume and the expired volume in CV negative patients at VT20=6 mL was 5 mL (range 0-120).

Discussion
Multiple clinical trials have demonstrated the benefits of BLVR with one-way endobronchial valves in patients with severe emphysema who have little to no collateral ventilation in the target lobe [1][2][3][4]. The assessment of collateral ventilation status ( presence or absence of collateral ventilation) is crucial in determining the eligibility of a patient for valve treatment for BLVR. The Chartis system provides a physiological assessment of airway under simulated conditions of valve placement in the target lobe to confirm the presence or absence of collateral ventilation [5,7,9,13]. It is important to get a valid Chartis  assessment, but sometimes the measurement can be challenging [10,14,15]. For example, if there is no flow due to obstruction of the Chartis catheter with mucus plugs or contact of the distal tip with the mucosa, or a no-flow pattern of the lower lobes, this can be interpreted falsely as absence of collateral ventilation [14][15][16]. Furthermore, Chartis assessments can show a low flow pattern, and it can take a long time before the flow actually reaches "zero" [14].
In order to reduce the Chartis assessment time in cases where very low air flow persists for a longer period of time, the VT20 measure that integrates the flow for the last 20 s has been incorporated into the Chartis software. We evaluated the effectiveness of the new VT20 feature through a review of 187 CV negative and 62 CV positive Chartis assessments.
This analysis shows that when the VT20 value was ⩽6 mL, all patients are CV negative. Therefore, if this threshold is achieved, an assessment can be terminated before the air flow actually reaches zero while still being confident that there is no collateral ventilation. This may shorten the Chartis assessment time by minutes and will significantly shorten the total procedure time. As a result, there is less manipulation of the airways, and this may facilitate an easier valve-treatment procedure.
Although this is a retrospective study, the previously obtained Chartis measurements were re-analysed prospectively using the raw output data and run again with the new software feature and hence reflect the actual measurements. The VT20 feature may not be applicable in all Chartis assessments, especially if the procedure is challenging. It is important that there is a continuous flow during the Chartis measurement to use the VT20 cut-off value. Therefore, the assessment should be evaluated critically during the procedure, and if the measurement does not fulfil the criteria described in the methods section, the VT20 value should not be used.
A limitation of this study is that the VT20 assessments analysed included only Chartis measurements performed under general anaesthesia with standard ventilator settings. As such, these results cannot be extrapolated to measurements in patients under conscious sedation and spontaneous breathing. Although this may yield comparable results, there is no positive pressure ventilation and the methods of measurement differ. Therefore, the cut-off value of VT20⩽6 mL should only be used in Chartis measurements in patients under general anaesthesia.

FIGURE 5
Chartis measurement output image showing the "volume trend for the previous 20 s" (VT20) value plotted for an assessment with continued high spikes in air flow (flow of 72 mL·min −1 at 5:22 min) values for the duration of the assessment. These spikes cause confounding peak flow trend values, while the VT20 is a good indicator of the continued decline in the amount of total exhaled volume. The VT20 is 6 mL at 5:22 min, whereas the total measurement was 9:14 min (difference: 232 s).