Sequelae of bronchoscopic lung volume reduction with endobronchial valves evaluated with quantitative VQ SPECT CT and quantitative CT—a sub analysis of the EMPHYSISE study

Introduction

Bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) involves collapsing a lobe to improve mechanical ventilation in patients with advanced emphysema who remain symptomatic despite maximum therapy. It is a reversible symptomatic treatment that has been shown to be effective and safe (1-4).

Pre-treatment assessment with imaging to identify a suitable target lobe (TL) to collapse has been performed with quantitative computed tomography (qCT) (4). This evaluates tissue density of each lobe to determine the percentage volume of the lobe that has a tissue density with a Hounsfield unit of less than −950, a threshold that defines the presence of emphysema. This percentage is defined as the destruction score, which is termed the emphysema ratio % (ER%). The emphasis is on targeting a lobe with the highest ER%, which is preferentially >20%. TL selection is also preferred on the presence of heterogeneous emphysema, which is defined as at least a 15-percentage point lower ER% in the ipsilateral untreated lobe (IUL). In the interest of avoiding collateral ventilation, which will prevent lobar collapse, the fissure integrity is also evaluated on the CT either by an expert chest radiologist or via automated software analysis.

Pre-BLVR-EBV assessment with quantitative ventilation/perfusion scan (qVQ) is less well adopted. Methods of quantification have been either with two-dimensional planar scans or three-dimensional single photon emission computed tomography (SPECT) fused with low-dose computed tomography (CT) scans. Planar scan quantification is reliant on the division of the data into linear geographical zones, which do not match lobar anatomy. Each zone accounts for the composite radioactivity that often includes more than one lobe. With the addition of SPECT CT, there are commercial programs that can quantify the radioactivity and volume of each lobe.

The qVQ is by convention expressed as a percentage of the total lung, be it a zone with planar or a lobe with SPECT CT. Quantification included lobar percentage radioactivity in the ventilation scan (Vent%) and lobar percentage radioactivity in the perfusion scan (Perf%), and lobar percentage volume (Vol%) using CT. Pre-BLVR-EBV assessments often address the Vent%, Perf% and Vol% as separate entities.

At our institution, we have developed an in-house program [which we have called Royal Adelaide Hospital (RAH) VQ SPECT CT quantification (RAHVQSQ)] that can quantify lobar Vent%, Perf% and Vol%, similar to the commercial programs. Unique to our program is the ability to quantify the amount of ventilation and perfusion per unit volume of each lobe to generate an index [which we have called ventilation/perfusion nuclear scan (VQ) capacity differential index (VQCDI)] that reflects the lobar differential contribution to total lung function as a percentage. We coined another index, which we called VQ differential index (VQDI), to assess lobar parenchymal function. VQCDI/Vol% is another index that we contend reflects lobar functional efficiency or gas trapping in emphysema.

EMPHYSISE (Emphysema, Physiology, and Exercise Response Study) is a study designed to evaluate cardiopulmonary remodeling post BLVR-EBV. Pre- and post-treatment qVQ SPECT CT with RAHVQSQ were included and the current investigation constitutes a separate sub-study. The main findings of the EMPHYSISE study are still under analysis and will be presented for peer review at a later date.

Our aim in this substudy is to apply all of our quantified parameters and indices to evaluate the effects of BLVR-EBV on all lobes. Specifically, we are interested in knowing what happens to the untreated lobes with regards to: (I) the redistribution of ventilation and perfusion from the collapsed treated lobe; (II) the possible dilutional effects of the expanded volume to the redistributed ventilation and perfusion; (III) the alterations to parenchymal function (VQDI), differential lobar contribution (VQCDI) and degree of gas trapping (VQCDI/Vol%) with qVQ, and lobar destruction (ER%) with qCT. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0138/rc).

Methods

Between Jan 2019 to Apr 2025, participants who were deemed suitable for BLVR-EBV were recruited from a pool of patients who were referred for treatment to a statewide service for the state of South Australia. Patients who consented to participate were treated at the Royal Adelaide Hospital and the Queen Elizabeth Hospital. Both institutions are under the jurisdiction of the Central Adelaide Local Health Network. All participants were discussed at a multidisciplinary meeting in which the suitability for BLVR-EBV was decided, and if so, a TL was recommended based on qCT. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study obtained Ethics and Governance approval from the Central Adelaide Local Health Network Human Research and Ethics Committee (HREC reference HREC/18/CALHN/389). Informed consent was obtained from all individual participants for the procedures performed.

As per routine clinical practice, the acquired VQ SPECT CTs were reported in the usual manner. Although the qVQ results were accessible, for the purpose of the trial, the TL was chosen based solely on the qCT results.

The following studies were performed pre- and post-BLVR-EBV:

• Pulmonary function test (PFT) and lung volume studies: forced expiratory volume in 1 second (FEV1), diffusing lung capacity of carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV).
• Cardiopulmonary exercise test (CPET): maximal oxygen uptake (VO₂max; mL/kg/min), lactate threshold, minute ventilation-carbon dioxide production (Ve-VCO₂) slope, minute ventilation-oxygen uptake (Ve/VO₂) slope, dynamic hyperinflation, exertional dyspnoea, constant work rate (CWR).

Inclusion criteria included FEV1 <50%, TLC >100%, RV >175%, fissure >90% intact, age: >18 years and cessation of smoking for >3 months. Exclusion criteria were co-existent lung disease, partial pressure of carbon dioxide (PCO₂) >60 mmHg, FEV1 <15%, cardiovascular disease (left ventricular ejection fraction <35%, myocardial ischaemia, cardiovascular accident, arrhythmias), VQ contraindicated and pregnancy.

All participants were required to have pre and post BLVR-EBV VQ SPECT scans; all studies were performed on GE Hawkeye 4 SPECT CT scan (GE Healthcare™, Haifa, Israel). Standard protocol was applied with 40–50 MBq 99mTc Technegas (Cyclomedica™, Kingsgrove, NSW, Australia) for the ventilation scan and 200–250 MBq 99mTc-labelled macro aggregated albumin (DRAXIMAGE MACROSALB™, Jubilant Radiopharma, Canada) for the perfusion scan. SPECT scans were acquired for both studies (Matrix 128×128; rotation: 3.0, zoom 1; ventilation 13 s/step, perfusion 8 s/step; 120 views; Butterworth filter, threshold 0.48, power 10 and OSEM 2 iterations 10 subsets).

In addition, pre- and post-BLVR-EBV CT acquired on Siemens SOMATOM X.ceed-128 slices (Siemens Healtheneers™, Forchheim, Germany). Scan protocol: thorax inspiration, 120 kV, CARE kV, IQ 100, pitch, 0.80; rotation time, 0.25 s. Reconstruction: slice thickness, 1.00 mm; increment, 0.80 mm; window: lung; Kernel Br40. Quantification was performed with either Philips Portal: COPD™ or with Siemens Pulmo 3D (Siemens Healtheneers™) to generate lobar ER%.

The aforementioned VQ and CT imaging were done together at the same institution with exception of one participant (participant number 9), who had the pre-treatment CT performed at a different radiology service and the quantification was with StratX™ (PulmonX™, Redwood City, CA, USA).

All VQ SPECT scan data were analysed with the CT data using RAHVQSQ. This in-house method is an interactive data language (IDL) based program that allows flexible lobar segmentation of a three-dimensional display generated from the diagnostic CT data. The reproducibility (5) and accuracy (6) of our method have been peer reviewed. The segmented representation is then fused with the VQ data to quantify the lobar radioactivity as a percentage of the whole lung for the ventilation scan (Vent%), and the perfusion scan (Perf%). From the CT segmentation, the program quantifies the lobar volume (Vol%). We have taken the non-conventional approach to the interpretation of the quantified data with the following indices:

• Vent%/Vol%: which reflects the concentration of ventilation. A decline in concentration post BLVR-EBV could imply a dilutional effect from increased lobar volume gained from the collapsed TL if the magnitude of redistributed Vent% is higher than the redistributed Vol%.
• Perf%/Vol%: which reflects the concentration of perfusion. A decline in concentration post BLVR-EBV could imply a dilutional effect from increased lobar volume gained from the collapsed TL if the magnitude of redistributed Perf% is higher than the redistributed Vol%.
• VQCDI: within the SPECT CT matrix of each lobe, the numerical datum of each voxel in the ventilation and perfusion scans is multiplied. The array of product values for each voxel that the lobe occupies is then summed and divided by the lobar volume determined from the CT map. The resultant quantity is thus a measure of the amount of air and blood per unit lung volume. For example, the right upper lobe (RUL) is represented by:

  $$a\left(RUL\right)=\frac{{\displaystyle \sum \left(Ventilation\times Perfusion\right)ateachvoxelofRUL}}{Volume\left(RUL\right)}$$[1] The quantity of each lobe is then expressed as a percentage of all 5 lobes. This percentage, which we called VQCDI, is a reflection of the percentage differential contribution to total lung function. For example, for the RUL:

  $$VQCDI\left(RUL\right)=\frac{a\left(RUL\right)}{a\left(RUL\right)+b\left(RML\right)+c\left(RLL\right)+d\left(LUL\right)+e\left(LLL\right)}\times 100\%$$[2] where by RML: right middle lobe; RLL: right lower lobe; LUL: left upper lobe; LLL: left lower lobe. To support the validity of this index, we have used it to pre-operatively predict reductions in FEV1 and DLCO in a study of participants who had lobectomy and sub-lobar resection. We showed a high degree of correlation and agreement between the predicted and the post-operatively measured PFT parameters (7).

• VQCDI/Vol%: by dividing VQCDI by the Vol% (VQCDI/Vol%), we have a ratio that serves as an index that reflects lobar inefficiency. For example, a lobe that occupies 30% of total lung volume (Vol%), but has a differential contribution of 15% (VQCDI), will have a ratio of 0.5. This implies 50% inefficiency, which is attributed to gas trapping in emphysema.
• VQDI: this is a product of Vent%/Vol% and Perf%/Vol%. For gas exchange, we contend that the concentration of ventilation and perfusion is more relevant than the amount of radioactivity. If so, this index is a reflection of gas exchange performance. The lower the index the poorer the parenchymal function. To support the value of this index, we have shown a close correlation in the choice of TL based on this index compared to qCT in a group of participants who proceeded to BLVR-EBV with proven treatment response (8).

For each lobe, pre- and post-BLVR-EBV values of Vent%, Vent%/Vol%, Perf%, Perf%/Vol%, VQCDI, VQCDI/Vol%, VQDI, and ER% were compared.

Statistical analysis

The Wilcoxon signed-rank test was used to assess differences in pre- vs. post-BLVR-EBV paired measurements. SPSS version 31 was used. Median paired differences were used for statistical inference. Mean pre-post differences were additionally calculated to describe the magnitude and direction of change for each parameter within each lobe. For the treated lobe, percentage changes in mean values were also reported.

Results

Thirteen participants were recruited into the EMPHYSISE study. Of these, there were 10 who completed pre and post BLVR-EBV qVQ and qCT for analyses. Of these, pre- and post-BLVR-EBV CPET were completed in 9 participants and PFT in 9 participants. There were 5 male and 5 female participants. Their ages ranged from 48–82 years. The treated lobes were 4 in the left upper lobe, 5 in the left lower lobe, 1 in RUL/RML combined. The number of days between the BLVR-EBV and the combined VQ and CT were between 63 to 329 days (Table 1).

By convention, we defined treatment responses by minimal clinically important differences (MCIDs) of: lobar volume reduction of ≥563 mL or >50%; FEV1 improvement of ≥100 mL; residual volume reduction of ≥430 mL (9). As part of the EMPHYSISE study, we also added CWR MCID of ≥101 seconds. All 10 participants achieved at least one of these thresholds of treatment response (Table 2).

Overall qVQ and qCT results

The paired comparisons of pre vs. post treatment results of all parameters in all of the lobes were statistically significant (P<0.05) with the exception of 3 pairs: contralateral RUL/RML Vent%/Vol% (P=0.06); contralateral lower lobe Perf%/Vol% (P=0.06); and contralateral RML Perf%/Vol% (P=0.07) (Table 3).

The mean differences in all parameters for all lobes are presented in Table 3 to demonstrate the changing trends in each of the lobes following treatment. The percentage changes in the mean of all parameters for the treated lobe are also included to provide a longitudinal reflection of the functional alteration. The RUL/RML together was included as a separate category because the horizontal fissure is commonly deficient, necessitating combined treatment of both lobes to circumvent collateral ventilation.

Among the treated lobes, total collapse was noted in 6 participants. The lowest reduction of Vol% was noted to be 27.7% (Table 4). In this participant, similar to all other participants with subtotal collapse, there was a marked reduction in all functional parameters post treatment (Table 5).

Redistribution of ventilation, perfusion and volume

The redistribution of mean Vent%, Perf% and Vol% to the untreated lobes is outlined in Table 6. The IUL appears to receive most of the redistributions. In the contralateral lung, the lower lobe appears to benefit the most.

Dilution from increased volume

If a lobe receives a redistributed volume that is of a lower order of magnitude than the redistributed ventilation (i.e., increase in mean Vent% > Vol%) and the result is a mean increase in the concentration (Vent%/Vol%), then the lobe has had a net gain affording a higher gas exchange performance. If the same lobe has a decrease or no change in mean Vent%/Vol%, then the implication would be that the gain in ventilation has been negated or diluted by the rise in volume.

On the other hand, if the increase in mean Vent% is of a lower order of magnitude than the increase in Vol% and yet the Vent%/Vol% increases, then the implication would be that the lobe has had a net gain with no dilution. However, if there is a decrease in mean Vent%/Vol%, the likelihood is that the lobe has not benefited and there is dilution. If there is no net change in Vent%/Vol% despite the lesser rise in Vent%, then there is probably a net gain with no dilution.

The same analysis is applied for perfusion.

These analyses are shown in Table 7. A mild dilutional effect on ventilation was noted for all untreated lobes. No dilutional effect noted in the perfusion, with the exception of the contralateral lower lobe, although the comparison for this pair was not statistically significant.

In the contralateral RML, the mean Perf% rose equally with the mean Vol%. There was a rise in mean Perf%/Vol%, which implied no dilution.

Changes in the functional indices (Table 8)

• VQCDI: the IUL showed the highest increase in mean VQCDI of +11%. In the contralateral lung, the lower lobe appears to have the highest increase of +4.2%.
• VQCDI/Vol%: a minor reduction in this index for all except for the contralateral RML, which showed no change.
• VQDI: a minor worsening of mean VQDI for all, with the highest recorded for the contralateral upper lobe of −0.4.

Changes in ER% (Table 9)

In cases of total collapse, the ER% could not be determined, thus a comparison was not analysed for the treated lobes.

In the untreated lobes, the IUL appears to show the greatest improvement with a mean reduction in score of 3.5% (a negative result indicates a reduction in parenchymal destruction, implying an improvement). In the contralateral lung, the greatest improvement is noted in the middle lobe.

Discussion

Lobar collapse following BLVR-EBV leads to an adjustment in the volume of the untreated lobes to fill the void in the hemithorax. The IUL is expected to expand the most and is the lobe that is likely the only beneficiary of the improved mechanical ventilation.

There is a redistribution of ventilation and perfusion from the collapsed lobe to the other lobes, which could theoretically improve gas exchange. The division of the redistribution is favoured to be to the IUL from the past studies using VQ SPECT CT. However, the dilutional effect of the increase in volume within the untreated lobes, which are also burdened with emphysema, could also negate or reverse the benefits of increased ventilation and perfusion for improvement in gas exchange performance.

RAHVQSQ and our non-conventional indices permit the evaluation of:

• The redistribution of volume, ventilation and perfusion to the untreated lobes, with changes in mean Vol%, Vent% and Perf%;
• Dilution of any increase in ventilation and perfusion from increased volume in the untreated lobes—with changes in the Vent%/Vol% and Perf%/Vol%;
• The effects on the lobar differential function (VQCDI), gas trapping (VQCDI/Vol%) and parenchymal gas exchange performance (VQDI) of all lobes.

Published data on the use of qVQ in pre and post BLVR-EBV assessment include the following:

VQ planar quantification

Pizaro et al. (10) performed pre- and post- (8 weeks) BLVR-EBV planar qVQ in a group of 26 participants who were shown to be treatment responders. They found a significant reduction in perfusion and ventilation in the treated zone; a significant increase in perfusion to the contralateral whole lung and the zone non-concordant to the treatment zone. The authors concluded that the ventilation and perfusion redistribution are predominantly to the contralateral lung.

Chung et al. (11) performed pre and post (days +30 and +90) BLVR-EBV quantitative planar VQ in 6 participants who all had BLVR-EBV of the LUL and were treatment responders. The lungs were divided into four quadrants. They found: significant reduction in ventilation and perfusion to the treated zone; significant increase in ventilation and perfusion to the contralateral whole lung and lower zone; significant reduction in perfusion to the ipsilateral lower zone. The authors concluded that the contralateral lung appears to receive most of the redistributed ventilation and perfusion.

These planar quantification studies contradict our study findings. It is our contention that the major limitation in planar quantification using geometric zones that do not match lobar anatomy will significantly limit the accuracy of the quantification. A zone could easily incorporate more than one lobe and the quantifications do not properly reflect individual lobar physiology.

Jamadar et al. (12) devised a qualitative score of disease severity and size in four quadrants of planar and SPECT perfusion only scans performed preoperatively and reviewed retrospectively in a cohort of 30 participants who proceeded to biapical lung resection for advanced emphysema, compared to another 17 participants who were deemed unfit for surgery. They found that the upper lung zones had scored higher for disease in the treated group and a significant correlation was noted between the scores and the measured post-operative improvements in FEV1 and a subjective dyspnoea index. They noted that scoring with SPECT scans did not offer any additional benefit to planar scans. The authors contend that the semi-quantitative evaluation might have predictive value for post-operative outcome. However, the geometric zones do not match lobar anatomy and BLVR-EBV treatment is not confined to the upper lobes. Using SPECT alone predictably did not add value, as the same non-anatomical segmentation was used. The study findings also have limited application in BLVR-EBV, whereby only 1 lobe is treated.

VQ planar and SPECT CT quantification

Ide Bolet et al. (13) used VQ SPECT CT to quantify differential lobar perfusion before and between 3 to 6 months post BLVR-EBV in 92 participants with homogenous emphysema to study shifts in perfusion. The TL was chosen based on the lowest Perf%/Vol% and treatment response was noted, supporting the value of qVQ. Post-treatment lobar perfusion was quantified to evaluate redistribution and results were tabulated according to the lobe treated. There was a common finding of a statistically significant increase in perfusion in the IUL. With the exception of LUL as the target, the IULs appear to achieve the highest increase in the redistributed perfusion. With LUL as the target, the RLL achieved a slightly higher increase in perfusion compared to the LLL. The authors concluded that lobar quantification of perfusion with SPECT CT could be beneficial for pre BLVR-EBV assessment.

Kristiansen et al. (14) used quantitative planar and SPECT CT to quantify differential lobar volume, ventilation and perfusion before and after (mean: 8.3 months; range, 4–15 months) BLVR-EBV in 24 participants who achieved treatment response thresholds. They found significant increases in volume, ventilation and perfusion in the IUL, but no significant changes in the lobes of the contralateral lung. The ventilation and perfusion changes correlated with the FEV1 changes with planar and SPECT CT quantification. The contralateral lung ventilation changes correlated with the FEV1 changes. They surmised that it is “plausible that treatment-induced functional shifts are more likely to benefit the remaining ipsilateral lung”.

The findings of these VQ SPECT CT studies appear to concur with our findings that the IUL could be the main beneficiary of BLVR-EBV treatment.

RAHVQSQ

It is our contention that pre and post BLVR-EBV assessments with qVQ require the evaluation of lobar volume, ventilation and perfusion together rather than as separate entities. This is evident on VQ scan appearances of emphysematous lungs, which show diseased segments with more pronounced reduction in ventilation than perfusion. Evaluating perfusion alone will overestimate the functional contribution from segments that are receiving poor ventilation. The degree of the ventilation to perfusion mismatch is also frequently not equivalent in all lobes, which reflects the differences in disease burden between segments. This difference can only be nuanced by incorporating lobar volume to quantify concentrations of ventilation and perfusion, which is addressed with VQDI. To the best of our knowledge, our technique is unique in the incorporation of volume, ventilation and perfusion.

Pertaining to the treated lobe, a significant observation is that there was a marked reduction of all functional parameters, even when there was a subtotal collapse as low as 27.7% reduction in Vol%. This observation highlights the disparity between lobar volume and ventilation and perfusion in this cohort. With subtotal collapse, the lobe retained volume presumably due to some unexpected collateral ventilation. However, on VQ assessment there was very poor functional ventilation which then led to marked shunting of perfusion to the other lobes. Evaluation of the untreated lobes that does not incorporate volume, ventilation and perfusion together will not truly appreciate the net effects of redistribution and dilution.

The IUL appeared to have received the highest share of the redistributed volume, ventilation and perfusion. There was mild dilution with no change in mean Vent%/Vol%, and no dilution of Perf%/Vol% with a mild increase in mean of 0.5 unit. As a consequence, there was a mild but significant worsening of VQDI of 0.2 unit. However, the net effect of the redistributed ventilation and perfusion and the improved mechanical ventilation was a significant increase in mean VQCDI (lobar differential contribution to total lung function) of 11% (Table 3).

We also noted that the IUL had the highest mean decline in ER% score of 3.5%. Whilst this parallels the functional improvement, the exact mechanism of the concordance is unclear. We have shown in a blinded study of treatment responders that the choice of the TL based on the lowest VQDI has close concordance with the choice based on the lowest ER% (8). Nijor et al. showed that their participants whose TL had the lowest Perf%/Vol% based on perfusion SPECT CT had significantly higher ER% than those whose TL Perf%/Vol% that were not the lowest (15). Demirkol et al. showed a high concordance between TL choice based on the lobar perfusion from planar scan quantification and ER% (16). Concordance implies an association but does not prove causation. The destruction score is a measure of tissue density. Our functional indices assess lobar ventilation and perfusion status. The two categories of quantification probably provide separate but associated and complementary assessments of the degree of emphysema in each lobe. In this cohort with demonstrable treatment response, the measured structural improvement could potentially represent the benefits of better mechanical ventilation with lesser dead space ventilation and gas trapping. In support of this theory, we showed that in the face of an increase in mean Vol% of 13.3%, there was a disproportionately minor worsening of mean VQCDI/Vol% (gas trapping) of 0.1 unit (Table 3).

In the contralateral lung, the lower lobe (RLL in 9 out 10 participants) appears to be the one receiving the highest redistribution of volume, ventilation and perfusion (Table 3). Mild dilution was noted in Vent%/Vol% and Perf%/Vol% (Table 7), although the paired comparison of the latter did not reach statistical significance (P=0.06). There was a significant increase in mean VQCDI of 4.2%. A minor decrease in the mean VQCDI/Vol% of −0.05 unit and VQDI of −0.1 unit were noted. The mean ER% improved slightly with a reduction of mean of 0.6%.

In this study, with participants who had achieved at least 1 threshold of treatment response, it would appear that when choosing a TL pre BLVR-EBV, the IUL is almost as important as the TL itself because it is likely to receive the highest gain. The healthier the IUL, the more likely it would be able to withstand the dilutional effect of an increase in volume to take advantage of the redistributed ventilation and perfusion, which could translate to a favourable effect on its gas exchange performance (VQDI), its contribution to total lung function (VQCDI) and gas trapping (VQCDI/Vol%).

As for the contralateral lung, the lower lobe health may also be relevant. Consideration of the possible pattern of redistribution and dilution of this lobe might be worth factoring in when choosing the TL.

Our study has several limitations. RAHVQSQ is an in-house program, thus not generally available. However, the capabilities of the program have allowed a unique and more in-depth understanding of the alterations in lobar physiology following BLVR-EBV. We have a small sample, which was partly contributed to by the limitations of the coronavirus disease 2019 (COVID-19) pandemic. Our study is confined to a single tertiary referral centre. However, the cohort of participants is not dissimilar to most tertiary units that offer BLVR-EBV treatment.

Conclusions

In this study, we found that following BLVR-EBV, there is a marked functional decline in the treated lobe even when there is subtotal collapse. The functional benefits appear to be the most pronounced in the IUL, whilst the lower lobe is the highest beneficiary in the contralateral lung. These findings highlight the importance of choosing a TL that is paired with the healthiest IUL for optimizing clinical outcomes. Our novel quantitative approach to VQ SPECT CT permits a comprehensive evaluation of lobar physiology that strongly complements the structural evaluation of qCT during TL selection. A larger study with a longer follow-up would be of value.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0138/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0138/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0138/prf

Funding: This work was supported by Industry (PulmonX™), University of Adelaide Research Scholarship, Thoracic Society of Australia and New Zealand (SA/NT) New Investigator Award Research Grant, and Thoracic Society of Australia and New Zealand (SA/NT) ASM 3-minute Thesis Research Grant.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0138/coif). C.G.C. reports article processing fee from South Australia Medical Imaging (Royal Adelaide Hospital). A.F. reports funding for the EMPHYSISE study from PulmonX™, University of Adelaide Research Scholarship, Thoracic Society of Australia and New Zealand (SA/NT) New Investigator Award Research Grant, and Thoracic Society of Australia and New Zealand (SA/NT) ASM 3-minute Thesis Research Grant. P.N. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Olympus medical corporation Australia, PulmonX™ Australia, Fisher Paykel, AstraZeneca, Boston Scientific. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study obtained Ethics and Governance approval from the Central Adelaide Local Health Network Human Research and Ethics committee (HREC reference HREC/18/CALHN/389). Informed consent was obtained from all individual participants for the procedures performed.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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