Introduction: Endobronchial valve (EBV) treatment has been shown to be beneficial for patients with severe emphysema. The forced expiratory volume in 1 s (FEV1) was found to be significantly higher compared to baseline for up to 3 years after treatment although the magnitude of improvement gradually decreases over time. So far, it has not been investigated whether this treatment decelerates the decline in lung function. Therefore, our aim was to investigate the lung function decline before and after EBV treatment. Methods: We included patients who were treated with EBVs in our hospital, of whom pre-treatment spirometry results were available (at least 4 measurements within at least 2 years before treatment) and who had an annual FEV1 measurement up to 3 years after treatment. Results: In total, 45 patients were included (73% female, FEV1: 28 ± 7% of predicted, residual volume: 232 ± 32% of predicted) who had a mean pre-treatment FEV1 decline of −64 mL/year. Mean FEV1 “decline” after treatment was +13 mL/year, since FEV1 was still above the baseline level at 3-year follow-up. However, the FEV1 decline between 1 and 3 years of follow-up was not significantly different compared to the pre-treatment decline (−73 mL/year, p = 0.179). Conclusions: Our results show that the EBV treatment does not influence the progression of disease in terms of lung function decline. However, the treatment does improve the FEV1 up to a level that is still comparable 3 years after treatment with the baseline level.

Endobronchial valve (EBV) treatment has been shown to be beneficial for patients with severe emphysema and has been a guideline treatment for more than 5 years [1, 2]. Recently, we showed that lung function and quality of life were still significantly and clinically meaningfully improved compared to the baseline up to 3 years after EBV treatment, although the magnitude of improvement gradually decreased over time [3]. So far, it has not been investigated whether EBV treatment decelerates the natural decline in lung function. Therefore, our aim was to investigate the lung function decline before and after EBV treatment.

Between August 2014 and July 2019, 1,030 patients were evaluated in our hospital for a bronchoscopic lung volume reduction treatment and signed informed consent to be included in the Groningen severe COPD cohort (NCT04023409). This study was approved by the Ethics Committee of the University Medical Center Groningen (METc 2014.104), and patients provided informed consent. Part of the cohort study was to obtain pre-treatment spirometry values from the referring hospitals. Of this cohort, 236 patients were treated with EBVs, and these patients were annually invited for follow-up visits. Patients also signed informed consent to use data of these visits for scientific purposes (NCT02815683). The Ethics Committee of the University Medical Center Groningen granted exemption of ethics approval for this data registry (METc 2016.483).

For this analysis, we included patients from this cohort who underwent the EBV treatment, of whom pre-treatment spirometry results were available, and who performed spirometry annually up to 3 year of follow-up. Pre-treatment spirometry results were only used when at least 4 spirometry measurements were performed within at least 2 preceding years prior to EBV treatment to be able to calculate a reliable decline. We were able to obtain reliable pre-treatment spirometry results of 168 patients. Most frequent reasons for not being able to visit us annually until 3 years after treatment were death, EBV removal, or not being able to visit our hospital due to the COVID-19 pandemic.

In total, 45 patients were included (73% female, mean age 61 ± 7 years, forced expiratory volume in 1 s [FEV1]: 28 ± 7% predicted, residual volume: 232 ± 32% predicted, all ex-smokers). The mean FEV1 decline before treatment was −64 mL/year. The FEV1 decline between 1 and 3 years of follow-up was −73 mL/year, which is not significantly different compared to the pre-treatment decline (p = 0.179) (Table 1; Fig. 1). The mean FEV1 change between baseline and 3 years of follow-up was +13 mL/year, which is significantly different compared to pre-treatment (p < 0.001, Table 1).

Table 1.

FEV1 and FEV1 decline pre-treatment and during follow-up (n = 45)

Baseline1-year FUp value2-year FUp value3-year FUp value
mean±SDmean±SDmean±SDmean±SD
FEV1, mL 736±239 935±364 <0.001 850±339 <0.001 774±314 0.055 
Baseline1-year FUp value2-year FUp value3-year FUp value
mean±SDmean±SDmean±SDmean±SD
FEV1, mL 736±239 935±364 <0.001 850±339 <0.001 774±314 0.055 
Pre-treatmentBaseline–3-year FU1-year FU–3-year FU
mean±SDmean±SDp valuemean±SDp value
FEV1 decline, mL/year −64±42 13±5 <0.001 −73±66 0.179   
Pre-treatmentBaseline–3-year FU1-year FU–3-year FU
mean±SDmean±SDp valuemean±SDp value
FEV1 decline, mL/year −64±42 13±5 <0.001 −73±66 0.179   

Data are presented as mean ± standard deviation. FEV1, forced expiratory volume in 1 s; FU, follow-up; SD, standard deviation; mL, milliliter.

Difference between follow-up and the baseline FEV1 or pre-treatment FEV1 decline was tested with a paired sample t test.

Fig. 1.

Decline in FEV1 before and after EBV treatment. Baseline and post-treatment FEV1 are shown as mean (±standard deviation). Blue line: mean decline in FEV1 before treatment; red line: change in FEV1 after treatment; dotted line: predicted trend based on the mean decline before treatment. FEV1, forced expiratory volume in 1 s; mL, milliliter.

Fig. 1.

Decline in FEV1 before and after EBV treatment. Baseline and post-treatment FEV1 are shown as mean (±standard deviation). Blue line: mean decline in FEV1 before treatment; red line: change in FEV1 after treatment; dotted line: predicted trend based on the mean decline before treatment. FEV1, forced expiratory volume in 1 s; mL, milliliter.

Close modal

The pre-treatment FEV1 decline was comparable with the treatment decline we reported earlier in patients undergoing either bronchoscopic lung volume reduction coil or targeted lung denervation treatment [4, 5]. However, the decline was larger compared to earlier reported values in severe COPD. On the other hand, it was also reported that patients with emphysema have a faster lung function decline, and our population exists of patients with severe emphysema [6]. In line, the reported FEV1 decline before lung volume reduction surgery in severe emphysema patients was even higher [7].

Our results show that after 3 years of follow-up, the FEV1 level was still above the baseline level. This is in positive contrast with other bronchoscopic treatments in which the pre- and post-treatment FEV1 decline was investigated and in which the FEV1 had already returned to baseline values after 2 years [4, 5].

We found that the treatment did not influence the slope of the FEV1 decline, which actually is in line with reports on both the bronchoscopic lung volume reduction with coils and lung volume reduction surgery [5, 7, 8]. These findings indicate that COPD is a progressive disease, and the pathological process of the disease is not influenced by a lung volume reduction treatment. Recently, we also showed that the magnitude of the decline in improvement in residual volume and quality of life at 3-year follow-up was less pronounced compared to the more rapid decline in FEV1 or exercise capacity [3]. It would also have been interesting to investigate whether the EBV treatment influences the decline in hyperinflation, quality of life, and exercise capacity, but unfortunately, these parameters are scarcely monitored in regular care.

A limitation of our analysis is the relative low sample size. However, we believe that only including patients who have measurements at all timepoints as well as a significant number of pre-treatment measurements increases the reliability of our analysis. Furthermore, when including all patients with pre-treatment measurements but who did not attend all 3 annual follow-up visits (n = 168), outcomes were similar (data not shown).

To conclude, our results show that EBV treatment in patients with severe emphysema does not influence the progression of diseases in terms of natural FEV1 decline. However, the treatment does improve the FEV1 up to a level that is still comparable to the baseline level 3 years after treatment.

Between August 2014 and July 2019, 1,030 patients were evaluated in our hospital for a bronchoscopic lung volume reduction treatment and signed informed consent to be included in the Groningen severe COPD cohort (NCT04023409). This study was approved by the Ethics Committee of the University Medical Center Groningen (METc 2014.104), and patients provided informed consent. Part of the cohort study was to obtain pre-treatment spirometry values from the referring hospitals. Of this cohort, 236 patients were treated with EBVs and these patients were annually invited for follow-up visits. Patients also signed informed consent to use data of these visits for scientific purposes (NCT02815683). The Ethics Committee of the University Medical Center Groningen granted exemption of ethics approval for this data registry (METc 2016.483).

J.E.H., T.D.K., M.D., and O.C. have nothing to disclose. K.K. discloses honoraria for lectures from PulmonX. D.-J.S. discloses grants or contracts from PulmonX Corp, PneumRx/BTG/Boston Sc, FreeFlowMedical, Nuvaira, Gala, CSA Medical, and Apreo (all USA), consulting fees from PulmonX Corp, PneumRx/BTG/Boston Sc, Nuvaira, and Apreo (all USA), support for attending meetings and/or travel from PulmonX Corp, PneumRx/BTG/Boston Sc, and Nuvaira (all USA), and receipt of equipment, material, or other services from PulmonX Corp., PneumRx/BTG/Boston Sc, FreeFlowMedical, Nuvaira, PulmAir, GALA, and CSA Medical (all USA).

The authors did not receive any funding or other support for this project.

J.E.H. and D.J.S. designed the analysis, wrote the first draft of the manuscript, and made revisions after feedback from co-authors. J.E.H., K.K., T.D.K., O.C., M.D., and D.-J.S. meet the definition of an author as stated by the International Committee of Medical Journal Editors. All authors have seen and approved the final manuscript.

Data are not publicly available due to ethical reasons. Further inquiries can be directed to the corresponding author.

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