Endobronchial valve (EBV) treatment can significantly improve pulmonary function, exercise capacity, and quality of life in patients with advanced emphysema and lung hyperinflation. However, the impact of age on treatment response to EBV remains unclear, despite its increasing relevance in an aging population. This study aimed to assess the effect of age on clinical outcomes following EBV treatment in a real-world population.
MethodsBaseline, 6-month, and 12-month follow-up data were obtained from our registry of EBV procedures performed between 2016 and 2024. Patients were stratified according to age: <70 years and ≥70 years. Age-related differences in relative changes in forced expiratory volume in 1 second (FEV1), residual volume (RV), 6-minute walk distance (6MWD), and St George's Respiratory Questionnaire (SGRQ) scores were assessed, together with safety outcomes, achievement of patient-specific goals, and patient satisfaction.
ResultsA total of 476 patients were included, of whom 79 (17%) were aged ≥70 years (range, 70–80 years). Both age groups demonstrated significant improvements in FEV1, RV, 6MWD, and SGRQ scores at both follow-up visits, with no significant differences between groups. Importantly, adverse events did not occur more frequently among older patients. Additionally, achievement of patient-specific goals was comparable between groups, although patients aged ≥70 years reported slightly greater satisfaction with treatment outcomes than those aged <70 years.
ConclusionsOur findings indicate that EBV treatment resulted in comparable clinical improvements and similar safety profiles regardless of patient age. These findings highlight the importance of referral and screening of older patients with emphysema to assess their eligibility for EBV treatment.
Endobronchial valve (EBV) treatment is a bronchoscopic procedure tailored for carefully selected patients with chronic obstructive pulmonary disease (COPD) characterized by advanced emphysema, severe lung hyperinflation, and substantial disease burden despite optimal pharmacological and nonpharmacological therapy [1]. This treatment aims to reduce lung hyperinflation, thereby improving pulmonary function, quality of life, and exercise capacity [2,3]. However, little is currently known regarding the impact of patient age on response to EBV treatment.
In the latest expert panel recommendations for bronchoscopic lung volume reduction (BLVR), age is not considered during the patient selection process [4]. Likewise, age is not included among the selection criteria for lung volume reduction surgery (LVRS) [5]. However, a previous study by Welling et al. showed that, during the selection process for EBV treatment, patients selected for treatment were significantly younger than those excluded (59 vs 63 years) [6]. To our knowledge, no studies have specifically investigated the impact of age on treatment response. However, survival analyses of patients undergoing BLVR or LVRS indicate that increasing age is associated with poorer survival outcomes [7,8].
In line with lung volume reduction treatment, most countries worldwide do not impose an upper age limit as an absolute contraindication for lung transplantation [9]. Nevertheless, patients older than 70 years have a substantially increased risk of poor posttransplant outcomes [9]. Simultaneously, due to population aging and the increasing prevalence of advanced COPD among older adults, the proportion of lung transplant candidates older than 65 years doubled from 18.6% in 2011 to 33.0% in 2020 in the United States, with obstructive lung diseases accounting for 26.5% of this group [10].
As stated above, current knowledge regarding the effect of age on response to EBV treatment is limited, whereas the importance of effective treatment options for older populations is increasing because of population aging. Therefore, the aim of this study was to assess the effect of age on changes in clinical outcomes following EBV treatment in a real-world population. Furthermore, safety outcomes, achievement of patient-specific goals, and patient satisfaction following EBV treatment were assessed.
MethodsStudy population and study designData for the current study were obtained from the Bronchoscopic Emphysema Treatment in the Netherlands (BREATHE-NL) registry, a prospective Dutch database designed to record the clinical outcomes of BLVR in routine clinical practice (NCT02815683). The BREATHE-NL registry was determined not to be subject to the Dutch Medical Research Involving Human Subjects Act (WMO) by the medical ethics review committee of our hospital (EC No.: 2016/483). Nevertheless, all patients provided informed consent for the use of their data. As the current study was conducted within the scope of the BREATHE-NL registry, no additional ethical approval was required. All patients underwent BLVR using EBVs (Zephyr; PulmonX Inc, Redwood City, California, United States) [4].
For this study, data were collected from patients scheduled for EBV treatment between September 2016 and May 2024 at University Medical Center Groningen, the Netherlands, at baseline and at 6- and 12-month follow-up visits. Patients were stratified into two groups according to age: <70 years and ≥70 years. This cutoff was chosen pragmatically based on both the increased risk of poor outcomes following lung transplantation among patients aged ≥70 years and the availability of a sufficient number of patients aged ≥70 years for analysis [9]. Patients who underwent permanent removal of all EBVs were excluded from further statistical analyses of treatment efficacy, whereas those with successful revision bronchoscopy remained included. All patients who underwent valve removal remained included in safety outcome analyses.
Study measurementsAt all study visits, the following assessments were performed: postbronchodilator spirometry [11], body plethysmography [12], and the 6-minute walk distance (6MWD) test [13], all according to European Respiratory Society (ERS) or American Thoracic Society (ATS) guidelines, in addition to the St George's Respiratory Questionnaire (SGRQ) [14] and the COPD Assessment Test (CAT) [15]. Demographic characteristics, comorbidity history in a subset of patients [16], diffusion capacity [17], and arterial blood gas analyses were also obtained at baseline. Furthermore, at the 12-month follow-up visit, patients completed a self-designed patient satisfaction questionnaire consisting of five questions [18]. Duration of hospitalization, adverse events, revision bronchoscopies, and follow-up attendance after EBV treatment were also recorded and analyzed.
The Dutch patient-specific complaint (PSC) questionnaire was used to evaluate patient-specific goals [18,19]. At baseline, patients reported their three most important personal treatment goals and rated the level of disability associated with each goal using a numeric rating scale (NRS; range, 0–10). The same goals were reassessed 12 months after treatment. The PSC total score was calculated as the sum of the three individual goals. For this study, the five most frequently reported goals (walking, showering/washing/getting dressed, completing household chores, exercising, and cycling) were assessed based on previous research [18].
Statistical analysesPearson or Spearman correlation coefficients (ρ) were calculated to assess the strength of the association between age and relative changes in clinical outcomes at 6 and 12 months following EBV treatment. Based on the predefined age cutoff, patients were categorized into two subgroups: <70 years and ≥70 years. Additionally, patients were classified as treatment responders or nonresponders according to predefined minimal important difference (MID) thresholds: change (Δ) in forced expiratory volume in 1 second (FEV1) ≥10%, residual volume (RV) ≤−8.6% [20], 6MWD ≥10% [21], SGRQ ≤−11.1% [22], and PSC sum score ≤−5.9 points [23]. Within-group changes were analyzed using the paired t test or Wilcoxon signed-rank test, where appropriate. Between-group comparisons were performed using the independent t test, Mann–Whitney U test, or chi-square test, where appropriate. Additional multivariable regression analyses were conducted to account for potential confounding if significant baseline differences between age groups were identified. Furthermore, sensitivity analyses using alternative age cutoffs of 65 and 75 years were performed to assess whether the selected cutoff of 70 years influenced the results. All statistical analyses were performed using IBM SPSS Statistics version 28.0.1.0 (IBM Corp, Armonk, New York, United States), and figures were created using R Statistical Software version 4.5.1 (R Foundation for Statistical Computing, Vienna, Austria). P values <.05 were considered statistically significant.
ResultsStudy populationBetween September 2016 and May 2024, a total of 476 patients were scheduled for EBV treatment, of whom 397 (83%) were aged <70 years and 79 (17%) were aged ≥70 years (Supplementary Figs. 1 and 2). Exclusion rates for EBV treatment were comparable between groups, with the presence of collateral ventilation being the primary reason for exclusion (Supplementary Fig. 2). A quarter of patients aged ≥70 years did not attend the 6-month follow-up visit, compared with 19% of those aged <70 years. In contrast, attendance at the 12-month follow-up visit was slightly higher in the ≥70-year group (Supplementary Fig. 2). However, neither difference in follow-up attendance between age groups reached statistical significance. The three most frequently reported reasons for nonattendance were EBV removal, intercurrent comorbidities, and the need for revision bronchoscopy, each occurring at comparable rates in both age groups (Supplementary Fig. 2).
Baseline characteristics of the overall study population and stratified data according to age are presented in Table 1. Patients aged ≥70 years comprised a significantly higher proportion of men than patients aged <70 years. In addition, the older age group demonstrated significantly less airflow obstruction and lung hyperinflation at baseline. No significant differences were observed between groups regarding comorbidities, exercise capacity, diffusion capacity, or quality of life (Table 1).
Baseline characteristics of the study population.
| Total population(n=476) | <70 years(n=397) | ≥70 years(n=79) | P value | |
|---|---|---|---|---|
| Female sex | 315 (66%) | 281 (71%) | 34 (43%) | <.001 |
| Age, y | 63.2±SD, 7.5 | 61.1±SD, 6.2 | 73.8±SD, 2.8 | <.001 |
| BMI, kg/m2 | 23.8±SD, 4.0 | 23.9±SD, 4.1 | 23.5±SD, 3.4 | .451 |
| Smoking history, pack-years (n=472) | 39 (0–148) | 38 (0–147) | 45 (6–148) | .004 |
| Total number of comorbidities (n=202) | 3 (0–7) | 3 (0–7) | 3 (0–6) | .951 |
| FEV1, % predicted | 27.3±SD, 7.6 | 26.6±SD, 7.2 | 30.9±SD, 8.5 | <.001 |
| FVC, % predicted | 70.4±SD, 15.2 | 69.5±SD, 14.8 | 74.9±SD, 16.4 | .004 |
| RV, % predicted (n=473) | 247±SD, 51 | 253±SD, 51 | 215±SD, 39 | <.001 |
| TLC, % predicted (n=473) | 132±SD, 14 | 132±SD, 14 | 132±SD, 14 | .741 |
| RV/TLC ratio, % (n=473) | 63.4±SD, 7.1 | 63.4±SD, 7.2 | 63.0±SD, 6.5 | .611 |
| DLCO, % predicted (n=433) | 37.7±SD, 10.5 | 37.6±SD, 10.3 | 38.4±SD, 11.0 | .546 |
| 6MWD, m (n=473) | 320±SD, 100 | 323±SD, 103 | 308±SD, 83 | .231 |
| PaCO2, kPa (n=453) | 5.3 (4.1–7.8) | 5.3 (4.1–7.8) | 5.2 (4.1–7.5) | .971 |
| PaO2, kPa (n=453) | 9.3 (5.8–12.9) | 9.3 (5.8–12.9) | 9.2 (5.8–11.5) | .561 |
| SGRQ total score (n=453) | 56.8±SD, 12.7 | 57.0±SD, 12.6 | 55.7±SD, 13.0 | .402 |
| CAT total score (n=451) | 21.7±SD, 5.5 | 21.8±SD, 5.6 | 21.1±SD, 5.3 | .297 |
Data are presented as No. (%), mean±SD, or median (range). Differences in baseline characteristics between patients aged <70 years and ≥70 years were assessed using the independent t test for normally distributed continuous variables, the Mann–Whitney U test for nonnormally distributed continuous variables, and the Pearson chi-square test for categorical variables. Fisher exact test was used when chi-square assumptions were not met.
BMI, body mass index; CAT, COPD Assessment Test; DLCO, diffusion capacity for carbon monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; PaCO2, partial pressure of carbon dioxide; PaO2, partial pressure of oxygen; RV, residual volume; SGRQ, St George's Respiratory Questionnaire; TLC, total lung capacity; 6MWD, 6-minute walk distance.
Associations between age and relative changes in clinical outcome parameters following EBV treatment are presented in Fig. 1 and Supplementary Table 1. Age was significantly associated with relative changes in quality of life (SGRQ), with older patients showing greater improvement at the 12-month follow-up (r=−0.131; P=.022). There were no significant associations between age and relative changes in pulmonary function, exercise capacity, or patient-specific goals (Fig. 1, Supplementary Table 1, Supplementary Fig. 3).
Scatterplots and fitted regression lines with 95%CI depicting the association between age and relative change (Δ) in (A) forced expiratory volume in 1 second (FEV1), (B) residual volume (RV), (C) 6-minute walk distance (6MWD), and (D) St George's Respiratory Questionnaire (SGRQ) total score, all assessed 12 months after endobronchial valve treatment. Colored blocks indicate categorization of patients according to age (<70 years and ≥70 years) and treatment response status (responders: change reached the minimal important difference threshold; nonresponders: change did not reach the minimal important difference threshold).
Both age groups demonstrated significant improvements in relative changes in FEV1, RV, 6MWD, SGRQ total score, and PSC sum score at both follow-up time points (Supplementary Table 2). These improvements did not differ significantly between groups. However, improvement in SGRQ total score at the 12-month follow-up approached statistical significance (P=.086), suggesting a trend toward greater improvement in quality of life among patients aged ≥70 years (Supplementary Table 2). Given the significant differences in sex, pack-years, baseline FEV1, and RV between patients aged ≥70 years and those aged <70 years, additional multivariable linear regression analyses were performed adjusting for these variables to account for potential confounding effects. Adjustment for these baseline characteristics did not alter the results. Age was not independently associated with changes in FEV1, RV, or 6MWD after adjustment for potential confounders (P>.05). Age was independently associated with changes in SGRQ, although this finding was borderline (OR, −8.8; P=.047) (Supplementary Table 3).
Responder rates were slightly higher across all treatment outcomes in the ≥70-year group; however, these differences did not reach statistical significance (Fig. 2 and Supplementary Fig. 4). Nonetheless, the difference in responder rates for exercise capacity approached statistical significance, indicating a possible trend toward better outcomes among older patients (Fig. 2). To assess whether the selected age cutoff of 70 years influenced the results, sensitivity analyses using alternative cutoffs of 65 and 75 years were performed. These analyses also revealed no significant differences in changes in clinical outcomes or responder rates between patients aged <65 years vs ≥65 years or <75 years vs ≥75 years (Supplementary Tables 4 and 5; Supplementary Figs. 5 and 6).
Responder rates following endobronchial valve treatment in patients aged <70 years and ≥70 years for (A) forced expiratory volume in 1 second (FEV1), (B) residual volume (RV), (C) 6-minute walk distance (6MWD), and (D) St George's Respiratory Questionnaire (SGRQ) total score. Differences between patients aged <70 years and ≥70 years were assessed using the Pearson chi-square test.
There were no significant differences in duration of hospital admission following EBV treatment, with both age groups showing a median hospital stay of 4 days (Table 2). Mortality within the first year after EBV treatment was rare and comparable between groups. The incidence of pneumothorax following treatment was slightly higher among patients aged ≥70 years than among those aged <70 years (23% vs 18%), although this difference was not statistically significant.
Post-endobronchial valve treatment hospitalization, adverse events, and revisions.
| <70 years(n=351) | ≥70 years(n=69) | P value | |
|---|---|---|---|
| Hospital admission duration after EBV treatment, d | 4 (1–92) | 4 (2–22) | .434 |
| Pneumothorax after EBV treatment | 63 (17.9%) | 16 (23.2%) | .303 |
| Death within 1 year after EBV treatment | 9 (2.6%) | 1 (1.4%) | 1.000 |
| Underwent revision bronchoscopy within 1 year after EBV treatment | 96 (27.4%) | 13 (18.8%) | .140 |
| Number of revision bronchoscopies within 1 year | 0 (0–4) | 0 (0–2) | .245 |
| 0 revisions | 255 (72.6%) | 56 (81.2%) | |
| 1 revision | 65 (18.5%) | 4 (5.8%) | |
| 2 revisions | 26 (7.4%) | 9 (13.0%) | |
| 3 revisions | 4 (1.1%) | 0 | |
| 4 revisions | 1 (0.3%) | 0 | |
| Permanent removal of all EBVs within 1 year after treatment | 44 (12.5%) | 7 (10.1%) | .578 |
Data are presented as No. (%) or median (range). Differences between patients aged <70 years and ≥70 years were assessed using the Mann–Whitney U test for nonnormally distributed continuous variables and Pearson chi-square test for categorical variables. Fisher exact test was used when chi-square assumptions were not met.
EBV, endobronchial valve; FU, follow-up.
Conversely, the proportion of patients requiring revision bronchoscopy within the first year was higher in the <70-year group than in the ≥70-year group (27% vs 19%), although this difference also did not reach statistical significance. Definitive treatment reversal, defined as permanent removal of all EBVs, was observed in approximately 10% of patients, with similar rates in both study groups (Table 2).
Patient-specific goalsNo significant differences between age groups were observed in the number of patients reporting walking, showering/washing/getting dressed, completing household chores, exercising, and cycling as treatment goals (Table 3). However, exercising as a treatment goal was reported more frequently among patients aged ≥70 years than among those aged <70 years (35% vs 18%).
Patient-specific goals.
| Variable | <70 years(n=137) | ≥70 years(n=23) | P value |
|---|---|---|---|
| PSC walking* | 104 (76%) | 16 (70%) | .515 |
| ΔPSC walking, PSC NRS score | −1.5 (−10.0 to 4.0) | −1.0 (−6.0 to 2.0) | .549 |
| PSC showering/washing/getting dressed* | 35 (26%) | 6 (26%) | .956 |
| ΔPSC showering/washing/getting dressed, PSC NRS score | −2.0 (−7.0 to 3.0) | −1.5 (−6.0 to 2.0) | .823 |
| PSC household chores* | 44 (32%) | 6 (26%) | .564 |
| ΔPSC household chores, PSC NRS score | −2.0 (−7.0 to 4.0) | −1.5 (−7.0 to 0.0) | .850 |
| PSC exercise* | 25 (18%) | 8 (35%) | .070 |
| ΔPSC exercise, PSC NRS score | −3.0 (−10.0 to 2.0) | −2.0 (−7.0 to 0.0) | .958 |
| PSC cycling* | 32 (23%) | 5 (22%) | .865 |
| ΔPSC cycling, PSC NRS score | −3.0 (−10.0 to 3.0) | −2.0 (−3.0 to 0.0) | .482 |
Data are presented as No. (%) or median (range). Differences between patients aged <70 years and ≥70 years were assessed using the Mann–Whitney U test for nonnormally distributed continuous variables and the Pearson chi-square test for categorical variables.
NRS, numeric rating scale; PSC, patient-specific complaint questionnaire; Δ, change in NRS score between baseline and 1-year follow-up.
Median changes in perceived disability levels for each goal, assessed using a numeric rating scale (NRS; range, 0–10) 1 year after treatment, demonstrated improvement across all five treatment goals in both age groups, with no significant differences between groups (Table 3).
Patient satisfactionPatient-reported satisfaction 1 year after EBV treatment was generally high in both age groups, with slightly greater, although nonsignificant, satisfaction observed among patients aged ≥70 years (Table 4). The item specifically addressing perceived symptom reduction following treatment approached statistical significance (P=.056) in favor of the ≥70-year group. Additionally, more than 90% of patients in both groups indicated that they would recommend the treatment to other patients. Patients aged ≥70 years also tended to report more frequently that treatment met their expectations than patients aged <70 years (Table 4).
Patient satisfaction one year following endobronchial valve treatment.
| <70 years | ≥70 years | P value | |
|---|---|---|---|
| How satisfied are you with the treatment? | n=245 | n=47 | |
| Very satisfied | 126 (51.4%) | 28 (59.6%) | .620 |
| Satisfied | 72 (29.4%) | 15 (31.9%) | |
| Not satisfied/unsatisfied | 30 (12.2%) | 3 (6.4%) | |
| Unsatisfied | 9 (3.7%) | 1 (2.1%) | |
| Very unsatisfied | 8 (3.3%) | 0 (0%) | |
| How satisfied are you with the reduction of your symptoms after treatment? | n=246 | n=45 | |
| Very satisfied | 82 (33.3%) | 17 (37.8%) | .056 |
| Satisfied | 75 (30.5%) | 20 (44.4%) | |
| Not satisfied/unsatisfied | 62 (25.2%) | 4 (8.9%) | |
| Unsatisfied | 18 (7.3%) | 4 (8.9%) | |
| Very unsatisfied | 9 (3.7%) | 0 (0%) | |
| Would you recommend the treatment to other patients? | n=250 | n=47 | |
| Yes | 233 (93.2%) | 43 (91.5%) | .704 |
| Maybe | 14 (5.6%) | 4 (8.5%) | |
| No | 3 (1.2%) | 0 (0%) | |
| Does the result of the treatment fulfil your expectations? | n=243 | n=46 | |
| Completely – 5 | 84 (34.6%) | 20 (43.5%) | .537 |
| 4 | 58 (23.9%) | 12 (26.1%) | |
| 3 | 57 (23.5%) | 7 (15.2%) | |
| 2 | 22 (9.1%) | 5 (10.9%) | |
| Totally not – 1 | 22 (9.1%) | 2 (4.3%) | |
Data are presented as No. (%). Differences between patients aged <70 years and ≥70 years were assessed using the Pearson chi-square test for categorical variables. Fisher exact test was used when assumptions for the chi-square test were not met.
EBV, endobronchial valve.
This study is the first to assess the impact of age on response to EBV treatment in a large real-world population. Our findings indicate that patients aged ≥70 years demonstrated similarly favorable treatment outcomes up to 1 year following EBV placement compared with patients aged <70 years. Notably, there was a slight, although nonsignificant, trend toward greater improvements in exercise capacity and quality of life among the older group. Importantly, adverse events did not occur more frequently among older patients. Additionally, achievement of patient-specific goals was comparable between age groups, with patients aged ≥70 years reporting slightly higher levels of satisfaction with treatment outcomes than patients aged <70 years.
Both age groups demonstrated significant improvements in airflow obstruction and lung hyperinflation, with no significant differences between groups. These comparable improvements in pulmonary function may have been expected because they primarily depend on successful induction of atelectasis. The ability to induce atelectasis is determined by technical success of the procedure, which relies on anatomical feasibility for complete occlusion of all segmental bronchi leading to the target lobe in the absence of collateral ventilation, factors independent of patient age [24].
In contrast, exercise capacity is a multifactorial outcome influenced by physiological systems extending beyond pulmonary function [13]. Elderly patients with similar degrees of airflow obstruction have been reported to experience greater declines in exercise capacity because of reduced cardiac function and decreased limb muscle strength and endurance [25]. Based on this, older patients might be expected to exhibit less improvement in exercise capacity following EBV treatment. Surprisingly, patients aged >70 years demonstrated improvements in exercise capacity comparable to those observed in younger patients, with responder rates approaching statistical significance in favor of the older age group. This finding is consistent with previous pulmonary rehabilitation studies reporting no significant differences in exercise capacity improvements between patients aged 65–74 years and those aged ≥75 years [26].
The subgroup aged ≥70 years comprised a significantly higher proportion of men than the subgroup aged <70 years. This finding is consistent with previous literature, including a study evaluating two large COPD cohorts stratified according to a 65-year age cutoff [27]. That study also reported greater smoking exposure in the older age group, consistent with our observations [27]. Furthermore, the older subgroup in our study demonstrated significantly better baseline pulmonary function. Taken together, these findings suggest that age-based stratification resulted in the formation of two distinct clinical phenotypes. The older group was predominantly male, had a more extensive smoking history, and exhibited less airflow obstruction. In contrast, the younger group included more women, had a less extensive smoking history, and demonstrated greater pulmonary impairment. This pattern may indicate a subgroup of female patients particularly vulnerable to parenchymal lung destruction resulting from cigarette smoke exposure [28,29]. Future research focusing on COPD phenotyping may further clarify these observed differences.
Age was significantly associated with changes in quality of life as measured by SGRQ total scores. However, the magnitude of this association was modest, and the mean difference between groups did not reach the minimal important difference threshold. Nevertheless, age remained a significant independent determinant in multivariable regression analysis. Collectively, these findings suggest that older patients experienced slightly greater, although clinically modest, improvements following EBV treatment.
This finding may be partially explained by previous research demonstrating that older patients with COPD are less likely to report significant impairment in daily activities than younger patients, suggesting a lower perceived disease burden [30]. One explanation may be that younger individuals perceive greater limitations because of increased work and family responsibilities coupled with higher expectations regarding functional status. This perspective may explain why patient-reported quality of life tended to improve more in the older age group. Additionally, this observation is consistent with the finding that patients aged ≥70 years reported slightly greater satisfaction with treatment outcomes than those aged <70 years.
No differences in adverse event occurrence were observed between patients aged ≥70 years and those aged <70 years. This contrasts with findings from lung transplantation and other thoracic surgical procedures, in which older patients generally have a higher risk of poor outcomes and postoperative complications [9,31]. However, a study evaluating anesthetic management during EBV treatment found that general anesthesia and mechanical ventilation were well tolerated, with no catastrophic anesthesia-related events, such as same-day death, cardiopulmonary resuscitation, intensive care unit admission, or reintubation [32]. Although that study did not compare age groups, combined with our findings it supports the conclusion that the minimally invasive nature of BLVR makes EBV treatment safe even among elderly patients. These findings suggest that age alone should not be considered a reason to withhold EBV treatment from older individuals.
The strengths of our study include the large scale and prospective design of our patient registry, supported by a substantial amount of follow-up data extending up to 1 year after EBV treatment. Nevertheless, several limitations should be acknowledged. Baseline characteristics revealed that patients aged ≥70 years had significantly less airflow obstruction, suggesting that older patients selected for treatment may have been in relatively better health and less severely affected by COPD than those aged <70 years. This may have inadvertently introduced selection bias and potentially influenced the observed outcomes. Nevertheless, by analyzing relative changes, accounting for each patient's pretreatment condition rather than relying on absolute values, and adjusting for potential confounders in multivariable regression analyses, we minimized the impact of this potential bias on our findings.
However, it remains possible that frail older patients with multimorbidity were excluded from treatment, thereby limiting the generalizability of our findings to the broader elderly emphysema population. Another limitation is the relatively small sample size of patients aged ≥70 years compared with those aged <70 years, which may have affected statistical power. Additionally, although the use of real-world data offers several advantages, it also entails limitations, including higher rates of loss to follow-up and consequently more missing data, which may have affected our results. However, loss to follow-up was similar between age groups. Finally, comorbidity data were available only for a subset of patients, limiting our ability to fully assess their potential clinical relevance in older patients.
ConclusionsOur results indicate that endobronchial valve treatment provided similarly favorable clinical improvements and comparable safety profiles in older and younger patients. These findings highlight the importance of referring and screening older patients with severe emphysema to assess their eligibility for bronchoscopic lung volume reduction treatment.
Given that alternative interventions, such as lung transplantation and lung volume reduction surgery, are frequently limited by age because of higher complication risks, EBV treatment offers a valuable therapeutic option for appropriately selected older patients, particularly in the context of an aging population and growing demand for effective treatments tailored to elderly individuals.
Authors’ contributionsConcept and design: E.A.M.D.t.H., J.E.H., D.J.S. Data analysis: E.A.M.D.t.H., L.E.v.d.B., A.M., C.H.W.M., S.W.v.R. Patient inclusion and data collection: E.A.M.D.t.H., J.E.H., K.K., S.W.S.A., D.J.S., M.v.D., T.D.K. Project supervision: D.J.S., J.E.H. Manuscript preparation: E.A.M.D.t.H. Manuscript revision: E.A.M.D.t.H., J.E.H., D.J.S., M.v.D., T.D.K., K.K., S.W.S.A., L.E.v.d.B., A.M., C.H.W.M., S.W.v.R.
Ethics statementThe BREATHE-NL registry was determined not to be subject to the Dutch Medical Research Involving Human Subjects Act (WMO) (EC number: 2016/483). Nevertheless, all patients provided informed consent for the use of their data in the registry. As the current study was conducted within the scope of the BREATHE-NL registry, no additional ethical approval was required.
Declaration of generative AI and AI-assisted technologies in the writing processChatGPT version 5.2 was used to review and refine grammar where necessary. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of this publication.
FundingNone declared.
Conflicts of interestD.J.S. reports grants and consultancy fees paid to his institution from PulmonX (USA), MoreAir (USA), Nuvaira (USA), PulmAir (USA), Ryme Medical (USA), and Apreo (USA), all outside the submitted work. K.K. reports speaker fees from PulmonX outside the submitted work. M.v.D. reports speaker fees from GSK and Sanofi outside the submitted work. A.M., C.H.W.M., E.A.M.D.t.H., J.E.H., L.E.v.d.B., S.W.S.A., S.W.v.R., and T.D.K. declared no conflicts of interest whatsoever.
Data availabilityThe data supporting the findings of this study are available from the corresponding author upon reasonable request.
The following are the supplementary data to this article:
