Transforming pulmonary care with applications of endobronchial valves beyond emphysema: a narrative review

Introduction

Endobronchial one-way valves (EBVs) (e.g., Zephyr^®, Spiration^®) are one-way valves placed bronchoscopically into the airways supplying a diseased lobe, allowing air to exit on exhalation while blocking inflow on inhalation. EBVs were originally developed as a bronchoscopic therapy for severe hyperinflation in emphysema, where they induce atelectasis of diseased lung segments to achieve lung volume reduction (1). In this setting, multiple randomized trials have shown that EBVs can improve lung function, exercise capacity, and quality of life in selected chronic obstructive pulmonary disease (COPD) patients (2-5). Apart from this, these valves provide a minimally invasive way to occlude a bronchus, which can help manage prolonged air leaks, complex fistulas, life-threatening haemoptysis, and even cavitary lung diseases. In the United States (U.S.), only the Spiration intrabronchial valve (Olympus, Redmond, WA, USA) is currently authorised for prolonged air leaks after lobectomy, segmentectomy, or lung volume reduction surgery. The Zephyr endobronchial valve (Pulmonx, Redwood City, CA, USA) is U.S. Food and Drug Administration (FDA) approved for bronchoscopic lung volume reduction in severe emphysema has not been evaluated for air leak management, so its use for persistent air leaks (PALs) remains off-label (6).

This review focuses on the evidence for EBVs in non-emphysema indications, summarizing their role in PALs and bronchopleural fistulas (BPFs), haemoptysis, multidrug-resistant tuberculosis (MDR-TB), and other emerging applications. We present this article in accordance with the Narrative Review reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-25-138/rc).

Methods

We searched PubMed, Embase, Scopus, and Google Scholar (January 1, 2000–August 1, 2025) for English-language human studies on EBVs in non-emphysema human studies [PALs, BPFs, haemoptysis, cavitary tuberculosis (TB), and others]. Both medical subject headings (MeSH) terms and free-text keywords, including device brand names (Zephyr^®, Spiration^®), were combined with target conditions. No study design restrictions were applied. Reference lists of key articles were also screened. Titles and abstracts were independently screened, and duplicates were removed. Eligible full texts were retrieved, with discrepancies resolved by consensus. No formal risk-of-bias appraisal was performed due to the narrative scope; findings were synthesized descriptively. The key elements of the strategy are summarized in Table 1 with a detailed PubMed search string in Table 2.

PAL and BPF

A PAL is generally defined as an air leak from the lung lasting more than 5–7 days despite chest tube drainage (7). PALs are typically caused by bronchopleural fistula/alveolopleural fistula. BPF—a persistent communication between a bronchus and the pleural space, often complicating pulmonary resection, can be associated with high morbidity and mortality (8). Traditional management (surgical repair, prolonged chest drainage, pleurodesis) can be risky or ineffective, especially in frail patients (9,10). Since the mid-2000s, EBVs have been repurposed to treat BPFs and other PALs by occluding the affected airway while allowing trapped air to escape (9,10).

Evidence snapshot

Our search identified more than 30 published reports of EBV therapy for PALs, including at least five prospective studies, over a dozen retrospective series, several case series, and numerous case reports. Altogether, more than 4,000 patients have been treated in the literature, with success rates around 75–90% and low complication rates. Most studies are retrospective; prospective trials remain small (typically <40 patients).

Technique

EBV placement is performed via bronchoscopy in a controlled setting (operating room or bronchoscopy suite). The procedure can be done under moderate sedation (11) or general anaesthesia, but many experts prefer general anaesthesia with endotracheal intubation to minimize air leak fluctuations and protect the airway (12). A flexible bronchoscope (typically with a large working channel of 2.8 mm) is used for navigation through the bronchial tree. If general anaesthesia is employed, using an endotracheal tube of size 8.5 or larger is recommended to minimize the risk of reduced ventilation and air leak suppression caused by limited airflow around the bronchoscope (13). A larger tube also minimises tube movements and facilitates easier manipulation of the scope within the airway. Pre-procedure planning includes reviewing chest computed tomography (CT) to identify the likely source lobe or segment of the fistula (8). If a chest tube is in place, the air leak rate can be monitored (often with a digital drainage system) during bronchoscopic manoeuvres. Initial bronchoscopy assesses the airways for inflammation or pus that may need management before valve placement. Ensuring any airway and/or pleural infection is controlled with antibiotics is important before valve therapy (14).

Precise identification of the bronchial segment leading to the fistula is the first critical step. An occlusion test using the Chartis™ balloon is commonly employed: the Chartis™ balloon is passed through the bronchoscope and inflated sequentially in target bronchi (lobar initially to locate the air leak and segmental after the major air leak has been located). A transient reduction or cessation of air leak (observed via the chest tube output or digital monitor) within approximately 15–20 seconds of occlusion indicates the fistula’s source airway (15). The Chartis^® system (Pulmonx) is an adjunct that measures airflow and pressure during balloon occlusion; it not only helps confirm the leaking segment but also assesses collateral ventilation (16). Lack of collateral ventilation in the target lobe predicts that an EBV can effectively induce lobar atelectasis and seal the leak (17). When bronchoscopy and balloon testing are inadequate to locate the BPF, adjunctive methods such as injecting dyes through the chest tube (e.g., methylene blue) can visualise the leaking airway during bronchoscopy and aid localisation (18-22).

Once the target airway is identified, the bronchial diameter is measured to select an appropriately sized valve. The chosen valve is loaded into a delivery catheter. Under bronchoscopic visualization, the catheter is advanced to the target bronchus, and the valve is deployed by pushing it out of the catheter so that it expands and lodges in the airway (23). Proper positioning is confirmed endoscopically—the valve should seat snugly to occlude the lumen. If multiple segmental fistulas are present, additional valves are placed in the same session; however, using the fewest number of valves necessary is preferable (8). After deployment, the air leak is reassessed; successful occlusion often results in immediate reduction of noted air leak in the chest drain (in the form of bubbling via a non-digital drain or reduction in the recorded air leak calculated via a digital drain). At this point, further decisions to deploy or to reposition valves can be made. A chest radiograph is obtained post-procedure to check for re-expansion of the lung, verify valve positions (12), and exclude complications like worsening of pneumothorax. After valve placement, patients are observed for improvement in respiratory status and reduction in air leak.

In complex situations, other personalised approaches with the use of adjuncts, for example, the use of valves combined with sealants, may be required. For instance, the 2024 case report by Liu et al. used placement of an EBV combined with gelfoam to seal multiple BPFs in a ventilated patient and empyema; the air leak ceased immediately, and no recurrence occurred (24). Wadiwala et al. similarly used robotic-assisted bronchoscopy to deliver Histoacryl^® sealant and a Zephyr valve to the right middle lobe in a lung transplant patient with BPF. The pneumothorax cleared in 12 days, and the patient remained asymptomatic ever since (25).

Outcomes

Published evidence indicates that EBV placement is highly effective in reducing or eliminating PALs in most patients. Patients selected for EBV in PAL scenarios are typically high surgical risk or have failed conservative treatment; valves are intended as a bridge to possible more definite treatment or aim to make air leaks more “manageable” so that other treatment measures can work more effectively (17,26).

In a systematic review of 208 patients with PAL, Ding et al. found complete leak resolution within 24 hours in the majority of the patients (17). Gkegkes et al. similarly found that about two-thirds of patients achieved rapid leak closure (6). Damaraju et al.’s meta-analysis of 28 observational studies (2,472 patients) reported an overall success rate of 82% (27). Similarly, the multicentre European case series by Smesseim et al. (66 patients) reported leak resolution within 30 days in 60.6% of their patient cohort (28).

Compiled case series show that immediate or rapid leak cessation is common, often allowing chest tube removal within a few days. For example, Travaline et al. (40 patients) reported that 92% of patients had a significant reduction in air leak (with about 47.5% achieving complete closure) after EBV therapy (29). In that series, most leaks stopped in less than 24 hours, and chest tubes could be removed shortly thereafter. A larger multi-centre study of 75 PAL cases similarly found that 56% of patients had their air leak resolve within one day of valve placement; even among the others, many improved over time with a median of 16 days to leak resolution (range, 2–156 days) (30). Across reports, the typical time from EBV insertion to chest tube removal is around 1–3 weeks, with several studies noting a median of ~7–8 days (8,17). For instance, in a recent single-centre trial of 26 patients with BPFs, Song et al. found EBV treatment had an effective success rate of 73.1%, and the median time to chest tube removal after valve placement was only 7 days (range, 2–90 days) (8). In recent series, the median time to chest tube removal after EBV placement was only about one week, significantly shorter than the pre-intervention duration (8).

Notably, even partial improvement in the air leak can be considered a clinical success, since reducing a large air leak to a “manageable”, as mentioned before, one may permit lung re-expansion and allow the chest tube to be removed. Many reports use composite endpoints of “success” defined by significant leak reduction or removal of chest drain, not necessarily 100% stoppage of air flow (30). In Song et al.’s series, although 73% had complete closure, all remaining patients still derived some benefit (e.g., smaller leak and improved lung expansion) (8). Thus, clinicians should expect that roughly two-thirds to three-quarters of inoperable PAL patients will have their leak sealed completely by EBVs, and most of the rest will improve enough to stabilize or shorten hospitalization.

EBVs have been lifesaving in several high-risk PAL scenarios. Kalatoudis et al. described three critically ill patients on mechanical ventilation with acute respiratory distress syndrome (ARDS) who developed refractory air leaks; bronchoscopic valve placement led to immediate leak cessation in all three, facilitating ventilator weaning and eventual extubation (31). Similarly, during the coronavirus disease 2019 (COVID-19) pandemic, cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia with persistent pneumothorax and air leak have been managed with EBVs as a bridge to surgery. In one report, a COVID-19 patient with a large pneumothorax and continuous air leak (on two chest tubes and a ventilator) underwent EBV occlusion of the left upper lobe after balloon localization—this reduced the leak from high-grade to minimal, enabling extubation 2 days later and chest tube removal soon after (32). The patient then later had definitive surgical bullectomy once recovered from COVID, after the valves were removed (32). A report by Abia-Trujillo and colleagues described bronchoscopic resolution of a broncho-pleuro-spinal-subcutaneous fistula presenting as a painful subcutaneous mass using an endobronchial valve (33). Such examples highlight that EBV therapy can temporize and stabilize complex air leaks in unstable patients who cannot tolerate immediate surgery, and even tracts that extend beyond the pleural space. Table 3 summarizes the key outcomes from clinical studies of EBV therapy for PALs.

Safety

The use of EBVs for PAL is generally very well tolerated. Unlike in emphysema treatment, procedure-induced pneumothorax is not a big concern here (since patients often already have a chest tube in place for the existing air leak). Damaraju et al. found a complication rate of ~9%, while the 2024 European series by Smesseim et al. reported minor complications in only 6.1% (27,28). Patients should be monitored for complications such as fever or new infiltrates suggestive of post-obstructive pneumonia (55); this risk is mitigated by the valve’s one-way design, but vigilant pulmonary toilet and sometimes prophylactic antibiotics are employed. Other potential complications include valve migration (65), granulation tissue formation (27,66), or bacterial colonisation of the pleural space. However, such events are scarce in practice.

Transient hypoxemia can occur if a large portion of the lung is collapsed, but this is usually manageable with supplemental oxygen (17). The most reported procedure-related issues are valve migration or expectoration, and these occur in ~5% of cases (17). Minor complications like a brief increase in sputum or coughing have been noted, but serious adverse events attributable to EBV in PAL patients are rare (17). Post-obstructive infections (pneumonia behind a valve) are possible but infrequent; prophylactic antibiotics are sometimes considered, especially if the treated segment was infected.

To date, no deaths have been attributed to the valve therapy in the literature. Even in the hypothetical situation where death was to occur following valve placement, such an outcome must be weighed against the expected prognosis without EBV intervention. Without EBVs, many patients with persistent BPFs face limited treatment options, often involving high-risk redo thoracic surgery or prolonged chest drainage with ongoing air leaks, which are themselves associated with significant morbidity and mortality. In this context, the use of EBVs can be seen not only as a potentially life-saving measure but also as one that can improve quality of life, shorten hospital stays, and reduce the need for more invasive procedures.

Valve removal

Follow-up bronchoscopy is generally recommended about 4–6 weeks after the procedure (67).

A practical consideration is whether and when to remove the valves after the air leak has resolved. Since these patients are often being “bridged” to recovery or a later definitive surgery, EBVs are typically intended as a temporary measure. Expert consensus is that valves should be removed once the leak has stopped and the chest tube is out (12,17,68). Many centres wait a few weeks (e.g., 4–8 weeks) after air-leak cessation to ensure healing, then retrieve the valves. Removing the devices eliminates any long-term risks of airway foreign bodies (such as granulation tissue or recurrent infection). On the other hand, if a patient is a poor surgical candidate and doing well, some physicians elect to leave the valves indefinitely. Short-term studies suggest this is safe—for instance, in the 26-patient BPF study, 20 patients still had their valves in place at 3–6-month follow-up with no valve-related complications observed (8). The six patients who underwent elective valve removal had the procedure safely under light sedation, with no recurrence of the air leak (8). Thus, the strategy can be individualized: in general, plan to retrieve the valves after a couple of months, but if the patient would not tolerate another procedure, or the clinical indication does not mandate removal, the valves can be left in place with careful monitoring. Overall, EBVs have proved to be a safe, effective, and reversible tool for managing PAL/BPF, often obviating the need for risky re-operations in frail patients (17).

Valve removal is usually straightforward: using a bronchoscope and forceps, the valve is grasped and withdrawn, typically under anaesthesia to protect the airway during extraction (13). Removing the valves in a timely fashion helps reduce long-term infection risk and bronchial wall reaction, especially since the devices are intended as a temporary bridge to healing.

Haemoptysis control

Severe haemoptysis is another challenging situation where EBVs have shown promise. Massive or recurrent haemoptysis—whether due to malignancy, TB, or other lung diseases—is traditionally managed by bronchial artery embolization (BAE) and/or ablative bronchoscopic methods (like electrocautery and argon plasma coagulation) (69). In cases where bleeding continues despite embolization or when surgery is contraindicated, bronchoscopic valve placement can serve as a rescue therapy to tamponade the haemorrhage. By occluding the bronchus leading to the bleeding source, the affected lung region collapses, which both physically plugs the bleeding site and reduces pulmonary arterial blood flow via reflex hypoxic vasoconstriction (69). Essentially, an EBV can induce an “autologous tamponade” of the haemorrhaging lobe, allowing clots to form and bleeding to stop (69).

Evidence snapshot

Evidence for EBV use in massive haemoptysis is limited to case reports; no prospective or retrospective series exist. We found five publications describing 6–8 patients (mainly with TB cavities or tumours) in whom EBV placement stopped life-threatening bleeding when embolization or surgery were not feasible. All reported successful haemostasis and subsequent definitive management, but the evidence base remains anecdotal.

While no large trials exist, there are multiple compelling case reports of EBVs controlling life-threatening haemoptysis in situations where other measures failed. Solis Solis et al. describe a 29-year-old man with recurrent massive haemoptysis from tuberculous lung cavities (with aspergilloma colonization). He had six embolization sessions with only temporary relief. As a last resort, two Spiration™ valves were placed to block the apical and lingular segmental bronchi of the left upper lobe (where the cavities were located). This resulted in the immediate cessation of haemoptysis; the patient had no further bleeding for 6 months and was later able to undergo a definitive left pneumonectomy in a much-improved condition (69). Similarly, Koegelenberg et al. reported a case of haemoptysis from a TB cavity with an aspergilloma—two valves (one in each upper lobe) effectively stopped the bleeding, bridging the patient to a more elective surgical resection later (70). In another instance, Lalla et al. used a Zephyr™ valve in a human immunodeficiency virus (HIV)-positive patient with active TB and haemoptysis; the valve was removed after 6 months once the infection was controlled, with no recurrence of bleeding (71). These demonstrate success in benign disease contexts (TB cavities, fungal colonization, etc.), where the EBV can be a true temporizing measure until the underlying condition is treated.

EBVs have also been used in malignancy-related haemoptysis. Patel et al. published two cases: one patient with squamous cell lung carcinoma causing massive haemoptysis, and another with an oesophageal cancer invading the lung and bronchus. In both, Spiration™ valves were placed into the bleeding lobe bronchi, immediately controlling the haemorrhage; neither patient had recurrent haemoptysis during the short-term follow-up (72). In such malignant cases, an EBV may be left in place permanently either as a palliative measure, if the patient is not a candidate for resection of the tumour, or can be removed during later resection surgery.

Outcomes

All published cases to date report successful cessation of haemoptysis following EBV deployment, which is remarkable given these were often “last-ditch” efforts. Patients typically stabilize hemodynamically once the bleeding lung is collapsed. The valves essentially convert an emergent situation into a semi-elective one—for benign aetiologies like TB or fungus, they allow time for medications to sterilize the lesion before valve removal, and for cancers, they palliate symptoms while more definitive therapy (or hospice care) is arranged. The physiological mechanism has been described as a combination of lobar atelectasis causing tamponade (directly blocking blood from leaking into airways) and reduced perfusion (via hypoxic vasoconstriction in the collapsed region) (69). This dual effect helps achieve haemostasis without resorting to lung resection in an acutely bleeding patient.

Safety in haemoptysis cases appears favourable. By avoiding thermal modalities (like laser or cautery), EBVs eliminate the risk of airway fire in an oxygen-rich environment. They also do not cause additional injury to friable tumour or cavity tissue. One concern is whether blocking a bronchus in an infected TB cavity, for example, might precipitate post-obstructive pneumonia. In reported cases, this has not been a major issue, likely because the treated lung was already largely non-functioning or cavitary. Short-term complications have not been noted, and in cases where the aetiology is reversible (e.g., TB responding to therapy), the valve has been removed after a few months with no bleeding recurrence (69). If the cause is irreversible (like an inoperable cancer), the valve can remain indefinitely as part of palliative management (69). The main limitation is that this approach is applicable only when the bleeding source can be reasonably localized to a lobe or segment. In diffuse pulmonary haemorrhage, valves would not be beneficial. But for focal catastrophes—even in distal lung areas that aren’t reachable by cautery, valves provide a unique option. In summary, while data come from case reports, EBV therapy has potential in treatment of haemoptysis, offering a bridge to definitive treatment or a meaningful palliative benefit in otherwise hopeless situations.

Cavitary MDR-TB

One of the most intriguing new applications of endobronchial valves is in the treatment of cavitary MDR-TB. Cavitary TB lesions can maintain high bacterial loads and often respond poorly to antibiotics alone, in part because cavities allow ongoing communication between infected tissue and airways. Interventions like surgical resection of cavities or artificial pneumothorax (collapse therapy) have been employed to help close cavities and hasten sputum conversion. EBVs essentially offer a modern bronchoscopic way to collapse infected lobes without surgery. By occluding the airway supplying a tuberculous cavity, the cavity can be collapsed, and eventually, fibrosis can seal it off, all while the patient continues standard drug therapy.

Evidence snapshot

For cavitary MDR-TB, there is one randomised controlled trial (n=102), one prospective observational study (n=35), one non-randomised observational series (n=74), a small case series (n=5), and one published case report (n=1)—together enrolling about 217 patients.

Clinical trials

Remarkably, there have been randomized trials investigating this approach. Levin et al. conducted a controlled study in Russia with 102 patients who had destructive MDR-TB cavities in their lungs (73). One group (49 patients) received EBV placement plus second-line anti-TB chemotherapy, while the control group (53 patients) received chemotherapy alone. The results were notable: at 3 months, 95.9% of the EBV group had achieved sputum culture conversion (from positive to negative) compared to only 37.7% of the control group (P<0.0001) (73). Similarly, chest imaging showed far higher rates of cavity closure in the EBV-treated patients (in roughly two-thirds of cases) versus about 20% in controls by 3 months. After a median occlusion time of about 6 to 7 months, the valves were removed when the cavities had closed; at the 3-year follow-up, 80.5% of patients in the EBV group met the World Health Organization criteria for cure of TB, compared to just 25.0% of the control patients (73). Conversely, disease progression or treatment failure was far more common in the control arm. These differences highlight how beneficial inducing lung collapse can be in refractory TB: by quickly reducing bacterial burden and removing a nidus of infection, valves give drugs a much better chance to work.

Similar findings came from a Chinese study by An et al. (74). In that single-arm trial, 35 patients with cavitary MDR-TB received EBV implants in addition to individualized TB medications. The EBVs led to radiographic cavity size reduction in all patients, with complete cavity closure in 68.8% of cases (74). Impressively, 100% of patients had sputum culture conversion to negative, and this was typically achieved within weeks of the valve placement. No severe adverse events were reported in this cohort. Although this was not randomized, the 100% conversion rate is well above historical controls for MDR-TB therapy alone, again suggesting a major therapeutic benefit.

In a large Russian case series of 74 patients, Popova et al. explored EBV therapy using locally designed valves, with a focus on pulmonary function changes. EBVs were placed to achieve cavity closure in chronic cavitary TB; notably, they observed that patients with normal baseline lung function often experienced some transient functional decline post-EBV (due to loss of ventilated volume), whereas those with poor baseline function tended to show improvement in overall lung function after EBV-induced collapse (75). Despite these physiological changes, the EBV procedure was considered safe and became widely implemented in over 200 TB centres in Russia as a standard adjunct for difficult cavities (75). This broad experience reinforced the feasibility of EBV “bronchial blocking” in routine MDR-TB care.

The high sputum-culture conversion rates reported in the above studies should be interpreted with caution because of the small sample size. Nevertheless, endobronchial valves do not ‘seal off’ a segment entirely; they maintain a one-way lumen that allows mucus and sputum to drain. In the randomized Russian trial, culture conversion was defined by three consecutive negative cultures spaced ≥30 days apart and valves were removed only after sustained conversion. These design features make it unlikely that conversion was solely due to lack of sputum from the treated lobe. Even so, long-term recurrences were documented (~5% of patients relapsed despite initial conversion), underscoring that EBV therapy should be viewed as an adjunct rather than a curative monotherapy.

Tolerability and management

EBV implantation in TB cavities appears to be safe and well-tolerated. In Levin’s study, they noted some minor symptoms (like transient cough in ~25% of patients and low-grade fever or mild dyspnoea in <10%), but these were self-limited, and no procedure-related deaths occurred. Importantly, valves can be removed once the disease is controlled—in Levin’s series, valves were left in for a median of about 6–7 months, and in the subset of patients where they were removed (after cavity closure), none had TB recurrence during follow-up (76). This indicates that valve removal is feasible and does not lead to re-opening of cavities once adequate healing and sterilization have occurred. A small percentage of patients may experience issues like valve obstruction or localized inflammation (in one report, ~14% had some device-related complication), but those cases were managed by simply removing the valve earlier. Overall, the risk-benefit profile is favourable: given the life-threatening nature of extensive MDR-TB, the procedural risks are low in comparison.

Implications

The success of EBVs in MDR-TB presents a potential paradigm shift. By achieving rapid sputum negativity and cavity closure, EBVs can reduce infectiousness and possibly shorten the duration of chemotherapy needed (76). Faster cavity closure might also lower the risk of developing additional drug resistance (since persistent cavities under drug pressure are a breeding ground for resistant mutants). Patients who otherwise might require a thoracotomy and lobectomy to remove a cavity might avoid surgery entirely if valves can collapse it instead. Of course, this approach is still in its infancy. The evidence, while compelling, comes from limited settings, and the availability of valves in high TB-burden countries is a challenge (76).

Table 4 summarizes the clinical studies on EBV for cavitary MDR-TB.

Other emerging applications

Evidence snapshot

A handful of case reports and small series describing EBV use in niche situations—such as refractory air leaks in patients on extracorporeal membrane oxygenation (ECMO) or with acquired immunodeficiency syndrome (AIDS)-associated pneumothorax. These reports collectively include fewer than 15 patients and demonstrate that EBV placement can facilitate weaning from mechanical ventilation or ECMO when other measures fail. However, robust data are lacking, and these cases should be considered experimental.

EBVs in lung cancer patients

Many patients in the PAL/BPF case series had underlying lung cancer or were post-lung resection (lobectomy, pneumonectomy) for tumours. The same principles apply as in other BPFs—the surgeon or interventional pulmonologist localizes the stump leak and deploys valves to occlude it. Notably, deploying valves does not preclude further cancer therapy. Tumour recurrence or new lesions can still be managed: for instance, one case required removing a valve to bronchoscopically biopsy a suspicious lesion that later proved to be lung cancer (79). Once the diagnosis was made, the patient proceeded to surgery. In general, prior EBV placement does not seem to complicate subsequent lung resections. In the same report, eight patients underwent lung cancer resection after having EBVs placed for emphysema lung volume reduction (79). All surgeries (wedge resections, a lobectomy, and a segmentectomy) were successful with no unusual intraoperative findings and no major postoperative complications (79). Lung function improvements from the valves made the patients better surgical candidates, and importantly, removing the valves and operating did not cause any significant loss of lung function postoperatively (79). This demonstrates that EBV therapy can be an adjunct to optimize high-risk lung cancer patients (improving their COPD status pre-surgery) and can be safely reversed to allow curative surgery when needed.

Iatrogenic air leaks, such as those from percutaneous lung tumour ablation (radiofrequency or microwave ablation) or even persistent pneumothorax after transbronchial lung biopsies, have been treated with EBVs in select instances. Alexander et al. reported successful use of valves to treat BPFs that developed after thermal ablation of lung tumours (80). This hints at a role for EBVs in interventional radiology complications—an area that might expand as ablative therapies for lung nodules become more common.

Pneumothorax in advanced lung disease

Beyond COVID-19 cases mentioned earlier, valves have been tried in other complex scenarios like persistent pneumothoraxes in cystic fibrosis, Pneumocystis pneumonia, or other settings where fragile lung tissue won’t seal on its own (15,81). For example, one report described EBV closure of an alveolopleural fistula in cystic fibrosis that persisted despite chest tube drainage (81). Another complicated case involved a patient with Cryptococcus pneumonia and AIDS who had a stubborn air leak, successfully managed by valve insertion when surgery was not an option (15). These are essentially extensions of the PAL indication into specific disease contexts. Each case reinforces the concept that when faced with a prolonged air leak in a patient who is a poor surgical candidate, placing of an EBV should be considered since the odds of success are reasonably high, and the risk is low.

One-lung ventilation facilitation

There have been exploratory uses of EBVs in critical care settings to intentionally collapse a lobe or even an entire lung as a means of facilitating one-lung ventilation in complex scenarios (31,82). This strategy is particularly relevant in cases of severe unilateral lung injury or BPF associated with acute ARDS, where occluding the affected lung with EBVs effectively isolates it and allows ventilation of the contralateral, healthier lung (82). Such an approach has been described in critically ill patients on mechanical ventilation (and even on ECMO) to reduce massive air leaks and improve oxygenation when conventional methods fail.

For example, Ghiani et al. [2018] reported the bedside deployment of two EBVs in a patient with ARDS and a PAL on veno-venous ECMO (VV-ECMO), which led to immediate lung re-expansion and subsequent liberation from both ECMO support and mechanical ventilation (83). Similarly, a 2023 case series of mechanically ventilated COVID-19 patients with refractory air leaks (most on VV-ECMO) found that EBV placement resulted in immediate cessation of the air leak, enabled chest tube removal, and that 80% of these patients survived to hospital discharge (82). While this remains a highly specialized and niche application of EBVs, early anecdotal and observational evidence suggests it can be a valuable adjunct in select intensive care unit (ICU) patients with complex air-leak physiology, especially when conventional surgical or ventilatory interventions are not feasible or have failed (Table 5).

Limitations

As a narrative review, this article does not follow a systematic search protocol, and thus may not capture all relevant literature on the topic. The inclusion of studies was based on author discretion and relevance to the clinical questions, which introduces potential selection bias. Additionally, much of the evidence supporting the off-label use of endobronchial valves in non-emphysema indications comes from case reports, small series, or retrospective analyses, limiting the generalizability and strength of conclusions. The lack of randomized controlled trials in many of these areas means that causality cannot be firmly established, and publication bias may have influenced the representation of favourable outcomes. Future prospective studies and randomized trials are needed to validate and expand upon these findings.

Conclusions

EBVs, once developed purely for emphysema lung volume reduction, have evolved into a multi-purpose tool in pulmonary medicine. For PALs and BPFs, EBVs are now an established management option, with high success rates. In massive haemoptysis, EBVs provide a novel method to achieve airway control and haemostasis when other interventions fail, effectively collapsing the bleeding lung segment in life-saving situations. In cavitary MDR-TB, bronchoscopic valves have shown unprecedented improvements in sputum conversion and cure rates by collapsing cavitated, drug-resistant lesions, suggesting a promising adjunct to antibiotic therapy. Additionally, a range of miscellaneous uses—from managing post-transplant fistulas to aiding lung cancer patients with poor lung function—underscore the broad potential of these devices.

Several consistent themes emerge from the literature: EBV therapy is generally safe, minimally invasive, and does not burn bridges for future treatments. Complications are relatively infrequent and usually manageable. Another strength is the speed of action—many air leaks stop and many bleeds cease immediately upon valve deployment, which is critical in acute care scenarios. Future research should include formal studies comparing EBV therapy with established treatments for PAL and exploring its role in haemoptysis and multidrug-resistant TB. Technological innovations such as drug-eluting or bioabsorbable valves may improve safety and efficacy, and international collaboration will be important to broaden access to EBV technology.

In summary, the role of one-way endobronchial valves has expanded well beyond emphysema. These devices exemplify the trend toward non-surgical interventions in pulmonary disease. EBVs now serve as a critical part of the armamentarium for interventional pulmonologists and thoracic surgeons, offering hope in clinical situations that previously had limited solutions. EBV therapy’s continued evolution is an excellent example of medical innovation repurposing a technology from one disease to effectively tackle many others.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-25-138/rc

Peer Review File: Available at https://atm.amegroups.com/article/view/10.21037/atm-25-138/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-25-138/coif). V.K. serves as an unpaid editorial board member of Annals of Translational Medicine from December 2025 to December 2027. 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.

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