Version May 2024
INTRODUCTION — A pathologic connection between the main stem, lobar, or segmental bronchus and the pleural space is termed bronchopleural fistula (BPF). It is a source of morbidity and mortality in patients, particularly those who undergo lung resection.
This topic will review the etiologies, diagnosis, and treatment of patients with BPF. The diagnosis and management of tracheoesophageal and alveolopleural fistula are discussed separately. (See "Tracheo- and broncho-esophageal fistulas in adults" and "Alveolopleural fistula and prolonged air leak in adults".)
DEFINITION — BPF refers to fistula between major, lobar, or segmental bronchus and the pleural space. Alveolopleural fistula is a communication between the lung parenchyma (distal to the level of the subsegmental bronchus) and the pleural space.
ETIOLOGY
Lung resection — BPF (picture 1) is most commonly encountered after lung resection surgery (pneumonectomy, lobectomy, segmentectomy), with a frequency ranging from 1.5 to 4.5 percent after pneumonectomy and 0.5 to 1 percent after lobectomy and sublobar resection [1]. Several risk factors are associated with BPF in the postoperative setting [2-6]:
●Right-sided surgery
●Pneumonectomy
●Chemotherapy and radiation therapy
●Diabetes mellitus
●Heavy smoking
●Chronic obstructive pulmonary disease
●Low nutritional status or poor wound healing
●Previous ipsilateral thoracotomy
●Residual tumor at the bronchial margin
●A large diameter bronchial stump (>25 mm)
●Extensive lymph node dissection
●Older age (>60 years)
●Male sex
●Prolonged postoperative mechanical ventilation
The development of BPF may be influenced by the bronchial closure technique (manual versus stapled), although this is controversial [7,8].
Others — Other causes of BPF are uncommon. These include complications of treatments for malignancy including chemotherapy, radiation therapy, and chest trauma [9-11]. A meta-analysis reported that neoadjuvant chemotherapy alone did not increase the risk of BPF in patients with lung cancer. However, neoadjuvant radiotherapy alone or chemoradiotherapy significantly increased the risk of BPF [12]. Occasionally, bacterial, tuberculous, or fungal infection and, rarely, inflammatory reactions (eg, organizing pneumonia) extend into the pleural space, creating a BPF [13,14]. In cases of malignant- or infectious-related BPF, the bronchus is typically involved with disease, making these patients less attractive as candidates for surgical repair of the fistula. (See 'Post-lung resection' below.)
CLINICAL FEATURES — Patients with BPF can present with symptoms that range from acute symptoms of tension pneumothorax to subacute symptoms of empyema.
Most patients present in the first two weeks (<14 days) following lung resection, but the exact proportion is unknown. BPF should be suspected in the postoperative lung resection patient who presents with sudden onset of dyspnea, chest pain, hemodynamic instability, and subcutaneous emphysema (ie, symptoms of a tension pneumothorax). Symptoms may be less abrupt in those in whom the chest tube is still in place and a large persistent or new air leak through the chest tube drainage system may be the only sign present [9,15]. Examination findings are typically nonspecific but may reveal reduced air entry on the affected side and tracheal deviation if a tension pneumothorax is present. (See "Clinical presentation and diagnosis of pneumothorax".)
Patients who present in the late postoperative period (>14 days) or patients with BPF from other causes (eg, infection or malignancy) often present with symptoms and signs of empyema including fever, malaise, muscle wasting, and cough with purulent sputum (often high in volume due to drainage directly from the pleural space) as well as reduced air entry and dullness to percussion on the affected side. (See "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults", section on 'Clinical features'.)
In rare cases, when the BPF is associated with empyema that is not adequately drained, the infection can erode through the chest wall and a pleurocutaneous opening with drainage of mucopurulent material may be seen (empyema necessitans) (figure 1).
DIAGNOSTIC EVALUATION — The diagnosis of BPF is made using a combination of clinical, radiographic, and bronchoscopic findings that confirm an air leak from a major, lobar, or segmental bronchus to the pleural space. There are no specific laboratory findings, although some patients with an infected pleural space (due to the BPF) may have a leukocytosis or elevated erythrocyte sedimentation rate. (See "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults", section on 'Clinical features'.)
Imaging — While imaging features are often apparent on chest radiograph, they are better appreciated on chest computed tomography (CT). In the post-lung resection patient, these include (image 1):
●Pneumothorax including signs of tension pneumothorax (eg, contralateral mediastinal shift; features of tension may be absent if a chest tube is in place) (see "Clinical presentation and diagnosis of pneumothorax", section on 'Diagnostic imaging')
●Pneumomediastinum and/or subcutaneous emphysema
●Failure of the postpneumonectomy space to fill with fluid (typically takes one to four months after surgery) or decreasing air-fluid level over time (>2 cm)
●Presence of air bubbles around the surgical site or bronchial stump
●Visualization of the fistula
In those who have not undergone lung resection (eg, malignant BPF), features of the underlying etiology (eg, cavitating mass, air-fluid levels) may additionally be found.
Chest CT, especially with three-dimensional construction, is also useful for localization of the fistula with one study reporting that BPF was localized using CT in 55 percent of patients (image 1) [16].
Bronchoscopy — Bronchoscopy is critical for the diagnosis and localization of BPF (picture 1). Bronchoscopy additionally allows proper evaluation of the surgical site, assessment of fistula size, and exclusion of other etiologies. Bronchoscopy might show a mucosal defect, bubbling at the surgical site when saline is instilled or localization of the BPF by instillation of methylene blue into the pleural space through the chest tube with simultaneous bronchoscopic visualization of dye in the tracheobronchial tree. However, a defect may be difficult to appreciate if there is significant tissue swelling. While a large BPF is more likely to be seen on bronchoscopy, sequential balloon occlusion of the bronchi is sometimes used, particularly for the localization of a smaller or segmental (ie, more distal) BPF, the details of which are discussed separately. (See "Alveolopleural fistula and prolonged air leak in adults", section on 'Localizing the air leak (sequential balloon occlusion)'.)
Differential diagnosis — In patients who have had lung resection (especially pneumonectomy), acute findings of tension pneumothorax are almost pathognomonic of BPF. Although other conditions such as postoperative tension chylothorax or hemorrhage into the pleural space may also cause the findings of tension, the affected hemithorax should fill with fluid rather than air. Acute symptoms of tension may also be due to a displaced or blocked chest tube; ensuring a patent chest tube drainage system (eg, placing it to wall suction, removing debris using saline, repositioning, or replacement) while imaging is being obtained may distinguish this phenomenon from true BPF.
Although a fall in the postpneumonectomy fluid level is considered a sign of a BPF, a few patients may have a condition described as the benign emptying of the postpneumonectomy space (BEPS). To make a diagnosis of this condition, all patients should undergo an exhaustive evaluation and fulfill the following criteria:
●Asymptomatic with no fever
●Leukocytosis
●Fluid expectoration
●Negative pleural fluid culture
●No evidence of BPF on bronchoscopy and/or ventilation scintigraphy
Most BEPS cases occurred between 5 and 152 days and did not require intervention. This condition is thought to be a result from postoperative intrapleural pressure shifts with or without microscopic BPF that promote exit of pleural fluid without concomitant contamination of the pleural space [17].
In those who present with the findings of empyema, features that favor BPF as a cause of the empyema include the presence of air in the effusion and the presence of an air leak after chest tube placement. Culture of the effusion may help distinguish anaerobic infection (as a cause of air in the effusion) from BPF. (See "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults".)
Clinicians frequently confuse BPF with the term alveolopleural fistula (APF), which is a communication of the lung parenchymal distal to the level of the subsegmental bronchus and the pleural space. APF also occurs in the post-lung resection setting, but treatment is significantly different. (See "Alveolopleural fistula and prolonged air leak in adults".)
Ultimately, bronchoscopic findings of a bronchial defect will distinguish BPF from other competing etiologies.
MANAGEMENT AND PROGNOSIS
Our approach — There is a paucity of data and no consensus or guidelines on how best to manage BPF. Significant variation among clinicians exists, but practice is evolving as expertise in interventional pulmonology grows. The approach outlined here is influenced by our expertise in interventional pulmonology, and we recognize that this strategy may not always be universally applied, particularly when interventional expertise is not available.
BPFs do not typically spontaneously undergo closure and almost always require some type of surgical or bronchoscopic intervention such that a multidisciplinary discussion is warranted for all patients (image 1 and algorithm 1). Since most BPFs occur early in the postoperative period and are not infected, most patients undergo surgical repair with excellent success. Bronchoscopic approaches have variable success rates and are appropriate for those who are not suitable for surgical intervention including patients who present with septic shock and severe hypoxemia as well as patients who present on mechanical ventilation, patients in whom surgery is risky, and patients in whom a bridge to surgery is needed [9].
General supportive care — The following therapies should be performed, when indicated:
●Chest tube (minimize suction) – The first intervention for BPF should be drainage of air (and fluid) from the pleural space by chest tube thoracostomy (if not already in place), which is usually placed in supradiaphragmatic/midaxillary line under ultrasound guidance. In most cases, low wall suction (5 to 10 cm H2O) is applied or left on water seal alone and, in some cases (to avoid inadvertent shift of the mediastinum in postpneumonectomy cases), more than one tube is required. Pleural fluid should be sent for cell count, pH, total protein, lactate dehydrogenase, glucose, cytology, triglycerides, Gram stain, and culture (in blood cultures bottles) to assess for or rule out concomitant pleural infection.
●Assess and treat for potential pleural space infection – While not every patient has empyema, the following is appropriate (see "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults"):
•Broad-spectrum intravenous antibiotics against gram-positive, gram-negative, and anaerobic microorganisms should be given to all patients until Gram stain, cultures, and sensitivities are available.
•Intrapleural enzyme therapy may be appropriate for patients with infected multiloculated effusions where the chest tube is unable to completely drain the pleural cavity.
•Postural drainage – Although this is not our routine practice, some patients might also undergo postural drainage with either head-up (reverse Trendelenburg) or head-down (Trendelenburg) position based on the cavity being subsequent to prior upper or lower lobectomies. If postural drainage is performed, there are some prerequisites that need to be fulfilled to prevent contralateral spillage of infection:
-The patient should be able to expectorate
-Complete drainage of chest cavity and chest tube drainage should be <30 mL/day
-Technique is done with concomitant pleural irrigation [14]
●Maximize nutrition and treat medical comorbidities – Patients should receive adequate nutrition, and therapy for comorbidities should also be optimized.
●Optimize mechanical ventilator settings – For patients who are mechanically ventilated, lowering the level of positive pressure and selective intubation of the healthy lung is appropriate, the details of which are discussed separately. (See "Diagnosis, management, and prevention of pulmonary barotrauma during invasive mechanical ventilation in adults", section on 'Ventilator management'.)
One retrospective case series of 13 patients with BPF due to a variety of causes reported that a conservative approach of chest tube and postural drainage (and debridement in two cases) resulted in fistula closure in all patients, although chest tubes remained in place for well over a month in many cases and up to three months in some cases [14]. However, in our opinion, it is not advisable for patients to undergo prolonged periods of conservative management unless other options are not available.
Because most patients develop BPF as an early complication of their lung resection and do not have empyema, most can generally go directly to surgery. In contrast, those who develop BPF late and have empyema or those who develop the fistula as a complication of suppurative pleuropulmonary diseases are initially managed medically for two to four weeks before surgical repair can be considered. (See "Management and prognosis of parapneumonic pleural effusion and empyema in adults".)
Post-lung resection
Surgical repair (curative) — Most patients who develop BPF following lung resection, particularly those who develop BPF in the early postoperative period (<14 days), should undergo surgical repair provided that the patient is fit for surgery, the bronchial stump is not diseased, and postoperative extubation is expected. Usually, early dehiscence tends to be more amenable to immediate repair or stump revision, whereas late dehiscence can be more technically challenging to repair because of diminished tissue quality, development of a matured fistula tract, and significant pleural contamination and scarring. In patients who are on mechanical ventilation for significant hypoxia or hemodynamic instability, it is generally preferable to wait until they are extubated since positive pressure ventilation might interfere with stump healing. Thus, patients should be assessed medically for surgical risk and for any evidence of disease at the bronchial stump (eg, histologic evidence of malignancy at the resection margin) that might interfere with adequate healing. (See "Preoperative physiologic pulmonary evaluation for lung resection".)
Surgical repair involves revision of the stump with debridement of necrotic tissue and suture reclosure of the bronchial stump with vascularized flap tissue such as omentum or muscle [18]. In most cases, a video-assisted thoracoscopic surgical approach is performed but, rarely, a thoracotomy is needed.
For those who present later in the postoperative course (>14 days), surgery is generally indicated but may need to be delayed if the patient requires therapy to treat a complicating empyema or improve their physical strength and nutritional status. In such cases, some experts continue general measures (see 'General supportive care' above), while others choose bronchoscopic therapies as a bridge to surgery (see 'Non-lung resection patients (bronchoscopic intervention)' below). In patients with small fistulas (<8 mm), each strategy may theoretically result in fistula closure; however, we prefer bronchoscopic methods based upon the rationale that this approach likely eliminates lengthy periods of hospitalization and reduces morbidity in this population.
In patients who are unable to tolerate bronchial stump revision or if early repair fails, open-window thoracostomy (OWT), such as the Eloesser flap or Clagett procedure, should be considered as adequate drainage allows most BPFs to close over time. The duration of OWT usually depends on response to antibiotic therapy, obliteration of the empyema cavity, and nutrition status [19]. Also, OWT can be paired with vacuum-assisted closure devices to improve wound care and healing time [20]. Furthermore, some case series have shown that thoracoscopic debridement and stump revision are successful in managing BPF and thus avoid OWT in many patients [21-23].
Patients not surgical candidates — For postoperative patients with BPF who are at high risk for surgery (eg, suppurative pleuropulmonary disease, hemodynamic instability, severe hypoxemia), patients who need a bridge to surgery, or patients with advanced malignancy, bronchoscopic management is typically indicated. (See 'Non-lung resection patients (bronchoscopic intervention)' below.)
Non-lung resection patients (bronchoscopic intervention) — In general, patients with BPF for reasons other than lung resection (eg, those directly caused by malignancy and infection) are treated with bronchoscopic methods since in most cases, the bronchial stump is affected by disease and therefore stump revision is not feasible (eg, advanced malignancy). Bronchoscopic management is largely targeted at temporary fistula closure but can be used as a bridge to curative surgery in the event that the underlying cause is reversible. There is no single method that is superior. Selecting one method over another should be individualized and depends upon clinician expertise and fistula size. In general, outcomes are variable, with rates of successful closure ranging from 30 to 80 percent [24-26]. Interventional pulmonary expertise is required for the methods described in this section.
Fistulas ≥8 mm — In our experience, fistula closure with airway stents, coils, or Amplatzer devices are options in patients with larger BPFs (eg, ≥8 mm). If any of these techniques are performed, close follow-up is recommended to help identify complications and reassess possible removal if fistula closure is suspected. (See "Airway stents", section on 'Complications' and 'Fistulas <8 mm' below.)
Stents — Multiple case reports have described the successful use of silicone and covered metallic stents for BPF closure involving the central airway (ie, larger BPFs) [27-31]. Factors that affect stent selection are discussed separately. (See "Tracheo- and broncho-esophageal fistulas in adults", section on 'Airway stent'.)
Coils — Case reports suggest that angiographic coils, alone or in combination with other occlusive materials, can successfully treat BPF [32-35].
Amplatzer device — This device (two discs that sit on either side of the defect) is designed for atrial septal defect, patent foramen ovale, or vascular plug closure. Although not approved for this indication, they have also been used to successfully close BPFs, including large BPFs in the central airway [35,36]. The largest case series of 31 patients with BPF reported that these devices were effective in 96 percent of cases, lasting for up to 18 months [36]. These devices offer promise as therapeutic tools for BPF closure but remain investigational, and experience is limited.
Fistulas <8 mm — While stents, coils, and Amplatzer devices can be used to seal smaller fistulas, other methods have also been reported as successful and are considered less invasive, making them suitable for closing small fistulas, among which occlusive materials are the most commonly employed.
Occlusive materials — There have been several case series and reports of patients with BPF who were treated with occlusive materials, none of which have been compared. These include methyl-2-cyanoacrylate, N-butyl-cyanoacrylate, albumin-glutaraldehyde tissue adhesive, polyvinyl alcohol sponge, and fibrin glue (alone or with other adjuncts such as spongy calf bone fragments), all of which have been used to seal BPF with higher success rates in smaller fistulas [24,37-45].
In general, occlusive material should be injected through a catheter passed inside the working channel of the bronchoscope since they all have the potential to occlude and damage the bronchoscope.
Others — Several other methods have been described for the closure of small BPF:
●Sclerosants – A few case series have reported successful closure of small BPFs using endobronchial injection of ethanol, polidocanol, and tetracycline followed by autologous blood [46-48].
●Ablative therapy – Argon plasma coagulation and neodymium-doped yttrium aluminum garnet (Nd:YAG) laser have been described for patients with small BPF with very limited experience [49,50]. In our opinion, excessive care should be taken not to risk enlarging the fistula and for this reason, we do not in general recommend using such therapy. (See "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and "Bronchoscopic laser in the management of airway disease in adults".)
●Endobronchial valves – Cases of fistula closure with endobronchial valves [51,52] have been reported.
●Others – Transplanted bone marrow-derived mesenchymal stem cells [53,54] and dehydrated amniotic membrane allograft [55] have been reported as successful in the closure of BPFs but are investigational therapies only.
FOLLOW-UP — Most patients should be monitored after fistula closure for clinical symptoms of recurrence, chest tube output of air, and chest imaging (chest radiography and occasionally CT of the chest). Patients in whom the fistula is sealed should not have an air leak, and imaging should demonstrate stability or resolution of air in the pleural space. Repeat bronchoscopy is not routine and only performed if fistula recurrence or a complication is suspected (eg, stent migration). Also, if valves or stents are used, a chest CT scan and bronchoscopy are repeated at six weeks to assess for complications and/or possible removal if fistula closure is suspected.
REFRACTORY PATIENTS — For patients who fail surgical or bronchoscopic intervention, options include repeat surgery, an alternate bronchoscopic method, or in rare cases, an open-window thoracostomy such as Eloesser flap thoracostomy or a Claggett window. An Eloesser flap is a U-shaped incision and the resection of a number of subjacent posterolateral ribs; the U-shaped flap is then folded into the pleural space, creating a permanent communication. A Clagett window is the resection of a posterolateral lower rib and the formation of an open window in the lateral aspect of the chest to allow continuous drainage and irrigation of the cavity.
PROGNOSIS — BPFs are associated with significant morbidity and a mortality that ranges from 21 to 71 percent in the setting of postpneumonectomy empyema [21]. Since most BPFs occur early in the postoperative period and are not infected, most patients undergo surgical repair with excellent success. Bronchoscopic approaches have variable success rates, and prognosis may be determined by the underlying illness or morbid state that prevents surgery. (See 'Surgical repair (curative)' above and 'Patients not surgical candidates' above and 'Non-lung resection patients (bronchoscopic intervention)' above.)
SUMMARY AND RECOMMENDATIONS
●Definition – Bronchopleural fistula (BPF) is a communication between a main stem, lobar, or segmental bronchus and the pleural space (image 1 and picture 1). (See 'Introduction' above and 'Definition' above.)
●Etiology – BPF is most commonly encountered after pulmonary resection (pneumonectomy, lobectomy, segmentectomy), with a frequency ranging from 4.5 to 20 percent after pneumonectomy and 0.5 to 1 percent after lobectomy. Other less common causes include BPF due to malignancy and infection. (See 'Etiology' above.)
●Clinical features – Patients with BPF can present with symptoms that range from acute symptoms of tension pneumothorax (eg, dyspnea, chest pain, tracheal deviation to the contralateral side) to subacute symptoms of empyema (eg, fever, cough with large volumes of purulent sputum) or a new or persistent air leak via chest tube. (See 'Clinical features' above.)
●Diagnostic evaluation – The diagnosis of BPF is made using a combination of clinical, radiographic (eg, air around the bronchial stump or in pleural fluid, pneumothorax, visualization of the fistula), and bronchoscopic findings (eg, mucosal defect, air leak at the bronchial stump upon instillation of saline) that confirm an air leak from a major, lobar, or segmental bronchus to the pleural space. (See 'Diagnostic evaluation' above.)
●Management – BPFs do not typically spontaneously undergo closure and almost always require some type of surgical or bronchoscopic intervention such that a multidisciplinary discussion is warranted for all patients (image 1 and algorithm 1). (See 'Management and prognosis' above.)
•General – All patients should have a chest tube placed to drain air. In those with empyema, infected pleural fluid should be drained and patients should undergo postural drainage and receive antibiotic therapy. Supplemental nutrition and therapy for comorbidities should be optimized. (See 'General supportive care' above.)
•Post-operative patients – For most postoperative lung resection patients with BPF who are good surgical candidates, we recommend surgical repair rather than bronchoscopic intervention or continued conservative therapy (Grade 1B) based upon the rationale that surgical repair is a definitive therapy with excellent success and that spontaneous closure is unlikely. (See 'Post-lung resection' above.)
•All other patients – For all other patients with BPF (eg, those who are poor surgical candidates, those who need a bridge [eg, severe hypoxemia, respiratory failure, or hemodynamic instability], or patients with BPF due to disease [eg, advanced cancer]), bronchoscopic fistula closure is appropriate. This is based upon the rationale that temporary fistula closure can usually be achieved, thereby avoiding lengthy periods of hospitalization and a reduction in morbidity in this population. (See 'Patients not surgical candidates' above and 'Non-lung resection patients (bronchoscopic intervention)' above.)
Bronchoscopic approaches have variable success rates but are typically more successful in those with small fistulas (<8 mm). For patients with BPF <8 mm, occlusive materials and sclerosants may be effective, while in patients with BPF ≥8 mm and/or proximal fistulas (eg, level of a major bronchus), stents, or Amplatzer devices, alone or in combination with sealants, may be more appropriate. (See 'Fistulas ≥8 mm' above and 'Fistulas <8 mm' above.)
●Follow-up – Following fistula closure, patients should be monitored for clinical symptoms of recurrence, chest tube output of air, and chest imaging (chest radiography and occasionally CT of the chest). Repeat bronchoscopy is not routine and only performed if fistula recurrence or a complication is suspected (eg, stent migration). (See 'Follow-up' above.)
●Refractory patients – For patients who fail surgical or bronchoscopic intervention, options include repeat surgery, an alternate bronchoscopic method, or, in rare cases, an open-window thoracostomy such as Eloesser flap thoracostomy or a Claggett window. (See 'Refractory patients' above.)
●Prognosis – BPFs are associated with significant morbidity and a mortality that ranges from 21 to 71 percent, especially in the setting of postpneumonectomy empyema. Success is best in those who undergo surgery. (See 'Prognosis' above.)
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