INTRODUCTION — Central airway obstruction (CAO) is a potentially life-threatening condition that can be due to a number of malignant and nonmalignant processes. A low threshold of suspicion for CAO is critical so that it can be recognized and managed promptly. The diagnosis and general approach to CAO will be reviewed here. Specific bronchoscopic management modalities are discussed in detail separately. (See "Endobronchial brachytherapy" and "Bronchoscopic laser in the management of airway disease in adults" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and "Endobronchial photodynamic therapy in the management of airway disease in adults" and "Bronchoscopic cryotechniques in adults".)
DEFINITION
●Central airway obstruction – Central airway obstruction (CAO) refers to the obstruction of airflow in the trachea and mainstem bronchi (figure 1).
●Upper airway obstruction – Upper airway obstruction (UAO) refers to the obstruction of flow in the portion of the airway that extends from the mouth through the length of the trachea and therefore also includes the nasopharynx and larynx (figure 2). It is not discussed in this topic, although some conditions that involve this region of the airway may also involve the proximal trachea (eg, laryngeal, esophageal, or nasopharyngeal cancer), such that CAO and UAO can coexist. (See "Flow-volume loops", section on 'Abnormal inspiratory loop'.)
●Lower airway obstruction – Airflow obstruction due to chronic obstructive lung diseases including asthma, bronchiectasis, and chronic obstructive pulmonary disease (COPD) involves the smaller bronchi in the lower airway distal to the mainstem bronchi and is not typically associated with CAO or UAO.
EPIDEMIOLOGY — Airway obstruction complicates approximately 20 to 30 percent of patients with lung cancer (eg, shortness of breath, atelectasis) although not all reported cases are associated with central airway obstruction (CAO) [1].
Similarly, because the incidence of conditions such as tracheobronchomalacia, and tracheal strictures in the general population are unknown, the incidence of CAO due to these and other benign conditions that cause CAO are also unknown.
ETIOLOGY AND PATHOPHYSIOLOGY
Etiology — Central airway obstruction (CAO) has a wide range of etiologies, among which airway malignancy (usually non-small cell lung cancer [NSCLC]) is the most common.
While the causes of CAO are typically classified as malignant and nonmalignant (table 1), some experts classify according to the location (intrinsic or extrinsic CAO; eg, intraluminal or extraluminal cancers), or according to the nature of the obstruction (dynamic or fixed; eg, tracheobronchomalacia or tracheal stenosis, respectively).
●Malignant — Primary lung cancer is the most common cause of CAO. Although squamous cell lung cancer more commonly affects the major airways than adenocarcinoma, both forms of NSCLC can present with CAO [2,3]. Airway obstruction occurs via direct compression by or extension from a parenchymal tumor into the airway lumen, or via direct or metastatic involvement of the airway by tumor. (See "Clinical manifestations of lung cancer".)
Primary tumors of the airway, other than lung cancer (eg, adenoid cystic carcinoma, carcinoid) and metastatic disease from distant tumors (eg, breast, colorectal, renal, thyroid) are less common causes of malignant CAO. Similarly, direct invasion or extrinsic compression from anatomically adjacent tumors including, laryngeal, nasopharyngeal, or esophageal tumors can occur, as can extrinsic obstruction from mediastinal tumors or adenopathy.
●Nonmalignant — Common conditions associated with nonmalignant CAO are tracheal strictures due to endotracheal or tracheostomy tubes, foreign body aspiration, and tracheobronchomalacia. These and other nonmalignant etiologies are discussed in detail separately. (See "Presentation and diagnostic evaluation of non-life-threatening and nonmalignant subglottic and tracheal stenosis in adults", section on 'Evaluating the etiology'.)
Pathogenesis — The mechanisms that underlie CAO vary with the etiology and include:
●Intraluminal compromise due to intrinsic or extrinsic compression from benign or malignant tumors
●Endobronchial granulation tissue or calcium deposition from trauma, inflammation, or infection
●Airway wall thinning or collapse from cartilage disorders or tracheobronchomalacia
●Airway wall edema from inflammation, infection, and bleeding
These pathogenetic processes can result in fixed or variable obstruction. As an example, CAO from most tumors is due to a mechanical obstruction to the flow of air (ie, fixed obstruction during inspiration and expiration). In contrast, tracheobronchomalacia results in dynamic airflow obstruction (usually obstruction during expiration) (figure 4B and figure 3). These types of obstruction manifest differently on the flow volume loop recorded during pulmonary function testing, the details of which are discussed separately. (See "Flow-volume loops", section on 'Abnormal inspiratory loop'.)
Some cases of CAO are multifactorial. As an example, patients with CAO following lung transplant can have both strictures (from anastomotic ischemia, infection, necrosis, excess granulation tissue formation) and tracheobronchomalacia. As another example, patients with long-term artificial airways are at increased risk for subglottic or tracheal stenosis as well as tracheobronchomalacia. (See "Tracheomalacia and tracheobronchomalacia in adults", section on 'Classification' and "Noninfectious complications following lung transplantation", section on 'Airway anastomotic complications' and "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Laryngotracheal stenosis' and "Tracheostomy: Postoperative care, maintenance, and complications in adults", section on 'Complications'.)
CLINICAL PRESENTATION — Central airway obstruction (CAO) should be suspected in patients who are at risk of developing airflow obstruction (eg, lung cancer, prolonged endotracheal or tracheostomy tube placement). Presenting symptoms are nonspecific and can be subacute/chronic or acute. The clinical manifestations typically depend upon the degree of luminal obstruction, as well as the location and length of time that obstruction has been present. Common features include dyspnea, cough, hemoptysis, and wheeze. In contrast, the demonstration of acute inspiratory stridor and respiratory distress in an at-risk patient are worrisome signs of CAO that should prompt immediate diagnostic evaluation and therapeutic intervention. Whereas exertional dyspnea typically indicates a tracheal lumen <8 mm, stridor develops when the tracheal lumen is <5 mm and hence should be considered a life-threatening presentation. Patients who present subacutely are often incorrectly diagnosed as having asthma, chronic obstructive pulmonary disease (COPD), or pneumonia, which contributes to delayed recognition and therapy.
History and examination — Patients with CAO usually present over weeks to months (subacute/chronic) but may, in some cases, present acutely (within minutes to hours).
Sub-acute or chronic — Patients with minor obstruction are often asymptomatic since airflow limitation is mild.
Symptoms and signs develop when airflow impairment reaches a critical ventilatory threshold (ie, with exertion or increased ventilatory demands due to a postobstructive pneumonia). Common features include dyspnea, cough, hemoptysis, and wheeze. Dysphonia, dysphagia, odynophagia, tenderness of the throat, pain on coughing or speaking, and difficulty clearing secretions are less common but should raise the suspicion for tracheal stenosis. However, none of these symptoms are diagnostic of CAO since they can be due to the underlying disorder, even if CAO is absent.
Patients may also present with additional signs and symptoms of the underlying disorder. As examples:
●Patients with cancer may also present with constitutional symptoms (eg, weight loss), hoarseness or hemoptysis (laryngeal or lung cancer), dysphagia (esophageal cancer), and chest pain. (See "Clinical manifestations of lung cancer", section on 'Intrathoracic clinical manifestations'.)
●A smoker or a patient with COPD may have dyspnea, sputum retention, or recurrent infections that may suggest underlying tracheobronchomalacia. (See "Tracheomalacia and tracheobronchomalacia in adults", section on 'Clinical manifestations'.)
●Patients with endotracheal or tracheostomy tubes who develop acute shortness of breath or stridor during weaning, following removal of an airway, or capping of a tracheostomy tube should prompt a thorough airway inspection for subglottic or tracheal stenosis. (See "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Laryngotracheal stenosis' and "Tracheostomy: Postoperative care, maintenance, and complications in adults", section on 'Complications'.)
●Patients with foreign body aspiration may present with a previous aspiration event or risk factor for aspiration. (See "Airway foreign bodies in adults", section on 'Presentation'.)
Many of these patients are misdiagnosed as suffering from an exacerbation of asthma or COPD, or as having bronchitis or a pneumonia. Clues that may suggest that these nonspecific symptoms are due to CAO include dyspnea that is constant and unresponsive to bronchodilators, or unilateral monophonic wheeze (if the lesion is distal to the carina), and symptoms and/or radiographic infiltrates that do not resolve within four to six weeks following a course of antibiotics. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging", section on 'Clinical features' and "Diagnosis and management of asthma in older adults", section on 'Clinical manifestations' and "Nonresolving pneumonia".)
Acute — Many patients with acute airway compromise have acute onset tachypnea, tachycardia, inspiratory stridor, or wheeze (eg, patients with acute foreign body aspiration). In patients with a mild degree of CAO, rapid deterioration may occur if swelling, bleeding, or secretions increase the degree of luminal impingement (eg, during a respiratory tract infection, trauma). Importantly, these findings together with impairment of oxygenation and/or ventilation indicate a severely compromised airway and should prompt immediate evaluation and implementation of life-saving therapies.
Imaging — A number of imaging modalities are typically performed to facilitate the diagnosis of CAO and in some cases, estimate its magnitude (eg, tracheobronchomalacia). However, in general, none are sensitive or specific for the diagnosis of CAO or its underlying cause. Importantly, if life-threatening obstruction is suspected, stabilization of the airway with intubation followed by direct inspection (typically with bronchoscopy) should not be delayed to obtain imaging. Once the airway is stable, we typically perform the following:
●Chest radiography – Although rarely diagnostic, chest radiographs are typically performed since they may provide clues to the underlying etiology or show evidence of CAO-related complications. As an example, a radiograph may reveal tracheal deviation or mediastinal shift from a lung or esophageal mass, with the signs of chronic obstructive pulmonary disease (ie, a risk factor for tracheobronchomalacia), a tracheobronchial filling defect, or the signs of an obstructing intraluminal lesion (eg, postobstructive pneumonia, atelectasis, or lobar/total lung collapse).
●Chest computed tomography (CT) Chest – When CAO is suspected, a conventional transaxial CT of the chest should be performed. CT may show similar findings to those seen on chest radiography but with better resolution for parenchymal lesions as well as for intraluminal defects in the trachea and bronchi and assessment of abnormalities in the mediastinum and hilum [4]. Newer imaging protocols that include multiplanar and three-dimensional reconstructions (eg, "virtual bronchoscopy") may assist in both the initial assessment of the lesion and in objective grading of therapeutic success and follow-up (image 1). CT may also identify foreign bodies that are metallic or bony in nature or dynamic CT may reveal >50 percent reduction in cross-sectional area on expiration suggestive of tracheobronchomalacia ("Golden S sign") (image 2). (See "Radiology of the trachea".)
Magnetic resonance imaging (MRI) is rarely useful unless vascular or soft tissue pathology is suspected (eg, vascular rings, vascular aneurysms, soft tissue sarcoma or neuroma of the thoracic outlet). (See "Vascular rings and slings" and "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Imaging of the primary tumor'.)
Pulmonary function tests — Pulmonary function tests (PFTs) should be performed in patients with suspected CAO who have subacute symptoms. Provided the patient does not have underlying lung disease, spirometry and lung volumes and diffusion may be relatively spared or mildly reduced but the flow volume loop (FVL) can be helpful.
Flow volume loops (FVLs) can show the characteristic signs of airway obstruction, even before a reduction in the spirometric volumes are noted (figure 4A-E). It should be noted, however, that there can be a significant loss in airway cross-sectional area before the textbook flattening of the inspiratory or expiratory loops are visualized. The FVL is insensitive as a diagnostic tool, but when abnormal can help distinguish between fixed obstruction, variable intrathoracic obstruction, and variable extrathoracic obstruction (figure 4B). However, individual etiologies cannot be determined. The FVL may also assist in assessing the degree of narrowing (figure 4A). For example, the FVL can provide clues as to the severity based on the degree of loop flattening. Some studies also suggest that the ratio of the area under the expiratory and inspiratory curve also correlate with the severity of laryngotracheal obstruction [5].
PFTs may also show a disproportionate reduction in the peak expiratory flow (PEF) rate or maximum minute volume (MVV) compared with the forced expiratory volume in one second (FEV1). Reductions in basic peak expiratory flow rate measurement may also correlate with luminal dimension [5].
PFTS may also be helpful in the detection of underlying lung disorders and in the preoperative or preprocedural evaluation of lung cancer should surgery or bronchoscopic ablative procedures be an option once a diagnosis is made. Determining the severity of underlying lung dysfunction may also assist in assessing prognosis if therapeutic options are limited.
Interpretation of FVLs and pulmonary function tests is discussed separately. (See "Flow-volume loops".)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of the signs and symptoms of central airway obstruction (CAO) include pneumonia, chronic obstructive pulmonary disease (COPD), asthma, and obstruction of the upper airway at or above the level of the vocal cords.
●Pneumonia – The major differentiating feature between CAO and pneumonia is the radiologic evidence on chest radiograph together with fever and a leukocytosis. However, pneumonia may be due to underlying obstruction including tracheobronchomalacia such that follow up chest radiography six weeks after a course of appropriate antibiotics is appropriate to ensure resolution. When postobstructive pneumonia is suggested by the presence of a nonresolving pneumonia or pneumonia is recurrent, then chest tomography (CT) and/or bronchoscopy is indicated. (See "Nonresolving pneumonia".)
●COPD or asthma – In patients with COPD or asthma, the symptoms may be episodic, wheeze bilateral, and the symptoms responsive to bronchodilators. Pulmonary function tests may reveal the classic features of lower airway obstruction including reduced forced expiratory volume in one second (FEV1) and FEV1 to forced vital capacity (FEV1/FVC) ratio, and increased lung volumes (consistent with hyperinflation), reduced diffusing capacity for carbon monoxide, and reversibility with bronchodilators. Similarly, the chest radiograph or CT may show evidence of hyperinflation or emphysema. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging".)
●Upper airway obstruction – In patients with upper airway obstruction (UAO; eg, from vocal cord dysfunction), stridor may be a more prominent symptom and breath sounds may be harsh and louder in the neck than chest. The flow-volume loop on pulmonary function testing may show a pattern of variable extrathoracic upper airway obstruction, "saw toothing" or fluttering on the inspiratory limb, which represents fluctuations in abnormal vocal cord motion, or significant variability on the flow volume loop shape from test to test which may suggest vocal cord dysfunction. UAO may be evident on direct visualization by bronchoscopy or laryngoscopy. (See "Flow-volume loops".)
Most of the etiologies associated with CAO are distinguished from each other by direct visualization on bronchoscopy (eg, tracheobronchomalacia) and/or by tissue biopsy or occasionally on imaging (table 1). (See 'Etiology' above.)
DIAGNOSTIC EVALUATION AND INITIAL MANAGEMENT — When central airway obstruction (CAO) is suspected, we prefer that patients be managed using a multidisciplinary approach in a center with expertise in airway management. However, transfer to a specialized center should not delay life-saving therapies.
●In cases of life-threatening asphyxiation from CAO, initial support should be focused on oxygenation and securing a safe airway. Once the airway is secured, a brief clinical and bronchoscopic evaluation of the trachea and bronchi should be performed promptly to diagnose and, in some cases, also treat the underlying disorder. (See 'Life-threatening central airway obstruction' below.)
●In patients who are stable or in those who become stable following initial airway management, the evaluation should be directed towards assessing the degree and type of obstruction with clinical, radiologic, and physiologic assessment followed by bronchoscopic diagnosis and etiology-specific therapy. (See 'Non-life-threatening central airway obstruction' below.)
Life-threatening central airway obstruction
Airway management — When severe life-threatening CAO (ie, in the trachea and main stem bronchi) is suspected, it is critical that patients be oxygenated and their airway secured for adequate ventilation. Support typically includes initial bag valve mask ventilation followed by endotracheal intubation. For those in whom intubation is not feasible or is unsuccessful, options include an emergency cricothyrotomy or tracheostomy, or rigid bronchoscopic intubation. Choosing among these options is dependent upon the degree and location of obstruction and available airway expertise.
Airway management of patients with CAO should be performed by skilled personnel with expertise in intubating difficult airways. If no dedicated airway team is available, patient transfer to a specialized center should be considered after the patient’s airway has been secured and their condition has been stabilized. A multidisciplinary approach that involves a pulmonologist, thoracic surgeon, oncologist, ear nose and throat specialist, and radiologist is important for maintenance of patency.
Most patients can be adequately oxygenated with standard equipment for oxygen (ie, nasal cannulae, face mask). Heliox may be of benefit by reducing turbulent flow in large airways and at branch points in the tracheobronchial tree (eg, masses at the junction of the right mainstem bronchus and upper lobe) and act as a “bridge” to definitive therapy. (See "Physiology and clinical use of heliox".)
Although larger ET tubes are preferred for subsequent diagnostic bronchoscopy (eg, 8 mm inner diameter), securing the airway should not be prolonged or delayed for this purpose. Occasionally, an ETT is placed under bronchoscopic assistance when proximal friable tracheal lesions are present in order to reduce the risk of exacerbating intraluminal obstruction from bleeding due to a traumatic intubation. A laryngeal mask may be used if the clinician assesses that the risk of traumatic intubation is high. Detailed discussion regarding ETT placement and management of the difficult airway is provided separately. (See "Direct laryngoscopy and endotracheal intubation in adults" and "Basic airway management in adults" and "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients" and "Emergency cricothyrotomy (cricothyroidotomy)" and "Needle cricothyroidotomy with percutaneous transtracheal ventilation" and "Approach to the anatomically difficult airway in adults outside the operating room" and "Emergency airway management in the morbidly obese patient" and "Management of the difficult airway for general anesthesia in adults".)
Cricothyrotomy or tracheostomy may be preferred in patients with lesions at or above the vocal cords; however, they may be of little help with lesions obstructing the distal trachea. (See "Emergency cricothyrotomy (cricothyroidotomy)" and "Needle cricothyroidotomy with percutaneous transtracheal ventilation" and "Approach to the anatomically difficult airway in adults outside the operating room".)
Rigid bronchoscopy or, occasionally, retrograde intubation, may be required in select circumstances when other methods have failed or are not feasible. Among these, rigid bronchoscopy has been traditionally used as the modality of choice when the airway is considered severely obstructed and respiratory failure is impending since it can be used for oxygenation and ventilation, as well as for therapeutic coring and dilation. (See "Rigid bronchoscopy: Intubation techniques" and "Management of the difficult airway for general anesthesia in adults" and "Approach to the anatomically difficult airway in adults outside the operating room" and 'Dilation' below and 'Debridement' below.)
Bronchoscopy — Once the airway is secured and adequate gas exchange is documented, a brief history may be obtained to elucidate a likely etiology of the CAO, and bronchoscopic inspection is indicated. While the initial bronchoscopy is mostly diagnostic and used to plan further interventions, in some patients, bronchoscopy can be both diagnostic and therapeutic (eg, foreign body retrieval, rigid bronchoscopy coring) [6]. (See 'Clinical presentation' above.)
Bronchoscopy should be done either immediately (eg, foreign body or almost complete occlusion of the airway distal to the endotracheal or tracheostomy tube) or within the first 12 to 24 hours (eg, high grade occlusion in an otherwise stable, ventilated patient).
During bronchoscopy, lesions are assessed visually, distal secretions are suctioned, and diagnostic tissue is obtained, if feasible (movie 1). When obstructive lesions are confirmed, a similar assessment to that described in non-life-threatening CAO should be obtained. (See 'Bronchoscopic evaluation' below.)
In this population, the initial bronchoscopic evaluation is typically performed using a flexible bronchoscope, since equipment of sufficient diameter is required to pass through an endotracheal or tracheostomy tube. However, if rigid bronchoscopy is used to secure the airway, similar information can be obtained at the time of intubation. In addition, during rigid bronchoscopy, therapeutic dilation can be performed for severely occluded airways. (See "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Indications and contraindications" and "Rigid bronchoscopy: Instrumentation".)
Imaging with computed tomography (CT) is typically deferred until the patient is considered by their clinician as suitably stable for transfer and the risk of complete tracheal obstruction is low. Similarly, chest radiography, although frequently performed for ETT placement, should not preclude airway inspection in a true emergency. (See 'Imaging' above.)
Non-life-threatening central airway obstruction
Clinical evaluation — In a stable patient or in a patient who is stabilized following the initial airway management, sufficient time is available to obtain a thorough history, relevant lab and imaging studies (chest radiography and CT), and pulmonary function tests (in nonintubated patients). This testing typically provides enough information to narrow the differential to one or a few diagnostic possibilities. (See 'Clinical presentation' above.)
Bronchoscopic evaluation — Following clinical assessment, bronchoscopy should be performed. It is crucial, however, to understand that performing bronchoscopy can precipitate acute/critical central airway obstruction in a patient with a relatively stable airway. As such, we recommend bronchoscopy be performed by teams equipped to manage complex airways.
Direct bronchoscopic visualization is the gold standard for confirming the presence of airway obstruction and also aids in discerning its underlying etiology.
●Visual inspection – In most cases, flexible bronchoscopy, with or without endobronchial ultrasound (EBUS), is sufficient for the diagnostic evaluation of central airway lesions. This includes the following:
•Visual inspection for the location, extent, and nature of the obstruction (eg, intrinsic versus extrinsic obstruction (figure 5))
•Involvement of the carina, oropharynx, or distal bronchi
•The presence of dynamic airway changes or cartilage loss (the latter may require radial probe EBUS or optical coherence tomography [OCT]) [7,8]
•Estimation of the airway diameter (by comparing with the outer diameter of the scope)
•The safe acquisition of tissue when indicated
•Planning for additional interventions, if needed [6]
●Obtaining samples – Depending upon the suspected etiology, not every patient requires a tissue diagnosis (eg, patients with tracheobronchomalacia, suspected vascular ring), but in most patients, particularly those with suspected cancer, the acquisition of tissue is necessary for therapy.
Patients with suspected infectious etiologies should have bronchial washes sent for routine bacterial, fungal, and mycobacterial culture.
While forceps biopsy is usually sufficient for the diagnosis of visible endobronchial lesions, EBUS-guided biopsy may be indicated for the diagnosis of extrinsic masses (eg, lymphadenopathy or tumors), causing compression of the airway. (See "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Indications and contraindications" and "Endobronchial ultrasound: Technical aspects" and "Endobronchial ultrasound: Indications, contraindications, and complications" and "Bronchoscopy: Transbronchial needle aspiration".)
In some cases, brief therapeutic interventions can be performed simultaneously with the initial bronchoscopy (eg, suctioning impacted secretions or blood, foreign body removal). In other patients, additional etiology-specific interventions may be required in order to achieve or maintain airway patency. (See "Airway foreign bodies in adults" and 'Management of the underlying cause' below.)
Diagnosis — In most patients, visual inspection of the trachea and bronchi with bronchoscopy is typically needed for the diagnosis of CAO. In addition, tissue biopsy is also required in most cases when cancer or other serious pathology is suspected as the etiology for CAO. Occasionally, in patients who are asymptomatic or who have mild symptoms and in whom cancer is not suspected (eg, vascular ring, enlarged goiter), imaging with CT and supportive clinical and physiologic findings may be sufficient. (See 'Clinical presentation' above and 'Bronchoscopic evaluation' above.)
MANAGEMENT OF THE UNDERLYING CAUSE — Etiology-specific interventions for central airway obstruction (CAO) are typically planned following the initial assessment and diagnosis [1] (see 'Diagnostic evaluation and initial management' above). The goals of treatment are airway patency and symptom palliation which are usually performed by debulking or removing the obstruction, and/or by stenting an airway such that patients can safely breathe spontaneously. In most cases, this is achieved bronchoscopically but occasionally surgery is required. The number of interventional bronchoscopic options has increased such that multimodality approaches are often preferred, particularly for patients with lung cancer (algorithm 1 and table 2 and table 3 and table 4) [1,9]. Evaluation in a center with bronchoscopic interventional expertise for the management of the impaired airway is preferred.
Choosing among the interventions is dependent upon factors including the cause of the lesion, predicted response to therapy, operator experience, available expertise, patient prognosis or health status, patient preference, and the ability of the patient to tolerate a selected procedure [1,9-12]. As an example, in patients with severe life-threatening intraluminal obstruction from lung cancer, initial tumor ablation (eg, with laser) followed by maintenance therapy (eg, stenting, external beam radiation) may be preferred. In contrast, surgical resection may be preferred in patients with significant short segment tracheal stenosis that is resistant to other local therapies. Preferred therapies for patients with select etiologies for CAO are discussed separately. (See 'Patients with lung cancer' below and 'Patients with other types of malignancy' below and "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)
For most bronchoscopic interventions, the flexible bronchoscope with use of moderate sedation is sufficient. However, the rigid bronchoscope may be preferred for unstable patients and when significant bleeding is expected [6]. (See "Rigid bronchoscopy: Instrumentation" and "Flexible bronchoscopy in adults: Overview".)
Patients with lung cancer — The modalities discussed below usually apply to the treatment of non-small cell lung cancer (NSCLC), which is the most common etiology for lung cancer-associated CAO. Anecdotal and case reports suggest that some of the bronchoscopic ablative modalities may be appropriate for cancers other than NSCLC (eg, carcinoid, small cell carcinoma, metastatic cancer from non-pulmonary sites).
Choosing among modalities — Although there are an increasing number of bronchoscopic therapies available to locally treat lung cancer involving the central airway, patients should be primarily treated according to the appropriate stage using a multidisciplinary approach that involves pulmonologists, surgeons, radiotherapists, and oncologists. Thus, if surgical cure is appropriate (eg, a young patient with focal adenoid cystic carcinoma), then surgical resection should be considered as the primary mode of therapy, while external beam radiation or chemotherapy may be more appropriate for patients with more extensive disease (table 5). Surgical resection is not feasible in most cases, such that most of the modalities listed in the sections below (bronchoscopic and non-bronchoscopic) are typically adjunctive or palliative, and are therefore targeted at achieving patency, decreasing dyspnea and hemoptysis, improving quality of life, and/or reducing time to extubation [2,3,13-16]. They are also often administered when an immediate life-saving therapy is required, or when a bridging therapy is needed while waiting for a more definitive therapy (eg, salvage chemotherapy or surgical resection). (See "Management of stage I and stage II non-small cell lung cancer" and "Management of stage III non-small cell lung cancer" and "Overview of the initial treatment of advanced non-small cell lung cancer" and "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer" and "Selection of modality for diagnosis and staging of patients with suspected non-small cell lung cancer", section on 'Role of multidisciplinary teams'.)
Choosing among these modalities depends upon a number of factors including available equipment and expertise, degree of obstruction, tumor characteristics, tumor location, and general health status of the patient (algorithm 1 and table 2 and table 3). In general, the following principles apply:
●If immediate therapeutic effect, mostly due to severe shortness of breath or severe hemoptysis, is required for life-threatening intraluminal CAO, coring or mechanical debridement using a rigid bronchoscope, with or without dilation and stenting is often preferred. Bronchoscopic ablative techniques including argon plasma coagulation (APC), electrocautery, and laser are suitable alternatives. In contrast, the effects of cryosurgery, photodynamic therapy, and endobronchial brachytherapy [EBBT] are delayed and should not be used in this population.
●For patients who have non-life-threatening airway obstruction from an intraluminal mass, all bronchoscopic ablative techniques including APC, electrocautery, laser, cryosurgery, endobronchial brachytherapy, and photodynamic therapy, external beam radiation therapy (EBRT), airway debridement/coring, airway dilation, and airway stenting can be used. The effects of radiation therapies tend to last longer than locally ablative therapies such that both forms are typically used (eg, local ablation for the immediate effect and radiation for maintenance of patency).
●For patients with extraluminal lesions, dilation and stenting are often the only therapies that can result in immediate patency and as a consequence are more frequently used to treat severe life-threatening disease. In such cases, immediate therapy is usually followed by EBRT or less commonly by EBBT. In contrast, patients with non-life-threatening extraluminal disease are typically treated with EBRT first, while dilation and stenting are less frequently needed.
●Importantly, for each patient the decision should be individualized. As an example, although a patient may be suitable for a thermally ablative technique (APC, electrocautery, and laser), the fraction of inspired oxygen (FiO2) should preferably be below 0.4 to avoid an airway fire, such that a clinician may choose non-thermal ablation (eg, cryosurgery) for patients on high-flow FiO2. As another example, APC may be more efficient than electrocautery or laser in achieving hemostasis and may be more suitable for patients with CAO who also have significant hemoptysis.
In general, when these modalities are used appropriately, up to 90 percent of patients will achieve patency and symptom control (average 60 to 80 percent). Success rates appear to be similar among APC, electrocautery, laser, cryotherapy, brachytherapy, and photodynamic therapy [15,17-20]. A database of therapeutic bronchoscopy has shown that, despite the lack of comparative studies, APC has replaced laser as the most popular thermal ablation modality [21]. The patency rate for individual procedures and the tumor characteristics that are best suited to individual procedures are discussed separately. (See 'Bronchoscopic ablative therapies' below and "Endobronchial electrocautery", section on 'Indications and efficacy' and "Endobronchial brachytherapy", section on 'Efficacy' and "Bronchoscopic laser in the management of airway disease in adults", section on 'Indications and efficacy' and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults", section on 'Indications and efficacy' and "Endobronchial photodynamic therapy in the management of airway disease in adults", section on 'Indications and efficacy'.)
Multimodality approaches featuring a combination of several bronchoscopic interventions (eg, laser resection plus stenting) are often preferred by experts for their mucosal sparing effects and long-term success in achieving patency [1,9]. Thus, treatment in a center that specializes in the evaluation and management of the impaired airway from lung cancer is preferred. Evidence on the palliative role of multimodality therapeutic bronchoscopy comes from the following studies:
●One prospective study of 37 patients who underwent a variety of bronchoscopic interventions (eg, laser, cautery, cryotherapy, dilation, and/or stenting) for high grade central obstruction reported significant improvement in exercise capacity, lung function, and dyspnea at 30 days [22].
●Another prospective study of multimodality bronchoscopic interventions in a similar population reported on average a greater than 80 percent patency in the originally affected airway and improved dyspnea in the majority of patients at six months [23].
●Another retrospective multicenter study that included 1157 procedures on 947 patients reported an overall complication rate of 4 percent with significant variation among centers ranging from 1 to 12 percent [24]. Risk factors for complications included urgent procedures, poor health status (American Society of Anesthesiologist score >3; (table 6)) and need for repeat procedures. The 30-day mortality rate was 14 percent and ranged from 8 to 20 percent.
External beam radiotherapy — In general, external beam radiation therapy (EBRT) is the preferred treatment for patients with non-small cell cancer of the airway, who have non-life-threatening intraluminal or extraluminal obstruction and in whom surgical resection is not feasible or has failed. However, because the effects are delayed, unreliable, and associated with initial worsening of intraluminal obstruction (from radiation-induced edema), when CAO is severe, EBRT is used after initial airway stabilization and debulking (usually by bronchoscopic ablation) and/or stenting has been performed. The role of EBRT in treatment of lung cancer is discussed in detail separately. (See "Management of stage I and stage II non-small cell lung cancer", section on 'Postoperative RT' and "Management of stage III non-small cell lung cancer".)
There are no high quality randomized trials that compare EBRT with local ablative therapies. However, most experts consider an individual approach that personalizes the radiation dose and often combines EBRT with local ablation to optimize and maintain patency [13,25]. As an example EBRT may be preferred in patients with distal disease since distal obstruction (eg, lobar or segmental obstruction) is less amenable to ablative therapy. The studies that compared EBRT and EBBT in patients with central obstructing tumors are described separately. (See "Endobronchial brachytherapy" and "Endobronchial brachytherapy", section on 'Palliation of central obstructing airway tumors'.)
Bronchoscopic ablative therapies — Available bronchoscopic therapies are listed below. As a general rule, lesions that are truly central (ie, trachea, mainstem and lobar bronchi) are amenable to these therapies, whereas lesions distal to the lobar bronchus are not usually suitable for ablation (figure 1). Laser, electrocautery, and argon plasma coagulation are used for immediate-relief from obstruction due to intraluminal tumors, while brachytherapy, photodynamic therapy, and cryosurgery are delayed in their effects and cannot be used for this purpose. Only brachytherapy can be used for cancers that cause extrinsic compression. The advantages and disadvantages of each modality are listed in the tables (table 2 and table 3 and table 4).
Laser therapy — Laser therapy is a commonly used thermally-ablative non-contact technique. It is an immediate-acting therapy with excellent debulking capacity, best suited to treating patients with intraluminal tumors causing CAO, as well as those associated with bleeding. Ideal lesions are localized and short (ie, <4 cm) such that the region beyond the obstruction can be visualized and the distal lung is functional. It is not suitable for extraluminal lesions and its effects are not generally long lasting such that it is usually combined with other therapies (eg, EBRT or stent).
It is frequently performed via the rigid bronchoscope, but can be safely performed with the flexible bronchoscope by experienced endoscopists [26]. Compared to other immediate-acting thermally-ablative therapies (electrocautery, argon plasma coagulation), laser therapy has the highest risk of airway perforation. Indications, complications, and efficacy of bronchoscopic laser therapy, are described separately. (See "Basic principles of medical lasers" and "Bronchoscopic laser in the management of airway disease in adults".)
Electrocautery — Electrocautery, which induces contact electrical thermal injury (often administered via a flexible bronchoscope), is an alternative to laser therapy or argon plasma coagulation for the acute treatment of intraluminal tumors causing CAO. It is an immediate-acting therapy that requires frequent cleaning of debris on the probe. Although it has a risk of airway fire, the risk of airway perforation is lower when compared with laser. It is not suitable for extraluminal lesions and its effects are short-lived such that it is usually combined with other therapies. Indications, complications, and efficacy of endobronchial electrocautery are described separately. (See "Endobronchial electrocautery".)
Argon plasma coagulation — Argon plasma coagulation (APC) is a commonly used immediate-acting non-contact thermal-ablation technique. It is usually administered through a flexible bronchoscope. Because it lacks the depth of penetration of laser it is not as good at debulking intraluminal tumors but is associated with a reduced risk of airway penetration. Due to the superficial spread of heat associated with this procedure, it is better suited to treating superficial vascular lesions that bleed easily, flat polypoid lesions (eg, papillomas) (picture 1), or lesions at and around bifurcations in airways, especially those in the upper lobe bronchi and apical segments of the lower lobes. It cannot be used for treating extrinsic lesions and is frequently combined with other therapies. Indications and complications of bronchoscopic laser therapy are described separately. (See "Bronchoscopic argon plasma coagulation in the management of airway disease in adults".)
Endobronchial brachytherapy — Endobronchial brachytherapy (EBBT), which is usually administered through a flexible bronchoscope, can be used successfully for the palliation of obstructive symptoms caused by large central airway tumors that are not amenable to surgical resection and/or external beam radiation. It may also be administered to patients who have already received maximal doses of EBRT. Its major advantage compared with immediate-acting locally ablative techniques (laser, cautery, APC) is that it is longer lasting and can be used for debulking intraluminal as well as extraluminal tumors. It is not used when immediate relief from life-threatening obstruction is required but may be combined with locally ablative techniques, especially when tumor external to the airway wall needs to be treated. The indications, complications, and efficacy of EBBT in treating central airway obstruction, are discussed in detail separately. (See "Endobronchial brachytherapy".)
Photodynamic therapy — Photodynamic therapy is a non-thermal modality that may be used for airways that are completely (or partially) obstructed due intraluminal tumors. It cannot be used for tumors causing extrinsic compression. It has a predictable penetration depth (typically 5 to 10 mm), thus, it can be useful for patients that are unresponsive or unsuitable for laser therapy. Because light therapy is administered bronchoscopically after the intravenous injection of a photosensitizing agent (typically 72 hours), it is not used when immediate relief from life-threatening obstruction is needed. It is usually administered via a flexible bronchoscope and often combined with other local bronchoscopic therapies. Its major disadvantage over the other local ablative therapies is that follow-up bronchoscopy is necessary to remove debris and secretions and that patients’ skin is photosensitized for at least six weeks after the procedure, and that it is significantly more expensive. (See "Endobronchial photodynamic therapy in the management of airway disease in adults".)
Cryotherapy — Cryotherapy is typically performed through the flexible bronchoscope. Among the locally ablative techniques, its main advantage is that the risk of airway perforation is low since cartilaginous structures are cryoresistant due to their poor vascularity, and that it can be performed safely in complete mainstem obstruction. Likewise, it can be utilized in high fraction of inspired oxygen (FiO2) environments. However, its effects on airway patency are not immediate, the hemostatic effect is also delayed which increases the risk for hemoptysis, and repeat bronchoscopy is needed for repeated freeze/thaw cycles and for clearance of debris and secretions [27,28]. It cannot be used for treating extrinsic lesions and is frequently combined with other therapies. The indications, complications, and efficacy of cryosurgery are discussed in detail separately. (See "Bronchoscopic cryotechniques in adults".)
Dilation — Airway dilation (also known as bronchoplasty) is sometimes used in patients with short, intrinsic or extrinsic cancerous lesions of the airway, although this procedure is also commonly used for benign stenoses. Although dilation is immediately effective, the results for cancerous stenosis are usually not sustained, especially for lesions causing external airway compression. In addition, mucosal disruption from dilation may in fact produce granulation tissue and accelerate recurrent stenosis, such that other techniques including laser, radiation, and/or stenting are often simultaneously used to maintain a patent airway [29,30].
The airway may be dilated with rigid or flexible bronchoscopy. During rigid bronchoscopy, the endoscope is advanced through the stenotic airway opening and the barrel is then pushed through the obstruction in a rotating motion ("coring") (figure 6). This procedure may be preferred when obstruction is severe since patients can be simultaneously intubated and treated with the rigid bronchoscope and bleeding is usually minimal (picture 2A-B). It is important, however, to know what lies distal to the obstruction in order to not injure the airway with the rigid bronchoscope. In less severe cases, sequential balloon dilation (flexible bronchoscopy) or sequential rigid dilators (rigid bronchoscopy) may be used (ie, dilators of increasing diameter are used in succession during the same session) (picture 3 and figure 7) [31]. The major advantage of sequential rigid versus balloon dilation is that there is generally is less mucosal trauma. (See "Flexible bronchoscopy balloon dilation for nonmalignant airway strictures (bronchoplasty)".)
Debridement — Forceps debridement can be performed for intraluminal CAO using a rigid bronchoscope and is commonly combined with coring when obstruction is severe. Microdebriders have also been used during rigid bronchoscopy to achieve the same effect; a hollow metal tube with a rapidly rotating blade (1000 to 3000 rpm) that is coupled to suction allows obstructing tissue to be dissected while simultaneously evacuating debris and blood [32]. Debridement is not commonly used for mild CAO that is non-life-threatening since alternative ablative therapies performed via flexible bronchoscopy are more readily available.
Airway stent — Stenting is often performed following locally ablative or dilation therapies to prevent reocclusion after patency has been restored. Silicone stents require introduction with a rigid bronchoscope and are in general preferred in patients with cancer. Although covered self-expanding metal stents, which are positioned using flexible bronchoscopy, are associated with complications (eg, reepithelization, fracture, retained fragments during removal), they may be used as a life-saving therapy in a fragile patient with limited life-expectancy who might not otherwise tolerate surgery; however, tumor growth through an uncovered portion of the metal stent at the proximal or distal ends is a risk. Uncovered metal stents should not be used for this reason. Airway stents can be utilized for both intrinsic and extrinsic lesions and require an assurance that the distal airway is patent. Notably, tumors or granulation tissue frequently grow in to the stent such that restenosis is common. Another disadvantage of stents is that follow-up with multiple bronchoscopies is required for the detection of complications which are common. Further details regarding airway stents are provided separately. (See "Airway stents".)
Surgical resection — Surgical intervention for CAO is desirable when a cure for lung cancer is feasible. However, for bronchial lesions, it usually involves a lobectomy, pneumonectomy, or a sleeve resection (eg, T2aN0M0; stage IB). Tracheal resection for isolated tracheal lesions is not commonly performed; most lesions are assessed as T4 (ie, stage IIIA) (table 5), such that only select patients undergo surgery when surgical cure is deemed feasible (eg, small lesions [2 to 3 cm] without nodal metastases [T4 N0M0]) and the surgery is technically difficult requiring expertise in airway surgery. The operative morbidity and mortality may be unacceptable in patients with limited cardiopulmonary reserve, such that patient selection is critical for success. (See "Management of stage I and stage II non-small cell lung cancer", section on 'Surgical candidates' and "Preoperative physiologic pulmonary evaluation for lung resection" and "Sequelae and complications of pneumonectomy" and "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)
Medication-focused palliation of symptoms — Some patients who are adverse to interventions and who are actively dying from their cancer or other comorbid illnesses may prefer to seek symptomatic comfort measures in the form of medications for the symptoms of CAO including dyspnea, hemoptysis, stridor, cough, and pain. (See "Palliative care: Issues in the intensive care unit in adults" and "Ethics in the intensive care unit: Responding to requests for potentially inappropriate therapies in adults" and "Assessment and management of dyspnea in palliative care" and "Palliative care: Overview of cough, stridor, and hemoptysis in adults".)
Investigational — Intratumoral injection of cisplatin has been reported but is considered investigational [33].
Tracheobronchial reconstruction is also investigational. In an uncontrolled study of 13 patients with end-stage tracheal lesions or proximal lung tumors who underwent radical resection, airway tracheobronchial reconstruction was performed using cryopreserved aortic allograft into which a custom-made stent was placed and subsequently removed at about 18 months, after a new trachea was regenerated [34]. There were no deaths at 90 days and no adverse events related to the surgical technique but the course was complicated in about one-third of patients by laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. At median follow up of almost four years, 79 percent remained alive, and among those alive, 80 percent were able to breathe through their newly formed trachea.
Patients with other types of malignancy — Patients with CAO due to tumors other than NSCLC should be treated with a therapy aimed at treating the underlying cancer (eg, external beam radiation for laryngeal cancer). Anecdotally, local ablative therapies similar to that described for NSCLC have been used to relieve life-threatening airway obstruction (eg, carcinoid), although this approach is unproven or anecdotal. Malignancies associated with central airway obstruction are listed in the table (table 1). (See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx" and "Management of locally advanced, unresectable and inoperable esophageal cancer".)
Patients with nonmalignant disease — Patients with CAO due to nonmalignant disorders are treated differently depending upon the underlying disorder. Therapy aimed at treating the underlying etiology is appropriate and may be combined with local bronchoscopic therapies, similar to those described for lung cancer. Further details are provided separately. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)
ADJUNCTIVE THERAPIES — Adjunctive therapies frequently considered by clinicians for central airway obstruction (CAO) include antibiotics and glucocorticoids.
Antibiotics — Many experts also administer a course of antibiotics after a patent airway has been reestablished in individuals with postobstructive infections. The usefulness of empiric antibiotic therapy after interventions in the absence of evidence of infection is unproven.
Glucocorticoids — Similarly, there is no evidence that glucocorticoids are effective in reducing complications (eg, tracheal restenosis after dilation) such that they are not routinely administered.
FOLLOW-UP — Following treatment of central airway obstruction (CAO), close follow-up is necessary in order to detect complications (eg, perforation, restenosis) and intervene accordingly.
●Clinical symptoms – Patients should be assessed clinically for resolution of symptoms immediately following treatment and indefinitely thereafter. It is advisable for all patients with a history of airway obstruction to carry a card or bracelet identifying them as patients with complicated airways or as having an indwelling airway stent. Similarly, patients should be identified during their inpatient stay as having an "at risk" airway such that staff and personnel are aware that expertise may be required for intubation. That being said, if a patient requires intubation, the presence of a stent may not be a contraindication and this history should not delay securing an airway.
●Airway patency – The optimal time and tool for follow-up to assess airway patency is unknown. However, with the exception of those who have had surgery, most patients should undergo a repeat chest computed tomogram. While those with life-threatening obstruction typically undergo repeat imaging within days, others who are more stable have repeat imaging performed within a few weeks or when symptoms recur. In addition, some patients may require repeat bronchoscopy for an alternate indication (eg, for stent surveillance or removal, secretion clearance, complication of therapy) which allows the clinician the opportunity to visually assess the response to therapy. Although attempts have been made to standardize or quantify improvement using an obstruction score, this is not widely utilized [35].
SUMMARY AND RECOMMENDATIONS
●Definition – Central airway obstruction (CAO) refers to the obstruction of airflow in the trachea and mainstem bronchi. CAO can be potentially life-threatening. It is therefore critical that it be recognized and managed promptly. (See 'Definition' above.)
●Epidemiology and etiology – The incidence of CAO is unknown. It has a wide range of etiologies, among which airway malignancy (usually non-small cell lung cancer [NSCLC]), is the most common. Other causes are listed in the table (table 1). (See 'Epidemiology' above and 'Etiology and pathophysiology' above.)
●Clinical features – CAO should be suspected in patients who are at risk of developing airflow obstruction (table 1). Common clinical manifestations include dyspnea, cough, hemoptysis, and wheeze, none of which are sensitive or specific for the diagnosis of CAO. In contrast, acute inspiratory stridor and respiratory distress in an at-risk patient are worrisome signs of CAO that should prompt immediate diagnostic evaluation (usually with bronchoscopy) and therapeutic intervention. (See 'Clinical presentation' above.)
●Diagnostic evaluation and initial management – When CAO is suspected, we prefer that patients be managed using a multidisciplinary approach in a center with expertise in airway management. However, transfer to a specialized center should not delay the administration of life-saving therapies (see 'Diagnostic evaluation and initial management' above):
•Life-threatening CAO – In cases of life-threatening asphyxiation from CAO, we recommend that initial support be focused on oxygenation and securing a safe airway. Once the airway is secured, a bronchoscopic evaluation of the trachea and bronchi should be performed promptly to diagnose and, in some cases, also treat the underlying disorder. Importantly, these life-saving maneuvers should not be delayed to obtain imaging. (See 'Life-threatening central airway obstruction' above.)
•Non-life-threatening CAO – In patients who are stable or in those who become stable following initial airway management, the evaluation should be directed toward assessing the degree and type of obstruction with clinical, radiologic, and physiologic assessment, followed by bronchoscopic diagnosis (movie 1) and etiology-specific therapy. (See 'Non-life-threatening central airway obstruction' above.)
●Management of the underlying cause – For patients diagnosed with CAO, further etiology-specific interventions are typically planned.
•Malignant etiologies – Patients with CAO from lung cancer should be primarily treated according to the appropriate stage (eg, surgical resection, chemotherapy, and/or external beam radiotherapy) (table 5). Locally ablative bronchoscopic modalities are typically adjunctive, palliative, life-saving, or bridging therapies that are targeted at achieving patency, decreasing dyspnea and hemoptysis, improving quality of life, and/or reducing time to extubation. Choosing among them depends upon a number of factors, including available equipment and expertise, degree of obstruction, tumor characteristics, tumor location, and general health status of the patient. Reported success rates are similar for all of the modalities (up to 90 percent of patients achieve patency) (algorithm 1 and table 2 and table 3).
•Nonmalignant etiologies – For patients with nonmalignant causes of CAO, therapy aimed at treating the underlying etiology is appropriate and may be combined with local bronchoscopic therapies, similar to those described for lung cancer. Further details are provided separately. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)
●Follow-up – Following therapy, patients should be assessed clinically for resolution of symptoms as well as for airway patency. The optimal time and tool for follow-up to assess airway patency is unknown. However, with the exception of those who have had surgery, most patients should undergo repeat chest CT. In addition, some patients may require repeat bronchoscopy for an alternate indication, which allows the clinician the opportunity to visually assess the response to therapy.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Armin Ernst, MD, who contributed to earlier versions of this topic review.
