Malignancy Associated Airway Obstruction

Malignancy Associated Airway Obstruction – 11 Interesting Facts

1. Malignancy Associated Airway Obstruction can complicate malignant diseases, with bronchogenic cancer being the most common underlying etiology
2. Prompt recognition and appropriate intervention are necessary to prevent complications that may lead to respiratory failure and death
3. There should be a low threshold to perform a CT scan of the chest and neck in patients at risk of CAO with supportive history or physical exam findings to determine the underlying etiology and classification of the airway obstruction
4. A diagnostic bronchoscopy provides definitive information about the location and severity of airway obstruction, as well as its functional impact
5. Treatment of patients with malignant CAO requires a multidisciplinary collaboration between the interventional pulmonologist, thoracic surgeon, anesthesiologist, oncologist, and radiation oncologist to develop an individualized management plan
6. Therapeutic bronchoscopy is often indicated; the procedure may need to be repeated in cases of disease recurrence and close monitoring following the procedure is required
7. When CAO is caused primarily by endobronchial tumor causing intrinsic compression, endobronchial debulking is indicated
8. When CAO is caused by extrinsic compression, airway dilatation and/or stenting is indicated
9. Various endobronchial ablative strategies are available; their unique technical considerations, risks, and benefits, along with provider expertise and institutional resources should be carefully considered under consultation with an interventional pulmonologist (see Tables 1 and 2)
10. Airway stents are associated with a number of risks postprocedure; an aggressive airway hygiene regimen and stent removal as soon as is reasonable is recommended
11. Follow-up CT imaging within 4 to 6 weeks after an initial bronchoscopic intervention is recommended to assess for disease recurrence or progression

Alarm Signs and Symptoms

• Any patient presenting with symptomatic CAO should receive prompt assessment and intervention given risk for rapid deterioration that may result in respiratory failure and death

Introduction

• Airway obstruction: defined as the loss of greater than 50% of the airway lumen on cross-sectional imaging;¹ can occur at any level from the mouth and nose to the sub-segmental bronchial airways and beyond
  • CAO (central airway obstruction): blockage of airflow in the trachea and mainstem bronchi, including bronchus intermedius
    • The main focus of this discussion will be CAO
  • Upper airway obstruction: blockage of air passages proximal to the trachea, including nasal and oral airways, pharynx, and larynx; may coexist with CAO
  • Peripheral airway obstruction: blockage of airways distal to the mainstem bronchi, including lobar, segmental, subsegmental, and subsequent generations of airways; typically associated with chronic lung diseases

Epidemiology – How common is this condition?

• Historically, the prevalence of CAO has been close to 20% to 30% in patients with lung cancer; a more recent cohort review in the UK showed only 13% of patients with new primary lung cancers were noted to have CAO²³
  • Shift might be related to the increased use of filters and low-tar cigarettes, which tends to result in more peripheral neoplastic disease⁴
  • Increased implementation of lung cancer screening programs and anti-smoking drives has led to a shift whereby cancer cases are being diagnosed at a relatively earlier stage when invasion into the central airways is less likely⁵

Etiology

• Malignant disorders that cause CAO include bronchogenic cancer, other primary airway tumors, lymphoma, and cancers of extrapulmonary organs both within and outside the thorax
  • The most common malignant cause of CAO is the direct spread of bronchogenic cancer from lung parenchyma into the adjacent central airway
  • While adenocarcinoma is the most common histologic type of lung cancer, squamous cell carcinoma is the most common type associated with airway obstruction⁶
  • Primary airway tumors are uncommon but are usually malignant
    • Squamous cell carcinoma is the most common primary airway tumor⁷
  • Other examples include carcinoid tumor (both typical and atypical), adenoid cystic carcinoma, small cell carcinoma, large cell carcinoma, and sarcoma⁷
  • Diffuse large B cell lymphoma appears to be the most common lymphoma causing airway obstruction⁸⁹¹⁰
  • While the exact incidence of airway obstruction in esophageal cancer is unknown, tracheal invasion can be seen in 20% to 36.6% of advanced esophageal cancers¹¹
  • Similarly, thyroid cancers are also known to invade the trachea either by direct extension or by metastasis
    • One study found airway invasion had occurred in 6.5% of the cases, with most cases being well-differentiated thyroid cancer¹²
  • Malignancies originating from almost all extrathoracic sites have the potential to metastasize to the airways and cause airway obstruction, including gastrointestinal malignancies, prostate cancer, renal cell cancer, and sarcoma¹³¹⁴¹⁵

Risk Factors

• Tobacco smoking is the biggest risk factor for bronchogenic cancer, the most common malignant cause of CAO¹⁶
  • Other risk factors for bronchogenic cancer include exposure to secondhand smoke, previous radiation therapy, exposure to radon gas, exposure to other environmental carcinogens including asbestos, family history of lung cancer, and alcohol consumption (in excess of approximately 1 drink a day)¹⁷

Diagnosis

Approach to Diagnosis

• Patients with CAO may initially present with active signs and symptoms; CAO can also be discovered incidentally on radiographic imaging obtained for other reasons
• The diagnosis of CAO can be missed; therefore, providers should keep a high index of suspicion
  • A UK cohort study found that CAO was missed on reporting of CT scans obtained at the time of lung cancer diagnosis in 31% of cases, despite being identified on a subsequent dedicated review of those scans³
• There can be a discrepancy between the degree of airway obstruction and the associated symptom burden which is affected by patient comorbidities and overall health status
• History and physical exam can provide vital clues to the presence of CAO
  • While a pre-existing cancer diagnosis, especially lung cancer, will be a clue for a significant number of patients, CAO can also be the presenting sign of an underlying malignancy
• Symptomatic patients may report a history of dyspnea, cough, hemoptysis, wheezing, and voice changes
• Some patients, particularly those with airway obstruction distal to the trachea, may present with sequela of airway obstruction such as post-obstructive pneumonia, atelectasis, or pleural effusion
• Obtain a chest radiograph to evaluate for lung atelectasis or collapse distal to an obstruction
• There should be a low threshold to perform a CT scan of the chest extending to the neck in patients at risk for CAO with supportive history or exam findings to determine the underlying etiology and classification of the airway obstruction
• A diagnostic bronchoscopy provides definitive information about the location and severity of airway obstruction and its functional impact

Staging or Classification

• CAO is classified based on the relationship of the underlying lesion to the airway¹⁸
• Extrinsic: compression occurs from an extramural structure (eg, malignant lesion) located adjacent to the airway; causes airway impingement without direct invasion of the airway wall
• Intrinsic: compression results from an underlying lesion that is entirely endoluminal
• Mixed: presents as a mixed picture of both intrinsic and extrinsic compression

Workup

History

• A history of nonresolving pneumonia despite appropriate antimicrobials should raise suspicion for the presence of airway obstruction
• Symptoms of CAO typically include dyspnea, cough, hemoptysis, wheezing, and voice changes
  • Dyspnea is typically the result of increased work of breathing to make up for the increased resistance to airflow in the setting of narrowed airways; patients can present without hypoxia or hypercapnia
  • Typically, the tracheal diameter must be reduced to 8 mm before dyspnea and reduced to 5 mm before exertion at rest and stridor develops¹⁹²⁰
  • Given the significant loss of airway lumen by the time symptoms develop, symptomatic patients are at risk for rapid deterioration and a significant number of these patients can present in frank respiratory distress²¹
• CAO may initially be misdiagnosed as asthma, COPD (chronic obstructive pulmonary disease), or heart failure due to the overlap of signs and symptoms
• The patient may report that inhaled bronchodilators, frequently prescribed on an empiric basis for respiratory symptoms (eg, dyspnea, dry cough, wheezing), do not provide significant symptomatic relief due to the fixed nature of airway obstruction

Physical Examination

• Vital signs
  • Tachypnea and tachycardia may be present
  • Hypoxia is rare except in very severe cases and, if present, may potentially be due to another cause
• General appearance
  • The patient may show signs of respiratory distress such as use of accessory muscles of respiration
• Respiratory exam
  • Stridor may be audible, particularly in cases of tracheal obstruction
  • Localized wheezing may be auscultated depending on the site and severity of airway obstruction
  • In cases of retained airway secretions distal to the site of airway obstruction, auscultation may reveal rhonchi

Laboratory Tests

• Obtain an arterial blood gas analysis as part of initial evaluation of patient with suspected airway obstruction
  • May reveal hypercarbia in cases of significant airway obstruction and lung atelectasis, leading to impairment of ventilation
  • Note that many patients are able to compensate for the airway stenosis through increased work of breathing and thus normal blood gas values do not exclude the diagnosis

Imaging Studies

• A chest radiograph is often the initial diagnostic test
  • Can identify sequelae of significant CAO (eg, the collapse of the entire lobe or lung)
• In patients at risk for CAO with supportive history or exam findings, there should be a low threshold to obtain cross-sectional imaging, preferably a CT scan of the chest and neck²²
  • CT scan will provide high-resolution imaging of the airways, lung parenchyma, mediastinum, and adjacent structures
  • A CT scan will help determine the underlying etiology and classification of the airway obstruction; it will also reveal if any complications have developed, such as atelectasis, postobstructive pneumonia, and pleural effusion
  • In the absence of contraindications, IV contrast is recommended to determine the relationship between a tumor and adjacent blood vessels and to better delineate mediastinal structures and the presence of any lymphadenopathy
  • There can be significant discordance between the extent of dynamic airway obstruction as compared to airway obstruction identified on CT imaging²³
    • A CT scan performed during an end-inspiratory breath hold might underestimate the severity of airway obstruction; conversely, in patients with significant airway secretions and mucus plugging, CT scan may overestimate the degree of obstruction
• Consider obtaining CT angiography when information about pulmonary blood flow may help to determine the viability of an atelectatic lung, which may influence the timing and choice of intervention²⁴
• PET imaging can be helpful in clarifying extent of tumor in situations where it is difficult to delineate tumor from adjacent postobstructive atelectasis; this may influence subsequent management²⁵

Diagnostic Procedures

• A diagnostic bronchoscopy typically provides definitive information about the site and degree of airway obstruction, the nature of obstruction (eg, intrinsic, extrinsic, or mixed), and its functional impact, such as retained distal secretions or post-obstructive pneumonia
• Consult interventional pulmonology to evaluate patient with CAO for bronchoscopic assessment with or without intervention

Diagnostic Tools

• Pulmonary function testing may reveal reduced peak inspiratory flow and peak expiratory flow; other commonly measured spirometry metrics, such as FEV₁ or FVC, may not be significantly reduced in the absence of severe obstruction¹⁸

Differential Diagnosis

Table 1. Differential Diagnosis: CAO.

Condition	Description	Differentiated by
Asthma	A chronic disease of the peripheral airways characterized by partially or completely reversible airway inflammation and obstruction that occurs in response to 1 or more triggersPatients have similar clinical manifestations (eg, cough, dyspnea, wheezing)	Symptoms often improve with inhaled bronchodilator therapy and with inhaled or systemic corticosteroids
Chronic obstructive pulmonary disease	A chronic disease characterized by inflammation of the peripheral airways (chronic bronchitis) and/or destruction of alveolar architecture (emphysema)Patients have similar clinical manifestations (eg, cough, dyspnea, wheezing)	Symptoms often improve with inhaled bronchodilator therapy and with inhaled or systemic corticosteroids
Congestive heart failure	Disorder of mechanical cardiac function characterized by impaired diastolic filling and/or impaired systolic performancePatients can have similar clinical manifestations (eg, dyspnea, wheezing)	Patients are more likely to complain of orthopnea, early satiety, and/or dependent edemaPhysical examination and chest imaging may reveal signs of fluid overloadEchocardiography is diagnosticSymptoms often improve with diuretic therapy or other pharmacologic agents aimed at optimization of cardiac preload and/or afterload

Treatment

Approach to Treatment

• Figure 2. Algorithmic approach to the management of central airway obstruction. – *Silicone/new hybrid stents generally preferred. †Rigid bronchoscopy preferred. ‡Careful airway evaluation and airway CT scan, ± flexible bronchoscopy, ± endobronchial ultrasound, ± autofluorescence. §Possibly with presurgical endoscopic intervention. ||Can be used singly or in combination, may need stenting.From Ernst A et al. Central airway obstruction. Am J Respir Crit Care Med. 2004;169(12):1278-1297. Figure 4.

• The general principles of management of CAO have remained unchanged over the last several decades
• Ernst et al have previously described an algorithmic approach to the management of CAO that remains valid today (Figure 2)²
• By promptly recognizing and instituting appropriate interventions, the life-threatening consequences of CAO can be avoided
• Endobronchial therapies for malignancy-associated airway obstruction are typically not curative and are usually offered as part of a multidisciplinary treatment plan that includes surgery, systemic, and/or radiation therapies
  • A combination of local interventional modalities and systemic treatment is often the most successful strategy²
• For patients with CAO who are in respiratory distress, consult an interventional pulmonologist to evaluate patient for urgent therapeutic bronchoscopy
• For clinically stable patients, recommend consultation with a multidisciplinary team that includes an oncologist, radiation oncologist, thoracic surgeon, and interventional pulmonologist early in the course of treatment to determine the optimal individualized treatment strategy for each patient
  • If the patient is stable, curative resection of the malignant lesion is generally considered the preferred option, when possible
  • In some cases, radiation therapy may be preferred before an interventional procedure
• In clinically stable patients where curative resection is not a feasible option, therapeutic bronchoscopy should be considered
  • The timing of bronchoscopic intervention may be deferred while the patient undergoes systemic therapy (eg, chemotherapy) and/or radiation treatments under close monitoring
    • This is especially true for airway obstructive masses associated with lymphoma and small-cell cancer, where the disease often regresses quickly with the initiation of appropriate therapy

Nondrug and Supportive Care

• The need and type of supportive care depends on each patient’s clinical condition, type and location of obstruction, and patient comorbidities
  • While clinically stable patients may proceed with definitive diagnostic and therapeutic procedures, patients in respiratory distress may need to be urgently or emergently stabilized while awaiting more definitive intervention
• Supplemental oxygen should be titrated to maintain adequate oxygenation
• Heliox (a mixture of helium and oxygen) can be used to reduce dyspnea by providing more laminar gas flow in cases of advanced CAO, particularly in cases of severe tracheal obstruction²⁶
• In some cases, non-invasive positive pressure ventilation or invasive mechanical ventilation may be needed
  • Bronchoscopic guidance should be used during endotracheal intubation in the presence of tracheal tumors to avoid contact with tumor and resultant bleeding²⁷

Drug Therapy

• Empiric broad spectrum antibiotics tailored to local resistance patterns are indicated in cases of suspected or confirmed post-obstructive pneumonia²⁸
• Bronchodilator therapy, while not otherwise indicated, may be helpful in cases of concurrent COPD, a frequent comorbidity, particularly in the setting of tobacco use history
• Systemic steroids may be beneficial in cases of concurrent acute exacerbations of COPD or interstitial lung disease
• Mucolytics and expectorants, such as guaifenesin, and inhaled agents, such as normal saline, hypertonic saline, and n-acetylcysteine, can help with mucus clearance when needed²⁹
• Systemic therapies for treatment of CAO may include traditional chemotherapy and targeted therapies such as tyrosine kinase inhibitors³⁰
  • Therapies are chosen based on the tumor type, molecular tests (eg, expression of programmed cell death ligand-1), and presence of actionable mutations
• Low-dose opioids may have a role for palliation of dyspnea where consistent with overall goals of care, keeping in mind the risk of life-threatening opioid-induced respiratory depression³¹

Treatment Procedures

• Therapeutic bronchoscopy
  • Indications and contraindications³²
    • Consider therapeutic bronchoscopy in all patients who are symptomatic or those who are developing sequelae of airway obstruction such as postobstructive pneumonia
      • Additionally, therapeutic bronchoscopy should be considered in patients with more than 50% airway narrowing
      • Despite the established benefits of therapeutic bronchoscopy, it continues to be underutilized, with 1 cohort study showing that it was performed in only 26% of eligible patients³
    • Therapeutic bronchoscopy is relatively contraindicated in cases of high bleeding risk (such as platelet count less than 50,000/µL or active pharmacologic anticoagulation); risk-benefit analysis, shared decision-making, and mitigation of risk factors (eg, platelet transfusion, holding anticoagulant therapy) are needed in such circumstances, when possible
    • Therapeutic bronchoscopy is absolutely contraindicated in cases where the patient is not a candidate for anesthesia, intubation, or mechanical ventilation
    • Therapeutic intervention is considered less likely to be successful if the airway obstruction is longstanding (greater than 4 to 6 weeks in duration), if there are no appreciable healthy airways distal to the stenosis, or if the stenotic segment is greater than 4 cm in length³³
    • Review all prior radiographic imaging to establish an accurate timeline of disease progression when making a decision regarding bronchoscopic intervention
      • Establishing the chronicity of an atelectatic lung is important though it can be challenging in some patients
        • Attempts to reestablish ventilation may not lead to symptomatic improvement in chronic cases where irreversible processes such as scarring may have already developed
  • Choice of bronchoscopy
    • The interventional pulmonologist must consider patient-specific factors, practitioners’ expertise, and equipment availability when deciding between flexible and rigid bronchoscopy
    • Flexible bronchoscopy is often performed through a laryngeal mask airway or an endotracheal tube
    • Rigid bronchoscopy involves intubating with a steel tube, which acts as a conduit for both ventilation and passage of instruments, and may confer additional benefits:
      • A rigid bronchoscope can allow for the passage of larger suction channels and rigid forceps; it can also function as a therapeutic device as its beveled edge can be used for coring out the tumor or traversing stenotic segments; this can facilitate rapid re-establishment of airway patency when necessary
      • A rigid bronchoscope has side ports that permit ventilation of both lungs even when it is present in one of the mainstem bronchi; this prevents contamination of the unaffected lung compromising ventilation
      • Rigid bronchoscope, when used alongside jet ventilation, allows for effective ventilation across a very narrow airway without increasing airway resistance as occurs with conventional closed-circuit ventilation systems
      • A rigid bronchoscope allows for the deployment of silicone stents
  • Choice of intervention
    • The choice of bronchoscopic intervention depends on the classification of the airway obstruction
    • For lesions with a significant endoluminal (intrinsic) component, tumor debulking should be considered
    • For extrinsic lesions, airway dilatation (balloon or rigid) and/or airway stenting is recommended
      • Multiple stent types are available, including silicone stents, self-expandable metallic stents, and balloon-expandable metallic stents³⁴
      • Self-expandable metallic stents are often preferable due to ease of deployment
      • Metallic stents are covered with a membrane of silicone or polyurethane, which helps limit the risk of tumor invasion into the stent
      • Tumor debulking is contraindicated for extrinsic lesions
• EAT (endobronchial ablative therapy)
  • EAT can be divided into those having an immediate effect or those having a delayed effect³⁵
    • In patients with critical airway obstruction, EAT with immediate effect should be employed for prompt re-establishment of the airway and includes mechanical debulking, laser ablation, electrocautery, cryoadhesion, argon plasma coagulation, microdebrider, and resector balloon (Table 2)
    • EAT with delayed effect is most suitable for lesions that are not acutely symptomatic but are at risk of causing significant hemorrhage, and includes contact cryotherapy, spray cryotherapy, photodynamic therapy, and brachytherapy (Table 3)
• Surgical resection
  • Consult thoracic surgery on all patients who are willing and potentially able to undergo surgical resection
  • In cases of localized disease, particularly in less aggressive malignancies such as carcinoid tumor, surgical resection can be curative³⁶³⁷
• Radiation therapy
  • Consult radiation oncology in cases where part or all of the tumor is extrinsic to the airways and causing significant impingement on airways or blood vessels (eg, superior vena cava syndrome, compression of a pulmonary arterial vessel)³⁸
  • According to a retrospective analysis of 237 patients with malignant CAO, therapeutic bronchoscopy (ie, stenting) combined with radiation therapy was associated with improved survival compared with either therapy alone³⁹

Table 2. Endobronchial ablative therapies with immediate effect.

Modality	Technique	Bronchoscopy	Advantages	Disadvantages	Complications
Mechanical debulking: Rigid40	Tumor coring out with the beveled edge of rigid bronchoscope Tumor excision with rigid forceps Tumor debulking with micro-debrider	Rigid only	Fastest modality for establishing airway patency	No hemostatic property so risk of hemorrhage Only suitable for central airways Requires significant expertise	Bleeding Airway perforation
Mechanical debulking: flexible	Tumor excision with flexible forceps	Flexible	Widely available Can be used in lobar and segmental airways	No hemostatic property so risk of hemorrhage Most suitable for smaller lesions	Bleeding
Cryoprobe debulking41	Cryoprobes of varying sizes from 1.1 to 2.4 mm Freeze-thaw cycles used to excise and retrieve tumor in a piecemeal fashion	Deployed through flexible bronchoscope However, often used as an adjunct to rigid bronchoscopy	Can be used for both central and distal lesions	No inherent hemostatic properties	Bleeding
Argon plasma coagulation42	Catheter delivers an inert gas, which in turn conducts high frequency current to the lesion Non-contact, thermal modality	Deployed through flexible bronchoscope However, often used as an adjunct to rigid bronchoscopy	Excellent hemostatic properties Minimal charring	Superficial effect so not good for tumor debulking Expensive FiO2 less than 40%	Airway fire Gas embolism (especially with inadvertent contact with lesion, or larger lesions, prolonged use)
Electrocautery	Can be delivered via rigid or flexible probes Alternating high frequency current generates heat Contact, thermal modality	Flexible or rigid	Tumor coagulation and debulking Electrosurgical units widely available	Can produce significant charring FiO2 less than 40%	Airway fire Airway perforation
Laser	Nd:YAG laser most commonly used Fiber emits laser, light energy converted to heat Noncontact, thermal	Deployed through flexible bronchoscope However, often used as an adjunct to rigid bronchoscopy	Tumor coagulation and destruction Less charring compared to electrocautery	Expensive Large team Specialized training and credentialling needed Expensive, not widely available Large machine	Airway fire Airway perforation

Caption: FiO2, fraction of inspired oxygen; Nd:YAG, neodymium-doped yttrium aluminum garnet.

Table 3. Endobronchial ablative therapies with delayed effect.

Modality	Technique	Bronchoscopy	Advantages	Disadvantages	Complications
Cryotherapy	Cryoprobes of varying sizes from 1.1 to 2.4 mm Freeze-thaw cycles used, without pulling on the tumor between freezing and thawing Repeated freezing and thawing, causes tumor devascularization Tumor sloughs off over 1 to 2 weeks	Flexible	No need to reduce FiO2 Low risk of bleeding and airway perforation	Time consuming May need repeat procedure to clean up the sloughed off tumor Different tissues may have varying response
Photodynamic Therapy43	Systemic injection of photosensitizing drug, preferentially absorbed by the tumor 2 to 3 days later, diode laser light shone on the tumor via bronchoscope to activate the photosensitizer. Free radicals cause cell death and tumor destruction Repeat bronchoscopy in 2 to 3 days to clear the sloughed off tumor	Flexible	Lower risk of bleeding even for highly vascular tumors Can be used for radio-occult tumors and stump recurrences	Requires inpatient stay Multiple procedure Time consuming Expensive FiO2 less than 40%	Photosensitivity Airway perforation Fistulas Airway fire Airway edema Retained secretions
Endobronchial brachytherapy44	Catheter placed in the airway close to the tumor, under bronchoscopic guidance Radiation delivered via this catheter	Flexible	Lower risk of bleeding Has an impact both on endobronchial and extrinsic lesions	Expensive Limited availability Time consuming	Bleeding Airway fistula formation

Caption: FiO2, fraction of inspired oxygen.

Persistent or Recurrent Disease

• Most patients with malignancy-associated airway obstruction, particularly CAO related to bronchogenic cancer, will require subsequent surgical resection, systemic therapy, and/or radiation therapy after initial intervention; these may be offered with curative or palliative intent depending on the disease stage³⁹⁴⁵
• Many patients with malignancy-associated CAO that undergo bronchoscopic treatment will experience recurrent airway-associated malignancy, even in the presence of adjuvant systemic or radiation therapy; close monitoring via cross-sectional imaging or interval bronchoscopic surveillance is recommended
  • A 4- to 6-week surveillance interval is often suitable, but this time frame should be individualized based on multidisciplinary input on the observed or anticipated rate of disease progression⁴⁶

Admission Criteria

• Patients with symptomatic CAO should be hospitalized with a low threshold for monitoring in the ICU, particularly cases involving hemoptysis at risk for hemodynamic decompensation
• Once therapeutic bronchoscopy has been performed, the majority of patients will have symptomatic improvement and can often be discharged within a day
• Given the urgency and complexity of the condition and the need for extensive work-up involving multi-disciplinary discussion, hospitalization to expedite the workup and formulation of a management plan may be prudent in select cases

Special Considerations

Need for ECMO (Extracorporeal Membrane Oxygenation)

• In a small number of patients with severe symptomatic CAO and respiratory distress, the risk of therapeutic bronchoscopy might be considered prohibitive
• This is especially true for tracheal and carinal obstruction, where there is a risk of compromising all ventilation in cases of bleeding, edema, or mass effect
• In these cases, the bronchoscopy can be performed while the patient’s gas exchange is supported with VV-ECMO (veno-venous ECMO) circuit⁴⁷⁴⁸
• Consult cardiothoracic surgery and mechanical circulatory teams for additional support required for the institution of ECMO; a careful risk-benefit assessment is recommended to determine which patients would most benefit from ECMO support given the risks associated with procedure and associated delays to definitive management of the CAO

Follow-up

Monitoring

• Recommend a follow-up CT scan after an initial bronchoscopic intervention to assess for disease recurrence or progression⁴⁶⁴⁹
  • A 4- to 6-week interval is often suitable, but this time frame should be customized based on multidisciplinary input on observed or anticipated rate of disease progression
  • Patients should be advised to monitor closely for symptoms including dyspnea, cough, and/or hemoptysis indicative of recurrence of CAO, with a low threshold to contact their pulmonary team with any concerns
• Recommend close outpatient monitoring of patients following airway stent placement, which can be associated with airway complications such as granulation tissue formation, migration, mucus plugging, and infection³⁴
  • Many institutions practice some form of a “stent regimen” to reduce the risk of mucus plugging within stents; this regimen may include oral guaifenesin, nebulized treatments (eg, saline nebulization twice daily), and airway clearance maneuvers (eg, regular use of flutter valve devices)⁵⁰
  • It is recommended that airway stents be removed as soon as feasible, preferably once adjuvant therapies have commenced and the tumor has demonstrated some regression

Complications

• The American College of Chest Physicians (CHEST) Quality Improvement
• Registry, Evaluation, and Education (AQuIRE) registry analysis remains the largest study to date assessing outcomes of therapeutic bronchoscopy in malignant CAO⁵¹
  • Included 1115 procedures in 947 patients across 15 centers
  • Overall complication rate was 3.9%; of these, 61% of patients required an escalation of the level of care
  • Most common complications included bleeding and respiratory failure
  • 0.5% of patients died due to procedural complications, while the 30-day mortality was 14.8%
  • Factors associated with complications included urgent/emergent procedures, sicker patients (American Society of Anesthesiologists score greater than III), redo therapeutic bronchoscopy, and the use of moderate sedation
• Complications associated with EAT are noted in Tables 2 and 3

Prognosis

• A successful therapeutic bronchoscopic procedure, defined as restoration of the airway lumen to more than 50% of the normal diameter, has been reported to occur in more than 90% of cases in multiple studies⁵¹⁵²
  • This does not always lead to clinical improvement
• Two prospective observational studies showed a majority of patients with improved dyspnea (85%) and quality of life scores (65%) 1 month following therapeutic bronchoscopy⁵³⁵⁴
• Therapeutic bronchoscopy has also been shown to be very effective at liberating patients with malignant CAO and respiratory failure from mechanical ventilation and facilitating their transfer out of ICU⁵⁵⁵⁶
• CAO is one of multiple complications of the overall malignant process; long-term prognosis of these patients is affected by multiple factors associated with their underlying malignancy

Referral

• Refer patients with symptomatic CAO to a tertiary care center with infrastructure to support complex airway diseases, when feasible
• Recommend consultation with a multidisciplinary team that includes an interventional pulmonologist, thoracic surgeon, and anesthesiology team, and confirm that the necessary equipment and expertise is available
• Consult with pulmonary and critical care specialists regarding most appropriate therapies to support patient during interfacility transport, when necessary
  • Patients can be bridged with heliox, supplemental, including high-flow, oxygen, or invasive or noninvasive mechanical ventilation during transport, as appropriate

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