Airway obstruction

Central airway obstruction refers to significant obstruction of the trachea and main bronchi. Patients with advanced-stage lung cancer who have this complication are likely to have significant dyspnea and hemoptysis, which can become life threatening, because the onset of stridor implies impending airway obstruction and requires immediate attention. Obstructive symptoms can be caused by intraluminal tumor obstruction, extraluminal tumor compression, or both; airway obstruction by the tumor can also produce aggravating factors due to excessive mucous production and plugging, postobstructive pneumonia, and hemoptysis. Appropriate therapeutic strategies must be anticipated to provide palliation and symptomatic relief.

Bronchoscopy remains the single most important diagnostic and therapeutic tool for managing airway obstruction. Several different bronchoscopic interventions are available to palliate airway obstruction in advanced-stage lung cancer. Choosing one bronchoscopic intervention over another is more often determined as much by physician bias as by the cause and anatomic location of the obstruction and patient comorbidities. It is very important to recognize that there are some patients with locally advanced lung cancer involving the central airways who may be amenable to a curative-intent resection involving a tracheoplastic or bronchoplastic procedure. Treatment decisions to offer only palliative endobronchial management in locally advanced lung cancer should be rigorously avoided when potential definitive tracheobronchial resection and reconstruction could be otherwise considered with complete resection. Patients with advanced non–small cell lung carcinoma (NSCLC) with malignant central airway obstruction who undergo local treatment by therapeutic bronchoscopy do not have worse survival than those with advanced-stage lung cancer without airway obstruction. Therefore, therapeutic bronchoscopy should be offered to those patients with advanced-stage NSCLC and airway obstruction as an effective palliative measure.

Patients with symptoms from central airway compromise can be offered several different bronchoscopic options. Tumors that invade into the airway can be treated by mechanical core-out, laser ablation, electrocautery, and dilatation and stent placement. Each of these approaches has the benefit of reliable and immediate improvement in appropriately selected patients. Cryotherapy, photodynamic therapy (PDT), and brachytherapy also are effective for treating endoluminal tumors but usually require several days to achieve a tumor response and so have a more limited role in the management of patients who are acutely symptomatic due to central airway obstruction. Extraluminal compression of central airways by tumor causing severe symptoms is not usually palliated well by techniques other than dilatation and stenting. When therapeutic bronchoscopy is unavailable for patients with impending death from airway compromise, endotracheal intubation passing the tube beyond the area of stenosis with the aid of flexible bronchoscopy can be temporarily lifesaving before the patient is transferred to a referral center.

Bronchoscopic debridement of intraluminal tumor obstruction can quickly and effectively palliate airway obstruction and relieve dyspnea. Rigid bronchoscopy is the preferred technique and is a safe effective method to evaluate and stabilize a patient with airway compromise from tumor invasion or compression. The rigid bronchoscope is much quicker and more effective in accomplishing this task than the flexible bronchoscope. Rigid bronchoscopes are available in different diameters; by maneuvering the bronchoscope beyond the area of obstruction, the patient can be ventilated during the intervention, and further evaluation of the nature of the obstruction can be done concomitantly. Flexible bronchoscopy can be performed through the rigid scope, which allows distal airway evaluation and treatment. In many situations, the act of performing a rigid bronchoscopy dilates the area of obstruction; however, the benefit of this method is brief in cases of obstruction from lung cancer, in which obstruction occurs predominantly from extrinsic compression of the airway. In situations in which there is an endoluminal component to airway obstruction, the rigid bronchoscope is used to core out the obstructing lesion with the beveled tip of the rigid bronchoscope applied at the base of the tumor. Retrieving the pieces with biopsy forceps piecemeal using the biopsy forceps through the rigid bronchoscope can be helpful. The benefit of such a core-out procedure is its technical simplicity and the lack of need for additional equipment beyond the standard instruments used in rigid bronchoscopy. Rigid bronchoscopy also allows access for additional therapies to palliate and alleviate the acute symptoms caused by central airway obstruction from lung cancer and has been shown to be an effective technique to permit immediate discontinuation of mechanical ventilation in patients who had required intubation for airway compromise from lung cancer.

Laser resection, electrocautery, and stenting are therapeutic bronchoscopic techniques that can provide immediate relief from endoluminal airway obstruction and can be used independently or in conjunction with bronchoscopic debridement. Laser resection can be performed via rigid bronchoscopy or flexible bronchoscopy and essentially has the same indications as mechanical core-out procedures for treatment of malignant airway obstruction. Laser resection is not effective in cases of dominant external compression, and a relative contraindication is hypoxemia because the risk of fire limits the inspired oxygen fraction to no greater than 40% fraction of inspired oxygen. When done using flexible bronchoscopy, laser resection using the Nd:YAG laser can be performed under topical anesthetic and is able to reach the lobar orifices more easily than mechanical debridement by rigid bronchoscopy. The main goal of laser resection is palliation of symptoms in patients with inoperable lung cancer with endobronchial manifestations, and, as such, there is little improvement in ventilation with laser resection of obstruction of the segmental bronchi. Laser resection is a substantially longer process than mechanical debridement, requires significant additional equipment and cost, and incurs the additional risks of airway fire, perforation, and fistula formation. In general, there is little practical benefit of laser resection alone over mechanical core-out procedures in cases of malignant endoluminal obstruction, but it is often combined with other treatment modalities, especially as a means of assuring hemostasis.

Electrocautery refers to application of electrical current to produce tissue heating and coagulation as electrons are conducted to the tissue because of voltage differences between the electrocautery probe and the target tissue. Argon plasma coagulation (APC) is also a mode of electrocoagulation. In APC, the ionized argon gas jet flow conducts electrons, allowing a noncontact mode of treatment. Both methods result in coagulative necrosis of the tumor lesion. The therapeutic goal of electrocautery/APC in advanced-stage lung cancer is the same as laser resection and mechanical debridement: to achieve immediate debulking of endobronchial lesions. In contrast to laser resection, electrocautery has a more superficial effect and does not produce deep tissue necrosis, which is preferable if major vessels are in the vicinity. In addition, electrocautery/APC does not have the logistical concerns of laser, such as, special eye protection is not necessary, and it can be performed by flexible bronchoscopy. From a cost standpoint, electrocautery/APC is less expensive to perform than laser resection. The success rate of this technique is comparable to other bronchoscopic debulking techniques, and the technique is on the order of 70% to 80% effective.

PDT, brachytherapy, and cryotherapy have also been used as palliative treatment in patients with advanced-stage lung cancer and obstructive central lesions. However, these techniques have a delay in treatment response and therefore are not suitable in patients with acute obstructive symptoms. Cryotherapy is more limited in use than either PDT or brachytherapy in bronchoscopic palliation of primary lung cancer. All 3 modalities, like the previously discussed interventions, are applicable only to tumors that have an endoluminal component requiring treatment.

PDT is a 2-stage treatment process that produces tumor necrosis by excitation of a chemical photosensitizing agent (eg, porfimer sodium) by a specific light wavelength that matches the absorption band of the agent. The first stage is photosensitization of the bronchial tumor lesion, which is then followed by the illumination stage with exposure of the agent to the light of specific wavelength. At present, Photofrin (Axcan Pharma Inc) is licensed for use in advanced-stage lung cancer by the Food and Drug Administration and is the most commonly used photosensitizer with a long-standing safety record. The recommended dose of the drug is 2 mg/kg body weight and is administered intravenously 24 to 72 hours before the illumination stage. The light that activates the porphyrin-based photosensitizer is within the red region of the light spectrum (630 nm), and different light sources have been used, including argon dye lasers and diode lasers. Because the photosensitizer is only activated in the presence of the laser light source, specific areas for PDT can be targeted. However, indiscriminate illumination could result in collateral damage to normal tissue. The light generated by the laser is delivered to the tumor by optical fibers that are introduced via either the rigid or fiber-optic bronchoscope. The delivery fibers can be either a cylindrical diffuser, which distributes light circumferentially to be used for interstitial treatment when placed within a tumor mass or a microlens delivery fiber, which is designed for surface application. Tissue necrosis and sloughing of tissue occurs within a few days, and a follow-up rigid and flexible bronchoscopy is necessary for removal of the necrotic debris and tissue and for airway clearance, particularly infected secretions collected beyond the bronchial obstruction. Repeat treatment can also be performed after debridement but needs to be performed within the prescribed time (within 7 days of Photofrin injection) to achieve additional tumoricidal effect. Several studies have confirmed the efficacy and safety of PDT procedures for cancer, and, in those with advanced-stage cancer and endoluminal bronchial obstruction, PDT is capable of providing significant palliative improvement and may have a more durable benefit than mechanical debridement or laser resection because of its wider radial effect of tumor necrosis, which may delay tumor regrowth and obstruction. In many cases of NSCLC, patients with inoperable cancer are referred for PDT following recurrence of tumor after chemotherapy/radiotherapy. Although PDT may be an effective palliative therapy, its response is slow and should not be used as the primary intervention for treatment of obstructing central airway lesions with a threatened airway. Also, PDT is associated with considerably greater complexity than the other approaches, which must be considered when PDT is performed in fragile patients with limited life spans. Complications specific to light sensitivity, notably skin burn, can occur, and this skin photosensitivity can last for 4 to 6 weeks during which patients must avoid exposure to sunlight, a significant negative factor for quality-of-life considerations in patients being palliated for cancer.

Endoluminal brachytherapy remains one of the oldest techniques of interventional bronchoscopy, and, like PDT, its effect on tumor debulking is delayed; therefore this technique is not indicated in situations in which immediate tumor debulking for airway obstruction is required. However, brachytherapy can be used to treat airway obstruction caused by extraluminal cancer located immediately adjacent to the airway. The radiation source, iridium 192, is delivered through endobronchial catheters positioned under flexible bronchoscopy, and the therapy sessions can be performed on an outpatient basis with minimal short-term complications. Brachytherapy, therefore, is of benefit, particularly in patients with reduced performance status. The effects of high–dose rate brachytherapy can be initially observed after 1 week, and the peak effect is seen usually after 3 weeks. This technique has the benefit of having a longer-lasting tumoricidal effect than the other described bronchoscopic therapies and can also destroy tumor beyond the bronchial wall. However, brachytherapy only has an effective treatment range of 1 to 2 cm from the endoluminal source and so has no significant impact on bulky tumors involving the airway. Therefore, brachytherapy should not be used to replace standard external beam radiation therapy in most patients. Brachytherapy is primarily used in patients who have already received maximal doses of external beam radiation, and current evidence supports its role as a complementary therapy to palliate patients with airway obstruction rather than as primary therapy alone. The major contraindication for this therapy is the presence or imminent danger of fistula formation between the treated bronchi and other adjacent structures. Complications associated with brachytherapy include radiation bronchitis and stenosis and can occur days or weeks after therapy. The most important adverse effect as mentioned earlier is fatal hemoptysis and bronchovascular fistula formation, which has an overall reported prevalence of 10%.

Cryotherapy offers another modality of treating endoluminal lesions and is based on the cytotoxic effects of cold on living tissue. Cryotherapy tumor destruction relies on the formation of intracellular and extracellular ice crystals, which damage intracellular organelles and cause cellular dehydration. An additional vascular effect occurs: the cold induces an initial tissue vasoconstriction followed by a delayed vasodilation. A zone of local infarct results 6 to 12 hours later. With a 3 mm diameter cryoprobe, the area of destruction is approximately 1 cm in diameter with a depth of 3 mm. Like PDT and brachytherapy, cryotherapy has a delayed effect for tumor destruction, but it differs in that it does not induce collagen damage or risk bronchial wall perforation because collagen and cartilage are quite cryoresistant. Nonhemorrhagic necrosis of the treated lesion occurs 1 to 2 weeks after the procedure, and, generally, the necrotic tissue is expectorated or removed with follow-up bronchoscopy. Flexible cryoprobes are available and can be performed by flexible bronchoscopy; however, the cryoprobes used with rigid bronchoscopy are more powerful and less time consuming to perform. Cryotherapy has been reported to have significant palliative improvement in patients with obstructive airway symptoms from advanced-stage lung cancer, with symptomatic improvement in cough, dyspnea, chest pain, and hemoptysis as well as performance status. Although the application of cryotherapy is less widely applied, it seems as effective as the other palliative methods that use thermal energy, such as laser and electrocautery. The major disadvantage of cryotherapy is that it does require repeated applications for treatment effectiveness and therefore is not ideal for relieving acute dyspnea from airway obstruction.

None of the therapies thus far described are effective for symptomatic airway obstruction caused by extraluminal compression, which represents a high percentage of patients with advanced lung cancer. These patients often have predominant extrinsic airway compression from the disease or have endoluminal tumor obstruction with significant extrinsic compression, and, under these conditions, airway stenting is the only immediate treatment that can provide prompt symptomatic relief. The goals of tracheobronchial stenting in palliation of advanced-stage malignancy are to relieve dyspnea and improve drainage of the obstructed distal lung. Indications for airway stenting in palliation of malignant airway obstruction include the following conditions: (1) extensive tracheal or bronchial compression by the primary lung tumor or central lymph node metastasis without other treatment options, (2) airway stabilization in the acutely symptomatic or compromised patient while the tumor is treated with chemotherapy or radiation therapy, and (3) airway maintenance following tumor debulking by the various therapeutic endoluminal bronchoscopic techniques described earlier. The benefit of stenting is that it provides immediate relief of obstruction, but stenting frequently requires debulking or dilatation of the tumor lesion in order to place the largest-diameter stent possible. The primary disadvantage of airway stenting is impairment of the innate mucociliary clearance mechanisms, which can result in airway obstruction from inspissated secretions, and also obstruction from granulation tissue or tumor ingrowth can become problematic, depending on the type of stent that is deployed. Stent migration and displacement occur but are usually less problematic if an appropriate-sized stent is placed.

There are a variety of commercially available tracheobronchial stents, and a full description of the various types is beyond the scope of this review. However, the selection of the optimal stent should be based on the knowledge of the advantages and disadvantages of the individual types of stent and of their method of deployment and on the anatomic location of the lesion. In general, there are 2 types of airway stents, silicone and expandable metal stents, which can be covered or uncovered. The Dumon or Hood stents are the most widely used silicone stents and come in different diameters and lengths as well as Y configuration for placement in the lower tracheal and carinal region. These stents have external silicone studs or flanges to decrease stent migration and require rigid bronchoscopy and general anesthesia for placement. Intrinsically, silicone stents have smaller inner diameter to outer diameter ratios than metal stents, but silicone stents are relatively less expensive and have minimal tissue reactivity, allowing them to be more easily removed or repositioned.

Self-expanding metal stents have gained in popularity over the years because of their ease of insertion because they can be deployed by flexible bronchoscopy with fluoroscopic guidance and under local anesthesia. Other advantages of self-expanding metal stents include their radiopaqueness, which allows radiographic visualization; the greater airway cross-sectional diameter area due to thinner walls; and the ability of these stents to conform to tortuous airways with minimal migration as the radial expansion force is distributed more uniformly across the stent. The major disadvantage of metal stents is that they are very difficult to reposition or remove and may become secondarily obstructed by tumor ingrowth or granulation tissue. Although the covered metal stents have fewer problems with tumor ingrowth or granulation, it can still occur at the bare metal ends of these stents. Third-generation stents are now available that combine much of the advantages of both expandable and solid silicone stents. These stents are expandable and easier to place yet are completely covered, allowing the option of repositioning or removal (at the cost of more dislodgement) and avoiding the complication of tumor or granulation tissue ingrowth and obstruction.

Airway stenting has been demonstrated to be beneficial in patients with severe symptomatic airway obstruction from advanced lung cancer. Stenting is commonly followed by adjuvant therapy such as radiation and chemotherapy and has been associated with improved median survival. However, airway stenting should also be considered as primary palliative treatment in patients with obstruction of the central airways who lack other treatment options. In one study from the Netherlands, tracheobronchial stenting as part of the palliative care of patients with terminal cancer was associated with immediate symptomatic relief and quality-of-life improvement, which was found to be worthwhile even in these patients who had very limited life expectancies.

In general, a combination of all the earlier-mentioned palliative techniques can be used in a given patient. The choice and sequence of techniques used depend on availability, surgeon expertise, and longevity. Patients are often treated with one modality, receive therapy and stabilize, and then later on develop further symptoms requiring alternative techniques.