Bronchial thermoplasty is an innovative, investigational procedure for the treatment of asthma designed to reduce the amount of airway smooth muscle1 with the goal of decreasing bronchoconstriction and the frequency and severity of asthma symptoms.2 Bronchial thermoplasty consists of the tightly controlled delivery of radiofrequency (RF) electrical energy to the airway wall via a special catheter electrode. This controlled delivery of electrical energy heats the airway wall to a specific target temperature. This in turn leads to a decrease in airway smooth muscle mass. RF electrical energy is systematically applied to the majority of airways between 3 and 10 mm in diameter throughout the tracheobronchial tree. Although similar in basic principles to conventional RF ablation, the delivery of the energy during bronchial thermoplasty uses continuous feedback to tightly control the degree of tissue heating to achieve the desired effect: decreased airway smooth muscle mass without airway perforation or stenosis.
Bronchial thermoplasty is currently an investigational, outpatient bronchoscopic procedure performed using the Alair Bronchial Thermoplasty System (Asthmatx, Inc, Mountain View, CA).3 The Alair System has been used safely in animals,2 and both nonasthmatic4 and asthmatic human subjects.5 Previous unblinded clinical studies comparing bronchial thermoplasty to standard medical therapy in asthmatic subjects have demonstrated an improvement in asthma control5,6 and quality of life.7 Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This manuscript discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely. The guidelines outlined here are based on the considerable experience of the authors with this procedure as investigators in prior and ongoing clinical trials.3,5,7–9
BRONCHIAL THERMOPLASTY PROCEDURE
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate (formerly called conscious) sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and nonoverlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously.1,2,5 The procedure is completed in 3 bronchoscopy sessions, each lasting less than 1 hour, and each spaced apart by about 3 weeks.
Bronchial thermoplasty is performed using the Alair Bronchial Thermoplasty System comprising the Alair RF Controller, and the Alair Catheter (Fig. 1). The Alair Catheter is a single use, long, flexible device with an expandable electrode array attached at one end and a deployment handle at the other. This device is designed to be delivered under direct visualization through the working channel of a standard bronchoscope. The electrode array is expanded to contact the airway walls and then activated to deliver RF electrical energy. The Alair RF Controller is a compact electronic instrument which generates controlled RF energy. As electrical energy is transferred from the electrode to the tissue, resistance causes the electrical energy to be converted to thermal energy. The controller delivers the correct intensity and duration of energy for the asthma treatment application, which reduces the amount of airway smooth muscle tissue, while minimizing collateral damage to other airway supporting structures. The controller also monitors the system to ensure proper set-up. Energy cannot be delivered until all accessories are properly connected, and if the electrode array is not in proper contact with the airway wall, the front panel notifies the bronchoscopist to reposition the electrode array to make proper contact. A standard gel-type patient return electrode is affixed to the patient and connected to the controller to provide a complete circuit.
The Alair Bronchial Thermoplasty System must be used in conjunction with RF or high frequency compatible flexible bronchoscopes, ideally with a 4.9 to 5.2-mm outer diameter and a 2.0-mm minimum working channel. Larger bronchoscopes (>5.2-mm OD) are not recommended because they limit access to smaller airways.
During the previous human clinical studies and for the present pivotal trial of bronchial thermoplasty, the entire bronchial thermoplasty treatment was performed during 3 bronchoscopy sessions, each separated by about 3 weeks. This divided treatment approach is designed to minimize the risk of inducing an asthma exacerbation or diffuse airways edema that might occur if the entire tracheobronchial tree is treated during a single session. This also avoids excessive procedural length. During the first bronchoscopy, the right lower lobe is treated. The left lower lobe of the lung is treated in the second bronchoscopy. Both the right and left upper lobes are treated in the third and final bronchoscopy.5 The right middle lobe is not treated because of theoretical concerns of inducing right middle lobe syndrome stemming from the long and narrow lobar airway typically leading to the right middle lobe.1,10 No experience exists in treating the right middle lobe with bronchial thermoplasty at the present time. During the second and third bronchoscopy sessions, previously treated airways are first visualized by bronchoscopy to ensure adequate healing of previously treated segments before proceeding with further treatment.
For an individual bronchoscopy session the patient is first prepared in the manner outlined in the patient management section below. The bronchoscope is then introduced and any previously treated airways are inspected to evaluate for possible mucous impaction or scarring and to ensure adequate healing. If previously treated areas have not healed, consideration is given to postponing treatment. After this inspection, the bronchoscope is navigated to the region of the lung that is to be treated next, and the bronchoscopist plans the order in which the airway segments are to be accessed and treated. This treatment planning is crucial to the success of bronchial thermoplasty. If the airways are approached in a random fashion, some airways may be treated twice whereas other airways may be skipped entirely. We recommend a systematic approach from distal to proximal, working methodically from airway to airway across the region of lung being treated to ensure that all accessible airways are carefully identified and treated only once. For example, planning for treatment of the right lower lobe working distal to proximal might allow initial treatment of the anterior basal segment followed by the lateral and posterior basal segments. The medial basal segment is then treated followed by the distal portion of the right lower lobe bronchus up to the level of the superior segment, and finally the superior segment. Within each segment, the subsegmental airways should also be treated in a systematic manner, moving from superior airways to those that are more inferior, or moving from airways to the right of the field of view to those that are more to the left.
After treatment planning, the bronchoscopist then navigates to the most distal region of the first airway to be treated, positioning the bronchoscope with the targeted treatment site in clear bronchoscopic view. The catheter is then introduced into the working channel of the bronchoscope and advanced until the distal end is in bronchoscopic view. Once at the targeted region, the electrode array is expanded until the 4 electrode wires firmly contact the airway wall, being careful not to over expand the electrodes as this may result in distortion of the electrode array. Proper contact of the electrodes with the airway wall should be confirmed visually (Fig. 2). With the electrode array properly positioned and expanded, the bronchoscopist initiates energy delivery by pressing and releasing the controller footswitch. The controller will deliver energy automatically for approximately 10 seconds according to preset treatment parameters programmed into the controller. After each activation the bronchoscopist partially collapses the electrode array and repositions it proximally about 5 mm, adjacent to and not overlapping the previous activation site. This process is repeated along the entire length of each targeted airway as shown in Figure 3 and progresses from airway to airway as determined during treatment planning. The electrode array position should be referenced to anatomic landmarks because of the potential for relative motion between the bronchoscope, catheter, and airways. The use of a “map” of the airways to plan and track the progression of the treatment for each session is recommended (Fig. 4).
On occasion, mucous may build up in the airways and obscure bronchoscopic visualization. When this occurs, the electrode array can be completely retracted and the catheter removed from the bronchoscope allowing irrigation and suctioning. We take advantage of this opportunity to gently clean the electrode array with sterile saline and to apply more topical anesthesia to the airways if needed.
Patients should be selected for bronchial thermoplasty by a medical team consisting of an asthma specialist closely associated with an experienced bronchoscopist. In some cases, the same physician could be responsible for both patient selection and treatment if they have the appropriate experience. The asthma specialist should ensure that patients:
- are selected appropriately, based on the patient populations that have been studied in clinical trials (Table 1),
- are on stable maintenance asthma medications according to accepted guidelines,11,12
- are stable with respect to asthma status (no current respiratory tract infection, no severe asthma exacerbation within the last 4 weeks, forced expiratory volume in 1 second (FEV1) within 10% of the best value),
- do not have any unstable comorbid conditions that would put them at risk for bronchoscopy, such as untreated obstructive sleep apnea or clinically significant cardiovascular disease, epilepsy, insulin-dependant diabetes, or cancer.
Before considering a patient for bronchial thermoplasty the physician should obtain a detailed medical history and perform appropriate medical evaluations to determine the patient's suitability to undergo this procedure. Table 1 outlines considerations for patient selection, based on the patient populations that have been studied in clinical trials to date. Analysis of the randomized, double-blinded sham controlled study currently underway may provide additional insight into the patient population that would benefit most from bronchial thermoplasty.
As with other medical procedures, the success of bronchial thermoplasty depends upon a number of variables. In particular, a successful procedure will depend on a carefully selected patient, the technique of the bronchoscopist, and adequate patient management at the time of the procedure. Bronchial thermoplasty can only be performed effectively when a patient is adequately medicated to provide anxiolysis, analgesia, and topical anesthesia, thereby ensuring patient comfort and reducing excessive patient movement. Reducing airway secretions is also important to the procedure's success. Good topical anesthesia of the airway with an appropriate level of sedation not only facilitates the procedure, but also will increase patient satisfaction. The approach to patient preparation and management is outlined in Table 2 and detailed below.
Patient Preparation and Premedication
The risks and benefits of the procedure and sedation should be fully discussed with the patient. To minimize postprocedure inflammation of the airways, patients should be given prophylactic prednisone or equivalent at a dosage of 50 mg/d for the 3 days before the procedure, the day of procedure, and the day after the procedure.3 With each procedure, the asthma specialist and/or bronchoscopist should ensure that patients:
- do not present with cold or flu symptoms the day before or day of the procedure,
- are kept under observation for an appropriate period of time after each procedure,
- are discharged when their asthma condition is acceptable, as outlined in the Postprocedure Care section below,
- receive appropriate follow-up after each procedure to ensure their asthma control remains acceptable, and are referred to the asthma specialist if they present with worsening of asthma symptoms or other unanticipated side effects.
On the day of each procedure, the bronchoscopist needs to reevaluate and ensure that the patient remains a good candidate for bronchial thermoplasty under moderate sedation (Tables 3, 4). The bronchoscopy should be postponed if any of the conditions listed in Table 3 apply. The patient should be educated on bronchoscopy and the sensations to anticipate during and after a bronchoscopic procedure to alleviate some of their anxiety. The bronchoscopist should confirm that the patient has had nothing by mouth after midnight to reduce the risk of pulmonary aspiration and that the appropriate fasting guidelines of the institution are followed. A peripheral intravenous (IV) line and supplemental oxygen via oral or nasal cannula are recommended with appropriate monitoring for moderate sedation. Such monitoring should include continuous electrical cardiac monitoring, continuous pulse oximetry, and noninvasive blood pressure monitoring.
Once IV access is established and monitors have been applied, premedications can be administered to the patient in preparation for bronchial thermoplasty. Preprocedure medications are outlined in Table 2. If the patient has not taken their prescribed oral prednisone on the day of the procedure, premedication should include IV administration of methylprednisolone or its equivalent. Albuterol and an antisialogogue agent such as glycopyrrolate should be administered a minimum of 30 minutes before the procedure. As an alternative to glycopyrrolate, atropine may be used. Caution should be used with these agents due to their chronotropic risks and physicians should consider their individual institutional guidelines regarding which drugs may be given intravenously. Glycopyrrolate is preferred over atropine because it is a superior drying agent with fewer propensities for adverse central nervous system effects or tachyarrhythmias. Glycopyrrolate administered IV reduces airway secretions much faster (approximately 5 min) than with an IM route (approximately 30 to 60 min). Properly treating the patient with an effective drying agent is important in bronchial thermoplasty as it reduces the amount of airway secretions and may improve visibility through the bronchoscope. Though perhaps not clinically proven to have a meaningful effect in improving topical anesthesia in other bronchoscopic procedures,13 the authors have experienced the benefits of an effective drying agent in bronchial thermoplasty.7–9 Additionally, the physician may give midazolam for anxiolysis while the patient is on the monitor with supplemental oxygen. The goal is to relax the patient in preparation for topical anesthesia of the airway.
Supraglottic Topical Anesthesia
Bronchial thermoplasty is performed with a bronchoscope either through an oral or nasal approach, with the majority of cases done via a nasal approach because patients seem to have less gagging and fewer secretions. Application of topical anesthesia may start with 5 mL of 1% lidocaine jelly applied to the nostril being used for inserting the bronchoscope. The physician may use more or less to achieve the end point, which is an anesthetized and lubricated nasal passage. Using 1% lidocaine allows the bronchoscopist to have more local anesthetic available for topicalizing the bronchial tree. If there are concerns with epistaxis, phenylephrine or oxymetazoline spray or topical cocaine may be used.
The next step is for the bronchoscopist to adequately anesthetize the hypopharynx. An approach that is easy and effective is to have the patient gargle with 5 mL of 2% lidocaine and then expectorate. This limits the systemic absorption of lidocaine and decreases the likelihood of toxicity. Another option is to aerosolize the posterior pharynx with 1% to 2% lidocaine. Regardless of technique, the goal is to anesthetize the patient's posterior pharynx to significantly diminish or eliminate the patient's gag reflex.
Vocal Cord and Subglottic Topical Anesthesia
Once the patient's upper airway has been sufficiently anesthetized, application of topical anesthesia to the vocal cords and bronchial tree can proceed. Although different concentrations of lidocaine may be used, 1% lidocaine is recommended to limit the potential for lidocaine toxicity. At the vocal cord level, 1% lidocaine can be applied in small (2 mL) aliquots until the patient seems comfortable with minimal coughing. After vocal cord topical anesthesia, the patient's sedation level is reassessed and considerations are made for supplementing with more anxiolytic or antitussive medications (see Sedation section) as needed. As the bronchoscopist proceeds down the airway, 1% lidocaine should be used in small (0.5 to 2 mL) aliquots down the bronchial tree. The bronchoscopist should apply the local anesthetic, focusing more attention on the airway segments being targeted for treatment. After 30 to 40 minutes into the procedure, the bronchoscopist may consider application of additional topical anesthesia if necessary.
The maximum dose of lidocaine is often institution specific; however, 600 mg or 8.2 mg/kg of lidocaine or less has been used safely in asthmatics undergoing bronchoscopy.14 The patient should be continuously monitored for signs and symptoms of lidocaine toxicity. Toxic reactions to local anesthetics most frequently involve the central nervous system and may include: lightheadedness, tongue numbness, visual changes, auditory disturbances, seizures, or loss of consciousness.15 If doses exceed the maximum limits, consider monitoring lidocaine levels postprocedure.
Once the patient's airway is adequately anesthetized it is critically important to achieve or maintain an optimal level of sedation. Most patients can undergo bronchial thermoplasty under moderate or conscious sedation. It is recommended that institutional sedation guidelines are followed. The American Society of Anesthesiologists (ASA) provides the following definitions for various levels of sedation that are recognized by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO)16:
- Minimal sedation (anxiolysis) is when a patient responds normally to verbal commands;
- Moderate sedation (formerly conscious sedation) is when a patient responds purposefully to either verbal commands alone or with light tactile stimulation;
- Deep sedation is when a patient cannot be easily aroused but responds purposefully with repeated or painful stimulation. Cardiovascular function is usually maintained.
Sedation is a continuum and health care providers intending to induce a given level of sedation need to closely observe the patient and have the skills necessary to support patients whose sedation becomes deeper than intended.
Sedation is generally achieved using a combination of a short acting benzodiazepine and a narcotic. The authors suggest that the optimal combination is midazolam and fentanyl, but other medications can be used. Midazolam is a fast acting benzodiazepine with a short half-life, and it can be easily titrated to effect. It is often initially given in a 1 to 2-mg loading dose followed by incremental doses of 0.5 to 1 mg as needed. The onset of the effect is within 1 to 3 minutes, with a maximum duration of about 2 hours. Midazolam also produces antegrade amnesia, anxiolysis, and has an anticonvulsant effect. The objective is patient anxiolysis and patient comfort while still maintaining adequate spontaneous ventilation during the procedure. The typical dose range for midazolam during bronchial thermoplasty is 2 to 10-mg IV. Supplemental doses should be given if the patient is anxious or has minimal sedation assuming adequate oxygenation and ventilation. The precise timing of sedation will vary between patients and largely depends upon the clinical judgment of the physician.
Fentanyl is also an effective sedating agent used during bronchial thermoplasty and it is beneficial because it has both potent analgesic and antitussive properties. An effective loading dose is 50 to 100-μg IV with additional doses of 25 to 50-μg IV as needed. Onset of action is 2 to 4 minutes with a peak effect at 10 to 15 minutes and duration ranging from 30 to 60 minutes. Supplemental doses should be administered if the patient has minimal sedation, is having pain, or coughing excessively. The typical dose range for fentanyl during bronchial thermoplasty is 50 to 300-μg IV. The ultimate objective is to provide the patient with adequate analgesia and sedation with minimal coughing.
It is important to note that benzodiazepines and opiates have different mechanisms of action, but potentiate each other's actions including respiratory depression and hypotension. Therefore, frequent smaller supplemental sedative/analgesic doses allow for more effective titration. When fentanyl and midazolam are used together in low incremental doses titrated to effect, excellent sedation can be produced while avoiding side effects. The main advantage of using midazolam and fentanyl to induce moderate sedation are their fast onset times, which make them more easily titratable. In addition, both medications have reversal agents (naloxone and flumazenil, respectively) that can be used to antagonize their effects if necessary.
The use of prophylactic antiemetics can be considered when performing bronchial thermoplasty under moderate sedation, especially when opiate drugs are used. Agents such as fentanyl can significantly contribute to postprocedure nausea, which is unpleasant for the patient and leads to longer recovery times. Antiemetics to be considered may include ondansetron, metoclopramide, promethazine, or dexamethasone. Giving an antiemetic is especially important in patients with motion sickness or with a history of postoperative nausea. The addition of antiemetics can make patients more comfortable and tolerant of additional procedures by minimizing any nausea they may experience. The complete patient management protocol is summarized in Table 2.
Postprocedure care should follow appropriate institutional guidelines, and it is recommended that patients should be carefully monitored and discharged only after they are deemed to be stable and have adequate (comparable to preprocedure) lung function, mental status, and are able to take liquids adequately. Immediate postprocedure follow-up should include assessment of gag reflex, vital signs, breath sounds, and spirometry to assess FEV1. A listing of recommended postprocedure assessments is provided in Table 4.
As with any bronchoscopic procedure, there is an expected increase and worsening of respiratory-related symptoms in the period immediately after bronchial thermoplasty, such as breathlessness, wheeze, cough, chest discomfort, night awakenings, and productive cough.5,7 These symptoms typically present within 1 week of bronchoscopy and resolve with standard medical care on average within 1 week. Therefore, it is recommended that the patient be contacted 24 hours, 48 hours, and 7 days postprocedure to assess their status after the bronchoscopy. In particular, there is also a potential for excess mucus production in response to bronchoscopy and bronchial thermoplasty in asthma patients. It is expected that coughing will clear any excess mucus; however, it is possible that the mucus may become thickened and occlude the airway. In the event thickened mucus is suspected, a chest radiograph should be obtained and, if mucus plugging is confirmed, patients should be treated with chest physiotherapy and/or therapeutic bronchoscopy as indicated. They should also be monitored carefully until resolution occurs. In considering the potential long-term role for bronchial thermoplasty in the treatment of asthma, the short-term risk of increased respiratory-related symptoms should be weighed against the potential for improvement in asthma control.
Bronchial thermoplasty delivered with the Alair Bronchial Thermoplasty System is an investigational procedure designed to reduce the amount of airway smooth muscle1 and hence the potential for bronchospasm and asthma symptoms. In an unblinded, multicenter, randomized clinical trial involving patients with asthma, bronchial thermoplasty was shown to improve asthma control and quality of life.7 Although the potential for a strong placebo effect exists in this unblinded study, the magnitude and persistence of the effects observed were likely greater than what could be attributed to placebo alone.
Successful bronchial thermoplasty requires that all accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, be treated once and only once. To achieve this goal, a systematic approach moving from distal to proximal within an airway and working methodically from airway to airway across the region of lung being treated is recommended. This systematic approach results in a bronchoscopy that is generally longer in duration than bronchoscopies performed for bronchoalveolar lavage or tissue biopsy. Excellent patient management during bronchial thermoplasty must be emphasized because optimal administration of the treatment requires minimal patient movement during the procedure. Thus, adequate and effective administration of sedatives and analgesics to achieve and maintain moderate sedation is critically important. Because the full treatment of the entire lung requires more than one bronchoscopy session, it is important that patient comfort is maximized so that the patient's anxiety for future bronchoscopies is minimized.
The choice of medications necessary for good patient management will ultimately be the choice of the physician performing the procedure and may vary based on country or institution-specific guidelines and practices. However, midazolam and fentanyl are currently recommended and are excellent choices because of their familiarity, ability to be carefully titrated, and if necessary, to be rapidly reversed. In the future, the use of other sedative/hypnotics such as propofol during bronchial thermoplasty may prove to be advantageous.17 The efficient initial induction and subsequent clearance of propofol from the plasma with minimal central nervous system effects is especially useful for outpatient procedures like bronchial thermoplasty. The use of propofol would likely reduce the postprocedure recovery time for patients. However, administration of propofol by someone other than an anesthesiologist remains controversial and its acceptance for use in the United States currently varies by hospital and also by state.
Current sedation guidelines (as adopted by JCAHO from the ASA definitions) acknowledge the sedation continuum and include the concept of rescue. Physicians administering moderate sedation should have the skills and equipment necessary to “rescue” a patient from unintended deep sedation. Practitioners should consider the sedation and procedure guidelines at their particular institution.
Bronchial thermoplasty is a complex procedure that requires considerable expertise in flexible bronchoscopy, and a systematic approach to ensure that all accessible airways are identified and treated properly. Bronchoscopists should perform bronchial thermoplasty in a supervised setting to establish basic competency in patients with asthma and to become comfortable with the intricacies of the procedure. The authors of this manuscript were trained by the manufacturer of the Alair Bronchial Thermoplasty System before participating in the clinical study. Individual institutions will ultimately decide on the competency of each bronchoscopist interested in performing bronchial thermoplasty.
Preliminary clinical results of bronchial thermoplasty seem encouraging,5,7 although these findings should be interpreted with caution, as these were unblinded studies of a procedure with a high potential for placebo effect. An appropriately powered, blinded, sham-controlled study is currently underway to assess the ultimate risk to benefit ratio of this procedure.
In conclusion, bronchoscopy experience, careful patient selection, patient management during the procedure and appropriate postprocedure follow-up should all be considered for bronchial thermoplasty to be safe and to achieve the best possible outcomes.
The authors are indebted to Gerard Cox, MB and John Miller, MD (McMaster University, Hamilton, Canada) for pioneering bronchial thermoplasty for the treatment of patients with asthma and to the AIR and RISA Trial Study Groups for their important contributions to the advancement of bronchial thermoplasty.
The Alair Bronchial Thermoplasty System has received a CE Mark to sell the device in the European Union and it is currently under investigation in a FDA approved IDE pivotal clinical trial in the United States (www.clinicaltrials.gov/ct/show/NCT00231114?order=1).
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